Synthesis of 2-oxophosphorindolines via the copper-catalyzed intramolecular aromatic C–H insertion of diazophosphonamidates

Abstract

An efficient synthetic method for 2-ethoxy-2-oxophosphorindolines, benzo-γ-phospholactams, has been successfully achieved through the copper-catalyzed intramolecular aromatic C–H insertion of diazophosphonamidates with up to 97% yield. The current method has advantages of mild and clean conditions, and an inexpensive catalyst.

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Introduction

Organophosphorus compounds have attracted increasing attention because of their extensive application in various fields such as pesticides, peptidic mimetics, pharmaceuticals, homogeneous catalysis, and chiral ligands.¹ In contrast to more studies that have proceeded on lactams and sultams, their analogue phospholactams,² as members of organophosphorus compounds, which are potential stocks for importantly biological compounds, have been paid less attention. Compared with the diverse synthetic methods for lactams³ and sultams,⁴ only limited methods have been reported for the synthesis of phospholactams.^2b–e,5

Indole and indoline derivatives are importantly biological compounds and extensively exist in natural products.⁶ 2-Oxophosphorindolines are phosphorus analogues of indolin-2-ones. To the best of our knowledge, very limited synthetic approaches toward 2-oxophosphorindolines have been reported.^7,8 The first synthesis of 2-oxophosphorindolines was introduced by Swan's group,⁷ involving thermal cyclization through intramolecular aminolysis of (2-aminophenyl)methylphosphinates or the zwitterionic inner salts of the corresponding amino phosphinic acids, and condensation of inner salts of the amino phosphinic acids with DCC (N,N′-dicyclohexylcarbodiimide) as coupling reagent (Scheme 1, eqn (1)). Both 2-oxophosphorindolines and 2-thioxophosphorindolines were obtained in moderate yields. Griffiths' group provided another strategy toward 2-oxophosphorindoline, only one example of 1,3-dimethyl-2-methoxy-3-dimethoxyphosphoryl-2-oxophosphorindoline separated by HPLC without reported yield,⁸ involving carbene-induced cyclization of dimethyl 2-(N-methylamino)benzoylphosphonate and trimethyl phosphate under heating and subsequently Steven-type rearrangement. Notably, both the methods of Swan and Griffiths suffer from extreme conditions and limited substrates. α-Diazo compounds have been widely applied in organic chemistry.⁹ The transition metal-catalyzed intramolecular aromatic C–H insertions of α-diazo compounds are useful methods to construct benzocyclic compounds.¹⁰ Herein, we present our convenient and efficient synthesis of 3-benzoyl-2-ethoxy-2-oxophosphorindolines, benzo-γ-phospholactams, from ethyl N-aryl-1-diazo-2-oxo-2-phenylethylphosphonamidates under the catalysis of inexpensive copper salts.

Scheme 1 Synthetic approaches toward 2-oxophosphorindolines.

Results and discussion

We initiated our investigation by examining intramolecular C–H insertion of ethyl 1-diazo-N-methyl-2-oxo-2,N-diphenylethylphosphonamidate (1a) (Table 1), which was prepared from the Arbuzov reaction of 2-bromo-1-phenylethanone and triethyl phosphite¹¹ followed by chlorination with oxalyl chloride,¹² treatment with N-methylaniline, and diazo transformation with p-acetamidobenzenesulfonyl azide (p-ABSA) in the presence of triethylamine (TEA) (Scheme 2). Delightly, diazophosphonamidate 1a was exhausted after refluxing in toluene for 0.5 h with 10 mol% Cu(acac)₂ as catalyst under N₂ atmosphere, affording the desired product 2-oxophosphorindoline 2a in 40% yield (Table 1, entry 1). The reaction could be accomplished under air in higher to 78% yield of the desired product (Table 1, entry 2). Either change solvent from toluene to dichloromethane (DCM) or decrease of the catalyst amount resulted in decrease of the product yield (Table 1, entries 3 and 4). The rhodium catalysts, such as Rh₂(oct)₂ (dirodium tetraoctanoate) and Rh₂(esp)₂ (bis[rhodium(α,α,α′,α′-tetramethyl-1,3-benzenedipropionic acid)]), were also able to catalyze the reaction to afford the product in 56% and 78% yields, respectively (Table 1, entries 5 and 6). Other cupric catalysts (Table 1, entries 7–10), such as Cu(OAc)₂·H₂O, CuCl₂·2H₂O, CuSO₄·5H₂O, and Cu(NO₃)₂·3H₂O, were also evaluated and inexpensive CuSO₄·5H₂O and Cu(OAc)₂·H₂O showed similar activities as Cu(acac)₂ and Rh₂(esp)₂ (Table 1, entries 2, 6, 7, and 9). The cuprous catalysts CuI and CuBr catalyzed the reaction well, leading to the formation of the desired product 2a in 67% and 75% yields, respectively (Table 1, entries 11 and 12). The inexpensive catalyst CuSO₄·5H₂O was further optimized. The product yield decreased slightly, but with long reaction time, when the solvent was changed into 1,2-dichloroethane (DCE) or DCM (Table 1, entries 13 and 14). The yield dropped obviously when the catalyst was reduced to 5 mol% (Table 1, entry 15). However, the yield dropped suddenly when lengthening reaction time (Table 1, entry 16), revealing that the product was destroyed possibly under refluxing for long time. Strangely, anhydrous CuSO₄ showed lower activity than CuSO₄·5H₂O (Table 1, entry 17), indicating that the reaction was not sensitive to water. Because water was applied as green solvent in the Cu(NO₃)₂·3H₂O-catalyzed carbene insertion reaction of diazoacetamides,⁸ the treatment of diazophosphonamidate 1a with Cu(NO₃)₂·3H₂O in water was performed, but very poor yield was obtained (Table 1, entry 18). Finally, although most copper salts are efficient catalysts for the reaction, the best conditions for the intramolecular C–H insertion of the diazophosphonamidate 1a was acquired, 10 mol% CuSO₄·5H₂O as catalyst in toluene at reflux for 0.5 h (Table 1, entry 9). The product 2a was isolated as a pair of interconvertible and inseparable diastereomers with different diastereomeric ratios in different trials. The ratio achieved approximate 1 : 1 after standing for a period of time (see ESI, Fig. S1†). We believed that cis-product 2a was first generated in the aromatic C–H insertion and it converted into a mixture of cis- and trans-isomeric product due to the existence of the acidic proton between the carbonyl and phosphonamidate group.¹³

Table 1 Optimization of conditions^a

Entry	Cat (mol%)	Solvent	Time (h)	Yield^b (%)
a All reactions were conducted on a 0.5 mmol scale in 10 mL of solvent.b Yields were calculated from the ^1H NMR spectra of the crude reaction mixtures.
1	Cu(acac)2 (10)	PhMe	0.5	40
2	Cu(acac)2 (10)	PhMe	0.5	78
3	Cu(acac)2 (10)	DCM	15	68
4	Cu(acac)2 (2)	PhMe	0.5	70
5	Rh2(oct)2 (2)	PhMe	0.5	56
6	Rh2(esp)2 (2)	PhMe	0.5	78
7	Cu(OAc)2·H2O (10)	PhMe	0.5	76
8	CuCl2·2H2O (10)	PhMe	0.5	62
9	CuSO4·5H2O (10)	PhMe	0.5	77
10	Cu(NO3)2·3H2O (10)	PhMe	0.5	72
11	CuI (10)	PhMe	0.5	67
12	CuBr (10)	PhMe	0.5	75
13	CuSO4·5H2O (10)	DCE	1	74
14	CuSO4·5H2O (10)	DCM	24	76
15	CuSO4·5H2O (5)	PhMe	0.5	70
16	CuSO4·5H2O (10)	PhMe	8	33
17	CuSO4 (10)	PhMe	0.5	57
18	Cu(NO3)2·3H2O (10)	H2O	0.5	25

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Scheme 2 Synthesis of ethyl N-alkyl-N-aryl-1-diazo-2-oxo-2-phenylethylphosphonamidates.

After optimization of the reaction conditions, various diazophosphonamidates 1 were prepared followed the procedures for the preparation of 1a. The substrate scope of the intramolecular aromatic C–H insertion of diazophosphonamidates 1 was investigated with the optimized conditions (Table 2). A series of 2-oxophosphorindoline derivatives 2 were obtained from diazophosphonamidates 1.

Table 2 Substrate cope of intramolecular C–H insertion of diazophosphonamidates^a

a Yields were obtained by chromatography on silica gel.

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The results indicated that diazophosphonamidates 1b and 1c with n-propyl and benzyl instead of methyl at the N atom also performed excellently, affording products 2b and 2c in 73% and 62% yields, respectively, without aliphatic C–H insertion product observed. Diazophosphonamidates 1d–j with para-substituents, either electron-donating or weakly withdrawing, on their N-phenyl group gave rise to the corresponding products 2d–j in relatively lower yields than the unsubstituted substrates 1a and 1b, respectively. The influence of substituted positions on the N-phenyl ring was further studied. Diazophosphonamidate 1k with N-2-methylphenyl at the N atom produced the desired 2-oxophosphorindoline 2k in low 45% yield due to steric hindrance. However, diazophosphonamidates 1l and 1m with N-3-methylphenyl at the N atom yielded two regioisomeric products 2la and 2lb, and 2ma and 2mb in high yields of 97% and 86%, respectively, with indistinguishable ratios because of the existence of two pairs of diastereomers in their product mixtures. Diazophosphonamidates 1n and 1o with sterically bulkyl isopropyl and tert-butyl groups on their N-phenyl group also yielded the corresponding 2-oxophosphorindolines 2n and 2o in 65% and 71% yields, respectively. With respect to diazophosphonamidate 1p with the N-naphth-2-yl group, it administered the desired product 2p in 69% yield regiospecifically at the sterically less β-position of the naphthyl group. Thus, it is reasonable to rationalize the regioisomers 2la and 2ma as major products in the reactions of 1l and 1m due to steric hindrance. Diazophosphonamidate 1q derived from tetrahydroquinoline generated the corresponding 2-oxo-2-phosphorindoline 2q in 79% yield under the optimized conditions.

To verify the stereostructure of prepared 2-oxophosphorindolines, after several attempts, suitable single crystals for X-ray diffraction analysis were obtained from a solution of freshly prepared 2-oxo-2-phosphorindoline 2q in ethyl acetate. The X-ray diffraction analysis results indicate that the freshly prepared 2-oxo-2-phosphorindoline 2q is cis-product as assumed (CCDC 1483899†) (Fig. 1).

Fig. 1 Stereostructure of freshly prepared 2-oxophosphorindoline 2q.

Similarly as the Cu(NO₃)₂·3H₂O-catalyzed transformation of α-diazo-β-ketoanilides to 3-alkylideneoxindoles,^10c a plausible mechanism for the CuSO₄·5H₂O-catalyzed transformation of α-diazo-β-oxo-N-phenylethanesulfonamides 1 to 3-benzoyl-2-ethoxy-2-oxo-2-phosphorindolines 2 is proposed in Scheme 3. Firstly, α-diazo-β-oxoethylphosphonamidates 1 release N₂ under the catalysis of Cu catalyst and heating, affording the Cu-carbenoids A, which subsequently undergo an intramolecular aromatic electrophilic addition through their zwitterionic intermediates from their less bulky side to generate cyclized intermediates B. The intermediates B can tautomerize into intermediates C. After an orbital symmetry allowed suprafacial H[1,5] sigmatropic shift and releasing of the Cu catalyst, zwitterionic enolic intermediates D are generated and further resonate into the final products cis-3-benzoyl-2-oxo-2-phosphorindolines cis-2. The products cis-2 are thermodynamically unstable and can further epimerize into their more thermodynamically stable form, trans-3-benzoyl-2-oxo-2-phosphorindolines trans-2, in the presence of acidic substances, even weak acidic chloroform and water. For example, trans-product is more stable in energy than the corresponding cis-product by 2.4 kcal mol⁻¹ for product 2a.¹³

Scheme 3 Proposed mechanism for the formation of cis-2-oxophosphorindolines and their epimerization.

Conclusions

In summary, an efficient synthesis of 1-alkyl-3-benzoyl-2-ethoxy-2-oxophosphorindolines that are not accessible by previous methods has been successfully achieved via the copper-catalyzed intramolecular aromatic C–H insertion of diazophosphonamidates. The current method is featured with mild and clean conditions, inexpensive catalyst, and simple operations.

Experimental

General information

Dichloromethane and 1,2-dichloroethane were refluxed over CaH₂ and freshly distilled prior to use. Toluene was refluxed over Na with benzophenone as an indicator and freshly distilled prior to use. Melting points were obtained on a Yanaco MP-500 melting point apparatus and are uncorrected. ¹H, ¹³C, ³¹P, and ¹⁹F NMR spectra were recorded on a Bruker 400 MHz spectrometer in CDCl₃ with TMS as an internal standard, 85% phosphoric acid and boron trifluoride etherate as external standards, respectively, and the chemical shifts (δ) are reported in parts per million (ppm). The IR spectra (KBr pellets, v [cm⁻¹]) were taken on a Nicolet 5700 FTIR spectrometer. HRMS measurements were carried out on an Agilent LC/MSD TOF mass spectrometer. TLC separations were performed on silica gel GF254 plates, and the plates were visualized under UV light. The ratios of the regiomers, if there were, were determined by ¹H NMR analyses of reaction mixtures via the integrals of the protons on the C3 atom in the γ-phospholactam ring.

Preparation of diethyl 2-oxo-2-phenylethylphosphonate¹¹ (4)

Bromoacetophenone (75 mmol, 14.94 g) and triethylphosphite (75 mmol, 12.45 g) were mixed and refluxed for 4 h. The resulting crude brown oil was purified on silica gel column (EA : PE = 1 : 3, v/v) to yield the pure phosphonate 4 as a yellow oil (13.11 g, 68% yield).

General procedure for the synthesis of ethyl N-alkyl-N-aryl-2-oxo-2-phenylethylphosphonamidates 3

To a mixed solution of phosphonate 4 (8 mmol, 2.05 g) and 2 drops of DMF in 8 mL of DCM was added oxalyl chloride (24 mmol, 3.05 g, 2.03 mL), and the mixture was stirred for 16 h at room temperature. After removal of solvent and low-boiling residues under reduced pressure, phosphonic chloride was obtained without any purification.¹² The crude phosphonic chloride was dissolved in 10 mL of DCM. To the solution was added a mixed solution of secondary amine (8 mmol) and TEA (8 mmol, 809.5 mg) in 10 mL of DCM. After stirred for another 2 h at room temperature, the mixture was washed with 10 mL of water and the organic phase was dried over anhydrous sodium sulfate. After removal of solvent under reduced pressure, the residual oil was purified on silica gel column (EA : PE = 1 : 3, v/v) to yield the pure phosphonamidate 3.

