One-pot formation of fluorescent γ-lactams having an α-phosphorus ylide moiety through three-component α(δ′)-Michael reactions of phosphines with an enyne and N-tosyl aldimines

Abstract

We demonstrate a straightforward synthesis of γ-lactams possessing an α-phosphorus ylide moiety from assembly of phosphines, N-tosyl aldimines and an enyne through an initial α(δ′)-attack of phosphines to an enyne in up to 79% yield. The investigated multicomponent reaction tolerates a variety of triarylphosphines and electron-poor aldimines to give γ-lactams in one pot. One of the lactams, with the tri(p-tol)phosphine and 4-cyanophenyl moiety, exhibits fluorescence emission at 447 nm with a quantum yield of 0.11.

---

Introduction

Multicomponent reactions (MCRs) are synthetic reactions showing expediency, molecular diversity and step-economy which are used to construct complex molecular structures from simple reactants in one pot.¹ In this context, the initial reactive intermediates could be generated from nucleophilic attack of amine,² phosphine³ or isocyanide⁴ species to electron-deficient acetylenes/allenes followed by subsequent addition to electrophiles. In recent years, versatile reactions using phosphine-catalysis have also been demonstrated for the syntheses of various heterocyclic natural products and bioactive compounds.⁵ For example, the highly functionalized coumarins,⁶ tetrahydropyridines,⁷ 2-pyrones⁸ and bicarbocyclic skeletons⁹ can be prepared efficiently through the methodology of phosphine-catalysis. Recently, we have developed a three-component reaction (3CR) of phosphines, enynes 1 and aldehydes through an initial region-selective α(δ′)-attack of phosphines to enynes that form γ-lactones possessing an α-phosphorus ylide moiety (Scheme 1).¹⁰ The same methodology can also be used to react with [60]fullerene to give cyclopentenofullerene derivatives in one pot,¹¹ and is also transferable to substrates such as dimethyl acetylenedicarboxylate (DMAD) in a particular molar ratio of the three reactants. The assembled products, γ-lactones possessing α-phosphorus ylides, are reactive toward electron-poor aldehydes as Wittig reagents to give substituted α-benzylidine lactones.¹² In addition, primary and secondary amines also undergo α(δ′)-nucleophilic attack to enyne 1.¹³

Scheme 1 Lactones and lactams by three-component reactions.

Due to our continuing interest in expanding this methodology for practical applications, we subsequently chose to develop the synthesis of the γ-lactam core structure by MCRs since we have noted that the natural products, isatin and its derivatives possessing a γ-lactam moiety, can be used as useful building blocks for the syntheses of other structurally relevant bioactive molecules.¹⁴ We are able to construct isatin derivatives through this developed α(δ′)-Michael addition.¹⁵ Further, the approaches to build up a γ-lactam moiety with multiple functional substituents in one step remain to be developed¹⁶ in addition to other previous examples.¹⁷ Herein, we wish to report the one-pot synthesis and characterization of fluorescent γ-lactams possessing α-phosphorus ylides through an initial α(δ′)-Michael addition of phosphines to an enyne by MCRs (Scheme 1).

Results and discussion

First of all, we briefly delineate the condition optimization of the synthesis of γ-lactams by three-component assembly of enyne 1, triphenylphosphine (2a), and aldimine 3a. We find that the reaction with a molar ratio of 1 : 2a : 3a = 1 : 1 : 1 gives a relatively better yield (32%) in the aprotic etherate solvent tetrahydrofuran (THF) at 60 °C for 2 h (Table 1, entries 1–5). When we increase the molar ratio of both 1 and 2a (1.5 equiv.) for generating relatively greater amounts of reactive 1,3-dipolar species, we observe an increase of reaction yield to 44% (entry 6). Further increment of the relative molar ratio of 1 : 2a : 3a to 2 : 2 : 1 gives the highest yield of 57% (entry 7). Other adjustments of the conditions such as time-shortening to 1 h (entry 8) or carrying out the reaction under milder conditions at r.t. (entries 9 and 10) do not improve the yields of the reaction notably.

Table 1 Reaction condition optimization^a

Entry	Solvent	Temp. (°C)	Time (h)	Yield^b (%)
a Reaction conditions: a mixture of 1 (0.30 mmol), 2a (0.30 mmol) and 3a (0.30 mmol) under nitrogen in anhydrous solvents. b Yield is determined by a ^1H NMR spectroscopic method using mesitylene as an internal standard. c Molar ratio of 1 : 2a : 3a = 1.5 : 1.5 : 1. d Molar ratio of 1 : 2a : 3a = 2 : 2 : 1. e 1,2-Dichloroethane.
1	DCM	r.t.	2	21
2	THF	60	2	32
3	Toluene	60	2	25
4	MeCN	60	2	27
5	DCE^e	60	2	22
6^c	THF	60	2	44
7^d	THF	60	2	57
8^d	THF	60	1	48
9^d	THF	r.t.	24	48
10^d	THF	r.t.	48	51

---

We investigate the scope of currently developed three-component reactions with other triarylphosphines and electron-poor aldimines. As shown in Table 2, γ-lactams can be assembled with isolated yields ranging from 49 to 79%, with variously substituted triarylphosphines 2a–f and 4-nitrobenzaldimine (3a) (entries 1–6); among these phosphines, tris(4-chlorophenyl)phosphine (2c) performs the best to give 79% yield (entry 4) and the reaction with a non-aryl hexamethylphosphorus triamide (2f, HMPT) produces 4f in a comparable yield of 53% (entry 6) as those with phosphines 2a–f. We next evaluate the performance with other substituted aldimines 3b–d and find that the reactions proceed to give yields spanning from 22 to 71%. It is worthy to note that the present assembly reaction proceeds with phosphines such as the more nucleophilic P(cHex)₃ (2h) and the less nucleophilic P(NMe₂)₃ (2f), but these two phosphines did not work well in the syntheses of the corresponding γ-lactones with aldehydes as substrates.⁹ The reaction with a more nucleophilic tricyclohexylphosphine (2h) gives a relatively poor yield (entry 16, 22%), likely due to the presence of a P(cHex)₃ moiety that makes the corresponding product (4p) unstable. This notion is further evidenced from the fact that reaction products are not isolable when we use trialkylphosphines such as PMe₃, PEt₃, P(n-Pr)₃ and P(n-Bu)₃; with these trialkylphosphines, only a trace amount of products resulting from P(n-Bu)₃ is observed.

Table 2 Reaction scope study^a

Entry	2; PR3	3; R′	4	Yield^b (%)
a Reaction conditions: a mixture of 1 (0.30 mmol), 2 (0.30 mmol) and 3 (0.15 mmol) under nitrogen in anhydrous THF. b Yields (%) were determined by a ^1H NMR spectroscopic method using mesitylene as an internal standard after isolation by flash SiO2 column chromatography. c Room temperature. d Molar ratio of 1 : 2 : 3 = 1 : 1 : 1.
1	2a; PPh3	3a; 4-NO2	4a	57
2	2b; P(pTol)3	3a; 4-NO2	4b	49
3	2c; P(4-Cl-C6H4)3	3a; 4-NO2	4c	57
4	2d; P(4-F-C6H4)3	3a; 4-NO2	4d	79
5	2e; P(2-thienyl)3	3a; 4-NO2	4e	56
6^c^,^d	2f; P(NMe2)3	3a; 4-NO2	4f	53
7	2a; PPh3	3b; 3-NO2	4g	59
8	2b; P(pTol)3	3b; 3-NO2	4h	54
9	2g; PPh2(pTol)	3b; 3-NO2	4i	62
10	2d; P(4-FC6H4)3	3b; 3-NO2	4j	61
11	2b; P(pTol)3	3c; 4-Cl-3-NO2	4k	51
12	2c; P(4-Cl-C6H4)3	3c; 4-Cl-3-NO2	4l	52
13	2d; P(4-F-C6H4)3	3c; 4-Cl-3-NO2	4m	56
14	2b; P(pTol)3	3d; 4-CN	4n	71
15	2c; P(4-Cl-C6H4)3	3d; 4-CN	4o	54
16	2h; P(cHex)3	3d; 4-CN	4p	22

