Highly regio- and diastereoselective construction of spirocyclopenteneoxindole phosphonates through a phosphine-catalyzed [3 + 2] annulation reaction

Chengbin Yua, Weiping Zhenga, Junchen Zhana, Yuchao Suna and Zhiwei Miao*ab
aState Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University, Weijin Road 94, Tianjin 300071, People's Republic of China
bCollaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, People's Republic of China

Received 23rd October 2014 , Accepted 14th November 2014

First published on 14th November 2014


Abstract

A phosphine-catalyzed [3 + 2] annulation of MBH phosphonates with isatylidene malononitriles is developed. The described method, which is different from most traditional phosphorus ylide intermediate reaction modes of MBH carbonates with isatylidene malononitriles, represents a novel approach to highly regioselective and diastereoselective synthesis of spirocyclopenteneoxindole phosphonates.


Introduction

The spirocyclic oxindoles bearing a tetrasubstituted carbon stereocenter at the 3-position feature in a large number of natural products and medicinally relevant compounds (Fig. 1).1 Among the many spirooxindole cores, the regioselective and stereoselective preparation of 3-spirocyclopentane-2-oxindoles containing two adjacent quaternary centers is challenging and has been identified as a formidable synthetic task.2 Although many synthetic methods have been developed for the stereoselective synthesis of spirooxindoles, their high-yielding synthesis with multiple stereocenters and a spiro-quaternary carbon is a still demanding task.3
image file: c4ra12997k-f1.tif
Fig. 1 Spirocyclicpentane oxindole structures having two contiguous quaternary centers.

The annulation of Morita–Baylis–Hillman acetates and carbonates with electron-deficient olefins is an extremely useful synthetic method to construct multifunctional cyclic compounds.4 In this context, Lu and co-workers first reported annulation reactions of MBH carbonates as a reactive functionalized 1,3-dipoles with various electron-deficient olefins catalyzed by tertiary phosphine, affording the corresponding cycloadducts in good yields.4d–i Trost and co-workers reported an enantioselective construction of spirocyclic oxindolic cyclopentanes by using a palladium catalysed [3 + 2] cycloaddition of trimethylenemethane.5 Recently, Barbas and his co-workers reported a novel asymmetric [3 + 2] cycloaddition of MBH carbonates with methyleneindolinones in the presence of a chiral phosphine to give the corresponding spirocyclopentaneoxindoles in good yields and high ee values.6 Lu disclosed an L-threonine-derived phosphines catalytic asymmetric [3 + 2] annulation of MBH adducts for the synthesis of 3-spirocyclopentene-2-oxindoles.2h In contrast, the direct catalytic asymmetric construction of the spirocyclopententene oxindole scaffold has remained an important challenge.

For the construction of five-membered ring systems, phosphine-mediated [3 + 2] annulation represents one of the most efficient approaches. However, the asymmetric cyclo-addition employing the MBH adducts is rare reported.7 Compared with allenes and alkynes, the MBH adducts are much more challenging substrates for such annulations. Their lower reactivity makes the development of an asymmetric catalytic annulation process particularly difficult. Furthermore, the previous researchers found that the transformations of MBH acetates and carbonates have been directed toward the annulation at the γ-position with electron-deficient olefins in the presence of tertiary phosphine (Scheme 1).4d–s


image file: c4ra12997k-s1.tif
Scheme 1 Phosphine-catalyzed [3 + 2] annulations of isatylidenenalononitirle to construct spirocyclopentene oxindoles.

The annulation of MBH adducts at the α-position with electron-deficient olefins is yet to be developed. Herein, we document the first highly regio- and diastereoselective [3 + 2] cyclo-addition between the MBH phosphonates and electron-deficient olefins. The electron-deficient alkene components necessary for the annulation reactions can be conveniently derived from isatins. Such tetrasubstituted activated alkenes are explored substrates in the asymmetric [3 + 2] cyclization processes, thereby creating 3-spirocyclopentene-2-oxindoles containing two contiguous quaternary centers.

Results and discussion

We initiated our studies by evaluating the reaction between isatin-derived α,α-dicyanoalkene 1a8 and the MBH phosphonate 2a9 using triphenylphosphine as the catalyst in toluene at room temperature (Table 1, entry 1). No product was obtained after 24 h, and 1a was completely recovered. We assumed that the lack of reaction was due to steric hindrance and the weak nucleophilic ability of the phosphine. Therefore, we turned our attention to more active phosphine catalysts (Table 1, entries 2–4). With tributylphosphine (Bu3P) as the catalyst, the desired cycloaddition product 3a was obtained in good yield with excellent diastereoselectivity (Table 1, entry 2). To further improve the reaction efficiency, a brief survey on the reaction conditions was conducted by using the reaction of 1a and 2a as a model. Among several phosphine catalysts tested, ethyldiphenylphosphine (Ph2PEt) emerged as the preferred catalyst in terms of the yield and diastereoselectivity (Table 1, entries 3–4). This result implied that the nucleophilicity of the phosphines had a significant influence on the outcome of the reaction.
Table 1 Optimization of conditions of the [3 + 2] cycloaddition of 1a and 2aa

image file: c4ra12997k-u1.tif

Entry Catalyst Solvent Temp. (°C) Time (h) 3a/3a′b d.r.b Yieldc (%)
a Unless otherwise noted, all reactions were carried out using isatylidenemalononitrile 1a (0.10 mmol, 1 equiv.), MBH phosphonate 2a (0.13 mmol) in 2 mL solvent with 30 mol% of catalyst at 25 °C.b The ratio of the 3a/3a′ and d.r. was determined by 31P NMR analysis of the crude product.c Yield of the isolated product.d MTBE = methyl tert-butyl ether.e 15% Ph2PEt was used.
1 Ph3P Toluene 25 24
2 Bu3P Toluene 25 15 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 83
3 Ph2PEt Toluene 25 35 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 88
4 PhPMe2 Toluene 25 35 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 80
5 Ph2PEt Toluene 50 10 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 98
6 Ph2PEt CH2Cl2 30 20 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 95
7 Ph2PEt THF 50 30 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 91
8 Ph2PEt MTBEd 50 48 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 85
9 Ph2PEt CH3CN 50 15 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 93
10e Ph2PEt Toluene 50 15 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 99


With Ph2PEt chosen as the catalyst, other parameters for the reaction conditions were further examined. An elevated temperature (50 °C) brought about a better yield of 3a with a ratio of 3a/3a′ 99[thin space (1/6-em)]:[thin space (1/6-em)]1 (Table 1, entry 5). A solvent screening was subsequently performed, and toluene was identified to be the best solvent for the reaction, whereas other solvent, such as CH2Cl2, THF, methyl tert-butyl ether (MTBE), and CH3CN, could readily afford the desired product in inferior yields (Table 1, entries 6–9).