Ethyl N-methyl-2-oxo-2,N-diphenylethylphosphonamidate (3a). Yellow oil, 3.98 g (20 mmol scale), 63% yield, R_f = 0.40 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 8.00–7.96 (m, 2H), 7.58–7.52 (m, 1H), 7.47–7.40 (m, 2H), 7.35–7.27 (m, 4H), 7.15–7.08 (m, 1H), 4.27–4.16 (m, 1H), 4.07–3.99 (m, 1H), 3.71 (dd, J = 21.4, 14.0 Hz, 1H), 3.60 (dd, J = 21.2, 14.4 Hz, 1H), 3.17 (d, J = 8.4 Hz, 3H), 1.28 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.6 (d, J_C–P = 5.7 Hz), 143.8 (d, J_C–P = 4.6 Hz), 136.8 (d, J_C–P = 1.7 Hz), 133.4, 129.1, 129.0, 128.5, 124.3, 123.2 (d, J_C–P = 3.4 Hz), 60.7 (d, J_C–P = 6.7 Hz), 38.8 (d, J_C–P = 117.8 Hz), 36.7 (d, J_C–P = 4.8 Hz), 16.0 (d, J_C–P = 7.0 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 22.4. IR (KBr, cm⁻¹): 1676, 1273 (P=O). HRMS (ESI) calcd for C₁₇H₂₁NO₃P⁺ [M + H⁺] 318.1254, found 318.1258.

Ethyl 2-oxo-2,N-diphenyl-N-propylethylphosphonamidate (3b). Yellow oil, 1 g, 36% yield, R_f = 0.52 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 8.02–7.96 (m, 2H), 7.58–7.51 (m, 1H), 7.48–7.40 (m, 2H), 7.36–7.28 (m, 4H), 7.22–7.15 (m, 1H), 4.27–4.14 (m, 1H), 4.14–4.00 (m, 1H), 3.69–3.47 (m, 3H), 3.47–3.36 (m, 1H), 1.52–1.37 (m, 2H), 1.25 (t, J = 7.0 Hz, 3H), 0.84 (t, J = 7.4 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.9 (d, J_C–P = 5.9 Hz), 141.5 (d, J_C–P = 4.2 Hz), 136.9 (d, J_C–P = 1.8 Hz), 133.3, 129.2 (d, J_C–P = 1.1 Hz), 129.0, 128.4, 127.2 (d, J_C–P = 3.1 Hz), 125.8 (d, J_C–P = 1.4 Hz), 60.6 (d, J_C–P = 6.7 Hz), 51.2 (d, J_C–P = 4.4 Hz), 39.1 (d, J_C–P = 117.9 Hz), 22.2 (d, J_C–P = 2.5 Hz), 16.1 (d, J_C–P = 7.1 Hz), 11.0. ³¹P NMR (162 MHz, CDCl₃) δ 22.1. IR (KBr, cm⁻¹): 1677, 1274 (P=O). HRMS (ESI) calcd for C₁₉H₂₅NO₃P⁺ [M + H⁺] 346.1567, found 346.1575.

Ethyl N-benzyl-2-oxo-2,N-phenylethylphosphonamidate (3c). Yellow oil, 429 mg, 14% yield, R_f = 0.64 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 8.02–7.97 (m, 2H), 7.59–7.52 (m, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.29–7.08 (m, 10H), 4.92 (dd, J = 15.2, 8.2 Hz, 1H), 4.61 (dd, J = 15.2, 8.8 Hz, 1H), 4.26–4.15 (m, 1H), 4.02–3.91 (m, 1H), 3.68 (dd, J = 20.8, 14.0 Hz, 1H), 3.55 (dd, J = 20.8, 14.0 Hz, 1H), 1.20 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.9 (d, J_C–P = 5.8 Hz), 141.6 (d, J_C–P = 4.4 Hz), 138.4 (d, J_C–P = 2.8 Hz), 136.9 (d, J_C–P = 2.1 Hz), 133.4, 129.2, 129.0, 128.5, 128.2, 128.21, 127.1, 127.0 (d, J_C–P = 3.1 Hz), 125.8 (d, J_C–P = 1.4 Hz), 60.9 (d, J_C–P = 6.7 Hz), 53.7 (d, J_C–P = 5.1 Hz), 39.0 (d, J_C–P = 118.8 Hz), 16.0 (d, J_C–P = 7.1 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 22.1. IR (KBr, cm⁻¹): 1678, 1274 (P=O). HRMS (ESI) calcd for C₂₃H₂₅NO₃P⁺ [M + H⁺] 394.1567, found 394.1575.

Ethyl N-methyl-N-(4-methoxyphenyl)-2-oxo-2-phenylethylphosphonamidate (3d). Yellow oil, 1.7 g, 61% yield, R_f = 0.28 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 8.03–7.97 (m, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.7 Hz, 2H), 7.22 (d, J = 8.8 Hz, 2H), 6.84 (d, J = 8.9 Hz, 2H), 4.26–4.15 (m, 1H), 4.10–3.99 (m, 1H), 3.77 (s, 3H), 3.68 (dd, J = 21.3, 13.8 Hz, 1H), 3.56 (dd, J = 21.2, 13.8 Hz, 1H), 3.11 (d, J = 8.5 Hz, 3H), 1.28 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.9 (d, J_C–P = 5.7 Hz), 157.1, 136.8 (d, J_C–P = 1.7 Hz), 136.5 (d, J_C–P = 4.3 Hz), 133.3, 129.0, 128.4, 126.5 (d, J_C–P = 3.0 Hz), 114.4, 60.5 (d, J_C–P = 6.7 Hz), 55.3, 38.8 (d, J_C–P = 117.2 Hz), 37.8 (d, J_C–P = 5.6 Hz), 16.0 (d, J_C–P = 7.0 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 22.6. IR (KBr, cm⁻¹): 1676, 1274 (P=O). HRMS (ESI) calcd for C₁₈H₂₃NO₄P⁺ [M + H⁺] 348.1359, found 348.1366.

Ethyl N-benzyl-N-(4-methoxyphenyl)-2-oxo-2-phenylethylphosphonamidate (3e). Yellow oil, 1.13 g, 33% yield, R_f = 0.48 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 8.05–7.98 (m, 2H), 7.60–7.53 (m, 1H), 7.49–7.42 (m, 2H), 7.25–7.16 (m, 5H), 7.10 (d, J = 8.0 Hz, 2H), 6.77 (d, J = 8.8 Hz, 2H), 4.82 (dd, J = 14.8, 7.7 Hz, 1H), 4.47 (dd, J = 14.8, 8.7 Hz, 1H), 4.25–4.13 (m, 1H), 4.02–3.91 (m, 1H), 3.75 (s, 3H), 3.67 (dd, J = 21.0, 13.9 Hz, 1H), 3.50 (dd, J = 21.1, 13.9 Hz, 1H), 1.21 (t, J = 7.0 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 193.1 (d, J_C–P = 5.7 Hz), 157.9 (d, J_C–P = 1.2 Hz), 138.4 (d, J_C–P = 2.9 Hz), 137.0 (d, J_C–P = 2.0 Hz), 133.9 (d, J_C–P = 4.2 Hz), 133.4, 129.6 (d, J_C–P = 2.8 Hz), 129.0, 128.6, 128.5, 128.2, 127.1, 114.4, 60.8 (d, J_C–P = 6.6 Hz), 55.3, 54.6 (d, J_C–P = 5.8 Hz), 38.9 (d, J_C–P = 118.9 Hz), 16.1 (d, J_C–P = 7.1 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 22.5. IR (KBr, cm⁻¹): 1677, 1275 (P=O). HRMS (ESI) calcd for C₂₄H₂₇NO₄P⁺ [M + H⁺] 424.1672, found 424.1682.

Ethyl N-methyl-N-(4-methylphenyl)-2-oxo-2-phenylethylphosphonamidate (3f). Yellow oil, 1.79 g, 67% yield, R_f = 0.47 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 8.01–7.95 (m, 2H), 7.58–7.52 (m, 1H), 7.46–7.40 (m, 2H), 7.18 (d, J = 8.1 Hz, 2H), 7.11 (d, J = 8.4 Hz, 2H), 4.26–4.12 (m, 1H), 4.11–3.97 (m, 1H), 3.68 (dd, J = 21.3, 13.9 Hz, 1H), 3.59 (dd, J = 21.2, 13.9 Hz, 1H), 3.14 (d, J = 8.5 Hz, 3H), 2.30 (s, 3H), 1.28 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.7 (d, J_C–P = 5.7 Hz), 141.1 (d, J_C–P = 4.5 Hz), 136.8 (d, J_C–P = 1.7 Hz), 134.3, 133.3, 129.7, 129.0, 128.4, 123.8 (d, J_C–P = 3.3 Hz), 60.6 (d, J_C–P = 6.7 Hz), 38.7 (d, J_C–P = 117.6 Hz), 37.0 (d, J_C–P = 5.1 Hz), 20.7, 16.0 (d, J_C–P = 7.0 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 22.1. IR (KBr, cm⁻¹): 1678, 1273 (P=O). HRMS (ESI) calcd for C₁₈H₂₃NO₃P⁺ [M + H⁺] 332.1410, found 332.1417.

Ethyl N-benzyl-N-(4-methylphenyl)-2-oxo-2-phenylethylphosphonamidate (3g). Yellow oil, 950 mg, 29% yield, R_f = 0.48 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 8.03–7.96 (m, 2H), 7.59–7.52 (m, 1H), 7.48–7.41 (m, 2H), 7.25–7.15 (m, 5H), 7.09 (d, J = 8.1 Hz, 2H), 7.05 (d, J = 8.5 Hz, 2H), 4.88 (dd, J = 15.1, 8.1 Hz, 1H), 4.55 (dd, J = 15.1, 8.8 Hz, 1H), 4.27–4.13 (m, 1H), 4.03–3.90 (m, 1H), 3.66 (dd, J = 20.9, 14.0 Hz, 1H), 3.53 (dd, J = 21.1, 14.0 Hz, 1H), 2.27 (s, 3H), 1.20 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 193.0 (d, J_C–P = 5.8 Hz), 138.8 (d, J_C–P = 4.2 Hz), 138.5 (d, J_C–P = 2.9 Hz), 137.0 (d, J_C–P = 2.0 Hz), 135.8 (d, J_C–P = 1.3 Hz), 133.34, 129.9, 129.0, 128.4, 128.3, 128.2, 127.3 (d, J_C–P = 3.0 Hz), 127.1, 60.8 (d, J_C–P = 6.7 Hz), 54.0 (d, J_C–P = 5.4 Hz), 38.9 (d, J_C–P = 118.9 Hz), 20.8, 16.0 (d, J_C–P = 7.1 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 22.4. IR (KBr, cm⁻¹): 1677, 1274 (P=O). HRMS (ESI) calcd for C₂₄H₂₇NO₃P⁺ [M + H⁺] 408.1723, found 408.1734.

Ethyl N-(4-bromophenyl)-N-methyl-2-oxo-2-phenylethylphosphonamidate (3h). Yellow oil, 565 mg, 18% yield, R_f = 0.26 (PE : EA = 1 : 1, v/v). Two rotamers exist, rotamers A : B = 1.00 : 0.30. ¹H NMR (400 MHz, CDCl₃) δ 8.00–7.94 (rotamers A and B, m, 4H), 7.59–7.52 (rotamers A and B, m, 2H), 7.47–7.41 (rotamers A and B, m, 4H), 7.40–7.36 (rotamers A and B, m, 3H), 7.32–7.29 (rotamers A and B, m, 2H), 7.19–7.14 (rotamers A and B, m, 3H), 4.27–4.15 (rotamers A and B, m, 2H), 4.09–3.97 (rotamers A and B, m, 2H), 3.79–3.54 (rotamers A and B, m, 4H), 3.17 (rotamer B, d, J = 8.4 Hz, 3H), 3.13 (rotamer A, d, J = 8.4 Hz, 3H), 1.33–1.25 (rotamers A and B, m, 6H). ¹³C NMR (101 MHz, CDCl₃) δ 192.6 (rotamer B, d, J_C–P = 5.9 Hz), 192.4 (rotamer A, d, J_C–P = 5.7 Hz), 143.8 (rotamer B, d, J_C–P = 4.6 Hz), 142.9 (rotamer A, d, J_C–P = 4.8 Hz), 136.8 (rotamer B, d, J_C–P = 1.6 Hz), 136.6 (rotamer A, d, J_C–P = 1.8 Hz), 133.5 (rotamer A), 133.4 (rotamer B), 132.0 (rotamer A), 129.1 (rotamer B), 128.9 (rotamer B), 128.91 (rotamer A), 128.5 (rotamer A), 128.4 (rotamer B), 124.6 (rotamer A, d, J_C–P = 3.4 Hz), 124.3 (rotamer B), 123.1 (rotamer B, d, J_C–P = 3.4 Hz), 117.3 (rotamer A), 60.8 (rotamer A, d, J_C–P = 6.7 Hz), 60.7 (rotamer B, d, J_C–P = 6.7 Hz), 38.7 (rotamer B, d, J_C–P = 118.3 Hz), 38.6 (rotamer A, d, J_C–P = 117.7 Hz), 36.7 (rotamer B, d, J_C–P = 4.8 Hz), 36.5 (rotamer A, d, J_C–P = 4.7 Hz), 16.1 (rotamer B, d, J_C–P = 7.6 Hz), 16.0 (rotamer A, d, J_C–P = 6.9 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 22.4 (rotamer B), 22.2 (rotamer A). IR (KBr, cm⁻¹): 1678, 1272 (P=O). HRMS (ESI) calcd for C₁₇H₂₀BrNO₃P⁺ [M + H⁺] 396.0359, found 396.0358.

Ethyl N-(4-chlorophenyl)-N-methyl-2-oxo-2-phenylethylphosphonamidate (3i). Yellow oil, 670 mg, 24% yield, R_f = 0.31 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.99–7.94 (m, 2H), 7.60–7.54 (m, 1H), 7.45 (t, J = 7.7 Hz, 2H), 7.28–7.19 (m, 4H), 4.27–4.17 (m, 1H), 4.09–3.99 (m, 1H), 3.73 (dd, J = 21.4, 14.0 Hz, 1H), 3.59 (dd, J = 21.2, 14.0 Hz, 1H), 3.14 (d, J = 8.4 Hz, 3H), 1.30 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.5 (d, J_C–P = 5.7 Hz), 142.5 (d, J_C–P = 4.8 Hz), 136.7 (d, J_C–P = 1.7 Hz), 133.6, 129.7, 129.1, 129.0, 128.6, 124.5 (d, J_C–P = 3.4 Hz), 60.9 (d, J_C–P = 6.7 Hz), 38.7 (d, J_C–P = 117.7 Hz), 36.7 (d, J_C–P = 4.7 Hz), 16.1 (d, J_C–P = 6.9 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 22.2. IR (KBr, cm⁻¹): 1678, 1272 (P=O). HRMS (ESI) calcd for C₁₇H₂₀ClNO₃P⁺ [M + H⁺] 352.0864, found 352.0872.