---

We characterized these γ-lactams 4a–p by using infrared (IR) and ¹H, ³¹P and ¹³C nuclear magnetic resonance (NMR) spectroscopy, electrospray ionization mass spectrometry (ESI-MS), and X-ray crystallography. All MS data corresponded to the expected formulae of the isolated γ-lactams. In their IR spectra, the C=O group, next to the ylidic carbanion, shows stretching bands at ca. 1629–1658 cm⁻¹, lower than that of a normal C=O stretching frequency due to electronic resonance. It is interesting to note that the C=O stretching frequency of the lactam 4f with a HMPT moiety appears at 1658 cm⁻¹ and that of lactam 4p with P(cHex)₃ appears at 1629 cm⁻¹. This indicated that P(cHex)₃ behaves as a strong electron-donating group and HMPT as a strong electron-pulling group—such an effect renders strong and weak delocalizations of the ylide carbanion through resonance to the lactam carbonyl moiety, respectively. For the characterization of an example of compound 4a by NMR, we observe a signal at 12.7 ppm in its ³¹P NMR spectrum, corresponding to a typical α-ylidic γ-lactam. Its ¹H NMR spectrum displays simple singlets at 2.46 and 3.38 ppm, corresponding to methyl and methoxy groups, respectively. Two signals at 165.7 and 167.0 (²J_PC = 15.8 Hz) ppm correspond to the carbonyl resonances of ester and lactam in the ¹³C NMR spectrum. The ylidic carbon (C2, Fig. 1) appears at 61.3 ppm with one bond coupling to phosphorus P1 (¹J_PC = 129.2 Hz).

Fig. 1 X-ray crystal structure of compound 4a.

Further, we find that these isolated ylide compounds tend to crystallize by slow evaporation of their dichloromethane or chloroform solution. We obtain the crystal structure of compounds 4a¹⁸ (Fig. 1) and 4l¹⁹ (Fig. 2) by X-ray diffraction analysis. The phosphorus atom P1 is clearly covalently bonded to C2 and C22 with a bond length of 1.7319(18) and 1.7360(4) Å for 4a and 4l, respectively. Due to the delocalization of negative charge from ylidic carbon C2 and C22 to the lactam carbonyl π bond (C1–O1 and C19–O1), the C1–C2 and C19–C22 bond lengths 1.4170(2) and 1.4280(7) Å for 4a and 4l, respectively, are shorter than a normal carbon to carbon single bond. The bond lengths of C1–O1 and C19–O1, 1.2350(2) and 1.2120(6) Å for 4a and 4l, respectively, are longer than a normal carbon to oxygen double bond. The relatively shorter C19–O1 in 4l may be inferred from the slightly larger electron-pulling ability of the tris(4-chlorophenyl)phosphine than a triphenylphosphine moiety, making the α-carbanion show lesser extent of resonance toward the carbonyl group.

Fig. 2 X-ray crystal structure of compound 4l.

We account for the formation of lactam ylide 4 by an initial nucleophilic attack of phosphine PR₃ (2) at α(δ′)-position of the enyne 1 (Scheme 2), generating a reactive zwitterionic species Ia bearing a carbenoid moiety at β(γ′)-carbon. Nucleophilic addition of Ia to the aldiminyl carbon of aldimines 3 generates Ib. Intramolecular cyclization of Ib gives Ic followed by release of a methoxide molecule. Finally, deprotonation on Id by the methoxide takes place to form the product 4.

Scheme 2 Proposed reaction mechanism.

These isolated lactam compounds 4a–4p exhibit remarkable visible colors from light yellow to orange. As a result, we measure the UV-vis absorption of compounds 4a–p, and these absorption data are shown in the ESI (Fig. S33 to S36†). In Fig. S33,† we find that benzaldimines equipped with the 4-NO₂ group display absorptions spanning from 330 to 600 nm. Among these compounds (4a–f), their maximum absorptions in the visible region are blue-shifted for phosphines with more electron-releasing groups—compound 4b with P(pTol)₃ shows absorption maxima at 458 nm and those of compounds 4a (with PPh₃), 4f (with P(NMe₂)₃), 4e (with P(2-thienyl)₃), 4d (with P(4-F-C₆H₄)₃) and 4c (with P(4-Cl-C₆H₄)₃) appear at 452, 452, 444, 441 and 436 nm, respectively (Fig. S33†). However, the switch of 4-nitro to 3-nitro substitution (compounds 4g–j) causes an apparent blue shift of the absorption maxima spanning from 376 to 400 nm, with compound 4j showing the most blue-shift (Fig. S33–S34†). Further, lactams with 3-chloro-4-nitro and 4-cyano substitutions (4k–4p) exhibit a pale-yellow solution in CHCl₃ and do not show intense absorptions (Fig. S34†).

Interestingly, we note that lactams 4a–p were fluorescent and measure their fluorescent emission spectra with a solution concentration of 5.0 × 10⁻⁵ M. As shown in Fig. 3, while compounds 4a–m and 4o show extremely poor fluorescent emission with quantum yields less than 0.01, compounds 4n and 4p exhibit relatively observable blue fluorescence. Their fluorescence quantum yields, determined by using anthracene as a reference standard (Φ = 0.27 in EtOH), are 0.112 and 0.038 with maximum emission wavelengths of 447 and 445 nm when excited at 363 nm, respectively (Fig. 4). Further, we note that the fluorescence of compound 4n is concentration-dependent in CHCl₃—the fluorescence emission is bathochromic-shifted while the concentration of solutions increases (Fig. 5). The emission wavelength maxima for solutions A to E of 4n are 447, 486, 491, 490 and 494 nm, respectively. However, this concentration-dependent notion is minute when 4n is dissolved in THF or dichloromethane. This typical change is attributed to more ordered packing of 4n in CHCl₃ than in THF or dichloromethane—consistent with the notion that 4n shows higher propensity for crystallization in CHCl₃.

Fig. 3 Fluorescent image of lactams 4a–p.

Fig. 4 Fluorescence emission spectra of 4n and 4p (excitation wavelength at 363 nm).

Fig. 5 Concentration-dependent emission phenomenon of compound 4n at concentrations of 5.0 × 10⁻⁵ (A), 7.5 × 10⁻⁵ (B), 1.0 × 10⁻⁴ (C), 2.0 × 10⁻⁴ (D), and 4.0 × 10⁻⁴ (E), respectively.

It is noteworthy that the assembled γ-lactam 4n with multiple functional groups exhibits fluorescent properties. We perform semiempirical calculations to retrieve the HOMO−1, HOMO, LUMO and LUMO+1 molecular orbitals of 4n. As shown in Fig. 6, the HOMO−1 and HOMO orbitals are primarily located at the lactam moiety while the LUMO and LUMO+1 orbitals are distributed over the 4-cyanophenyl and ester moiety. The electronic excitation may be contributed by the electron excited from the lactam core to the outer moiety to facilitate the subsequent fluorescent emission.

Fig. 6 HOMO−1 (−0.35227 eV), HOMO (−0.29164 eV), LUMO (−0.21441 eV) and LUMO+1 (−0.20384 eV) energy levels of 4n calculated by a semiempirical AM1 method.