It is worthwhile noting that the regioselectivity and diastereoselectivity of this reaction was excellence and the catalyst loading could be further reduced to 15 mol% with Ph2PEt (Table 1, entry 10). Thus, the optimal reaction conditions for this transformation were determined to be 0.1 mmol isatylidenemalononitrile 1a, 0.13 mmol MBH phosphonate 2a, and 15 mol% of Ph2PEt as a catalyst in 2 mL toluene as a solvent at 50 °C. The diastereomeric ratio of product was determined by 31P NMR spectroscopy of the crude product. In order to determine the relative configuration of the major diastereomer 3a, a single crystal X-ray diffraction study of 3a was performed.10 The molecular structure of 3a is shown in Fig. 2, and the structure showed that the relative configuration of the main product was assigned as threo.


image file: c4ra12997k-f2.tif
Fig. 2 The X-ray crystal structure of 3a.

Under the optimized reaction conditions, we set out to examine the scope and limitations of this reaction between isatylidenemalononitriles 1a–l and MBH phosphonates 2a–c (Table 2). Firstly, the annulation reactions of 1a–i and 2a proceeded smoothly to afford the desired products 3a–i in 85–99% yield with >99% d.r., irrespective of the variation in the electronic and steric properties of the substituents attached to the phenyl rings of the oxindole backbones (Table 2, entries 1–9). Notably, the reaction proceeded slowly when electron-withdrawing substituents were at the 5-position and electron-donating substituents at the 6-position on the aromatic ring (Table 2, entries 3 and 6).

Table 2 Substrate scope of the reactiona

image file: c4ra12997k-u2.tif

Entry R1 R2 R3 Time (h) d.r.b Yieldc (%)
a Reaction conditions: isatylidenemalononitrile 1 (0.10 mmol), MBH phosphonate 2 (0.13 mmol) in 2 mL of toluene at 50 °C in the presence of 15 mol% of Ph2PEt.b The d.r. was determined by 31P NMR analysis of the crude product.c Yield of the isolated product.d 30% Ph2PEt was used.
1 2a, Ph 1a, H Me 15 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3a, 99
2 Ph 1b, 5-Br Me 15 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3b, 87
3 Ph 1c, 5-Cl Me 30 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3c, 95
4 Ph 1d, 5-Me Me 11 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3d, 95
5 Ph 1e, 5-OMe Me 8 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3e, 99
6 Ph 1f, 6-OMe Me 50 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3f, 85
7 Ph 1g, 6-Me Me 30 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3g, 93
8 Ph 1h, 7-Me Me 8 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3h, 99
9 Ph 1i, 5-Me-7-Me Me 7 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3i, 99
10d 2b, n-Pr H Me 50 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3j, 99
11d n-Pr 5-Me Me 44 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3k, 95
12d n-Pr 7-Me Me 44 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3l, 98
13d n-Pr 5-Me-7-Me Me 44 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3m, 98
14 2c, furan H Me 8 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3n, 98
15 Furan 1j, H Bn 13 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3o, 95
16 Furan 5-OMe Me 8 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3p, 91
17 Furan 6-OMe Me 44 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3q, 97
18 Furan 7-Me Me 11 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3r, 98
19 Furan 5-Br Me 13 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3s, 85
20 Furan 6-Me Me 33 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3t, 88
21 Ph 1k, H H 72 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3u, 68
22 Ph H Bn 11 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3v, 88
23 Ph 1l, H Ac 72 >99[thin space (1/6-em)]:[thin space (1/6-em)]1 3w, <15


Substrate 2b was ineffective for this transformation under the identical conditions (Table 2, entries 10–13). The reactions of (2-BocO-1-methylene-pentyl)-phosphonate 2b, which bear straight-chain alkane substituent at the MBH phosphonate, proceeded sluggishly in the presence of 15 mol% of catalyst loading to give less than 40% yield of the desired products with 24 h. Consequently, the catalyst loading was increased to 30 mol%, which afforded the desired products 3j–m in good yields with almost perfect regio- and stereocontrol (up to 99[thin space (1/6-em)]:[thin space (1/6-em)]1) within 50 h (Table 2, entries 10–13). The reaction tolerated different substitute moieties in the MBH phosphonates 2. Notably, the presence of 3-furyl in 2c resulted in good to excellent yields and stereoselectivities (Table 2, entries 14–20).

We further demonstrated the electronic factor of N-substitution in the 2-(2-oxindolin-3-ylidene)malononitriles 1. Reaction of 2a with N-H olefin 1k under the catalysis of Ph2PEt in toluene at 60 °C for 72 h furnished 3u in 68% yield (Table 2, entry 21). In a similar manner, the annulation reaction of 2a with N-Me or N-Bn olefins 1a/1j under Ph2PEt catalysis within 15 h furnished 3a and 3v in 99/88% yield with >99% stereoselectivity (Table 2, entries 1 and 22). Surprisingly, when N-acetyl protected olefin 1l was employed as the substrate the reaction proceeded exclusively in lower yield (15%) despite a long reaction time (Table 2, entry 23). This result clearly shows that the single directional electrophilicity of olefin 1 is crucial to achieving high yields in this reaction.