Ethyl N-(4-fluorophenyl)-N-methyl-2-oxo-2-phenylethylphosphonamidate (3j). Yellow oil, 1.97 g, 73% yield, R_f = 0.34 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 8.02–7.96 (m, 2H), 7.60–7.53 (m, 1H), 7.49–7.42 (m, 2H), 7.29–7.22 (m, 2H), 7.02–6.94 (m, 2H), 4.27–4.15 (m, 1H), 4.13–3.99 (m, 1H), 3.71 (dd, J = 21.4, 13.9 Hz, 1H), 3.58 (dd, J = 21.3, 13.9 Hz, 1H), 3.12 (d, J = 8.5 Hz, 3H), 1.30 (t, J = 7.0 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.7 (d, J_C–P = 5.7 Hz), 156.0 (d, J_C–F = 245.4 Hz), 139.8 (dd, J_C–F = 4.5, J_C–P = 3.1 Hz), 136.7 (d, J_C–P = 1.6 Hz), 133.5, 129.0, 128.5, 126.1 (dd, J_C–P = 8.2, J_C–F = 3.1 Hz), 115.8 (d, J_C–F = 22.3 Hz), 60.7 (d, J_C–P = 6.7 Hz), 38.7 (d, J_C–P = 117.3 Hz), 37.4 (d, J_C–P = 5.0 Hz), 16.0 (d, J_C–P = 6.9 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ −117.8 (d, J = 1.5 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 22.3. IR (KBr, cm⁻¹): 1676, 1275 (P=O). HRMS (ESI) calcd for C₁₇H₂₀FNO₃P⁺ [M + H⁺] 336.1159, found 336.1171.

Ethyl N-methyl-N-(2-methylphenyl)-2-oxo-2-phenylethylphosphonamidate (3k). Yellow oil, 379 mg, 14% yield, R_f = 0.21 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 8.11–8.02 (m, 2H), 7.62–7.56 (m, 1H), 7.47 (t, J = 7.6 Hz, 2H), 7.37–7.33 (m, 1H), 7.26–7.15 (m, 3H), 4.26–4.14 (m, 1H), 4.13–4.02 (m, 1H), 3.77 (dd, J = 21.4, 13.4 Hz, 1H), 3.62 (dd, J = 21.4, 13.4 Hz, 1H), 3.02 (d, J = 9.0 Hz, 3H), 2.37 (s, 3H), 1.25 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 193.0 (d, J_C–P = 6.2 Hz), 142.1 (d, J_C–P = 3.3 Hz), 137.1 (d, J_C–P = 3.7 Hz), 136.9, 133.4, 131.4, 129.2, 128.9 (d, J_C–P = 1.9 Hz), 128.5, 127.3 (d, J_C–P = 1.3 Hz), 127.1 (d, J_C–P = 1.2 Hz), 61.2 (d, J_C–P = 6.7 Hz), 39.8 (d, J_C–P = 115.1 Hz), 37.7 (d, J_C–P = 5.3 Hz), 18.1, 16.1 (d, J_C–P = 6.8 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 21.7. IR (KBr, cm⁻¹): 1677, 1272 (P=O). HRMS (ESI) calcd for C₁₈H₂₃NO₃P⁺ [M + H⁺] 332.1410, found 332.1419.

Ethyl N-benzyl-N-(3-methylphenyl)-2-oxo-2-phenylethylphosphonamidate (3l). Yellow oil, 543 mg, 17% yield, R_f = 0.55 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 8.02–7.96 (m, 2H), 7.58–7.51 (m, 1H), 7.44 (t, J = 7.6 Hz, 2H), 7.25–7.16 (m, 5H), 7.13 (t, J = 7.7 Hz, 1H), 7.05–6.98 (m, 2H), 6.94 (d, J = 7.5 Hz, 1H), 4.90 (dd, J = 15.3, 8.3 Hz, 1H), 4.60 (dd, J = 15.2, 9.0 Hz, 1H), 4.25–4.13 (m, 1H), 4.02–3.89 (m, 1H), 3.66 (dd, J = 21.2, 14 Hz, 1H), 3.56 (dd, J = 21.2, 14 Hz, 1H), 2.26 (s, 3H), 1.20 (t, J = 7.0 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.9 (d, J_C–P = 5.9 Hz), 141.5 (d, J_C–P = 4.3 Hz), 139.0, 138.5 (d, J_C–P = 2.7 Hz), 136.9 (d, J_C–P = 2.1 Hz), 133.3, 128.9, 128.9, 128.4, 128.2, 128.1, 127.6 (d, J_C–P = 3.1 Hz), 127.0, 126.6 (d, J_C–P = 1.3 Hz), 124.0 (d, J_C–P = 3.1 Hz), 60.9 (d, J_C–P = 6.7 Hz), 53.7 (d, J_C–P = 5.1 Hz), 39.0 (d, J_C–P = 118.7 Hz), 21.3, 16.0 (d, J_C–P = 7.1 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 22.3. IR (KBr, cm⁻¹): 1677, 1274 (P=O). HRMS (ESI) calcd for C₂₄H₂₇NO₃P⁺ [M + H⁺] 408.1723, found 408.1733.

Ethyl N-methyl-N-(3-methylphenyl)-2-oxo-2-phenylethylphosphonamidate (3m). Yellow oil, 1.23 g, 46% yield, R_f = 0.34 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 8.03–7.93 (m, 2H), 7.55 (t, J = 7.2 Hz, 1H), 7.44 (t, J = 7.7 Hz, 2H), 7.19 (t, J = 7.7 Hz, 1H), 7.12–7.06 (m, 2H), 6.92 (d, J = 7.4 Hz, 1H), 4.26–4.15 (m, 1H), 4.09–3.98 (m, 1H), 3.69 (dd, J = 21.6, 13.8 Hz, 1H), 3.62 (dd, J = 21.2, 13.6 Hz, 1H), 3.15 (d, J = 8.4 Hz, 3H), 2.32 (s, 3H), 1.28 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.6 (d, J_C–P = 5.8 Hz), 143.7 (d, J_C–P = 4.6 Hz), 139.0, 136.8 (d, J_C–P = 1.6 Hz), 133.4, 129.0, 128.9, 128.5, 125.2, 124.0 (d, J_C–P = 3.5 Hz), 120.4 (d, J_C–P = 3.3 Hz), 60.6 (d, J_C–P = 6.7 Hz), 38.8 (d, J_C–P = 117.7 Hz), 36.8 (d, J_C–P = 4.8 Hz), 21.5, 16.0 (d, J_C–P = 7.0 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 22.4. IR (KBr, cm⁻¹): 1677, 1275 (P=O). HRMS (ESI) calcd for C₁₈H₂₃NO₃P⁺ [M + H⁺] 332.1410, found 332.1419.

Ethyl N-(4-isopropylphenyl)-N-methyl-2-oxo-2-phenylethylphosphonamidate (3n). Yellow oil, 1.31 g, 45% yield, R_f = 0.27 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 8.00–7.95 (m, 2H), 7.58–7.51 (m, 1H), 7.43 (t, J = 7.6 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 4.26–3.96 (m, 2H), 3.69 (dd, J = 21.2, 11.2 Hz, 1H), 3.61 (dd, J = 21.2, 11.2 Hz, 1H), 3.15 (d, J = 8.4 Hz, 3H), 2.87 (hept, J = 6.9 Hz, 1H), 1.28 (t, J = 7.1 Hz, 3H), 1.22 (d, J = 6.9 Hz, 6H). ¹³C NMR (101 MHz, CDCl₃) δ 192.7 (d, J_C–P = 5.8 Hz), 145.1, 141.4 (d, J_C–P = 4.5 Hz), 136.9 (d, J_C–P = 1.8 Hz), 133.4, 129.0, 128.5, 127.1, 123.6 (d, J_C–P = 3.4 Hz), 60.6 (d, J_C–P = 6.7 Hz), 38.8 (d, J_C–P = 117.5 Hz), 37.0 (d, J_C–P = 5.0 Hz), 33.4, 23.9, 16.0 (d, J_C–P = 7.0 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 22.6. IR (KBr, cm⁻¹): 1677, 1273 (P=O). HRMS (ESI) calcd for C₂₀H₂₇NO₃P⁺ [M + H⁺] 360.1723, found 360.1714.

Ethyl N-[4-(tert-butyl)phenyl]-N-methyl-2-oxo-2-phenylethylphosphonamidate (3o). Yellow oil, 1.06 g, 36% yield, R_f = 0.42 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 8.01–7.95 (m, 2H), 7.59–7.52 (m, 1H), 7.47–7.41 (m, 2H), 7.32 (d, J = 8.6 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 4.26–4.13 (m, 1H), 4.13–3.98 (m, 1H), 3.69 (dd, J = 21.2, 10 Hz, 1H), 3.61 (dd, J = 21.2, 10 Hz, 1H), 3.16 (d, J = 8.5 Hz, 3H), 1.30–1.26 (m, 12H). ¹³C NMR (101 MHz, CDCl₃) δ 192.75 (d, J_C–P = 5.8 Hz), 147.25, 141.06 (d, J_C–P = 4.5 Hz), 136.92, 133.38, 129.03, 128.49, 126.04, 122.98 (d, J_C–P = 3.4 Hz), 60.62 (d, J_C–P = 6.7 Hz), 38.85 (d, J_C–P = 117.6 Hz), 36.83 (d, J_C–P = 5.0 Hz), 34.26, 31.33, 16.07 (d, J_C–P = 7.0 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 22.6. IR (KBr, cm⁻¹): 1678, 1272 (P=O). HRMS (ESI) calcd for C₂₁H₂₉NO₃P⁺ [M + H⁺] 374.1880, found 380.1871.

Ethyl N-methyl-N-(naphthalen-2-yl)-2-oxo-2-phenylethylphosphonamidate (3p). Yellow oil, 1.7 g, 58% yield, R_f = 0.27 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.89–7.83 (m, 2H), 7.71–7.62 (m, 3H), 7.54 (s, 1H), 7.45–7.39 (m, 2H), 7.38–7.26 (m, 4H), 3.65 (dd, J = 21.3, 14.0 Hz, 1H), 3.56 (dd, J = 21.1, 14.0 Hz, 1H), 3.17 (d, J = 8.4 Hz, 3H), 1.21 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.5 (d, J_C–P = 5.8 Hz), 141.3 (d, J_C–P = 4.5 Hz), 136.7 (d, J_C–P = 1.8 Hz), 133.7, 133.3, 130.5, 128.8, 128.8, 128.4, 127.3, 126.2, 125.1, 122.8 (d, J_C–P = 2.8 Hz), 120.1 (d, J_C–P = 4.2 Hz), 60.8 (d, J_C–P = 6.7 Hz), 38.7 (d, J_C–P = 117.6 Hz), 36.8 (d, J_C–P = 4.7 Hz), 16.0 (d, J_C–P = 6.9 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 22.6. IR (KBr, cm⁻¹): 1677, 1274 (P=O). HRMS (ESI) calcd for C₂₁H₂₃NO₃P⁺ [M + H⁺] 368.1410, found 368.1420.

Ethyl (3,4-dihydroquinolin-1(2H)-yl)(2-oxo-2-phenylethyl)phosphinate (3q). Yellow oil, 1.48 g, 54% yield, R_f = 0.29 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.97–7.88 (m, 2H), 7.57–7.50 (m, 1H), 7.46–7.37 (m, 3H), 7.16–7.04 (m, 2H), 6.97–6.89 (m, 1H), 4.23–4.13 (m, 1H), 4.04–3.93 (m, 1H), 3.90–3.80 (m, 1H), 3.73 (d, J = 21.2 Hz, 2H), 3.48–3.39 (m, 1H), 2.85–2.70 (m, 2H), 1.92–1.75 (m, 2H), 1.28 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.0 (d, J_C–P = 5.9 Hz), 139.3 (d, J_C–P = 4.7 Hz), 136.7 (d, J_C–P = 1.4 Hz), 133.3, 130.1, 128.9, 128.4, 127.4 (d, J_C–P = 6.7 Hz), 126.4, 122.0, 119.0 (d, J_C–P = 1.5 Hz), 60.6 (d, J_C–P = 6.8 Hz), 44.5 (d, J_C–P = 2.9 Hz), 38.6 (d, J_C–P = 117.5 Hz), 27.3, 22.7 (d, J_C–P = 2.5 Hz), 15.9 (d, J_C–P = 7.1 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 21.8. IR (KBr, cm⁻¹): 1678, 1275 (P=O). HRMS (ESI) calcd for C₁₉H₂₃NO₃P⁺ [M + H⁺] 344.1410, found 344.1420.

General procedure for the synthesis of ethyl N-alkyl-N-aryl-1-diazo-2-oxo-2-phenylethylphosphonamidates 1

The corresponding phosphonamidate 3 (1 mmol) was dissolved in 5 mL of dry MeCN with p-acetamidobenzenesulfonyl azide (1.02 mmol, 245.04 mg). The resulting solution was cooled to 0 °C. Et₃N (1.5 mmol, 151.67 mg, 0.22 mL) was added, and the reaction mixture was warmed up to room temperature and stirred for 15 h. The volatiles were evaporated under reduced pressure to yield the crude product that was purified on silica gel column (EA : PE = 1 : 3, v/v) to yield the pure product 1.

Ethyl 1-diazo-N-methyl-2-oxo-2,N-diphenylethylphosphonamidate (1a). Yellow oil, 1.35 g (5 mmol scale), 79% yield, R_f = 0.41 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.52–7.45 (m, 3H), 7.42–7.35 (m, 2H), 7.30–7.26 (m, 2H), 7.14–7.08 (m, 3H), 4.34–4.22 (m, 2H), 3.16 (d, J = 9.0 Hz, 3H), 1.40 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 188.0 (d, J_C–P = 10.5 Hz), 143.2 (d, J_C–P = 5.5 Hz), 137.1 (d, J_C–P = 2.6 Hz), 132.1, 129.0, 128.5, 127.2, 124.7 (d, J_C–P = 1.2 Hz), 123.1 (d, J_C–P = 4.0 Hz), 62.2 (d, J_C–P = 5.6 Hz), 37.2 (d, J_C–P = 4.9 Hz), 16.1 (d, J_C–P = 6.8 Hz). IR (KBr, cm⁻¹): 2102, 1631, 1274 (P=O). HRMS (ESI) calcd for C₁₇H₁₉N₃O₃P⁺ [M + H⁺] 344.1159, found 344.1164.