Conclusions

We have demonstrated a one-pot multicomponent reaction for the synthesis of γ-lactams possessing an α-phosphorus ylide moiety from assembly of phosphines, N-tosyl aldimines and an enyne through an initial α(δ′)-Michael addition of phosphines to an enyne in up to 79% yield. The investigated MCRs tolerate a variety of phosphines such as triarylphosphines, tricyclohexylphosphine and hexamethylphosphorus triamide with electron-deficient aldimines, providing γ-lactams having α-phosphorus ylides in a one-pot procedure. One of these compounds, with the tri(p-tol)phosphine and 4-cyanophenyl moiety, exhibits blue fluorescence with a quantum yield of 0.112.

Experimental section

General methods

All reactions were performed under argon. Anhydrous benzene and THF were distilled from sodium/benzophenone under argon. The chemical shifts of ³¹P NMR were taken with reference to 85% H₃PO₄ in D₂O and that of ¹H and ¹³C with reference to TMS or CHCl₃.

Typical procedure for the synthesis of 4a–p

A benzene solution containing 1 (0.30 mmol) and aldimines 3 (0.15 mmol) was distilled three times to remove water using a Dean–Stark apparatus. Then, 8 mL of THF was added to the resulting mixture followed by phosphines 2 (0.30 mmol). The mixture was heated at 60 °C and monitored by thin layer chromatography (TLC). Upon completion of the reaction, THF was removed under reduced pressure and subjected to flash chromatography. Elution first with DCM–EA (3/1) gave products 4.

Measurement of fluorescence spectroscopy

The quantum yield was calculated according to the following equation: Φ_S/Φ_R = (A_S/A_R) × (Abs_R/Abs_S) × (ŋ_S²/ŋ_R²), where Φ_S and Φ_R are the fluorescence quantum yields of the sample and the reference, respectively; A_S and A_R are the emission areas of the sample and the reference; Abs_S and Abs_R are the corresponding absorbances of the sample and the reference solution at the wavelength of excitation; ŋ_S and ŋ_R are the refractive indices of the sample and the reference.²⁰

(E)-Methyl 3-(2-(4-nitrophenyl)-5-oxo-1-tosyl-4-(tri phenylphosphoranylidene)-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4a)

Red solid. M.p. 174–175 °C. R_f = 0.27 (DCM–EA, 3 : 1). Isolated yield 57% (0.0600 g). ¹H NMR (600 MHz, CDCl₃, 25 °C): δ = 2.46 (3H, s, Me), 3.38 (3H, s, CO₂Me), 5.01 (1H, d, J = 16.1 Hz, CH), 6.35 (1H, d, J = 16.0 Hz, CH), 7.25 (2H, d, J = 8.8 Hz, Ph), 7.38–7.42 (6H, m, Ph), 7.45 (6H, t, J = 7.8 Hz, Ph), 7.50 (2H, d, J = 8.5 Hz, Ph), 7.56, (3H, t, J = 7.1 Hz, Ph), 7.67 (2H, d, J = 8.1 Hz, Ph), 8.13 (2H, d, J = 8.6 Hz, Ph) ppm. ¹³C NMR (150 MHz, CDCl₃, 25 °C): δ = 21.6, 51.0, 61.3 (d, ¹J_PC = 129.2 Hz), 121.9, 122.6 (d, ¹J_PC = 92.3 Hz), 122.7, 122.8, 124.0 (d, ³J_PC = 11.9 Hz), 128.0, 129.0, 129.1 (d, ³J_PC = 12.8 Hz), 130.8, 133.1 (d, ⁴J_PC = 2.7 Hz), 133.8 (d, ²J_PC = 10.5 Hz), 135.7, 136.3, 140.0, 143.8, 146.1, 165.7, 167.0 (d, ²J_PC = 15.8 Hz) ppm. ³¹P NMR (202 MHz, CDCl₃, 25 °C): δ = 12.7 ppm. FTIR (KBr): [small nu, Greek, tilde] = 1640, 1716 cm⁻¹. λ_max(CHCl₃): 452 nm. HRMS (ESI⁺): calcd for C₃₉H₃₁N₂O₇PS [M⁺] 702.1590; found 702.1585.

(E)-Methyl 3-(2-(4-nitrophenyl)-5-oxo-1-tosyl-4-(tri-p-tolylphosphoranylidene)-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4b)

Red solid. M.p. 72–76 °C. R_f = 0.33 (DCM–EA, 3 : 1). Isolated yield 49% (0.0547 g). ¹H NMR (500 MHz, CDCl₃, 25 °C): δ = 2.40 (9H, s, Me), 2.51 (3H, s, Me), 3.45 (3H, s, CO₂Me), 5.00 (1H, d, J = 16.0 Hz, CH), 6.39 (1H, d, J = 15.5 Hz, CH), 7.21 (6H, dd, J = 3.0, 8.0 Hz, Ph), 7.28 (2H, d, J = 5.0 Hz, Ph), 7.33 (6H, dd, J = 8.5, 12.5 Hz, Ph), 7.51 (2H, d, J = 8.5 Hz, Ph), 7.73 (2H, d, J = 8.5 Hz, Ph), 8.17 (2H, d, J = 8.5 Hz, Ph) ppm. ¹³C NMR (125 MHz, CDCl₃, 25 °C): δ = 21.56, 21.62, 51.1, 62.2 (d, ¹J_PC = 129.3 Hz), 119.6 (d, ¹J_PC = 95.4 Hz), 121.7, 122.7, 122.8, 124.5 (d, ³J_PC = 12.2 Hz), 128.1, 129.0, 129.9 (d, ³J_PC = 13.3 Hz), 130.9, 133.8 (d, ²J_PC = 11.1 Hz), 135.9, 136.7, 140.2, 143.7, 144.0, 146.1, 166.0, 167.0 (d, ²J_PC = 15.5 Hz), ppm. ³¹P NMR (202 MHz, CDCl₃, 25 °C): δ = 11.8 ppm. λ_max(CHCl₃): 458 nm. FTIR (KBr): [small nu, Greek, tilde] = 1646, 1717 cm⁻¹. HRMS (ESI⁺): calcd for C₄₂H₃₇N₂O₇PS [M⁺] 744.2059; found 744.2058.

(E)-Methyl 3-(2-(4-nitrophenyl)-5-oxo-1-tosyl-4-(tris(4-chlorophenyl)phosphoranylidene)-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4c)

Red solid. M.p. 174–175 °C. R_f = 0.30 (hexanes–EA, 1.5 : 1). Isolated yield 79% (0.0953 g). ¹H NMR (300 MHz, CDCl₃, 25 °C): δ = 2.52 (3H, s, Me), 3.51 (3H, s, CO₂Me), 5.02 (1H, d, J = 16.2 Hz, CH), 6.36 (1H, d, J = 15.9 Hz, CH), 7.30 (2H, d, J = 8.1 Hz, Ph), 7.35–7.45 (12H, m, Ph), 7.51 (2H, d, J = 9.0 Hz, Ph), 7.73 (2H, d, J = 8.1 Hz, Ph), 8.18 (2H, d, J = 8.7 Hz, Ph) ppm. ¹³C NMR (100 MHz, CDCl₃, 25 °C): δ = 21.7, 51.5, 60.3 (d, ¹J_PC = 130.9 Hz), 120.5 (d, ¹J_PC = 95.2 Hz), 122.1, 122.6 (d, ²J_PC = 12.1 Hz), 122.8, 123.6 (d, ³J_PC = 12.6 Hz), 128.2, 129.1, 129.8 (d, ³J_PC = 13.7 Hz), 131.0, 134.9 (d, ²J_PC = 11.8 Hz), 135.6, 136.0, 139.6, 140.7 (d, ⁴J_PC = 3.8 Hz), 144.2, 146.4, 165.6, 166.9 (d, ²J_PC = 15.9 Hz) ppm. ³¹P NMR (202 MHz, CDCl₃, 25 °C): δ = 12.1 ppm. FTIR (KBr): [small nu, Greek, tilde] = 1640, 1717 cm⁻¹. λ_max(CHCl₃): 436 nm. HRMS (ESI⁺): calcd for C₃₉H₂₈Cl₃N₂O₇PS [M⁺] 804.0420; found 804.0428.