The mechanism of this [3 + 2] annulation reaction is proposed on the basis of previous literatures2h,4f,s as shown in Scheme 2. The first step involves the nucleophilic attack of the phosphine on the MBH phosphonate 2 to yield the phosphonium salt A. The in situ generated tert-butoxide anion deprotonates A to generate ylide B, which then undergoes α addition to alkene 1 to give the intermediate C. Subsequent Michael addition at the α-position of phosphorus cation to generate intermediate D. The elimination of the phosphine moiety along with the double bond formation furnishes the corresponding product 3 and then regenerates the catalyst. The observed α selectivity maybe attributed to the steric hindrance effects and electronic repulsions between the phosphonate group and ethyl-diphenyl-phosphonium.


image file: c4ra12997k-s2.tif
Scheme 2 Plausible reaction mechanism.

Conclusions

In conclusion, we have developed a phosphine-catalyzed highly regio- and diastereoselective [3 + 2] annulation of MBH phosphonates 2 with isatylidene malononitriles 1, affording the corresponding functionalized spirocyclopenteneoxindole phosphonates 3 in good to excellent yields. This is the first time for MBH phosphonates as C3 synthons in [3 + 2] annulation reactions. Compared with MBH carbonates, MBH phosphonates undergoes α addition to alkene from the ylide B. A plausible reaction mechanism has also been proposed on the basis of previous literature. Further investigations on the enantioselective phosphine-catalyzed annulation reaction are currently underway.

Experimental section

General methods

Solvents were dried and distilled prior to use according to the standard methods. Unless otherwise indicated, all materials were obtained from commercial sources, and used as purchased without dehydration. Flash column chromatography was performed on silica gel (particle size 10–40 μm, Ocean Chemical Factory of Qingdao, China). Nitrogen gas (99.999%) was purchased from Boc Gas Inc. 1H NMR, 13C NMR and 31P NMR spectra were recorded in CDCl3 at Bruker 400 MHz spectrometers, TMS served as internal standard (δ = 0 ppm) for 1H NMR and 13C NMR, H3PO4 served as internal standard (δ = 0 ppm) for 31P NMR. The crystal structure was determined on a Bruker SMART 1000 CCD diffractometer. Mass spectra were recorded on a LCQ advantage spectrometer with ESI resource. HR-MS were recorded on APEXII and ZAB-HS spectrometer. Melting points were determined on a T-4 melting point apparatus (uncorrected). Optical rotations were recorded on a Perkin Elmer 241 Polarimeter.