Ethyl 1-diazo-2-oxo-2,N-diphenyl-N-propylethylphenylphosphonamidate (1b). Yellow oil, 255 mg, 69% yield, R_f = 0.62 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.57–7.47 (m, 3H), 7.44–7.37 (m, 2H), 7.32–7.27 (m, 2H), 7.21–7.15 (m, 1H), 7.10 (d, J = 8.3 Hz, 2H), 4.36–4.22 (m, 2H), 3.70–3.59 (m, 1H), 3.49–3.38 (m, 1H), 1.48–1.36 (m, 5H), 0.85 (t, J = 7.4 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 188.1 (d, J_C–P = 9.9 Hz), 140.9 (d, J_C–P = 5.1 Hz), 137.1 (d, J_C–P = 2.8 Hz), 132.1, 129.1 (d, J_C–P = 1.0 Hz), 128.5, 127.4, 126.8 (d, J_C–P = 3.6 Hz), 126.1 (d, J_C–P = 1.4 Hz), 62.0 (d, J_C–P = 5.8 Hz), 51.9 (d, J_C–P = 4.5 Hz), 22.3 (d, J_C–P = 2.4 Hz), 16.1 (d, J_C–P = 6.9 Hz), 11.0. ³¹P NMR (162 MHz, CDCl₃) δ 12.9. IR (KBr, cm⁻¹): 2101, 1629, 1275 (P=O). HRMS (ESI) calcd for C₁₉H₂₃N₃O₃P⁺ [M + H⁺] 372.1472, found 372.1482.

Ethyl N-benzyl-1-diazo-2-oxo-2,N-diphenylethylphosphonamidate (1c). Yellow oil, 206 mg (0.57 mmol scale), 86% yield, R_f = 0.63 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.52 (t, J = 7.5 Hz, 3H), 7.46–7.39 (m, 2H), 7.25–7.15 (m, 7H), 7.15–7.09 (m, 1H), 7.06 (d, J = 8.3 Hz, 2H), 4.91 (dd, J = 15.5, 9.1 Hz, 1H), 4.67 (dd, J = 15.5, 9.2 Hz, 1H), 4.35–4.14 (m, 2H), 1.34 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 188.1 (d, J_C–P = 9.6 Hz), 141.0 (d, J_C–P = 5.2 Hz), 138.2 (d, J_C–P = 3.1 Hz), 137.0 (d, J_C–P = 3.3 Hz), 132.2, 129.1, 128.5, 128.2, 128.1, 127.3, 127.1, 126.7 (d, J_C–P = 3.6 Hz), 126.1 (d, J_C–P = 1.4 Hz), 62.3 (d, J_C–P = 5.8 Hz), 54.4 (d, J_C–P = 5.2 Hz), 16.0 (d, J_C–P = 6.9 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 13.1. IR (KBr, cm⁻¹): 2102, 1630, 1275 (P=O). HRMS (ESI) calcd for C₂₃H₂₃N₃O₃P⁺ [M + H⁺] 420.1472, found 420.1482.

Ethyl 1-diazo-N-(4-methoxyphenyl)-N-methyl-2-oxo-2-phenylethylphosphonamidate (1d). Yellow oil, 128 mg, 34% yield, R_f = 0.28 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.59–7.46 (m, 3H), 7.46–7.38 (m, 2H), 7.05 (d, J = 8.3 Hz, 2H), 6.80 (d, J = 8.9 Hz, 2H), 4.33–4.22 (m, 2H), 3.77 (s, 3H), 3.13 (d, J = 9.2 Hz, 3H), 1.39 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 188.1 (d, J_C–P = 10.0 Hz), 157.2, 137.1 (d, J_C–P = 2.8 Hz), 135.9 (d, J_C–P = 5.2 Hz), 132.1, 128.5, 127.3, 126.0 (d, J_C–P = 3.6 Hz), 114.3, 62.0 (d, J_C–P = 5.8 Hz), 55.3, 38.2 (d, J_C–P = 5.8 Hz), 16.1 (d, J_C–P = 6.8 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 13.4. IR (KBr, cm⁻¹): 2101, 1631, 1275 (P=O). HRMS (ESI) calcd for C₁₈H₂₁N₃O₄P⁺ [M + H⁺] 374.1264, found 374.1266.

Ethyl N-benzyl-1-diazo-N-(4-methoxyphenyl)-2-oxo-2-phenylethylphosphonamidate (1e). Yellow oil, 328 mg, 73% yield, R_f = 0.50 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.62–7.58 (m, 2H), 7.57–7.50 (m, 1H), 7.48–7.42 (m, 2H), 7.26–7.16 (m, 5H), 6.95–6.92 (m, 2H), 6.73 (d, J = 8.9 Hz, 2H), 4.82 (dd, J = 15.1, 8.7 Hz, 1H), 4.58 (dd, J = 15.1, 8.9 Hz, 1H), 4.34–4.24 (m, 1H), 4.24–4.13 (m, 1H), 3.73 (s, 3H), 1.34 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 188.2, 158.0 (d, J_C–P = 1.5 Hz), 138.3 (d, J_C–P = 3.3 Hz), 137.1 (d, J_C–P = 3.3 Hz), 133.3 (d, J_C–P = 5.0 Hz), 132.2, 129.0 (d, J_C–P = 3.3 Hz), 128.6, 128.4, 128.2, 127.4, 127.2, 114.3, 62.1 (d, J_C–P = 5.8 Hz), 55.3, 55.2 (d, J_C–P = 6.0 Hz), 16.1 (d, J_C–P = 6.9 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 13.2. IR (KBr, cm⁻¹): 2101, 1654, 1276 (P=O). HRMS (ESI) calcd for C₂₄H₂₅N₃O₄P⁺ [M + H⁺] 450.1577, found 450.1576.

Ethyl 1-diazo-N-methyl-N-(4-methylphenyl)-2-oxo-2-phenylethylphosphonamidate (1f). Yellow oil, 301 mg, 84% yield, R_f = 0.41 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.55–7.47 (m, 3H), 7.42–7.37 (m, 2H), 7.07 (d, J = 8.2 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 4.33–4.21 (m, 2H), 3.13 (d, J = 9.1 Hz, 3H), 2.30 (s, 3H), 1.39 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 188.1 (d, J_C–P = 10.4 Hz), 140.5 (d, J_C–P = 5.4 Hz), 137.1 (d, J_C–P = 2.4 Hz), 134.7 (d, J_C–P = 1.2 Hz), 132.1, 129.6, 128.4, 127.3, 123.5 (d, J_C–P = 3.9 Hz), 62.0 (d, J_C–P = 5.7 Hz), 37.6 (d, J_C–P = 5.2 Hz), 20.7, 16.1 (d, J_C–P = 6.7 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 13.2. IR (KBr, cm⁻¹): 2101, 1632, 1274 (P=O). HRMS (ESI) calcd for C₁₈H₂₁N₃O₃P⁺ [M + H⁺] 358.1315, found 358.1324.

Ethyl N-benzyl-N-(4-methylphenyl)-1-diazo-2-oxo-2-phenylethylphosphonamidate (1g). Yellow oil, 220 mg (0.77 mmol scale), 66% yield, R_f = 0.62 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.60–7.50 (m, 3H), 7.47–7.41 (m, 2H), 7.25–7.14 (m, 5H), 7.00 (d, J = 8.3 Hz, 2H), 6.91 (d, J = 7.6 Hz, 2H), 4.86 (dd, J = 15.4, 9.0 Hz, 1H), 4.60 (dd, J = 15.3, 9.2 Hz, 1H), 4.34–4.23 (m, 1H), 4.23–4.12 (m, 1H), 2.26 (s, 3H), 1.34 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 188.2 (d, J_C–P = 9.7 Hz), 138.3 (d, J_C–P = 3.1 Hz), 138.1 (d, J_C–P = 5.0 Hz), 137.1 (d, J_C–P = 3.2 Hz), 136.0 (d, J_C–P = 1.6 Hz), 132.2, 129.8, 128.5, 128.2, 127.4, 127.1, 126.9 (d, J_C–P = 3.5 Hz), 62.2 (d, J_C–P = 5.8 Hz), 54.6 (d, J_C–P = 5.6 Hz), 20.9, 16.1 (d, J_C–P = 6.9 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 13.1. IR (KBr, cm⁻¹): 2101, 1630, 1275 (P=O). HRMS (ESI) calcd for C₂₄H₂₅N₃O₃P⁺ [M + H⁺] 434.1628, found 434.1636.

Ethyl N-(4-bromophenyl)-1-diazo-N-methyl-2-oxo-2-phenylethylphosphonamidate (1h). Yellow oil, 378 mg, 90% yield, R_f = 0.38 (PE : EA = 1 : 1, v/v). Two rotamers exist, rotamers A : B = 1.00 : 0.27. ¹H NMR (400 MHz, CDCl₃) δ 7.53–7.47 (rotamers A and B, m, 6H), 7.43–7.35 (rotamers A and B, m, 8H), 7.30–7.25 (rotamer B, m, 1H), 7.14–7.08 (rotamer B, m, 1H), 7.04–6.98 (rotamer A, m, 2H), 4.34–4.23 (rotamers A and B, m, 4H), 3.16 (rotamer B, d, J = 3.0 Hz, 3H), 3.13 (rotamer A, d, J = 3.0 Hz, 3H), 1.40 (rotamer A, t, J = 7.2 Hz, 3H), 1.398 (rotamer B, t, J = 7.2 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 187.8 (rotamer A, d, J_C–P = 10.2 Hz), 142.4 (rotamer A, d, J_C–P = 5.8 Hz), 136.9 (rotamer A), 132.3 (rotamer A), 132.1 (rotamer B), 132.0 (rotamer A), 129.0 (rotamer B), 128.6 (rotamer A), 128.5 (rotamer B), 127.2 (rotamer B), 127.21 (rotamer A), 124.7 (rotamer B), 124.6 (rotamer A, d, J_C–P = 4.0 Hz), 123.0 (rotamer B, d, J_C–P = 4.1 Hz), 117.8 (rotamer A), 62.4 (rotamer A, d, J_C–P = 5.7 Hz), 62.2 (rotamer B, d, J_C–P = 5.9 Hz), 37.2 (rotamer B, d, J_C–P = 4.6 Hz), 37.2 (rotamer A, d, J_C–P = 4.7 Hz), 16.1 (rotamer A, d, J_C–P = 6.7 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 13.2 (rotamer B), 13.0 (rotamer A). IR (KBr, cm⁻¹): 2102, 1631, 1272 (P=O). HRMS (ESI) calcd for C₁₇H₁₈BrN₃O₃P⁺ [M + H⁺] 422.0264, found 422.0266.

Ethyl N-(4-chlorophenyl)-1-diazo-N-methyl-2-oxo-2-phenylethylphosphonamidate (1i). Yellow oil, 267 mg, 71% yield, R_f = 0.41 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.54–7.48 (m, 3H), 7.43–7.37 (m, 2H), 7.23 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.1 Hz, 2H), 4.35–4.23 (m, 2H), 3.13 (d, J = 9.0 Hz, 3H), 1.40 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 187.9 (d, J_C–P = 10.2 Hz), 141.9 (d, J_C–P = 5.7 Hz), 136.9 (d, J_C–P = 2.7 Hz), 132.3, 130.1 (d, J_C–P = 1.3 Hz), 129.0, 128.6, 127.2, 124.4 (d, J_C–P = 4.0 Hz), 62.4 (d, J_C–P = 5.7 Hz), 37.3 (d, J_C–P = 4.8 Hz), 16.1 (d, J_C–P = 6.6 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 13.1. IR (KBr, cm⁻¹): 2103, 1631, 1272 (P=O). HRMS (ESI) calcd for C₁₇H₁₈ClN₃O₃P⁺ [M + H⁺] 378.0769, found 378.0782.

Ethyl 1-diazo-N-(4-fluorophenyl)-N-methyl-2-oxo-2-phenylethylphosphonamidate (1j). Yellow oil, 205 mg, 57% yield, R_f = 0.34 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.55–7.49 (m, 3H), 7.44–7.39 (m, 2H), 7.14–7.07 (m, 2H), 7.00–6.93 (m, 2H), 4.34–4.22 (m, 2H), 3.15 (d, J = 9.0 Hz, 3H), 1.40 (t, J = 7.0 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 188.0 (d, J_C–P = 9.7 Hz), 160.1 (d, J_C–F = 244.3 Hz), 139.2 (dd, J_C–F = 5.5, J_C–P = 2.8 Hz), 137.0 (d, J_C–P = 3.0 Hz), 132.3, 128.6, 127.2, 125.8 (dd, J_C–P = 8.3, J_C–F = 3.7 Hz), 115.8 (d, J_C–F = 22.2 Hz), 62.3 (d, J_C–P = 5.7 Hz), 37.9 (d, J_C–P = 5.2 Hz), 16.1 (d, J_C–P = 6.7 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ −117.2 (d, J = 2.3 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 13.5. IR (KBr, cm⁻¹): 2103, 1632, 1275 (P=O). HRMS (ESI) calcd for C₁₇H₁₈FN₃O₃P⁺ [M + H⁺] 362.1064, found 362.1072.

Ethyl 1-diazo-N-methyl-N-(2-methylphenyl)-2-oxo-2-phenylethylphosphonamidate (1k). Yellow oil, 167 mg (0.59 mmol scale), 79% yield, R_f = 0.38 (PE : EA = 1 : 1, v/v).¹H NMR (400 MHz, CDCl₃) δ 7.63–7.59 (m, 2H), 7.57–7.52 (m, 1H), 7.49–7.43 (m, 2H), 7.26–7.13 (m, 4H), 4.28–4.18 (m, 2H), 3.13 (d, J = 9.6 Hz, 3H), 2.36 (s, 3H), 1.36 (t, J = 7.0 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 188.2 (d, J_C–P = 8.0 Hz), 141.5 (d, J_C–P = 4.4 Hz), 137.5 (d, J_C–P = 3.3 Hz), 137.2 (d, J_C–P = 4.3 Hz), 132.3, 131.4, 128.8, 128.7, 127.5 (d, J_C–P = 1.5 Hz), 127.3, 127.0 (d, J_C–P = 1.4 Hz), 62.6 (d, J_C–P = 5.7 Hz), 38.6 (d, J_C–P = 5.7 Hz), 17.9, 16.1 (d, J_C–P = 7.0 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 13.2. IR (KBr, cm⁻¹): 2101, 1630, 1275 (P=O). HRMS (ESI) calcd for C₁₈H₂₁N₃O₃P⁺ [M + H⁺] 358.1315, found 358.1321.