(E)-Methyl 3-(2-(4-nitrophenyl)-5-oxo-1-tosyl-4-(tris(4-fluorophenyl)phosphoranylidene)-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4d)

Red solid. M.p. 122–124 °C. R_f = 0.30 (hexanes–EA, 1.25 : 1). Isolated yield 57% (0.0646 g). ¹H NMR (500 MHz, CDCl₃, 25 °C): δ = 2.47 (3H, s, Me), 3.44 (3H, s, CO₂Me), 5.00 (1H, d, J = 16.0 Hz, CH), 6.28 (1H, d, J = 16.0 Hz, CH), 7.12 (6H, td, J = 2.5, 9.0 Hz, Ph), 7.26 (2H, d, J = 7.5 Hz, Ph), 7.44–7.48 (8H, m, Ph), 7.69 (2H, d, J = 8.5 Hz, Ph), 8.13 (2H, d, J = 8.5 Hz, Ph) ppm. ¹³C NMR (125 MHz, CDCl₃, 25 °C): δ = 21.6, 51.3, 61.3 (d, ¹J_PC = 132.1 Hz), 117.0 (dd, ³J_PC = 14.3, ²J_FC = 21.0 Hz), 118.2 (d, ¹J_PC = 97.7 Hz), 122.0, 122.8, 123.3 (d, ³J_PC = 12.2 Hz), 126.2, 128.1, 129.1, 131.0, 135.7, 136.0, 136.3, (dd, ²J_PC = 12.2, ³J_FC = 21.0 Hz), 139.7, 144.1, 146.4, 165.7, 165.8 (dd, ⁴J_PC = 3.3, ¹J_FC = 258.6 Hz), 166.8 (d, ²J_PC = 15.6 Hz) ppm. ³¹P NMR (202 MHz, CDCl₃, 25 °C): δ = 11.4 ppm. FTIR (KBr): [small nu, Greek, tilde] = 1640, 1721 cm⁻¹. λ_max(CHCl₃): 441 nm. HRMS (ESI⁺): calcd for C₃₉H₂₈F₃N₂O₇PS [M⁺] 756.1307; found 756.1298.

(E)-Methyl 3-(2-(4-nitrophenyl)-5-oxo-1-tosyl-4-(tri(thiophen-2-yl)phosphoranylidene)-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4e)

Red solid. M.p. 165–168 °C. R_f = 0.28 (hexanes–EA, 1 : 3). Isolated yield 56% (0.0604 g). ¹H NMR (300 MHz, CDCl₃, 25 °C): δ = 2.47 (3H, s, Me), 3.48 (3H, s, CO₂Me), 5.14 (1H, d, J = 16.2 Hz, CH), 6.57 (1H, d, J = 16.2 Hz, CH), 7.19 (3H, ddd, J = 2.1, 3.6, 4.7 Hz, Ph), 7.28 (2H, d, J = 7.2 Hz, Ph), 7.51–7.56 (5H, m, Ph), 7.74 (2H, d, J = 8.4 Hz, Ph), 7.86 (3H, td, J = 0.9, 4.8 Hz, Ph), 8.20 (2H, d, J = 8.7 Hz, Ph) ppm. ¹³C NMR (75 MHz, CDCl₃, 25 °C): δ = 21.7, 51.3, 63.2 (d, ¹J_PC = 142.6 Hz), 121.3, 122.6 (d, ²J_PC = 13.6 Hz), 122.9, 123.9 (d, ³J_PC = 13.3 Hz), 124.6 (d, ¹J_PC = 117.9 Hz), 128.1, 129.1 (d, ³J_PC = 15.9 Hz), 129.2, 131.0, 135.7, 135.8, 137.0 (d, ²J_PC = 6.0 Hz), 139.8, 140.0 (d, ³J_PC = 12.1 Hz), 143.9, 146.5, 166.6, 166.7 (d, ²J_PC = 18.9 Hz) ppm. ³¹P NMR (242 MHz, CDCl₃, 25 °C): δ = −10.6 ppm. FTIR (KBr): [small nu, Greek, tilde] = 1645, 1716 cm⁻¹. λ_max(CHCl₃): 444 nm. HRMS (ESI⁺): calcd for C₃₃H₂₅N₂O₇PS₄ [M⁺] 720.0282; found 720.0278.

(E)-Methyl 3-(2-(4-nitrophenyl)-5-oxo-1-tosyl-4-(tris(dimethylamino)phosphoranylidene)-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4f)

Red solid. M.p. 100–102 °C. R_f = 0.21 (EA). Isolated yield 53% (0.0480 g). Recrystallization from hexanes–EA gave pure products. ¹H NMR (300 MHz, CDCl₃, 25 °C): δ = 2.37 (3H, s, Me), 2.58 (18H, d, J = 9.7 Hz, NMe₂), 3.68 (3H, s, CO₂Me), 5.84 (1H, d, J = 16.2 Hz, CH), 7.21 (2H, d, J = 8.2 Hz, Ph), 7.25 (1H, d, J = 16.2 Hz, CH), 7.56 (2H, d, J = 8.0 Hz, Ph), 7.70 (2H, d, J = 8.0 Hz, Ph), 8.26 (2H, d, J = 7.9 Hz, Ph) ppm. ¹³C NMR (75 MHz, CDCl₃, 25 °C): δ = 21.5, 35.9 (d, ²J_PC = 5.2 Hz), 51.5, 65.1 (d, ¹J_PC = 190.0 Hz), 116.8, 122.8, 123.3 (d, ³J_PC = 10.6 Hz), 127.6, 127.9 (d, ³J_PC = 14.2 Hz), 128.8, 131.1, 135.9, 136.7, 139.5, 143.9, 146.6, 166.8 (d, ²J_PC = 21.5 Hz), 167.7 ppm. ³¹P NMR (242 MHz, CDCl₃, 25 °C): δ = 50.8 ppm. FTIR (KBr): [small nu, Greek, tilde] = 1658, 1723 cm⁻¹. λ_max(CHCl₃): 452 nm. HRMS (ESI⁺): calcd for C₂₇H₃₄N₅O₇PS [M⁺] 603.1917; found 603.1916.

(E)-Methyl 3-(2-(3-nitrophenyl)-5-oxo-1-tosyl-4-(triphenylphosphoranylidene)-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4g)

Orange solid. M.p. 96–99 °C. R_f = 0.13 (hexanes–EA, 2 : 1). Isolated yield 59% (0.0621 g). ¹H NMR (300 MHz, CDCl₃, 25 °C): δ = 2.48 (3H, s, Me), 3.38 (3H, s, CO₂Me), 5.01 (1H, d, J = 16.1 Hz, CH), 6.34 (1H, d, J = 16.1 Hz, CH), 7.29 (2H, d, J = 8.2 Hz, Ph), 7.41–7.77 (19H, m, Ph), 8.12 (1H, dd, J = 1.3, 8.2 Hz, Ph), 8.19 (1H, t, J = 1.8 Hz, Ph) ppm. ¹³C NMR (75 MHz, CDCl₃, 25 °C): δ = 21.6, 50.9, 60.0 (d, ¹J_PC = 129.8 Hz), 120.9, 122.4 (d, ²J_PC = 11.3 Hz), 122.7 (d, ³J_PC = 12.1 Hz), 122.8 (d, ¹J_PC = 92.8 Hz), 125.2, 127.9, 128.3, 129.0 (d, ³J_PC = 12.8 Hz), 129.1, 131.9, 133.0 (d, ⁴J_PC = 3.0 Hz), 133.8 (d, ²J_PC = 10.6 Hz), 134.8, 135.9, 136.3, 137.0, 143.8, 147.4, 165.9, 166.4 (d, ²J_PC = 15.9 Hz) ppm. ³¹P NMR (202 MHz, CDCl₃, 25 °C): δ = 12.8 ppm. FTIR (KBr): [small nu, Greek, tilde] = 1639, 1722 cm⁻¹. λ_max(CHCl₃): 385 nm. HRMS (ESI⁺): calcd for C₃₉H₃₁N₂O₇PS [M⁺] 702.1590; found 702.1581.