General procedure for the preparation of 3

A solution of MBH phosphonates 2 (0.13 mmol), isatylidene malononitrile 1 (0.1 mmol) and catalyst Ph2PEt (0.015 mmol) in toluene (2.0 mL) was stirred at 50 °C under N2 atmosphere. After isatylidene malononitrile 1 was completely consumed (monitored by TLC), the solvent was removed under reduced pressure and the residue was chromatographed on silica gel (elution with petroleum ether–EtOAc = 1[thin space (1/6-em)]:[thin space (1/6-em)]1) to afford product 3 as a white solid.
Diethyl(5,5-dicyano-1′-methyl-2′-oxo-4-phenylspiro [cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3a). White solid; mp 233 °C. 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 7.6 Hz, 1H), 7.60 (d, J = 4.5 Hz, 2H), 7.50 (dd, J = 16.7, 5.7 Hz, 4H), 7.25 (t, J = 7.7 Hz, 1H), 6.99 (d, J = 7.8 Hz, 1H), 6.57 (dd, J = 11.0, 2.2 Hz, 1H), 5.51 (s, 1H), 4.00–4.17 (m, 2H), 3.80–4.01 (m, 2H), 3.34 (s, 3H), 1.31 (t, J = 7.0 Hz, 3H), 1.12 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 171.00, 145.82 (d, J = 12.4 Hz), 144.08, 140.18 (d, J = 190.8 Hz), 132.51, 131.46, 130.18, 129.74, 128.55, 126.93, 123.95, 123.09, 112.73, 111.84, 109.19, 65.58 (d, J = 18.7 Hz), 62.85 (d, J = 5.9 Hz), 62.74 (d, J = 6.5 Hz), 60.81 (d, J = 15.1 Hz), 52.87 (d, J = 13.0 Hz), 27.13, 16.23 (d, J = 6.5 Hz), 16.03 (d, J = 6.5 Hz); 31P NMR (162 MHz, CDCl3): δ 9.41; HRMS calculated [M + Na]+ for C25H24N3O4P: 484.1402, found: 484.1399.
Diethyl(5′-bromo-5,5-dicyano-1′-methyl-2′-oxo-4-phenylspiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3b). White solid; mp 185 °C. 1H NMR (400 MHz, CDCl3) δ 7.81 (s, 1H), 7.64 (dt, J = 9.8, 4.9 Hz, 1H), 7.55–7.61 (m, 2H), 7.40–7.53 (m, 3H), 6.88 (d, J = 8.3 Hz, 1H), 6.54 (dd, J = 10.9, 2.5 Hz, 1H), 5.49 (s, 1H), 4.01–4.19 (m, 2H), 3.82–4.00 (m, 2H), 3.31 (s, 3H), 1.29 (t, J = 7.0 Hz, 3H), 1.14 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 170.47, 144.86 (d, J = 12.7 Hz), 143.14, 140.87 (d, J = 190.6 Hz), 134.40, 132.26, 130.17, 130.10, 129.85, 128.59, 124.96, 116.54, 112.47, 111.63, 110.59, 65.31 (d, J = 19.2 Hz), 62.85 (t, J = 5.9 Hz), 60.89 (d, J = 14.7 Hz), 52.73 (d, J = 13.0 Hz), 27.24, 16.22 (d, J = 6.4 Hz), 16.05 (d, J = 6.5 Hz); 31P NMR (162 MHz, CDCl3): δ 9.02. HRMS calculated [M + Na]+ for C25H23BrN3O4P: 562.0507, found: 562.0504.
Diethyl(5′-chloro-5,5-dicyano-1′-methyl-2′-oxo-4-phenylspiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3c). White solid; mp 225 °C. 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 1.7 Hz, 1H), 7.59 (dd, J = 6.2, 2.7 Hz, 2H), 7.44–7.53 (m, 4H), 6.93 (d, J = 8.4 Hz, 1H), 6.54 (dd, J = 11.0, 2.6 Hz, 1H), 5.50 (s, 1H), 4.02–4.18 (m, 2H), 3.85–4.01 (m, 2H), 3.32 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H), 1.14 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 170.57 (d, J = 2.3 Hz), 144.89 (d, J = 12.8 Hz), 142.64, 140.82 (d, J = 190.6 Hz), 132.25, 131.50, 130.17, 129.86, 129.47, 128.59, 127.36, 124.60, 112.47, 111.64, 110.17, 65.37 (d, J = 19.0 Hz), 62.86 (t, J = 6.0 Hz), 60.87 (d, J = 14.9 Hz), 52.70 (d, J = 12.9 Hz), 27.27, 16.23 (d, J = 6.4 Hz), 16.05 (d, J = 6.5 Hz); 31P NMR (162 MHz, CDCl3): δ 9.05. HRMS calculated [M + Na]+ for C25H23ClN3O4P: 518.1012, found: 518.1005.
Diethyl(5,5-dicyano-1′,5′-dimethyl-2′-oxo-4-phenylspiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3d). White solid; mp 195 °C. 1H NMR (400 MHz, CDCl3) δ 7.60 (dd, J = 6.5, 2.8 Hz, 2H), 7.49 (dd, J = 8.7, 4.7 Hz, 4H), 7.30 (d, J = 8.2 Hz, 1H), 6.88 (d, J = 8.0 Hz, 1H), 6.56 (dd, J = 11.0, 2.7 Hz, 1H), 5.51 (t, J = 2.2 Hz, 1H), 4.01–4.18 (m, 2H), 3.82–4.00 (m, 2H), 3.31 (s, 3H), 2.42 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H), 1.12 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 170.93, 146.02 (d, J = 12.4 Hz), 141.67, 139.99 (d, J = 190.7 Hz), 133.73, 132.61, 131.68, 130.20, 129.70, 128.51, 127.68, 123.13, 112.79, 111.88, 108.87, 65.65 (d, J = 19.1 Hz), 62.81 (d, J = 6.0 Hz), 62.69 (d, J = 6.3 Hz), 60.85 (d, J = 15.0 Hz), 52.89 (d, J = 13.0 Hz), 27.12, 21.15, 16.22 (d, J = 6.4 Hz), 16.02 (d, J = 6.6 Hz); 31P NMR (162 MHz, CDCl3): δ 9.49. HRMS calculated [M + Na]+ for C26H26N3O4P: 498.1559, found: 498.1561.