Ethyl N-benzyl-N-(3-methylphenyl)-1-diazo-2-oxo-2-phenylethylphosphonamidate (1l). Yellow oil, 315 mg (0.89 mmol scale), 81% yield, R_f = 0.68 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.59–7.50 (m, 3H), 7.48–7.40 (m, 2H), 7.25–7.14 (m, 5H), 7.09 (t, J = 7.8 Hz, 1H), 6.94 (d, J = 7.5 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 6.81 (s, 1H), 4.88 (dd, J = 15.5, 9.3 Hz, 1H), 4.63 (dd, J = 15.5, 9.5 Hz, 1H), 4.33–4.12 (m, 2H), 2.21 (s, 3H), 1.34 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 188.2 (d, J_C–P = 9.9 Hz), 140.9 (d, J_C–P = 5.0 Hz), 138.9 (d, J_C–P = 0.9 Hz), 138.4 (d, J_C–P = 2.9 Hz), 137.2 (d, J_C–P = 3.0 Hz), 132.2, 128.8, 128.5, 128.2, 128.1, 127.4, 127.3, 127.1, 127.0 (d, J_C–P = 1.3 Hz), 123.9 (d, J_C–P = 3.5 Hz), 62.2 (d, J_C–P = 5.7 Hz), 54.4 (d, J_C–P = 5.2 Hz), 21.3, 16.1 (d, J_C–P = 7.0 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 13.1. IR (KBr, cm⁻¹): 2101, 1630, 1275 (P=O). HRMS (ESI) calcd for C₂₄H₂₅N₃O₃P⁺ [M + H⁺] 434.1628, found 434.1639.

Ethyl 1-diazo-N-methyl-N-(3-methylphenyl)-2-oxo-2-phenylethylphosphonamidate (1m). Yellow oil, 249 mg, 70% yield, R_f = 0.38 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.53–7.46 (m, 3H), 7.43–7.36 (m, 2H), 7.15 (t, J = 7.8 Hz, 1H), 6.93 (d, J = 7.7 Hz, 2H), 6.83 (s, 1H), 4.34–4.22 (m, 2H), 3.13 (d, J = 9.1 Hz, 3H), 2.28 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 188.1 (d, J_C–P = 10.5 Hz), 143.1 (d, J_C–P = 5.5 Hz), 138.9, 137.1 (d, J_C–P = 2.2 Hz), 132.1, 128.8, 128.4, 127.3, 125.6, 123.9 (d, J_C–P = 4.2 Hz), 120.3 (d, J_C–P = 3.8 Hz), 62.1 (d, J_C–P = 5.8 Hz), 37.3 (d, J_C–P = 5.0 Hz), 21.4, 16.1 (d, J_C–P = 6.8 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 13.2. IR (KBr, cm⁻¹): 2101, 1632, 1285 (P=O). HRMS (ESI) calcd for C₁₈H₂₁N₃O₃P⁺ [M + H⁺] 358.1315, found 358.1316.

Ethyl 1-diazo-N-(4-isopropylphenyl)-N-methyl-2-oxo-2-phenylethylphosphonamidate (1n). Yellow oil, 270 mg, 74% yield, R_f = 0.46 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.51–7.43 (m, 3H), 7.37 (t, J = 7.6 Hz, 2H), 7.12 (d, J = 8.2 Hz, 2H), 7.04 (d, J = 8.2 Hz, 2H), 4.35–4.20 (m, 2H), 3.15 (d, J = 9.0 Hz, 3H), 2.86 (hept, J = 7.0 Hz, 1H), 1.39 (t, J = 7.1 Hz, 3H), 1.22 (d, J = 6.9 Hz, 6H). ¹³C NMR (101 MHz, CDCl₃) δ 188.2 (d, J_C–P = 10.2 Hz), 145.5, 140.8 (d, J_C–P = 5.3 Hz), 137.2 (d, J_C–P = 2.8 Hz), 132.0, 128.4, 127.2, 127.0, 123.4 (d, J_C–P = 4.0 Hz), 62.0 (d, J_C–P = 5.8 Hz), 37.5 (d, J_C–P = 5.0 Hz), 33.5, 23.9 (d, J_C–P = 1.7 Hz), 16.1 (d, J_C–P = 6.6 Hz). IR (KBr, cm⁻¹): 2100, 1633, 1273 (P=O). HRMS (ESI) calcd for C₂₀H₂₅N₃O₃P⁺ [M + H⁺] 386.1628, found 386.1619.

Ethyl N-[4-(tert-butyl)phenyl]-1-diazo-N-methyl-2-oxo-2-phenylethylphosphonamidate (1o). Yellow oil, 270 mg, 80% yield, R_f = 0.46 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.51–7.42 (m, 3H), 7.40–7.34 (m, 2H), 7.28 (d, J = 8.7 Hz, 2H), 7.05 (d, J = 8.2 Hz, 2H), 4.35–4.20 (m, 2H), 3.15 (d, J = 9.0 Hz, 3H), 1.39 (t, J = 7.0 Hz, 3H), 1.29 (s, 9H). ¹³C NMR (101 MHz, CDCl₃) δ 188.2 (d, J_C–P = 10.2 Hz), 147.7, 140.5 (d, J_C–P = 5.4 Hz), 137.2 (d, J_C–P = 2.7 Hz), 132.0, 128.4, 127.2, 125.9, 122.8 (d, J_C–P = 4.0 Hz), 62.0 (d, J_C–P = 5.7 Hz), 37.3 (d, J_C–P = 5.1 Hz), 34.3, 31.3, 16.1 (d, J_C–P = 6.7 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 13.5. IR (KBr, cm⁻¹): 2100, 1632, 1273 (P=O). HRMS (ESI) calcd for C₂₁H₂₇N₃O₃P⁺ [M + H⁺] 400.1785, found 400.1777.

Ethyl 1-diazo-N-methyl-N-(naphthalen-2-yl)-2-oxo-2-phenylethylphosphonamidate (1p). Yellow oil, 309 mg, 79% yield, R_f = 0.38 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.80–7.73 (m, 2H), 7.70 (d, J = 7.7 Hz, 1H), 7.49–7.41 (m, 6H), 7.37–7.31 (m, 3H), 4.40–4.28 (m, 2H), 3.25 (d, J = 9.0 Hz, 3H), 1.43 (t, J = 7.0 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 188.0 (d, J_C–P = 10.5 Hz), 140.7 (d, J_C–P = 5.4 Hz), 137.1 (d, J_C–P = 2.2 Hz), 133.6, 132.1, 130.8, 128.8, 128.5, 128.4, 127.5, 127.3, 126.4, 125.4, 122.6 (d, J_C–P = 3.3 Hz), 120.6 (d, J_C–P = 4.8 Hz), 62.3 (d, J_C–P = 5.8 Hz), 37.5 (d, J_C–P = 4.9 Hz), 16.1 (d, J_C–P = 6.7 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 13.3. IR (KBr, cm⁻¹): 2102, 1631, 1276 (P=O). HRMS (ESI) calcd for C₂₁H₂₁N₃O₃P⁺ [M + H⁺] 394.1315, found 394.1324.

Ethyl (1-diazo-2-oxo-2-phenylethyl)(3,4-dihydroquinolin-1(2H)-yl)phosphinate (1q). Yellow oil, 242 mg, 66% yield, R_f = 0.41 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 7.49–7.41 (m, 3H), 7.39–7.32 (m, 2H), 7.30 (d, J = 8.2 Hz, 1H), 7.16–7.10 (m, 1H), 7.00 (d, J = 7.5 Hz, 1H), 6.92 (t, J = 7.3 Hz, 1H), 4.33–4.15 (m, 2H), 3.78–3.69 (m, 1H), 3.64–3.55 (m, 1H), 2.71–2.61 (m, 1H), 2.61–2.53 (m, 1H), 1.86–1.66 (m, 2H), 1.36 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 187.8 (d, J_C–P = 10.6 Hz), 138.5 (d, J_C–P = 5.5 Hz), 137.2 (d, J_C–P = 2.3 Hz), 132.0, 129.8, 128.4, 128.1 (d, J_C–P = 7.3 Hz), 127.2, 126.2, 122.3, 119.1 (d, J_C–P = 2.5 Hz), 62.0 (d, J_C–P = 5.8 Hz), 45.2 (d, J_C–P = 2.9 Hz), 27.2, 22.2 (d, J_C–P = 3.1 Hz), 16.0 (d, J_C–P = 6.8 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 11.4. IR (KBr, cm⁻¹): 2101, 1633, 1283 (P=O). HRMS (ESI) calcd for C₁₉H₂₁N₃O₃P⁺ [M + H⁺] 370.1315, found 370.1325.

General procedure for the synthesis of 1-alkyl-3-benzoyl-2-ethoxy-2-oxophosphorindolines 2

To a suspension of CuSO₄·5H₂O (0.05 mmol, 12.5 mg) in 10 mL of toluene was added the corresponding diazo compound 1 (0.5 mmol), and the mixture was refluxed for 0.5 h. The volatiles were removed under reduced pressure and the crude reaction mixture was purified on silica gel column (PE : EA = 3 : 1, v/v) to afford the desired product 2.

3-Benzoyl-2-ethoxy-1-methyl-2-oxophosphorindoline (2a). Colorless crystals, 127 mg (0.5 mmol scale), 77% yield, mp 148–149 °C. R_f = 0.38 (PE : EA = 1 : 1, v/v). cis-Isomer : trans-isomer = 1.00 : 0.43. ¹H NMR (400 MHz, CDCl₃) δ 8.30–8.21 (trans-isomer, m, 2H), 8.05–7.92 (cis-isomer, m, 2H), 7.66 (trans-isomer, t, J = 7.4 Hz, 1H), 7.62–7.58 (cis-isomer, m, 1H), 7.57 (trans-isomer, t, J = 7.7 Hz, 2H), 7.49 (cis-isomer, t, J = 7.7 Hz, 2H), 7.27 (trans-isomer, d, J = 5.7 Hz, 1H), 7.31 (cis-isomer, d, J = 7.8 Hz, 1H), 7.12 (trans-isomer, d, J = 7.3 Hz, 1H), 7.04 (cis-isomer, d, J = 7.4 Hz, 1H), 6.95 (trans-isomer, t, J = 7.6 Hz, 1H), 6.90 (cis-isomer, t, J = 7.5 Hz, 1H), 6.72 (cis-isomer, d, J = 8.0 Hz, 1H), 6.69 (trans-isomer, d, J = 8.0 Hz, 1H), 5.25 (trans-isomer, d, J = 23.7 Hz, 1H), 5.02 (cis-isomer, d, J = 20.9 Hz, 1H), 4.26–4.13 (cis-isomer, m, 2H), 3.95–3.83 (trans-isomer, m, 1H), 3.61–3.49 (trans-isomer, m, 1H), 3.04 (cis-isomer, d, J = 8.7 Hz, 3H), 3.00 (trans-isomer, d, J = 8.8 Hz, 3H), 1.38 (cis-isomer, t, J = 7.1 Hz, 3H). 0.96 (trans-isomer, t, J = 7.0 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 191.5 (trans-isomer, d, J_C–P = 4.7 Hz), 192.2 (cis-isomer, d, J_C–P = 3.2 Hz), 145.1 (cis-isomer, d, J_C–P = 26.4 Hz), 144.7 (trans-isomer), 136.7 (cis-isomer), 136.67 (trans-isomer), 134.1 (trans-isomer), 133.7 (cis-isomer), 129.4 (cis-isomer), 129.2 (trans-isomer), 129.1 (cis-isomer), 128.8 (cis-isomer), 128.7 (trans-isomer), 128.2 (trans-isomer, d, J_C–P = 13.3 Hz), 127.5 (cis-isomer, d, J_C–P = 13.7 Hz), 121.9 (cis-isomer, d, J_C–P = 4.3 Hz), 120.8 (trans-isomer, d, J_C–P = 4.9 Hz), 120.7 (cis-isomer, d, J_C–P = 1.3 Hz), 120.6 (trans-isomer), 108.9 (cis-isomer, d, J_C–P = 11.5 Hz), 108.4 (trans-isomer, d, J_C–P = 11.6 Hz), 64.2 (trans-isomer, d, J_C–P = 7.2 Hz), 63.3 (cis-isomer, d, J_C–P = 6.9 Hz), 48.7 (trans-isomer, d, J_C–P = 102.8 Hz), 48.1 (cis-isomer, d, J_C–P = 106.0 Hz), 27.4 (cis-isomer, d, J_C–P = 1.9 Hz), 27.1 (trans-isomer, d, J_C–P = 1.9 Hz), 16.7 (cis-isomer, d, J_C–P = 5.8 Hz) 16.1 (trans-isomer, d, J_C–P = 5.9 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 39.1 (cis-isomer), 38.6 (trans-isomer). IR (KBr, cm⁻¹): 1679, 1633, 1278 (P=O), 1236 (P=O). HRMS (ESI) calcd for C₁₇H₁₉NO₃P⁺ [M + H⁺] 316.1097, found 316.1106.

3-Benzoyl-2-ethoxy-2-oxo-1-propylphosphorindoline (2b). Colorless crystals, 102 mg (0.41 mmol scale), 73% yield, mp 145–147 °C. R_f = 0.43 (PE : EA = 1 : 1, v/v). cis-Isomer : trans-isomer = 1.00 : 0.00. ¹H NMR (400 MHz, CDCl₃) δ 8.04–7.94 (m, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.51–7.45 (m, 2H), 7.31–7.23 (m, 1H), 7.04 (d, J = 7.3 Hz, 1H), 6.87 (t, J = 7.5 Hz, 1H), 6.75 (d, J = 8.0 Hz, 1H), 4.97 (d, J = 20.7 Hz, 1H), 4.27–4.09 (m, 2H), 3.53–3.32 (m, 2H), 1.86–1.69 (m, 2H), 1.38 (t, J = 7.1 Hz, 3H), 0.99 (t, J = 7.4 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.2 (d, J_C–P = 3.2 Hz), 144.5 (d, J_C–P = 26.7 Hz), 136.7, 133.5, 129.2, 128.8, 128.7, 127.6 (d, J_C–P = 13.8 Hz), 122.1 (d, J_C–P = 4.3 Hz), 120.4, 109.4 (d, J_C–P = 11.7 Hz), 63.0 (d, J_C–P = 6.8 Hz), 48.3 (d, J_C–P = 105.0 Hz), 43.4, 21.4, 16.6 (d, J_C–P = 6.1 Hz), 11.3. ³¹P NMR (162 MHz, CDCl₃) δ 38.5 (cis isomer), 38.1 (trans-isomer). IR (KBr, cm⁻¹): 1680, 1231 (P=O). HRMS (ESI) calcd for C₁₉H₂₃NO₃P⁺ [M + H⁺] 344.1410, found 344.1414.