(E)-Methyl 3-(2-(3-nitrophenyl)-5-oxo-1-tosyl-4-(tri-p-tolylphosphoranylidene)-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4h)

Orange solid. M.p. 116–119 °C. R_f = 0.32 (hexanes–EA, 1.25 : 1). Isolated yield 54% (0.0603 g). ¹H NMR (500 MHz, CDCl₃, 25 °C): δ = 2.36 (9H, s, Me), 2.45 (3H, s, Me), 3.37 (3H, s, CO₂Me), 4.96 (1H, d, J = 16.0 Hz, CH), 6.33 (1H, d, J = 16.0 Hz, CH), 7.19 (6H, dd, J = 2.0, 8.5 Hz, Ph), 7.25 (2H, d, J = 7.0 Hz, Ph), 7.34 (6H, dd, J = 8.0, 13.0 Hz, Ph), 7.44 (1H, t, J = 8.0 Hz, Ph), 7.69 (1H, d, J = 7.5 Hz, Ph), 7.71 (2H, d, J = 8.5 Hz, Ph), 8.07 (1H, dt, J = 1.5, 8.0 Hz, Ph), 8.13 (1H, s, Ph) ppm. ¹³C NMR (125 MHz, CDCl₃, 25 °C): δ = 21.5, 21.6, 51.0, 61.0 (d, ¹J_PC = 129.8 Hz), 119.7 (d ¹J_PC = 95.8 Hz), 120.8, 121.9, 122.4 (d, ²J_PC = 12.2 Hz), 122.9 (d, ³J_PC = 11.1 Hz), 125.1, 127.9, 128.2, 129.0, 129.7 (d, ³J_PC = 13.3 Hz), 133.7 (d, ²J_PC = 11.2 Hz), 135.0, 136.1, 136.5, 137.0, 143.6, 143.8 (d, ⁴J_PC = 2.3 Hz), 147.4, 165.9, 166.4 (d, ²J_PC = 16.5 Hz) ppm. ³¹P NMR (202 MHz, CDCl₃, 25 °C): δ = 11.90 ppm. FTIR (KBr): [small nu, Greek, tilde] = 1637, 1723 cm⁻¹. λ_max(CHCl₃): 400 nm. HRMS (ESI⁺): calcd for C₄₂H₃₇N₂O₇PS [M⁺] 744.2059; found 744.2052.

(E)-Methyl 3-(4-(diphenyl(p-tolyl)phosphoranylidene)-2-(3-nitrophenyl)-5-oxo-1-tosyl-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4i)

Orange solid. M.p. 96–98 °C. R_f = 0.25 (hexanes–EA, 1 : 2). Isolated yield 62% (0.0666 g). ¹H NMR (400 MHz, CDCl₃, 25 °C): δ = 2.41 (3H, s, Me), 2.49 (3H, s, Me), 3.40 (3H, s, CO₂Me), 4.98 (1H, d, J = 16.0 Hz, CH), 6.33 (1H, d, J = 16.0 Hz, CH), 7.23–7.26 (2H, m, Ph), 7.36–7.46 (7H, m, Ph), 7.49–7.57 (8H, m, Ph), 7.72–7.77 (3H, m, Ph), 8.10–8.15 (2H, m, Ph) ppm. ¹³C NMR (75 MHz, CDCl₃, 25 °C): δ = 21.6 (d, ⁵J_PC = 1.6 Hz), 21.6, 51.0, 60.3 (d, ¹J_PC = 129.8 Hz), 119.1 (d, ¹J_PC = 95.1 Hz), 121.5 (d, ¹J_PC = 92.1 Hz), 122.5, 122.65, 122.70 (d, ³J_PC = 12.1 Hz), 123.7, 125.2, 128.0, 128.3, 129.0 (d, ³J_PC = 12.8 Hz), 129.1, 129.9 (d, ³J_PC = 12.8 Hz), 133.0 (d, ⁴J_PC = 3.0 Hz), 133.7 (d, ²J_PC = 10.6 Hz), 133.8 (d, ²J_PC = 10.6 Hz), 134.9, 136.0, 136.4, 137.0, 143.8, 144.1 (d, ⁴J_PC = 3.1 Hz), 147.4, 165.9, 166.5 (d, ²J_PC = 16.0 Hz) ppm. ³¹P NMR (242 MHz, CDCl₃, 25 °C): δ = 11.7 ppm. FTIR (KBr): [small nu, Greek, tilde] = 1632, 1726 cm⁻¹. λ_max(CHCl₃): 385 nm. HRMS (ESI⁺): calcd for C₄₀H₃₃N₂O₇PS [M⁺] 716.1746; found 716.1732.

(E)-Methyl 3-(2-(3-nitrophenyl)-5-oxo-1-tosyl-4-(tris(4-fluorophenyl)phosphoranylidene)-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4j)

Yellow solid. M.p. 104–107 °C. R_f = 0.28 (hexanes–EA, 1 : 1). Isolated yield 61% (0.0692 g). ¹H NMR (300 MHz, CDCl₃, 25 °C): δ = 2.50 (3H, s, Me), 3.45 (3H, s, CO₂Me), 4.99 (1H, d, J = 16.1 Hz, CH), 6.26 (1H, d, J = 16.1 Hz, CH), 7.17 (6H, td, J = 2.2, 8.7 Hz, Ph), 7.30 (2H, d, J = 8.3 Hz, Ph), 7.47–7.57 (7H, m, Ph), 7.71–7.77 (3H, m, Ph), 8.14–8.17 (2H, m, Ph) ppm. ¹³C NMR (75 MHz, CDCl₃, 25 °C): δ = 22.1, 51.7, 60.6 (d, ¹J_PC = 132.2 Hz), 117.5 (dd, ³J_PC = 14.3 Hz, ²J_FC = 21.9 Hz), 118.9 (dd, ⁴J_FC = 3.5 Hz, ¹J_PC = 97.4 Hz), 121.7, 121.9 (d, ²J_PC = 12.2 Hz), 123.0, 123.8 (d, ³J_PC = 12.5 Hz), 125.7, 128.6, 129.0, 129.7, 135.0, 136.4, 136.5, 136.9 (dd, ³J_FC = 9.2 Hz, ²J_PC = 12.4 Hz), 137.6, 144.6, 148.0, 166.3 (dd, ⁴J_PC = 3.3 Hz, ¹J_FC = 257.9 Hz), 166.3, 166.8 (d, ²J_PC = 16.2 Hz) ppm. ³¹P NMR (242 MHz, CDCl₃, 25 °C): δ = 10.77 ppm. FTIR (KBr): [small nu, Greek, tilde] = 1640, 1722 cm⁻¹. λ_max(CHCl₃): 376 nm. HRMS (ESI⁺): calcd for C₃₉H₂₈F₃N₂O₇PS [M⁺] 756.1307; found 756.1312.