Diethyl(5,5-dicyano-5′-methoxy-1′-methyl-2′-oxo-4-phenylspiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3e). White solid; mp 205 °C. 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 4.4 Hz, 2H), 7.48 (d, J = 3.8 Hz, 3H), 7.30 (s, 1H), 7.04 (d, J = 8.6 Hz, 1H), 6.90 (d, J = 8.6 Hz, 1H), 6.53–6.63 (m, 1H), 5.52 (s, 1H), 4.03–4.15 (m, 2H), 3.88–3.97 (m, 2H), 3.85 (s, 3H), 3.31 (s, 3H), 1.31 (t, J = 7.0 Hz, 3H), 1.11 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 170.71, 156.72, 145.79 (d, J = 12.7 Hz), 140.18 (d, J = 190.9 Hz), 137.24, 132.56, 130.18, 129.72, 128.53, 124.04, 116.86, 113.30, 112.70, 111.90, 109.74, 65.92 (d, J = 19.1 Hz), 62.86 (d, J = 5.9 Hz), 62.73 (d, J = 6.4 Hz), 60.83 (d, J = 14.9 Hz), 55.98, 52.95 (d, J = 13.0 Hz), 27.17, 16.22 (d, J = 6.4 Hz), 16.01 (d, J = 6.5 Hz); 31P NMR (162 MHz, CDCl3): δ 9.47. HRMS calculated [M + Na]+ for C26H26N3O5P: 514.1508, found: 514.1503.
Diethyl(5,5-dicyano-6′-methoxy-1′-methyl-2′-oxo-4-phenylspiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3f). White solid; mp 155 °C. 1H NMR (400 MHz, CDCl3) δ 7.55–7.64 (m, 3H), 7.42–7.52 (m, 3H), 6.72 (dd, J = 8.4, 2.1 Hz, 1H), 6.55 (dd, J = 11.0, 2.4 Hz, 2H), 5.46 (s, 1H), 4.02–4.16 (m, 2H), 3.83–3.97 (m, 5H), 3.31 (s, 3H), 1.30 (t, J = 7.0 Hz, 3H), 1.11 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 171.55, 162.60, 146.32 (d, J = 12.4 Hz), 145.51, 139.77 (d, J = 191.1 Hz), 132.67, 130.15, 129.66, 128.52, 127.87, 114.74, 112.84, 112.02, 107.51, 97.31, 65.52 (d, J = 19.3 Hz), 62.82 (d, J = 5.8 Hz), 62.70 (d, J = 6.3 Hz), 60.62 (d, J = 15.0 Hz), 55.73, 53.08 (d, J = 12.7 Hz), 27.11, 16.21 (d, J = 6.4 Hz), 16.01 (d, J = 6.5 Hz); 31P NMR (162 MHz, CDCl3): δ 9.56. HRMS calculated [M + Na]+ for C26H26N3O5P: 514.1508, found: 514.1508.
Diethyl(5,5-dicyano-1′,6′-dimethyl-2′-oxo-4-phenylspiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3g). White solid; mp 181 °C. 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 4.0 Hz, 2H), 7.49 (dd, J = 10.7, 5.7 Hz, 4H), 7.23 (d, J = 7.7 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 6.55 (d, J = 11.0 Hz, 1H), 5.50 (s, 1H), 4.00–4.15 (m, 2H), 3.83–3.98 (m, 2H), 3.60 (s, 3H), 2.64 (s, 3H), 1.30 (t, J = 7.0 Hz, 3H), 1.12 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 171.77 (d, J = 2.4 Hz), 146.05 (d, J = 12.6 Hz), 141.79, 139.94 (d, J = 190.8 Hz), 135.21, 132.58, 130.19, 129.70, 128.52, 124.84, 123.73, 123.69, 120.85, 112.88, 111.76, 65.17 (d, J = 18.9 Hz), 62.84 (d, J = 6.0 Hz), 62.72 (d, J = 6.3 Hz), 60.79 (d, J = 15.0 Hz), 53.28 (d, J = 12.8 Hz), 30.60, 19.06, 16.22 (d, J = 6.4 Hz), 16.03 (d, J = 6.5 Hz); 31P NMR (162 MHz, CDCl3): δ 9.49. HRMS calculated [M + Na]+ for C26H26N3O4P: 498.1559, found: 498.1558.
Diethyl(5,5-dicyano-1′,7′-dimethyl-2′-oxo-4-phenylspiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3h). White solid; mp 183 °C. 1H NMR (400 MHz, CDCl3): δ 7.56 (d, J = 19.9 Hz, 2H), 7.49 (d, J = 16.5 Hz, 4H), 7.23 (d, J = 7.6 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 6.55 (d, J = 11.0 Hz, 1H), 5.50 (s, 1H), 4.02–4.17 (m, 2H), 3.82–3.99 (m, 2H), 3.60 (s, 3H), 2.64 (s, 3H), 1.30 (t, J = 7.0 Hz, 3H), 1.12 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 171.77, 146.01 (d, J = 12.5 Hz), 141.80, 140.00 (d, J = 190.7 Hz), 135.21, 132.60, 130.19, 129.69, 128.51, 124.84, 123.72, 120.83, 112.88, 111.76, 65.18 (d, J = 18.8 Hz), 62.81 (d, J = 6.1 Hz), 62.70 (d, J = 6.2 Hz), 60.81 (d, J = 15.0 Hz), 53.30 (d, J = 12.8 Hz), 30.60, 19.05, 16.22 (d, J = 6.3 Hz), 16.02 (d, J = 6.4 Hz); 31P NMR (162 MHz, CDCl3): δ 9.49. HRMS calculated [M + Na]+ for C26H26N3O4P: 498.1559, found: 498.1555.
Diethyl(5,5-dicyano-1′,5′,7′-trimethyl-2′-oxo-4-phenylspiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3i). White solid; mp 183 °C. 1H NMR (400 MHz, CDCl3): δ 7.59 (d, J = 3.8 Hz, 2H), 7.47 (d, J = 3.3 Hz, 3H), 7.31 (s, 1H), 7.03 (s, 1H), 6.40–6.62 (m, 1H), 5.50 (s, 1H), 4.01–4.17 (m, 2H), 3.81–4.00 (m, 2H), 3.57 (s, 3H), 2.59 (s, 3H), 2.35 (s, 3H), 1.30 (t, J = 7.0 Hz, 3H), 1.11 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 171.71, 146.23 (d, J = 12.6 Hz), 139.77 (d, J = 190.7 Hz), 139.32, 135.61, 133.40, 132.68, 130.20, 129.66, 128.48, 125.52, 123.80, 120.46, 112.94, 111.79, 65.26 (d, J = 19.2 Hz), 62.79 (d, J = 5.9 Hz), 62.67 (d, J = 6.3 Hz), 60.84 (d, J = 15.0 Hz), 53.31 (d, J = 13.0 Hz), 30.52, 20.79, 18.86, 16.22 (d, J = 6.4 Hz), 16.02 (d, J = 6.5 Hz); 31P NMR (162 MHz, CDCl3): δ 9.57. HRMS calculated [M + Na]+ for C27H28N3O4P: 512.1715, found: 512.1707.