3-Benzoyl-1-benzyl-2-ethoxy-2-oxophosphorindoline (2c). Colorless crystals, 60 mg (0.24 mmol scale), 62% yield, mp 166–167 °C. R_f = 0.33 (PE : EA = 1 : 1, v/v). cis-Isomer : trans-isomer = 1.00 : 0.00. ¹H NMR (400 MHz, CDCl₃) δ 8.06–7.99 (m, 2H), 7.64–7.57 (m, 1H), 7.49 (t, J = 7.7 Hz, 2H), 7.43 (d, J = 7.4 Hz, 2H), 7.34 (t, J = 7.4 Hz, 2H), 7.29–7.24 (m, 1H), 7.14 (t, J = 7.8 Hz, 1H), 7.06 (d, J = 7.4 Hz, 1H), 6.87 (t, J = 7.5 Hz, 1H), 6.57 (d, J = 8.0 Hz, 1H), 5.10 (d, J = 20.9 Hz, 1H), 4.69 (d, J = 9.6 Hz, 2H), 4.26–4.04 (m, 2H), 1.33 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.1 (d, J_C–P = 3.1 Hz), 144.3 (d, J_C–P = 26.7 Hz), 136.7, 136.6 (d, J_C–P = 2.1 Hz), 133.6, 129.2, 128.8, 128.76, 128.7, 127.5, 127.4, 127.0, 121.9 (d, J_C–P = 4.3 Hz), 120.8, 110.3 (d, J_C–P = 11.6 Hz), 63.3 (d, J_C–P = 6.9 Hz), 48.4 (d, J_C–P = 106.3 Hz), 45.4 (d, J_C–P = 2.3 Hz), 16.6 (d, J_C–P = 6.0 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 38.8 (cis-isomer), 38.1 (trans-isomer). IR (KBr, cm⁻¹): 1688, 1274 (P=O). HRMS (ESI) calcd for C₂₃H₂₂KNO₃P⁺ [M + K⁺] 430.0969, found 430.0961.

3-Benzoyl-2-ethoxy-5-methoxy-1-methyl-2-oxophosphorindoline (2d). Colorless crystals, 53 mg (0.25 mmol scale), 60% yield, mp 179–181 °C. R_f = 0.17 (PE : EA = 1 : 1, v/v). cis-Isomer : trans-isomer = 1.00 : 0.19. ¹H NMR (400 MHz, CDCl₃) δ 8.28–8.23 (trans-isomer, m, 2H), 8.03–7.97 (cis-isomer, m, 2H), 7.69–7.64 (trans-isomer, m, 1H), 7.63–7.58 (cis-isomer, m, 1H), 7.58–7.55 (trans-isomer, m, 2H), 7.49 (cis-isomer, t, J = 7.7 Hz, 2H), 6.89–6.82 (cis-isomer and trans-isomer, m, 2H), 6.76–6.74 (trans-isomer, m, 1H), 6.67 (cis-isomer, d, J = 2.4 Hz, 1H), 6.64 (cis-isomer, d, J = 8.7 Hz, 1H), 6.61 (trans-isomer, d, J = 8.7 Hz, 1H), 5.24 (trans-isomer, d, J = 23.5 Hz, 1H), 4.98 (cis-isomer, d, J = 20.7 Hz, 1H), 4.23–4.12 (cis-isomer, m, 2H), 3.91–3.82 (trans-isomer, m, 1H), 3.76 (trans-isomer, s, 3H), 3.72 (cis-isomer, s, 3H), 3.59–3.50 (trans-isomer, m, 1H), 3.02 (cis-isomer, d, J = 8.9 Hz, 3H), 2.98 (trans-isomer, d, J = 9.0 Hz, 3H), 1.37 (cis-isomer, t, J = 7.1 Hz, 3H), 0.96 (trans-isomer, t, J = 7.0 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.1 (cis-isomer, d, J = 3.0 Hz), 191.4 (trans-isomer, d, J = 5.2 Hz), 154.1 (trans-isomer, d, J_C–P = 1.9 Hz), 138.9 (cis-isomer, d, J_C–P = 26.3 Hz), 136.6 (cis-isomer), 136.59 (trans-isomer), 134.0 (trans-isomer), 133.6 (cis-isomer), 129.0 (trans-isomer), 128.8 (cis-isomer), 128.7 (cis-isomer), 128.69 (trans-isomer), 122.8 (cis-isomer, d, J_C–P = 4.5 Hz), 114.7 (trans-isomer, d, J = 13.4 Hz), 114.3 (cis-isomer), 114.2 (cis-isomer, d, J_C–P = 13.9 Hz), 109.4 (cis-isomer, d, J_C–P = 10.8 Hz), 108.9 (trans-isomer, d, J = 11.1 Hz), 64.0 (trans-isomer, d, J = 7.1 Hz), 63.0 (cis-isomer, d, J_C–P = 7.0 Hz), 55.8 (trans-isomer), 55.7 (cis-isomer), 49.1 (trans-isomer, d, J = 103.9), 48.5 (cis-isomer, d, J_C–P = 106.3 Hz), 27.7 (cis-isomer, d, J_C–P = 1.8 Hz), 27.3 (trans-isomer, d, J = 1.6 Hz), 16.6 (cis-isomer, d, J_C–P = 5.8 Hz) 16.0 (trans-isomer, d, J = 6.0 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 39.1 (cis-isomer), 38.6 (trans-isomer). IR (KBr, cm⁻¹): 1675, 1631, 1255 (P=O), 1233 (P=O). HRMS (ESI) calcd for C₁₈H₂₁NO₄P⁺ [M + H⁺] 346.1203, found 346.1213.

3-Benzoyl-1-benzyl-2-ethoxy-5-methoxy-2-oxophosphorindoline (2e). Colorless crystals, 101 mg (0.49 mmol scale), 49% yield, mp 168–172 °C. R_f = 0.40 (PE : EA = 1 : 1, v/v). cis-Isomer : trans-isomer = 1.00 : 0.00. ¹H NMR (400 MHz, CDCl₃) δ 8.03 (d, J = 7.4 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.7 Hz, 2H), 7.41 (d, J = 7.4 Hz, 2H), 7.34 (t, J = 7.5 Hz, 2H), 7.29–7.22 (m, 1H), 6.71–6.65 (m, 2H), 6.47 (d, J = 8.3 Hz, 1H), 5.07 (d, J = 20.6 Hz, 1H), 4.69–4.63 (m, 2H), 4.26–4.04 (m, 2H), 3.67 (s, 3H), 1.33 (t, J = 7.0 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.0 (d, J_C–P = 3.1 Hz), 154.1 (d, J_C–P = 1.9 Hz), 138.0 (d, J_C–P = 26.8 Hz), 136.8 (d, J_C–P = 2.4 Hz), 136.7, 133.6, 128.8, 128.7, 128.6, 127.3, 127.0, 123.0 (d, J_C–P = 4.3 Hz), 114.2, 114.1 (d, J_C–P = 14.0 Hz), 111.0 (d, J_C–P = 10.9 Hz), 63.1 (d, J_C–P = 6.9 Hz), 55.6, 48.8 (d, J_C–P = 106.6 Hz), 45.6 (d, J_C–P = 2.2 Hz), 16.6 (d, J_C–P = 6.1 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 38.8 (cis-isomer), 38.2 (trans-isomer). IR (KBr, cm⁻¹): 1676, 1278 (P=O), 1245 (P=O). HRMS (ESI) calcd for C₂₄H₂₅NO₄P⁺ [M + H⁺] 422.1516, found 422.1528.

3-Benzoyl-2-ethoxy-1,5-dimethyl-2-oxophosphorindoline (2f). Colorless crystals, 81 mg (0.53 mmol scale), 47% yield, mp 161–163 °C. R_f = 0.23 (PE : EA = 1 : 1, v/v). cis-Isomer : trans-isomer = 1.00 : 0.00. ¹H NMR (400 MHz, CDCl₃) δ 8.03–7.97 (m, 2H), 7.62–7.56 (m, 1H), 7.49 (t, J = 7.7 Hz, 2H), 7.09 (d, J = 8.0 Hz, 1H), 6.87 (s, 1H), 6.62 (d, J = 8.1 Hz, 1H), 4.98 (d, J = 20.7 Hz, 1H), 4.22–4.12 (m, 2H), 3.02 (d, J = 8.8 Hz, 3H), 2.25 (s, 3H), 1.37 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.3 (d, J_C–P = 3.1 Hz), 142.7 (d, J_C–P = 26.2 Hz), 136.7, 133.5, 130.0 (d, J_C–P = 1.3 Hz), 129.7, 128.7, 128.7, 128.0 (d, J_C–P = 13.5 Hz), 121.7 (d, J_C–P = 4.3 Hz), 108.7 (d, J_C–P = 11.2 Hz), 63.0 (d, J_C–P = 6.9 Hz), 48.1 (d, J_C–P = 106.0 Hz), 27.4 (d, J_C–P = 1.9 Hz), 20.7, 16.6 (d, J_C–P = 5.9 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 39.2 (cis-isomer), 38.8 (trans-isomer). IR (KBr, cm⁻¹): 1679, 1274 (P=O), 1248 (P=O). HRMS (ESI) calcd for C₁₈H₂₁NO₃P⁺ [M + H⁺] 330.1254, found 330.1265.

3-Benzoyl-1-benzyl-2-ethoxy-5-methyl-2-oxophosphorindoline (2g). Colorless crystals, 75 mg (0.32 mmol scale), 57% yield, mp 188–190 °C. R_f = 0.50 (PE : EA = 1 : 1, v/v). cis-Isomer : trans-isomer = 1.00 : 0.18. ¹H NMR (400 MHz, CDCl₃) δ 8.32–8.25 (trans-isomer, m, 2H), 8.03 (cis-isomer, d, J = 7.4 Hz, 2H), 7.69–7.62 (trans-isomer, m, 1H), 7.65–7.54 (cis-isomer and trans-isomer, m, 3H), 7.50 (cis-isomer, t, J = 7.7 Hz, 2H), 7.44–7.39 (cis-isomer and trans-isomer, m, 4H), 7.36–7.30 (cis-isomer and trans-isomer, m, 4H), 7.29–7.22 (cis-isomer and trans-isomer, m, 2H), 6.97–6.90 (cis-isomer and trans-isomer, m, 3H), 6.89 (cis-isomer, s, 1H), 6.46 (cis-isomer, d, J = 8.1 Hz, 1H), 6.42 (trans-isomer, d, J = 8.1 Hz, 1H), 5.32 (trans-isomer, d, J = 26 Hz, 1H), 5.07 (cis-isomer, d, J = 20.7 Hz, 1H), 4.67 (cis-isomer, d, J = 9.6 Hz, 2H), 4.62 (trans-isomer, d, J = 10.6 Hz, 2H), 4.24–4.03 (cis-isomer, m, 2H), 3.88–3.76 (trans-isomer, m, 1H), 3.59–3.47 (trans-isomer, m, 1H), 2.25 (trans-isomer, s, 3H), 2.21 (cis-isomer, s, 3H), 1.32 (cis-isomer, t, J = 7.0 Hz, 3H), 0.88 (trans-isomer, t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.3 (cis-isomer, d, J_C–P = 3.1 Hz), 141.9 (cis-isomer, d, J_C–P = 26.7 Hz), 136.74 (trans-isomer), 136.7 (cis-isomer, d, J_C–P = 2.4 Hz), 134.0 (trans-isomer), 133.6 (cis-isomer), 130.2 (cis-isomer), 129.6 (cis-isomer), 129.4 (trans-isomer), 129.0 (trans-isomer), 128.8 (cis-isomer), 128.71 (trans-isomer), 128.7 (cis-isomer), 128.6 (cis-isomer), 128.1 (cis-isomer), 128.0 (cis-isomer), 127.4 (trans-isomer), 127.3 (cis-isomer), 127.0 (cis-isomer), 126.99 (trans-isomer), 121.9 (cis-isomer, d, J_C–P = 4.0 Hz), 110.2 (cis-isomer, d, J_C–P = 11.2 Hz), 109.7 (trans-isomer, d, J_C–P = 11.7 Hz). 64.1 (trans-isomer, d, J_C–P = 7.2 Hz), 63.1 (cis-isomer, d, J_C–P = 6.9 Hz), 48.9 (trans-isomer, d, J_C–P = 113.0 Hz), 48.4 (cis-isomer, d, J_C–P = 106.4 Hz), 45.4 (cis-isomer, d, J_C–P = 2.3 Hz), 45.2 (trans-isomer), 20.8 (trans-isomer), 20.7 (cis-isomer), 15.9 (trans-isomer, d, J_C–P = 6.0 Hz). 16.5 (cis-isomer, d, J_C–P = 6.2 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 38.9 (cis-isomer), 38.3 (trans-isomer). IR (KBr, cm⁻¹): 1678, 1229 (P=O). HRMS (ESI) calcd for C₂₄H₂₅NO₃P⁺ [M + H⁺] 406.1567, found 406.1578.

3-Benzoyl-5-bromo-2-ethoxy-1-methyl-2-oxophosphorindoline (2h). Colorless crystals, 110 mg (0.52 mmol scale), 54% yield, mp 162–166 °C. R_f = 0.22 (PE : EA = 1 : 1, v/v). Two pairs of diastereomeric rotamers exist. Their stereostructures cannot be identified. ¹H NMR (400 MHz, CDCl₃) δ 8.29–8.20 (m, 4H), 8.04–7.96 (m, 4H), 7.72–7.60 (m, 4H), 7.63–7.54 (m, 4H), 7.56–7.46 (m, 4H), 7.45–7.37 (m, 2H), 7.31 (d, J = 7.8 Hz, 1H), 7.30–7.23 (m, 2H), 7.21–7.15 (m, 2H), 7.16–7.09 (m, 1H), 7.00–6.93 (m, 1H), 6.69 (d, J = 8.0 Hz, 1H), 6.60 (d, J = 8.5 Hz, 1H), 6.60–6.53 (m, 1H), 5.25 (d, J = 23.6 Hz, 1H), 5.23 (d, J = 23.4 Hz, 1H), 5.02 (d, J = 20.8 Hz, 1H), 5.01 (d, J = 20.8 Hz, 1H), 4.27–4.14 (m, 4H), 3.94–3.81 (m, 2H), 3.61–3.47 (m, 2H), 3.04 (d, J = 8.8 Hz, 3H), 3.01 (d, J = 11.6 Hz, 3H), 3.00 (d, J = 13.2 Hz, 3H), 2.98 (d, J = 8.7 Hz, 3H), 1.42–1.37 (m, 6H), 0.99–0.93 (m, 6H). ¹³C NMR (101 MHz, CDCl₃) δ 190.7 (d, J_C–P = 4.7 Hz), 143.9 (d, J_C–P = 26.5 Hz), 136.6, 136.5, 134.2, 134.0, 133.9, 132.1, 131.9, 131.0 (d, J_C–P = 13.4 Hz), 130.3 (d, J_C–P = 13.9 Hz), 129.1, 129.0, 128.8, 128.6, 128.0, 122.6 (d, J_C–P = 5.4 Hz), 120.5, 112.5 (d, J_C–P = 2.0 Hz), 110.3 (d, J_C–P = 10.9 Hz), 109.9 (d, J_C–P = 11.1 Hz), 108.4 (d, J_C–P = 11.7 Hz), 64.3 (d, J_C–P = 7.2 Hz), 64.1 (d, J_C–P = 7.5 Hz), 63.4 (d, J_C–P = 7.1 Hz), 49.7 (d, J_C–P = 102.5 Hz), 48.5 (d, J_C–P = 102.8 Hz), 47.6 (d, J_C–P = 100.1 Hz), 27.5 (d, J_C–P = 1.9 Hz), 27.1 (d, J_C–P = 1.9 Hz), 27.0 (d, J_C–P = 2.0 Hz), 16.6 (d, J_C–P = 5.8 Hz), 16.0 (d, J_C–P = 5.8 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 39.0, 38.5, 38.3, 37.9. IR (KBr, cm⁻¹): 1690, 1659, 1267 (P=O), 1244 (P=O). HRMS (ESI) calcd for C₁₇H₁₈BrNO₃P⁺ [M + H⁺] 394.0202, found 394.0209.