(E)-Methyl 3-(2-(4-chloro-3-nitrophenyl)-5-oxo-1-tosyl-4-(tri-p-tolylphosphoranylidene)-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4k)

Orange solid. M.p. 102–104 °C. R_f = 0.15 (hexanes–EA, 1 : 1). Isolated yield 51% (0.0595 g). ¹H NMR (300 MHz, CDCl₃, 25 °C): δ = 2.39 (9H, s, Me), 2.49 (3H, s, Me), 3.44 (3H, s, CO₂Me), 5.03 (1H, d, J = 16.2 Hz, CH), 6.34 (1H, d, J = 15.9 Hz, CH), 7.20–7.38 (14H, m, Ph), 7.45 (1H, d, J = 8.4 Hz, Ph), 7.53 (1H, dd, J = 8.0, 1.8 Hz, Ph), 7.74 (2H, d, J = 8.1 Hz, Ph), 7.82 (1H, d, J = 1.5 Hz, Ph) ppm. ¹³C NMR (100 MHz, CDCl₃, 25 °C): δ = 21.55 (d, ⁵J_PC = 1.1 Hz), 21.64, 51.1, 61.5 (d, ¹J_PC = 129.0 Hz), 119.6 (d, ¹J_PC = 94.9 Hz), 120.9 (d, ²J_PC = 11.8 Hz), 121.4, 123.9 (d, ³J_PC = 11.7 Hz), 125.2, 127.2, 128.0, 129.1, 129.8 (d, ³J_PC = 12.9 Hz), 130.8, 133.4, 133.7 (d, ²J_PC = 10.6 Hz), 135.4, 135.9, 136.4, 143.8, 143.9 (d, ⁴J_PC = 2.6 Hz), 146.7, 165.8, 166.5 (d, ²J_PC = 15.9 Hz) ppm. ³¹P NMR (242 MHz, CDCl₃, 25 °C): δ = 11.1 ppm. FTIR (KBr): [small nu, Greek, tilde] = 1643, 1723 cm⁻¹. λ_max(CHCl₃): 398 nm. HRMS (ESI⁺): calcd for C₄₂H₃₆ClN₂O₇PS [M⁺] 778.1669; found 778.1670.

(E)-Methyl 3-(2-(4-chloro-3-nitrophenyl)-5-oxo-1-tosyl-4-(tris(4-chlorophenyl)phosphoranylidene)-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4l)

Yellow solid. M.p. 182–185 °C. R_f = 0.30 (hexanes–EA, 2 : 1). Isolated yield 56% (0.0704 g). ¹H NMR (300 MHz, CDCl₃, 25 °C): δ = 2.51 (3H, s, Me), 3.51 (3H, s, CO₂Me), 5.04 (1H, d, J = 15.9 Hz, CH), 6.32 (1H, d, J = 16.2 Hz, CH), 7.30 (2H, d, J = 8.1 Hz, Ph), 7.37–7.45 (12H, m, Ph), 7.51–7.52 (2H, m, Ph), 7.74 (2H, d, J = 8.1 Hz, Ph), 7.81 (1H, d, J = 1.5 Hz, Ph) ppm. ¹³C NMR (100 MHz, CDCl₃, 25 °C): δ = 21.7, 51.6, 59.7 (d, ¹J_PC = 130.9 Hz), 120.6 (d, ¹J_PC = 95.2 Hz), 121.9, 122.1, 122.2 (d, ³J_PC = 12.6 Hz), 126.1, 127.3, 128.2, 129.3, 129.9 (d, ³J_PC = 13.3 Hz), 131.1, 132.8, 135.0 (d, ²J_PC = 11.8 Hz), 135.5, 135.8, 135.9, 140.7 (d, ⁴J_PC = 3.4 Hz), 144.3, 146.8, 165.6, 166.5 (d, ²J_PC = 16.3 Hz) ppm. ³¹P NMR (242 MHz, CDCl₃, 25 °C): δ = 11.4 ppm. FTIR (KBr): [small nu, Greek, tilde] = 1640, 1721 m⁻¹. λ_max(CHCl₃): 380 nm. HRMS (ESI⁺): calcd for C₃₉H₂₇Cl₄N₂O₇PS [M⁺] 838.0031; found 838.0030.

(E)-Methyl 3-(2-(4-chloro-3-nitrophenyl)-5-oxo-1-tosyl-4-(tris(4-fluorophenyl)phosphoranylidene)-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4m)

Yellow solid. M.p. 124–126 °C. R_f = 0.33 (hexanes–EA, 1 : 1). Isolated yield 52% (0.0616 g). ¹H NMR (300 MHz, CDCl₃, 25 °C): δ = 2.50 (3H, s, Me), 3.49 (3H, s, CO₂Me), 5.06 (1H, d, J = 16.1 Hz, CH), 6.27 (1H, d, J = 16.1 Hz, CH), 7.16 (6H, td, J = 2.2, 7.2 Hz, Ph), 7.30 (2H, d, J = 8.1 Hz, Ph), 7.32–7.29 (8H, m, Ph), 7.74 (2H, d, J = 8.3 Hz, Ph), 7.82 (1H, d, J = 1.7 Hz, Ph) ppm. ¹³C NMR (75 MHz, CDCl₃, 25 °C): δ = 21.6, 51.3, 60.7 (d, ¹J_PC = 132.1 Hz), 117.0 (dd, ³J_PC = 14.3, ²J_FC = 21.9 Hz), 118.2 (dd, ⁴J_FC = 3.4, ¹J_PC = 97.6 Hz), 121.7, 121.8 (d, ²J_PC = 12.5 Hz), 122.3 (d, ³J_PC = 12.1 Hz), 125.9, 127.3, 128.0, 129.2, 131.1, 132.8, 132.9, 135.5, 135.8, 136.4 (dd, ³J_FC = 9.2, ²J_PC = 12.3 Hz), 144.2, 146.8, 165.7, 165.8 (dd, ⁴J_PC = 3.3, ¹J_FC = 257.9 Hz), 166.4 (d, ²J_PC = 16.2 Hz) ppm. ³¹P NMR (242 MHz, CDCl₃, 25 °C): δ = 10.6 ppm. FTIR (KBr): [small nu, Greek, tilde] = 1640, 1720 cm⁻¹. λ_max(CHCl₃): 363 nm. HRMS (ESI⁺): calcd for C₃₉H₂₇ClF₃N₂O₇PS [M⁺] 790.0917; found 790.0904.

(E)-Methyl 3-(2-(4-cyanophenyl)-5-oxo-1-tosyl-4-(tri-p-tolylphosphoranylidene)-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4n)

Yellow solid. M.p. 130–132 °C. R_f = 0.16 (hexanes–EA, 1 : 1). Isolated yield 71% (0.0771 g). ¹H NMR (300 MHz, CDCl₃, 25 °C): δ = 2.39 (9H, s, Me), 2.49 (3H, s, Me), 3.44 (3H, s, CO₂Me), 5.00 (1H, d, J = 16.1 Hz, CH), 6.40 (1H, d, J = 16.1 Hz, CH), 7.20–7.36 (14H, m, Ph), 7.48 (2H, d, J = 8.2 Hz, Ph), 7.57 (2H, d, J = 7.8 Hz, Ph), 7.72 (2H, d, J = 7.8 Hz, Ph) ppm. ¹³C NMR (75 MHz, CDCl₃, 25 °C): δ = 21.4, 21.5, 50.9, 61.5 (d, ¹J_PC = 128.7 Hz), 109.7, 119.0, 119.4 (d, ¹J_PC = 95.2 Hz), 121.1, 122.9 (d, ²J_PC = 12.1 Hz), 123.8 (d, ³J_PC = 10.1 Hz), 127.8, 128.8, 129.6 (d, ³J_PC = 13.2 Hz), 130.8, 130.9, 133.5 (d, ²J_PC = 10.9 Hz), 135.5, 136.5, 138.0, 143.5, 143.7 (d, ⁴J_PC = 2.9 Hz), 165.8, 166.7 (d, ²J_PC = 16.0 Hz) ppm. ³¹P NMR (242 MHz, CDCl₃, 25 °C): δ = 10.8 ppm. FTIR (KBr): [small nu, Greek, tilde] = 1648, 1717 cm⁻¹. λ_max(CHCl₃): 363 nm. HRMS (ESI⁺): calcd for C₄₃H₃₇N₂O₅PS [M⁺] 724.2160; found 724.2291.