Diethyl(5,5-dicyano-1′-methyl-2′-oxo-4-propylspiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3j). White solid; mp 150 °C. 1H NMR (400 MHz, CDCl3): δ 7.64 (d, J = 7.6 Hz, 1H), 7.51 (t, J = 7.8 Hz, 1H), 7.24 (t, J = 7.6 Hz, 1H), 6.98 (d, J = 7.8 Hz, 1H), 6.41 (d, J = 11.1 Hz, 1H), 4.30 (d, J = 10.1 Hz, 1H), 4.20 (dd, J = 7.0, 4.1 Hz, 4H), 3.29 (s, 3H), 2.29 (ddd, J = 20.2, 10.6, 5.1 Hz, 1H), 1.87–2.03 (m, 1H), 1.69–1.80 (m, 1H), 1.57–1.69 (m, 1H), 1.41 (t, J = 7.0 Hz, 6H), 1.09 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 170.88, 144.44, 144.26 (d, J = 11.1 Hz), 141.08 (d, J = 186.4 Hz), 131.41, 126.56, 123.81, 123.16, 113.41, 111.71, 109.16, 65.47 (d, J = 19.2 Hz), 62.83 (d, J = 4.3 Hz), 62.78 (d, J = 4.8 Hz), 53.99 (d, J = 15.2 Hz), 49.52 (d, J = 13.3 Hz), 32.93, 27.03, 20.52, 16.38 (d, J = 6.2 Hz), 13.90; 31P NMR (162 MHz, CDCl3): δ 10.66. HRMS calculated [M + Na]+ for C22H26N3O4P: 450.1559, found: 450.1554.
Diethyl(5,5-dicyano-1′,5′-dimethyl-2′-oxo-4-propylspiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3k). White solid; mp 153 °C. 1H NMR (400 MHz, CDCl3): δ 7.44 (s, 1H), 7.29 (s, 1H), 6.86 (d, J = 8.0 Hz, 1H), 6.40 (d, J = 11.1 Hz, 1H), 4.30 (d, J = 9.6 Hz, 1H), 4.21 (dd, J = 12.5, 6.8 Hz, 4H), 3.27 (s, 3H), 2.42 (s, 3H), 2.29 (ddd, J = 15.4, 10.9, 5.3 Hz, 1H), 1.88–2.01 (m, 1H), 1.68–1.79 (m, 1H), 1.56–1.66 (m, 1H), 1.41 (t, J = 7.0 Hz, 6H), 1.09 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 170.78, 144.64 (d, J = 12.7 Hz), 141.79, 139.96, 133.59, 131.63, 127.27, 123.17, 113.45, 111.72, 108.86, 65.49 (d, J = 19.2 Hz), 62.77 (t, J = 4.8 Hz), 53.95 (d, J = 15.5 Hz), 49.57 (d, J = 13.0 Hz), 32.91, 27.02, 21.16, 20.51, 16.37 (d, J = 6.3 Hz), 13.89; 31P NMR (162 MHz, CDCl3): δ 10.76. HRMS calculated [M + Na]+ for C23H28N3O4P: 464.1715, found: 464.1710.
Diethyl(5,5-dicyano-1′,7′-dimethyl-2′-oxo-4-propylspiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3l). White solid; mp 151 °C. 1H NMR (400 MHz, CDCl3): δ 7.44 (d, J = 7.5 Hz, 1H), 7.23 (d, J = 7.7 Hz, 1H), 7.10 (t, J = 7.7 Hz, 1H), 6.38 (d, J = 11.1 Hz, 1H), 4.29 (d, J = 9.6 Hz, 1H), 4.15–4.26 (m, 4H), 3.56 (s, 3H), 2.63 (s, 3H), 2.22–2.35 (m, 1H), 1.94 (td, J = 14.8, 4.3 Hz, 1H), 1.73 (dd, J = 11.8, 6.3 Hz, 1H), 1.59 (dd, J = 22.9, 6.9 Hz, 1H); 13C NMR (101 MHz, CDCl3): δ 171.66, 144.60 (d, J = 12.6 Hz), 141.92, 140.87 (d, J = 186.6 Hz), 135.16, 124.45, 123.76, 123.59, 120.81, 113.54, 111.62, 65.02 (d, J = 19.5 Hz), 62.80 (d, J = 2.4 Hz), 62.75 (d, J = 3.7 Hz), 53.95 (d, J = 15.7 Hz), 49.96 (d, J = 12.7 Hz), 32.92, 30.49, 20.51, 19.07, 16.37 (d, J = 6.2 Hz), 13.90; 31P NMR (162 MHz, CDCl3): δ 10.75; HRMS calculated [M + Na]+ for C23H28N3O4P: 464.1715, found: 464.1715.
Diethyl(5,5-dicyano-1′,5′,7′-trimethyl-2′-oxo-4-propylspiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3m). White solid; mp 151 °C. 1H NMR (400 MHz, CDCl3): δ 7.24 (s, 1H), 7.03 (s, 1H), 6.38 (d, J = 11.2 Hz, 1H), 4.30 (d, J = 9.7 Hz, 1H), 4.13–4.26 (m, 4H), 3.53 (s, 3H), 2.58 (s, 3H), 2.35 (s, 3H), 2.28 (ddd, J = 15.3, 10.8, 5.1 Hz, 1H), 1.94 (td, J = 14.9, 4.6 Hz, 1H), 1.69–1.80 (m, 1H), 1.60 (td, J = 13.9, 7.0 Hz, 1H), 1.41 (t, J = 7.0 Hz, 6H), 1.08 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 171.56 (d, J = 2.2 Hz), 144.89 (d, J = 12.9 Hz), 140.67 (d, J = 186.6 Hz), 139.44, 135.58, 133.29, 125.09, 123.84, 120.43, 113.59, 111.62, 65.07 (d, J = 19.1 Hz), 62.75 (t, J = 4.8 Hz), 53.91 (d, J = 15.4 Hz), 50.01 (d, J = 13.3 Hz), 32.91, 30.42, 20.82, 20.52, 18.89, 16.37 (d, J = 6.3 Hz), 13.90; 31P NMR (162 MHz, CDCl3): δ 10.86. HRMS calculated [M + Na]+ for C24H30N3O4P: 478.1872, found: 478.1869.