3-Benzoyl-5-chloro-2-ethoxy-1-methyl-2-oxophosphorindoline (2i). Colorless crystals, 101 mg (0.45 mmol scale), 63% yield, mp 172–175 °C. R_f = 0.19 (PE : EA = 1 : 1, v/v). cis-Isomer : trans-isomer = 1.00 : 0.18. ¹H NMR (400 MHz, CDCl₃) δ 8.27–8.20 (cis-isomer, m, 2H), 8.04–7.96 (trans-isomer, m, 2H), 7.72–7.62 (trans-isomer and cis-isomer, m, 2H), 7.58 (cis-isomer, t, J = 7.6 Hz, 2H), 7.54–7.48 (trans-isomer, m, 2H), 7.30–7.22 (trans-isomer and cis-isomer, m, 2H), 7.16–7.10 (cis-isomer, m, 1H), 7.07–7.02 (trans-isomer, m, 1H), 6.64 (trans-isomer, d, J = 8.6 Hz, 1H), 6.61 (cis-isomer, d, J = 8.5 Hz, 1H), 5.22 (cis-isomer, d, J = 23.4 Hz, 1H), 5.01 (trans-isomer, d, J = 20.7 Hz, 1H), 4.27–4.14 (trans-isomer, m, 2H), 3.95–3.83 (cis-isomer, m, 1H), 3.62–3.47 (cis-isomer, m, 1H), 3.02 (trans-isomer, d, J = 8.7 Hz, 3H), 2.98 (cis-isomer, d, J = 8.7 Hz, 3H), 1.39 (trans-isomer, t, J = 7.1 Hz, 3H), 0.96 (cis-isomer, t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 190.7 (cis-isomer, d, J_C–P = 4.6 Hz), 143.4 (cis-isomer, d, J_C–P = 26.5 Hz), 136.5 (trans-isomer), 136.3 (cis-isomer), 134.2 (cis-isomer), 133.8 (trans-isomer), 129.2 (trans-isomer), 129.1 (cis-isomer), 129.0 (cis-isomer), 128.8 (trans-isomer), 128.7 (cis-isomer), 128.3 (cis-isomer, d, J_C–P = 13.4 Hz), 127.6 (trans-isomer, d, J_C–P = 13.8 Hz), 125.4 (cis-isomer, d, J_C–P = 2.0 Hz), 122.2 (cis-isomer, d, J_C–P = 5.4 Hz), 109.8 (trans-isomer, d, J_C–P = 10.9 Hz), 109.4 (cis-isomer, d, J_C–P = 11.1 Hz), 64.3 (cis-isomer, d, J_C–P = 7.2 Hz), 63.4 (trans-isomer, d, J_C–P = 7.0 Hz), 48.5 (cis-isomer, d, J_C–P = 103.6 Hz), 47.8 (trans-isomer, d, J_C–P = 106.4 Hz), 27.5 (trans-isomer, d, J_C–P = 1.9 Hz), 27.2 (trans-isomer, d, J_C–P = 1.8 Hz), 16.6 (trans-isomer, d, J_C–P = 5.8 Hz) 16.0 (cis-isomer, d, J_C–P = 5.7 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 38.1 (trans-isomer), 37.7 (cis-isomer). IR (KBr, cm⁻¹): 1690, 1630, 1267 (P=O), 1240 (P=O). HRMS (ESI) calcd for C₁₇H₁₈ClNO₃P⁺ [M + H⁺] 350.0707, found 350.0714.

3-Benzoyl-2-ethoxy-5-fluoro-1-methyl-2-oxophosphorindoline (2j). Colorless crystals, 55 mg (0.38 mmol scale), 43% yield, mp 162–163 °C. R_f = 0.17 (PE : EA = 1 : 1, v/v). cis-Isomer : trans-isomer = 1.00 : 0.18. ¹H NMR (400 MHz, CDCl₃) δ 8.28–8.21 (cis-isomer, m, 2H), 8.04–7.96 (trans-isomer, m, 2H), 7.72–7.59 (trans-isomer and cis-isomer, m, 2H), 7.58 (cis-isomer, t, J = 7.6 Hz, 2H), 7.51 (trans-isomer, t, J = 7.8 Hz, 2H), 7.05–6.97 (trans-isomer and cis-isomer, m, 2H), 6.93–6.88 (cis-isomer, m, 1H), 6.85–6.81 (trans-isomer, m, 1H), 6.66–6.63 (trans-isomer, m, 1H), 6.63–6.58 (cis-isomer, m, 1H), 5.23 (cis-isomer, d, J = 23.5 Hz, 1H), 5.01 (trans-isomer, d, J = 20.9 Hz, 1H), 4.25–4.16 (trans-isomer, m, 2H), 3.96–3.81 (cis-isomer, m, 1H), 3.61–3.46 (cis-isomer, m, 1H), 3.02 (trans-isomer, d, J = 8.7 Hz, 3H), 2.99 (cis-isomer, d, J = 8.8 Hz, 3H), 1.39 (trans-isomer, t, J = 7.0 Hz, 3H), 0.96 (cis-isomer, t, J = 7.0 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 190.9 (cis-isomer, d, J_C–P = 4.6 Hz), 157.2 (cis-isomer, dd, J_C–F = 238.8, 1.9 Hz), 141.0 (cis-isomer, dd, J_C–P = 26.6, J_C–F = 2.0 Hz), 136.4 (cis-isomer), 134.2 (cis-isomer), 129.1 (cis-isomer), 128.7 (cis-isomer), 122.0 (cis-isomer, dd, J_C–F = 8.5, J_C–P = 5.4 Hz), 115.9 (cis-isomer, dd, J_C–F = 24.7, J_C–P = 13.4 Hz), 115.5 (cis-isomer, d, J_C–F = 22.9 Hz), 108.8 (cis-isomer, dd, J_C–P = 10.8 Hz, J_C–F = 8.1 Hz), 64.2 (cis-isomer, d, J_C–P = 7.3 Hz), 63.4 (trans-isomer, d, J_C–P = 6.9 Hz), 48.9 (cis-isomer, d, J_C–P = 105.2 Hz), 48.3 (trans-isomer, d, J_C–P = 110.6 Hz), 27.7 (trans-isomer, d, J_C–P = 2.2 Hz), 27.3 (cis-isomer, d, J_C–P = 1.8 Hz), 16.7 (trans-isomer, d, J_C–P = 6.0 Hz), 16.0 (cis-isomer, d, J_C–P = 5.8 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ −122.7 (trans-isomer), −122.8 (cis-isomer). ³¹P NMR (162 MHz, CDCl₃) δ 38.8 (trans-isomer), 38.4 (cis-isomer). IR (KBr, cm⁻¹): 1689, 1659, 1264 (P=O), 1230 (P=O). HRMS (ESI) calcd for C₁₇H₁₈FNO₃P⁺ [M + H⁺] 334.1003, found 334.1008.

3-Benzoyl-2-ethoxy-1,7-dimethyl-2-oxophosphorindoline (2k). Colorless crystals, 44 mg (0.30 mmol scale), 45% yield, mp 124–126 °C. R_f = 0.31 (PE : EA = 1 : 1, v/v). cis-Isomer : trans-isomer = 1.00 : 0.78. ¹H NMR (400 MHz, CDCl₃) δ 8.28–8.21 (trans-isomer, m, 2H), 8.05 (cis-isomer, m, J = 7.1, 1.4 Hz, 2H), 7.69–7.47 (cis-isomer and trans-isomer, m, 6H), 7.13–7.02 (cis-isomer and trans-isomer, m, 2H), 6.97 (trans-isomer, d, J = 7.4 Hz, 1H), 6.96–6.87 (cis-isomer and trans-isomer, m, 3H), 5.27 (trans-isomer, d, J = 23.0 Hz, 1H), 4.95 (cis-isomer, d, J = 19.8 Hz, 1H), 4.24–4.06 (cis-isomer, m, 2H), 3.99–3.84 (trans-isomer, m, 1H), 3.70 (trans-isomer, m, J = 9.8, 7.1 Hz, 1H), 3.28 (trans-isomer, d, J = 9.2 Hz, 3H), 3.24 (cis-isomer, d, J = 9.5 Hz, 3H), 2.48 (trans-isomer, s, 3H), 2.45 (cis-isomer, s, 3H), 1.32 (cis-isomer, t, J = 7.1 Hz, 3H), 1.00 (trans-isomer, t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.55 (cis-isomer, d, J = 2.6 Hz), 191.77 (trans-isomer, d, J = 5.3 Hz), 144.79 (cis-isomer, d, J = 22.9 Hz), 143.68 (trans-isomer, d, J = 24.3 Hz), 136.85 (trans-isomer), 136.51 (cis-isomer), 133.85 (trans-isomer), 133.59 (cis-isomer), 132.64 (trans-isomer), 132.41 (cis-isomer), 128.94 (trans-isomer), 128.90 (cis-isomer), 128.76 (cis-isomer), 128.65 (trans-isomer), 126.31 (trans-isomer, d, J = 3.4 Hz), 126.17 (cis-isomer, d, J = 13.5 Hz), 125.56 (trans-isomer, d, J = 12.1 Hz), 124.91 (cis-isomer, d, J = 14.2 Hz), 123.47 (trans-isomer, d, J = 4.5 Hz), 123.14 (cis-isomer, d, J = 12.4 Hz), 122.86 (cis-isomer), 121.82 (trans-isomer), 63.44 (trans-isomer, d, J = 7.3 Hz), 61.91 (cis-isomer, d, J = 7.2 Hz), 49.0 (trans-isomer, d, J = 101.1 Hz), 48.11 (cis-isomer, d, J = 106.0 Hz), 34.02 (cis-isomer, d, J = 3.3 Hz), 32.49 (trans-isomer, d, J = 3.0 Hz), 19.70 (trans-isomer), 19.32 (cis-isomer), 16.38 (cis-isomer, d, J = 6.1 Hz), 15.98 (trans-isomer, d, J = 5.9 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 39.9 (cis-isomer), 38.5 (trans-isomer). IR (KBr, cm⁻¹): 1687, 1251 (P=O). HRMS (ESI) calcd for C₁₈H₂₁NO₃P⁺ [M + H⁺] 330.1254, found 330.1264.

Mixture of 3-benzoyl-1-benzyl-2-ethoxy-6-methyl-2-oxophosphorindoline (2la) and 3-benzoyl-1-benzyl-2-ethoxy-4-methyl-2-oxophosphorindoline (2lb). Isolated as a mixture of two pairs of regioisomeric diastereomers with indistinguishable ratio. Colorless crystals, 182 mg (0.46 mmol scale), 97% yield, mp 165–167 °C. R_f = 0.50 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 8.31–8.26 (m, 2H), 8.07–7.98 (m, 4H), 7.68–7.63 (m, 1H), 7.62–7.54 (m, 4H), 7.52–7.46 (m, 4H), 7.52–7.46 (m, 3H), 7.45–7.39 (m, 5H), 7.37–7.30 (m, 5H), 7.29–7.22 (m, 2H), 7.06 (t, J = 7.8 Hz, 1H), 7.02 (d, J = 7.6 Hz, 1H), 6.94 (d, J = 7.6 Hz, 1H), 6.74 (d, J = 7.6 Hz, 1H), 6.70 (d, J = 7.8 Hz, 1H), 6.69 (d, J = 7.6 Hz, 1H), 6.42 (d, J = 7.8 Hz, 1H), 6.40 (s, 1H), 6.36 (s, 1H), 5.30 (d, J = 23.7 Hz, 1H), 5.05 (d, J = 20.8 Hz, 1H), 5.03 (d, J = 20.8 Hz, 1H), 4.71–4.59 (m, 6H), 4.26–3.99 (m, 4H), 3.86–3.74 (m, 1H), 3.57–3.44 (m, 1H), 2.22 (s, 3H) × 2, 2.03 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H), 1.31 (t, J = 7.1 Hz, 3H), 0.85 (t, J = 7.0 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.3 (d, J_C–P = 3.2 Hz), 144.3 (d, J_C–P = 26.8 Hz), 139.4, 139.2, 136.8 (d, J_C–P = 2.3 Hz), 136.7 (d, J_C–P = 4.9 Hz), 136.5 (d, J_C–P = 1.9 Hz), 134.0, 133.5, 129.1, 129.0, 128.8, 128.76, 128.7, 128.69, 128.6, 128.62, 128.0 (d, J_C–P = 13.1 Hz), 127.3, 127.32, 127.2 (d, J_C–P = 13.6 Hz), 127.0, 126.96, 122.5, 121.6, 121.5, 118.9 (d, J_C–P = 3.9 Hz), 117.6, 111.0 (d, J_C–P = 11.3 Hz), 110.5 (d, J_C–P = 11.3 Hz), 108.0 (d, J_C–P = 11.6 Hz), 64.0 (d, J_C–P = 7.2 Hz), 63.1 (d, J_C–P = 6.8 Hz), 63.08 (d, J_C–P = 6.2 Hz), 48.6 (d, J_C–P = 104.3 Hz), 48.1 (d, J_C–P = 106.4 Hz), 45.4 (d, J_C–P = 2.5 Hz), 45.3 (d, J_C–P = 2.2 Hz), 45.1 (d, J_C–P = 2.3 Hz), 21.8, 21.81, 19.3, 16.5 (d, J_C–P = 6.1 Hz), 16.49 (d, J_C–P = 5.4 Hz), 15.9 (d, J_C–P = 5.9 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 39.4, 38.8, 38.3, 38.0. IR (KBr, cm⁻¹): 1683, 1612, 1279 (P=O), 1232 (P=O). HRMS (ESI) calcd for C₂₅H₂₇NO₃P⁺ [M + H⁺] 406.1567, found 406.1573.