(E)-Methyl 3-(2-(4-cyanophenyl)-5-oxo-1-tosyl-4-(tris(4-chlorophenyl)phosphoranylidene)-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4o)

Yellow solid. M.p. 134–136 °C. R_f = 0.44 (hexanes–EA, 1 : 1). Isolated yield 54% (0.0635 g). ¹H NMR (300 MHz, CDCl₃, 25 °C): δ = 2.51 (3H, s, Me), 3.50 (3H, s, CO₂Me), 4.98 (1H, d, J = 16.0 Hz, CH), 6.35 (1H, d, J = 16.0 Hz, CH), 7.29 (2H, d, J = 9.1 Hz, Ph), 7.34–7.47 (14H, m, Ph), 7.61 (2H, d, J = 8.1 Hz, Ph), 7.72 (2H, d, J = 8.1 Hz, Ph) ppm. ¹³C NMR (75 MHz, CDCl₃, 25 °C): δ = 21.7, 51.5, 59.7 (d, ¹J_PC = 132.0 Hz), 110.7, 118.9, 120.6 (d, ¹J_PC = 95.6 Hz), 121.7, 121.9, 124.3 (d, ³J_PC = 12.5 Hz), 128.1, 129.1, 129.8 (d, ³J_PC = 13.7 Hz), 131.0, 131.3, 134.9 (d, ²J_PC = 11.7 Hz), 135.7, 136.0, 137.5, 140.6 (d, ⁴J_PC = 3.5 Hz), 144.1, 165.8, 166.8 (d, ²J_PC = 16.1 Hz) ppm. ³¹P NMR (242 MHz, CDCl₃, 25 °C): δ = 11.1 ppm. FTIR (KBr): [small nu, Greek, tilde] = 1640, 1716 cm⁻¹. λ_max(CHCl₃): 359 nm. HRMS (ESI⁺): calcd for C₄₀H₂₈Cl₃N₂O₅PS [M⁺] 784.0522; found 784.0474.

(E)-Methyl 3-(2-(4-cyanophenyl)-5-oxo-1-tosyl-4-(tricyclohexylphosphoranylidene)-4,5-dihydro-1H-pyrrol-3-yl)acrylate (4p)

Yellow solid. M.p. 115–117 °C. R_f = 0.08 (hexanes–EA, 1 : 1). Isolated yield 22% (0.0231 g). ¹H NMR (300 MHz, CDCl₃, 25 °C): δ = 1.11–1.35 (18H, br, CH₂), 1.62–1.67 (12H, br, CH₂), 2.37 (3H, s, Me), 2.72–2.76 (3H, br, CH), 3.67 (3H, s, CO₂Me), 5.49 (1H, d, J = 15.9 Hz, CH), 7.22–7.25 (3H, m, Ph), 7.50 (2H, d, J = 8.4 Hz, Ph), 7.59 (2H, d, J = 8.1 Hz, Ph), 7.70 (2H, d, J = 8.1 Hz, Ph) ppm. ¹³C NMR (75 MHz, CDCl₃, 25 °C): δ = 21.5, 25.7, 26.9 (d, ³J_PC = 15.8 Hz), 27.0 (d, ²J_PC = 5.3 Hz), 30.8 (d, ¹J_PC = 46.8 Hz), 51.6, 57.5 (d, ¹J_PC = 105.7 Hz), 109.8, 113.8, 119.2, 120.1 (d, ²J_PC = 10.4 Hz), 123.0, 123.8 (d, ³J_PC = 9.4 Hz), 127.8, 128.7, 131.0, 131.2, 135.7, 138.1, 143.5, 166.6, 166.9 (d, ²J_PC = 15.1 Hz) ppm. ³¹P NMR (242 MHz, CDCl₃, 25 °C): δ = 27.6 ppm. FTIR (KBr): [small nu, Greek, tilde] = 1629, 1720 cm⁻¹. λ_max(CHCl₃): 413 nm. HRMS (ESI⁺): calcd for C₄₀H₄₉N₂O₅PS [M⁺] 700.3099; found 700.3090.

Acknowledgements

We thank the National Science Council for supporting this research financially (NSC 102-2113-M-009-011).