Diethyl(5,5-dicyano-4-(furan-2-yl)-1′-methyl-2′-oxospiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3n). White solid; mp 188 °C. 1H NMR (400 MHz, CDCl3): δ 7.70 (d, J = 7.5 Hz, 1H), 7.58 (s, 1H), 7.52 (t, J = 7.7 Hz, 1H), 7.26 (t, J = 8.0 Hz, 1H), 7.00 (d, J = 7.8 Hz, 1H), 6.77 (s, 1H), 6.54 (d, J = 10.8 Hz, 1H), 6.50 (s, 1H), 5.64 (s, 1H), 4.01–4.20 (m, 4H), 3.33 (s, 3H), 1.35 (t, J = 6.9 Hz, 3H), 1.27 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 170.78, 145.92, 145.45 (d, J = 12.7 Hz), 144.14, 144.05, 138.17 (d, J = 191.6 Hz), 131.55, 126.86, 123.98, 122.86, 112.56, 112.41, 111.78, 111.13, 109.26, 65.34 (d, J = 18.7 Hz), 62.87 (t, J = 6.3 Hz), 54.42 (d, J = 14.1 Hz), 50.66 (d, J = 12.2 Hz), 27.14, 16.28 (d, J = 6.2 Hz), 16.19 (d, J = 7.2 Hz); 31P NMR (162 MHz, CDCl3): δ 8.81; HRMS calculated [M + Na]+ for C23H22N3O5P: 474.1195, found: 474.1192.
Diethyl(1′-benzyl-5,5-dicyano-4-(furan-2-yl)-2′-oxospiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3o). White solid; mp 155 °C. 1H NMR (400 MHz, CDCl3): δ 7.71 (d, J = 7.4 Hz, 1H), 7.59 (s, 1H), 7.38 (d, J = 12.0 Hz, 5H), 7.34 (d, J = 5.9 Hz, 1H), 7.21 (t, J = 7.4 Hz, 1H), 6.86 (d, J = 7.8 Hz, 1H), 6.79 (s, 1H), 6.59 (d, J = 10.9 Hz, 1H), 6.51 (s, 1H), 5.70 (s, 1H), 5.17 (d, J = 15.6 Hz, 1H), 4.80 (d, J = 15.5 Hz, 1H), 4.13 (d, J = 6.9 Hz, 4H), 1.35 (t, J = 6.9 Hz, 3H), 1.29 (t, J = 6.9 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 171.01, 145.86, 145.67 (d, J = 12.4 Hz), 144.19, 143.27, 138.30 (d, J = 191.5 Hz), 134.29, 131.43, 129.07, 128.20, 127.56, 126.95, 123.98, 122.92, 112.72, 112.48, 111.79, 111.15, 110.35, 65.19 (d, J = 19.0 Hz), 62.93 (d, J = 6.6 Hz), 62.87 (d, J = 6.4 Hz), 54.53 (d, J = 13.9 Hz), 50.68 (d, J = 12.1 Hz), 44.89, 16.31 (d, J = 6.6 Hz), 16.21 (d, J = 6.6 Hz); 31P NMR (162 MHz, CDCl3): δ 8.80; HRMS calculated [M + Na]+ for C29H26N3O5P: 550.1508, found: 550.1505.
Diethyl(5,5-dicyano-4-(furan-2-yl)-5′-methoxy-1′-methyl-2′-oxospiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3p). White solid; mp 175 °C. 1H NMR (400 MHz, CDCl3): δ 7.57 (s, 1H), 7.31 (s, 1H), 7.04 (d, J = 8.6 Hz, 1H), 6.90 (d, J = 8.5 Hz, 1H), 6.77 (s, 1H), 6.54 (d, J = 10.9 Hz, 1H), 6.50 (s, 1H), 5.63 (s, 1H), 4.02–4.16 (m, 4H), 3.85 (s, 3H), 3.30 (s, 3H), 1.35 (t, J = 6.9 Hz, 3H), 1.26 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 170.50, 156.71, 145.95, 145.44 (d, J = 12.6 Hz), 144.13, 139.10, 137.19, 123.83, 116.77, 113.33, 112.53, 112.41, 111.81, 111.13, 109.81, 65.68 (d, J = 18.6 Hz), 62.91 (d, J = 5.4 Hz), 62.83 (d, J = 5.7 Hz), 55.97, 54.44 (d, J = 14.0 Hz), 50.70 (d, J = 11.9 Hz), 27.19, 16.28 (d, J = 6.3 Hz), 16.18 (d, J = 6.6 Hz); 31P NMR (162 MHz, CDCl3): δ 8.86; HRMS calculated [M + Na]+ for C24H24N3O6P: 504.1300, found: 504.1299.
Diethyl(5,5-dicyano-4-(furan-2-yl)-6′-methoxy-1′-methyl-2′-oxospiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3q). White solid; mp 153 °C. 1H NMR (400 MHz, CDCl3): δ 7.49–7.65 (m, 2H), 6.67–6.80 (m, 2H), 6.52 (d, J = 15.5 Hz, 3H), 5.58 (s, 1H), 4.03–4.16 (m, 4H), 3.90 (s, 3H), 3.29 (s, 3H), 1.34 (t, J = 7.0 Hz, 3H), 1.26 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 171.38, 162.63, 146.07, 145.93 (d, J = 12.3 Hz), 145.48, 144.06, 137.78 (d, J = 191.4 Hz), 127.83, 114.51, 112.66, 112.29, 111.95, 111.10, 107.55, 97.34, 65.29 (d, J = 18.8 Hz), 62.86 (d, J = 6.8 Hz), 62.79 (d, J = 7.1 Hz), 55.74, 54.22 (d, J = 14.1 Hz), 50.85 (d, J = 11.9 Hz), 27.13, 16.28 (d, J = 6.6 Hz), 16.18 (d, J = 6.8 Hz); 31P NMR (162 MHz, CDCl3): δ 8.96; HRMS calculated [M + Na]+ for C24H24N3O6P: 504.1300, found: 504.1299.
Diethyl(5,5-dicyano-4-(furan-2-yl)-1′,7′-dimethyl-2′-oxospiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3r). White solid; mp 163 °C. 1H NMR (400 MHz, CDCl3): δ 7.57 (s, 1H), 7.50 (d, J = 7.5 Hz, 1H), 7.24 (d, J = 7.7 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 6.76 (s, 1H), 6.51 (d, J = 11.3 Hz, 2H), 5.62 (s, 1H), 4.03–4.16 (m, 4H), 3.59 (s, 3H), 2.64 (s, 3H), 1.34 (t, J = 7.0 Hz, 3H), 1.27 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 171.55, 146.00, 145.65 (d, J = 12.5 Hz), 144.10, 141.76, 137.95 (d, J = 191.3 Hz), 135.28, 124.77, 123.76, 123.47, 120.91, 112.70, 112.37, 111.69, 111.11, 64.94 (d, J = 18.7 Hz), 62.84 (t, J = 6.2 Hz), 54.42 (d, J = 13.9 Hz), 51.07 (d, J = 12.4 Hz), 30.60, 19.06, 16.28 (d, J = 6.8 Hz), 16.19 (d, J = 6.6 Hz); 31P NMR (162 MHz, CDCl3): δ 8.89; HRMS calculated [M + Na]+ for C24H24N3O5P: 488.1351, found: 488.1353.