Mixture of 3-benzoyl-2-ethoxy-1,6-dimethyl-2-oxophosphorindoline (2ma) and 3-benzoyl-2-ethoxy-1,4-dimethyl-2-oxophosphorindoline (2mb). Isolated as a mixture of two pairs of regioisomeric diastereomers with indistinguishable ratio. Colorless crystals, 147 mg (0.52 mmol scale), 86% yield, mp 155–157 °C. R_f = 0.22 (PE : EA = 1 : 1, v/v). ¹H NMR (400 MHz, CDCl₃) δ 8.28–8.21 (m, 2H), 8.04–7.95 (m, 4H), 7.68–7.63 (m, 1H), 7.62–7.54 (m, 4H), 7.52–7.44 (m, 4H), 7.21 (t, J = 7.9 Hz, 1H), 7.00 (d, J = 7.6 Hz, 1H), 6.92 (d, J = 7.6 Hz, 1H), 6.77 (d, J = 7.5 Hz, 1H), 6.76–6.70 (m, 2H), 6.58 (d, J = 7.9 Hz, 1H), 6.55 (s, 1H), 6.51 (s, 1H), 5.21 (d, J_C–P = 23.7 Hz, 1H), 4.96 (d, J = 20.9 Hz, 1H), 4.94 (d, J = 21.2 Hz, 1H), 4.25–4.12 (m, 4H), 3.92–3.82 (m, 1H), 3.60–3.48 (m, 1H), 3.03 (d, J_H–P = 8.7 Hz, 1H), 2.99 (d, J = 8.8 Hz, 1H), 2.98 (d, J = 8.8 Hz, 1H), 2.36 (s, 3H) × 2, 2.02 (s, 3H), 1.38 (t, J = 7.1 Hz, 3H) × 2, 0.96 (t, J = 7.0 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.3 (d, J_C–P = 3.1 Hz), 145.0 (d, J_C–P = 26.3 Hz), 139.8, 139.6, 136.9, 136.7, 133.9, 133.5, 129.2, 129.0, 128.8, 128.7, 128.5, 127.1 (d, J_C–P = 13.4 Hz), 122.4, 121.3, 118.8 (d, J_C–P = 4.3 Hz), 109.7 (d, J_C–P = 11.3 Hz), 106.4 (d, J_C–P = 11.5 Hz), 63.1 (d, J_C–P = 6.9 Hz), 47.8 (d, J_C–P = 105.7 Hz), 27.5 (d, J_C–P = 2.1 Hz), 27.4 (d, J_C–P = 2.0 Hz), 21.9, 19.2, 16.6 (d, J_C–P = 5.8 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 39.6, 39.2, 39.1, 38.2. IR (KBr, cm⁻¹): 1683, 1613, 1279 (P=O), 1241 (P=O). HRMS (ESI) calcd for C₁₈H₂₁NO₃P⁺ [M + H⁺] 330.1254, found 330.1263.

3-Benzoyl-2-ethoxy-5-isopropyl-1-methyl-2-oxophosphorindoline (2n). Colorless crystals, 116 mg, 65% yield, mp 145–147 °C, R_f = 0.28 (PE : EA = 1 : 1, v/v). cis-Isomer : trans-isomer = 1.00 : 0.00. ¹H NMR (400 MHz, CDCl₃) δ 8.04–7.97 (m, 2H), 7.59 (t, J = 7.3 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 7.15 (d, J = 8.1 Hz, 1H), 6.91 (s, 1H), 6.65 (d, J = 8.1 Hz, 1H), 5.00 (d, J = 20.8 Hz, 1H), 4.24–4.13 (m, 2H), 3.02 (d, J = 8.8 Hz, 3H), 2.81 (hept, J = 6.9 Hz, 1H), 1.38 (t, J = 7.0 Hz, 3H), 1.18 (t, J = 6.2 Hz, 6H). ¹³C NMR (101 MHz, CDCl₃) δ 192.4 (d, J_C–P = 3.0 Hz), 143.0 (d, J_C–P = 26.3 Hz), 141.3 (d, J_C–P = 1.4 Hz), 136.8, 133.5, 128.7, 128.7, 127.1, 125.6 (d, J_C–P = 13.6 Hz), 121.7 (d, J_C–P = 4.4 Hz), 108.6 (d, J_C–P = 11.1 Hz), 63.0 (d, J_C–P = 6.9 Hz), 48.3 (d, J_C–P = 105.9 Hz), 33.5, 27.5 (d, J_C–P = 2.0 Hz), 24.1 (d, J_C–P = 28.1 Hz), 16.6 (d, J_C–P = 5.8 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 39.4. IR (KBr, cm⁻¹): 1678, 1243 (P=O). HRMS (ESI) calcd for C₂₀H₂₅NO₃P⁺ [M + H⁺] 372.1723, found 372.1704.

3-Benzoyl-5-(tert-butyl)-2-ethoxy-1-methyl-2-oxophosphorindoline (2o). Colorless crystals, 131 mg, 71% yield, mp 120–121 °C, R_f = 0.28 (PE : EA = 1 : 1, v/v). cis-Isomer : trans-isomer = 1.00 : 0.00. ¹H NMR (400 MHz, CDCl₃) δ 8.02–7.98 (m, 2H), 7.63–7.56 (m, 1H), 7.49 (t, J = 7.6 Hz, 2H), 7.31 (d, J = 8.3 Hz, 1H), 7.06 (s, 1H), 6.66 (d, J = 8.4 Hz, 1H), 5.01 (d, J = 20.9 Hz, 1H), 4.24–4.13 (m, 2H), 3.02 (d, J = 8.7 Hz, 3H), 1.38 (t, J = 7.0 Hz, 3H), 1.24 (s, 9H). ¹³C NMR (101 MHz, CDCl₃) δ 192.4 (d, J_C–P = 3.1 Hz), 143.6, 142.7 (d, J_C–P = 26.2 Hz), 136.8, 133.5, 128.7, 128.69, 126.0, 124.6 (d, J_C–P = 13.6 Hz), 121.4 (d, J_C–P = 4.5 Hz), 108.3 (d, J_C–P = 11.2 Hz), 63.0 (d, J_C–P = 6.9 Hz), 48.4 (d, J_C–P = 105.9 Hz), 34.3, 31.4, 27.4 (d, J_C–P = 2.0 Hz), 16.6 (d, J_C–P = 5.7 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 39.4. IR (KBr, cm⁻¹): 1690, 1261 (P=O). HRMS (ESI) calcd for C₂₁H₂₇NO₃P⁺ [M + H⁺] 358.1567, found 358.1553.

3-Benzoyl-2-ethoxy-1-methyl-2-oxobenzo[f] phosphorindoline (2p). Colorless crystals, 131 mg (0.52 mmol scale), 69% yield, mp 168–172 °C. R_f = 0.19 (PE : EA = 1 : 1, v/v). cis-Isomer : trans-isomer = 1.00 : 0.79. ¹H NMR (400 MHz, CDCl₃) δ 8.31 (cis-isomer, d, J = 7.4 Hz, 2H), 8.13–8.05 (trans-isomer, m, 2H), 7.88 (trans-isomer, s, 1H), 7.86 (cis-isomer, s, 1H), 7.79 (trans-isomer, d, J = 3.6 Hz, 1H), 7.80–7.74 (cis-isomer, m, 1H), 7.74–7.65 (cis-isomer, m, 1H), 7.65–7.56 (trans-isomer and cis-isomer, m, 3H), 7.55–7.46 (trans-isomer, m, 2H), 7.38–7.29 (trans-isomer, m, 2H), 7.28–7.24 (cis-isomer, m, 2H), 7.23–7.21 (trans-isomer, m, 1H), 7.12 (cis-isomer, d, J = 3.6 Hz, 1H), 7.10 (trans-isomer, d, J = 3.1 Hz, 1H), 7.07 (cis-isomer, d, J = 8.8 Hz, 1H), 5.60 (cis-isomer, d, J = 22.6 Hz, 1H), 5.34 (trans-isomer, d, J = 20.8 Hz, 1H), 4.30–4.15 (trans-isomer, m, 2H), 4.08–3.95 (cis-isomer, m, 1H), 3.69–3.54 (cis-isomer, m, 1H), 3.16 (trans-isomer, d, J = 8.8 Hz, 3H), 3.10 (cis-isomer, d, J = 8.8 Hz, 3H), 1.38 (trans-isomer, t, J = 7.1 Hz, 3H), 1.00 (cis-isomer, t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.0 (trans-isomer, d, J_C–P = 2.9 Hz), 191.4 (cis-isomer, d, J_C–P = 4.3 Hz), 143.6 (trans-isomer, d, J_C–P = 26.4 Hz), 143.3 (cis-isomer, d, J_C–P = 28.0 Hz), 136.8 (trans-isomer), 136.6 (cis-isomer), 134.1 (cis-isomer), 133.6 (trans-isomer), 130.7 (cis-isomer), 130.6 (trans-isomer), 130.5 (cis-isomer), 129.1 (cis-isomer), 129.1 (cis-isomer), 128.8 (cis-isomer), 128.7 (cis-isomer), 128.7 (trans-isomer), 127.6 (trans-isomer), 127.4 (cis-isomer), 123.2 (trans-isomer), 123.1 (cis-isomer), 122.5 (cis-isomer), 122.0 (trans-isomer), 114.4 (trans-isomer, d, J_C–P = 5.4 Hz), 113.3 (cis-isomer, d, J_C–P = 6.3 Hz), 110.7 (trans-isomer, d, J_C–P = 11.3 Hz), 110.2 (cis-isomer, d, J_C–P = 11.8 Hz), 64.4 (cis-isomer, d, J_C–P = 6.8 Hz), 63.0 (trans-isomer, d, J_C–P = 7.0 Hz), 47.8 (cis-isomer, d, J_C–P = 102.5 Hz), 47.0 (trans-isomer, d, J_C–P = 104.7 Hz), 27.8 (trans-isomer, d, J_C–P = 2.1 Hz), 27.3 (cis-isomer, d, J_C–P = 1.7 Hz), 16.6 (trans-isomer, d, J_C–P = 5.9 Hz), 16.1 (cis-isomer, d, J_C–P = 5.8 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 40.5 (trans-isomer), 39.5 (cis-isomer). IR (KBr, cm⁻¹): 1687, 1625, 1278 (P=O), 1251 (P=O). HRMS (ESI) calcd for C₂₁H₂₁NO₃P⁺ [M + H⁺] 366.1254, found 366.1261.

2-Benzoyl-1-ethoxy-1-oxoazacyclohexano[3,2,1-hi]phosphorindoline (2q). Colorless crystals, 104 mg (0.38 mmol scale), 79% yield, mp 142–144 °C. R_f = 0.20 (PE : EA = 1 : 1, v/v). cis-Isomer : trans-isomer = 1.00 : 0.17. ¹H NMR (400 MHz, CDCl₃) δ 8.29–8.21 (cis-isomer, m, 2H), 8.03–7.96 (trans-isomer, m, 2H), 7.70–7.61 (cis-isomer, m, 1H), 7.63–7.52 (trans-isomer and cis-isomer, m, 3H), 7.52–7.44 (trans-isomer, m, 2H), 7.04–6.97 (trans-isomer and cis-isomer, m, 2H), 6.95 (cis-isomer, d, J = 7.4 Hz, 1H), 6.88 (trans-isomer, d, J = 7.5 Hz, 1H), 6.83 (cis-isomer, t, J = 7.6 Hz, 1H), 6.77 (cis-isomer, t, J = 7.6 Hz, 1H), 5.21 (cis-isomer, d, J = 23.5 Hz, 1H), 4.98 (trans-isomer, d, J = 20.9 Hz, 1H), 4.27–4.14 (trans-isomer, m, 2H), 3.95–3.82 (cis-isomer, m, 1H), 3.69–3.57 (trans-isomer and cis-isomer, m, 2H), 3.60–3.48 (cis-isomer, m, 1H), 3.48–3.42 (trans-isomer, m, 1H), 3.46–3.32 (cis-isomer, m, 1H), 2.79–2.71 (trans-isomer and cis-isomer, m, 4H), 2.05–1.94 (trans-isomer and cis-isomer, m, 4H), 1.40 (trans-isomer, t, J = 7.0 Hz, 3H), 0.96 (cis-isomer, t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 191.7 (cis-isomer, d, J_C–P = 4.5 Hz), 140.4 (cis-isomer), 136.8 (trans-isomer), 136.7 (cis-isomer), 133.9 (cis-isomer), 133.5 (trans-isomer), 129.0 (cis-isomer), 128.7 (trans-isomer), 128.66 (cis-isomer), 128.6 (trans-isomer), 128.4 (cis-isomer), 125.8 (cis-isomer, d, J_C–P = 12.8 Hz), 125.1 (trans-isomer, d, J_C–P = 13.1 Hz), 120.5 (trans-isomer, d, J_C–P = 21.7 Hz), 120.2 (cis-isomer), 120.1 (cis-isomer), 119.69 (trans-isomer), 119.7 (cis-isomer), 64.0 (cis-isomer, d, J_C–P = 7.3 Hz), 63.2 (trans-isomer, d, J_C–P = 6.9 Hz), 49.0 (cis-isomer, d, J_C–P = 103.4 Hz), 48.5 (trans-isomer, d, J_C–P = 105.6 Hz), 39.4 (trans-isomer), 39.2 (cis-isomer), 25.1 (trans-isomer), 25.0 (cis-isomer), 21.3 (trans-isomer, d, J_C–P = 5.3 Hz), 21.2 (cis-isomer, d, J_C–P = 5.5 Hz), 16.7 (trans-isomer, d, J_C–P = 5.9 Hz), 16.1 (cis-isomer, d, J_C–P = 5.7 Hz). ³¹P NMR (162 MHz, CDCl₃) δ 38.7 (trans-isomer), 38.1 (cis-isomer). IR (KBr, cm⁻¹): 1693, 1655, 1270 (P=O), 1244 (P=O). HRMS (ESI) calcd for C₁₉H₂₁NO₃P⁺ [M + H⁺] 342.1254, found 342.1257.

Acknowledgements

This work was supported in part by the National Basic Research Program of China (No. 2013CB328905), the National Natural Science Foundation of China (No. 21372025 and 21572017).

Notes and references

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13. DFT calculational results indicate that trans-product is more stable in energy than the corresponding cis-product by 2.4 kcal mol⁻¹ for product 2a (For details, see ESI†).

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Footnote

† Electronic supplementary information (ESI) available: ¹H and ¹³C NMR spectra of products 1, 2, and 3. CCDC 1483899. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ra10555f

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