References

1. (a) Z. Chen and J. Wu, Org. Lett., 2010, 12, 4856; (b) H.-R. Pan, Y.-J. Li, C.-X. Yan, J. Xing and Y. Cheng, J. Org. Chem., 2010, 75, 6644; (c) V. Nair, C. Rajesh, A. U. Vinod, S. Bindu, R. Sreekanth, J. S. Mathen and L. Balagopal, Acc. Chem. Res., 2003, 36, 899; (d) B. B. Touré and D. G. Hall, Chem. Rev., 2009, 109, 4439; (e) N. R. Candeias, F. Montalbano, P. M. S. D. Cal and P. M. P. Gois, Chem. Rev., 2010, 110, 6169; (f) A. V. Ivachtchenko, Y. A. Ivanenkov, V. M. Kysil, M. Y. Krasavin and A. P. Ilyin, Russ. Chem. Rev., 2010, 79, 787; (g) H. Zhou, W. Wang, O. Khorev, Y. Zhang, Z. Miao, T. Meng and J. Shen, Eur. J. Org. Chem., 2012, 5585; (h) B. O. A. Tasch, E. Merkul and T. J. J. Müller, Eur. J. Org. Chem., 2011, 4532; (i) N. George, M. Bekkaye, G. Masson and J. Zhu, Eur. J. Org. Chem., 2011, 3695; (j) M. Li, F.-M. Gong, L.-R. Wen and Z.-R. Li, Eur. J. Org. Chem., 2011, 3482; (k) J. Sun, Q. Wu, E.-Y. Xia and C.-G. Yan, Eur. J. Org. Chem., 2012, 2981; (l) S. T. Staben and N. Blaquiere, Angew. Chem., Int. Ed., 2010, 49, 325; (m) J. Li, N. Wang, C. Li and X. Jia, Chem.–Eur. J., 2012, 18, 9645; (n) T. Wennekes, K. M. Bonger, K. Vogel, R. J. B. H. N. van den Berg, A. Strijland, W. E. Donker-Koopman, J. M. F. G. Aerts, G. A. van der Marel and H. S. Overkleeft, Eur. J. Org. Chem., 2012, 6420; (o) E. Ruijter, R. Scheffelaar and R. V. A. Orru, Angew. Chem., Int. Ed., 2011, 50, 6234; (p) S. Brauch, S. S. van Berkel and B. Westermann, Chem. Soc. Rev., 2013, 42, 4948; (q) C. M. Marson, Chem. Soc. Rev., 2012, 41, 7712; (r) C. de Graaff, E. Ruijter and R. V. A. Orru, Chem. Soc. Rev., 2012, 41, 3969.
2. (a) O. Diels and K. Alder, Leibigs Ann. Chem., 1932, 498, 16; (b) R. M. Acheson, Adv. Heterocycl. Chem., 1963, 1, 125; (c) V. Nair, A. R. Sreekanth, A. T. Biju and N. P. Rath, Tetrahedron Lett., 2003, 44, 729; (d) V. Nair, A. R. Sreekanth, N. Abhilash, M. M. Bhadbhade and R. C. Gonnade, Org. Lett., 2002, 4, 3575; (e) J.-B. Gualtierotti, X. Schumacher, P. Fontaine, G. Masson, Q. Wang and J. Zhu, Chem.–Eur. J., 2012, 18, 14812.
3. (a) I. Ugi, R. Meyr, U. Fitzer and C. Steinbrücker, Angew. Chem., 1959, 71, 386; (b) R. Zhou, J. Wang, H. Song and Z. He, Org. Lett., 2011, 13, 580; (c) J. R. Harris, M. T. Haynes II, A. M. Thomas and K. A. Woerpel, J. Org. Chem., 2010, 75, 5083; (d) X.-Y. Guan, Y. Wei and M. Shi, Org. Lett., 2010, 12, 5024; (e) T. Wang and S. Ye, Org. Lett., 2010, 12, 4168; (f) S. Zheng and X. Lu, Org. Lett., 2009, 11, 3978; (g) X. Lu, Y. Du and C. Lu, Pure Appl. Chem., 2005, 77, 1985; (h) C.-W. Cho, J.-R. Kong and M. J. Krische, Org. Lett., 2004, 6, 1337; (i) C. Zhang and X. Lu, J. Org. Chem., 1995, 60, 2906; (j) V. Nair, J. S. Nair, A. U. Vinod and N. P. Rath, J. Chem. Soc., Perkin Trans. 1, 1997, 3129; (k) V. Nair, J. S. Nair and A. U. Vinod, Synthesis, 2000, 1713; (l) P. Xie, E. Li, J. Zheng, Y. Huang and R. Chen, Adv. Synth. Catal., 2013, 355, 161; (m) Z. Shi, Q. Tong, W. W. Y. Leong and G. Zhong, Chem.–Eur. J., 2012, 18, 9802; (n) J. Tian and Z. He, Chem. Commun., 2013, 49, 2058; (o) X. Li, F. Wang, N. Dong and J.-P. Cheng, Org. Biomol. Chem., 2013, 11, 1451; (p) L. Yang, P. Xie, E. Li, X. Li, Y. Huang and R. Chen, Org. Biomol. Chem., 2012, 10, 7628; (q) D. Wang, Y.-L. Yang, J.-J. Jiang and M. Shi, Org. Biomol. Chem., 2012, 10, 7158; (r) X.-N. Zhang, H.-P. Deng, L. Huang, Y. Wei and M. Shi, Chem. Commun., 2012, 48, 8664.
4. (a) V. Nair and A. U. Vinod, Chem. Commun., 2000, 1019; (b) V. Nair, C. Rajesh, A. U. Vinod, S. Bindu, R. Sreekanth, J. S. Mathen and L. Balagopal, Acc. Chem. Res., 2003, 36, 899; (c) S. S. van Berkel, B. G. M. Bögels, M. A. Wijdeven, B. Westermann and F. P. J. T. Rutjes, Eur. J. Org. Chem., 2012, 3543; (d) I. Ugi and B. Werner, The Four-Component Reaction and Other Multicomponent Reactions of the Isocyanides, in Methods and Reagents for Green Chemistry: An Introduction, ed. P. Tundo, A. Perosa and F. Zecchini, John Wiley & Sons, Inc., Hoboken, NJ, USA, 2007 DOI:10.1002/9780470124086.ch1; (e) K. Khoury, M. K. Sinha, T. Nagashima, E. Herdtweck and A. Domling, Angew. Chem., Int. Ed., 2012, 51, 10280; (f) S. K. Guchhait and C. Madaan, Org. Biomol. Chem., 2010, 8, 3631.
5. (a) Y. C. Fan and O. Kwon, Sci. Synth.: Asymm. Organocatal., 2012, 1, 723; (b) C. Gomez, J.-F. Betzer, A. Voituriez and A. Marinetti, ChemCatChem, 2012, 5, 1055.
6. C. E. Henry and O. Kwon, Org. Lett., 2007, 9, 3069.
7. X.-F. Zhu, J. Lan and O. Kwon, J. Am. Chem. Soc., 2003, 125, 4716.
8. X.-F. Zhu, A.-P. Schaffner, R. C. Li and O. Kwon, Org. Lett., 2005, 7, 2977.
9. J. Ma, P. Xie, C. Hu, Y. Huang and R. Chen, Chem.–Eur. J., 2011, 17, 7418.
10. J.-C. Deng and S.-C. Chuang, Org. Lett., 2011, 13, 2248.
11. (a) S.-C. Chuang, J.-C. Deng, F.-W. Chan, S.-Y. Chen, W.-J. Huang, L.-H. Lai and V. Rajeshkumar, Eur. J. Org. Chem., 2012, 2606; (b) P.-Y. Tseng and S.-C. Chuang, Adv. Synth. Catal., 2013, 355, 2165.
12. J.-C. Deng, F.-W. Chan, C.-W. Kuo, C.-A. Cheng, C.-Y. Huang and S.-C. Chuang, Eur. J. Org. Chem., 2012, 5738.
13. A. S. Chavan, J.-C. Deng and S.-C. Chuang, Molecules, 2013, 18, 2611.
14. G. S. Singh and Z. Y. Desta, Chem. Rev., 2012, 112, 6104.
15. Unpublished results—using N-cinnamylidene-p-toluenesulfonamide as an aldimine substrate, we isolated isatin derivatives having α-phosphorus ylides through [2 + 2 + 2] electrocyclization and oxidation in the air.
16. (a) S. Asghari, M. Tajbakhsh and V. Taghipour, Tetrahedron Lett., 2008, 49, 1824; (b) D. Q. Tan, K. S. Martin, J. C. Fettinger and J. T. Shaw, Proc. Natl. Acad. Sci. U. S. A., 2011, 108, 6781; (c) F. Pan, J.-M. Chen, Z. Zhuang, Y.-Z. Fang, S. X.-A. Zhang and W.-W. Liao, Org. Biomol. Chem., 2012, 10, 2214; (d) M. González-López and J. T. Shaw, Chem. Rev., 2009, 109, 164; (e) A. Younai, G. F. Chin and J. T. Shaw, J. Org. Chem., 2010, 75, 8333; (f) H. Zhang, Y. Leng, W. Liu and W. Duan, Synth. Commun., 2012, 42, 1115; (g) S. Roy and O. Reiser, Angew. Chem., Int. Ed., 2012, 51, 4722; (h) A. Alizadeh, A. Mikaeili and T. Firuzyar, Synthesis, 2012, 1380.
17. (a) R. B. Lettan II, C. C. Woodward and K. A. Scheidt, Angew. Chem., Int. Ed., 2008, 47, 2294; (b) A. Zamudio-Medina, M. C. García-González, J. Padilla and E. González-Zamora, Tetrahedron Lett., 2010, 51, 4837.
18. X-ray crystallographic data for compound 4a: red bricks; crystal size: 0.25 × 0.20 × 0.07 mm³; formula: C₃₉H₃₁N₂O₇PS; crystal system: monoclinic; space group P121/n1; d = 1.385 mg m⁻³, V = 3369.8(2) ų; a = 10.7329(4) Å; b = 16.5196(6) Å; c = 19.3778(8) Å; β = 101.2410(10)°; R₁ = 0.0365; R_w = 0.0849. CCDC-911444 contains the supplementary crystallographic data for this paper.
19. X-ray crystallographic data for compound 4l: orange-red blocks; crystal size: 0.15 × 0.12 × 0.05 mm³; formula: C₄₀H₂₈Cl₇N₂O₇PS; crystal system: triclinic; space group P1̄; d = 1.539 mg m⁻³, V = 2070.7(6) ų; a = 10.2628(16) Å; b = 14.1040(2) Å; c = 15.1470(2) Å; α = 85.999(3)°, β = 73.595(3)°, γ = 79.998(3)°; R₁ = 0.0726; R_w = 0.1825. CCDC-912012 contains the supplementary crystallographic data for this paper.
20. (a) A. M. Brouwer, Pure Appl. Chem., 2011, 83, 2213; (b) A. T. R. Williams, S. A. Winfield and J. N. Miller, Analyst, 1983, 108, 1067.

---

Footnote

† Electronic supplementary information (ESI) available. CCDC 911444 and 912012. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3ob41811a

---