Diethyl(5′-bromo-5,5-dicyano-4-(furan-2-yl)-1′-methyl-2′-oxospiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3s). White solid; mp 193 °C. 1H NMR (400 MHz, CDCl3): δ 7.83 (s, 1H), 7.66 (d, J = 8.2 Hz, 1H), 7.58 (s, 1H), 6.88 (d, J = 8.3 Hz, 1H), 6.77 (s, 1H), 6.51 (s, 2H), 5.61 (s, 1H), 4.10 (dt, J = 14.8, 7.4 Hz, 4H), 3.31 (s, 3H), 1.34 (t, J = 7.0 Hz, 3H), 1.28 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 170.28, 145.62, 144.46 (d, J = 12.7 Hz), 144.24, 143.09, 138.81 (d, J = 191.6 Hz), 134.48, 130.03, 128.64 (d, J = 81.4 Hz), 124.75, 116.57, 112.55, 111.92 (d, J = 78.6 Hz), 111.19, 110.67, 65.07 (d, J = 18.9 Hz), 62.96 (d, J = 4.0 Hz), 62.91 (d, J = 4.4 Hz), 54.56 (d, J = 13.9 Hz), 50.46 (d, J = 12.4 Hz), 27.26, 16.28 (d, J = 7.7 Hz), 16.21 (d, J = 7.7 Hz); 31P NMR (162 MHz, CDCl3): δ 8.43; HRMS calculated [M + Na]+ for C23H21BrN3O5P: 552.0300, found: 552.0293.
Diethyl(5,5-dicyano-4-(furan-2-yl)-1′,6′-dimethyl-2′-oxospiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3t). White solid; mp 181 °C. 1H NMR (400 MHz, CDCl3): δ 7.57 (s, 1H), 7.51 (d, J = 7.5 Hz, 1H), 7.24 (d, J = 7.7 Hz, 1H), 7.12 (t, J = 7.7 Hz, 1H), 6.76 (d, J = 3.0 Hz, 1H), 6.51 (d, J = 10.9 Hz, 2H), 5.63 (s, 1H), 4.02–4.15 (m, 4H), 3.59 (s, 3H), 2.64 (s, 3H), 1.34 (t, J = 7.0 Hz, 3H), 1.27 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 171.59, 145.99, 145.67 (d, J = 12.4 Hz), 144.10, 141.77, 137.96 (d, J = 191.5 Hz), 135.28, 124.79, 123.77, 123.48, 120.90, 112.70, 112.37, 111.69, 111.11, 64.95 (d, J = 18.6 Hz), 62.84 (t, J = 6.3 Hz), 54.43 (d, J = 13.9 Hz), 51.07 (d, J = 11.7 Hz), 30.61, 19.07, 16.28 (d, J = 6.6 Hz), 16.19 (d, J = 6.6 Hz); 31P NMR (162 MHz, CDCl3): δ 8.90; HRMS calculated [M + Na]+ for C24H24N3O5P: 488.1351, found: 488.1353.
Diethyl(5,5-dicyano-2′-oxo-4-phenylspiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3u). White solid; mp 253 °C. 1H NMR (400 MHz, CDCl3): δ 8.63 (s, 1H), 7.67 (d, J = 7.6 Hz, 1H), 7.58 (d, J = 3.8 Hz, 2H), 7.49 (d, J = 3.2 Hz, 3H), 7.43 (t, J = 7.8 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.01 (d, J = 7.8 Hz, 1H), 6.70 (d, J = 11.2 Hz, 1H), 5.46 (s, 1H), 3.97–4.08 (m, 4H), 1.22 (q, J = 6.9 Hz, 6H); 13C NMR (101 MHz, DMSO): δ 172.14, 146.54 (d, J = 12.8 Hz), 142.84, 138.75, 136.88, 133.04, 131.27, 129.46, 129.07 (d, J = 140.7 Hz), 126.64, 123.74, 122.57, 113.19, 112.13, 110.71, 65.75 (d, J = 19.1 Hz), 62.42 (d, J = 6.0 Hz), 62.19 (d, J = 5.9 Hz), 59.99 (d, J = 16.0 Hz), 52.35 (d, J = 12.8 Hz), 15.93 (d, J = 6.3 Hz), 15.75 (d, J = 6.2 Hz); 31P NMR (162 MHz, CDCl3): δ 9.99; HRMS calculated [M + Na]+ for C24H22N3O4P: 470.1246, found: 470.1237.
Diethyl(1′-benzyl-5,5-dicyano-2′-oxo-4-phenylspiro[cyclopent[2]ene-1,3′-indolin]-3-yl)phosphonate (3v). White solid; mp 168 °C. 1H NMR (400 MHz, CDCl3): δ 7.71 (d, J = 7.6 Hz, 1H), 7.60–7.65 (m, 2H), 7.46–7.52 (m, 3H), 7.40 (dt, J = 15.3, 7.5 Hz, 5H), 7.31–7.35 (m, 1H), 7.21 (t, J = 7.7 Hz, 1H), 6.86 (d, J = 7.9 Hz, 1H), 6.62 (dd, J = 11.0, 2.6 Hz, 1H), 5.58 (s, 1H), 5.20 (d, J = 15.6 Hz, 1H), 4.80 (d, J = 15.6 Hz, 1H), 4.20–4.02 (m, 2H), 4.01–3.85 (m, 2H), 1.31 (t, J = 7.1 Hz, 3H), 1.14 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 171.24, 146.02 (d, J = 12.6 Hz), 143.31, 140.26 (d, J = 190.6 Hz), 134.35, 132.47, 131.34, 130.24, 129.77, 129.06, 128.56, 128.18, 127.58, 127.01, 123.94, 123.16, 112.91, 111.85, 110.28, 65.43 (d, J = 18.8 Hz), 62.88 (d, J = 5.9 Hz), 62.76 (d, J = 6.3 Hz), 60.99 (d, J = 14.8 Hz), 52.84 (d, J = 13.2 Hz), 44.92, 16.24 (d, J = 6.3 Hz), 16.04 (d, J = 6.8 Hz); 31P NMR (162 MHz, CDCl3): δ 9.40; HRMS calculated [M + Na]+ for C31H28N3O4P: 560.1715, found: 560.1714.

Acknowledgements

We thank the National Natural Science Foundation of China (21072102), the Committee of Science and Technology of Tianjin (11JCYBJC04200) and State Key Laboratory of Elemento-Organic Chemistry in Nankai University for financial support.

Notes and references

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  10. ESI..

Footnote

Electronic supplementary information (ESI) available. CCDC 993220. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4ra12997k

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