Subscribe to RSS
DOI: 10.1055/a-1938-1243
Organocatalytic Asymmetric Oxa-Michael–Michael Reaction of 3-Aryl-2-Nitroprop-2-Enols with Unsaturated Pyrazolones: Synthesis of Spirotetrahydropyranopyrazolones
This work was supported by MHRD-FAST programme (file no 22-3/2016-TS.II/TC) and DST-SERB (file no CRG/2018/001154). We also thank the Department of Biotechnology (DBT), Govt. of India (project no. BT/COE/34/SP28408/2018) for the provision of instrumental facilities.
Abstract
An organocatalytic asymmetric oxa-Michael–Michael reaction of 3-aryl-2-nitroprop-2-enols with alkylidene pyrazolones has been developed. This report describes the first use of a 3-aryl-2-nitroprop-2-enol as an O-nucleophile in enantioselective catalysis. With 10 mol% of a quinine-derived squaramide catalyst, a variety of spirotetrahydropyranopyrazolones were obtained in moderate yields, excellent diastereomeric ratios, and high to excellent enantioselectivities under mild reaction conditions.
#
Key Words
spiropyrazolones - oxa-Michael reaction - organocatalysis - asymmetric catalysis - enantioselectivity - cascade reaction
The conjugate addition of oxygen-centered nucleophiles to Michael acceptors, namely the oxa-Michael reaction, is a versatile and powerful organic transformation for the preparation of oxygen–carbon bonds.[1] Also, oxa-Michael-addition-triggered organocatalytic cascade reactions are among the most efficient methods for the synthesis of oxygen-containing heterocycles.[2] Although phenol derivatives have been used successfully in organocatalytic oxa-Michael cascade reactions,[3] the corresponding reactions of alcohols are challenging owing to the poor nucleophilicity and reactivity of their hydroxy groups. In recent years, bidentate compounds containing an alcohol group, such as γ,δ-hydroxy enones,[4] ω-hydroxy enals,[5] p-hydroxycycloenones,[6] and hydroxypyranones,[7] among others, have been used in organocatalytic cascade reactions. Despite these discoveries, the use of bidentate alcohol compounds is still required to prepare a diverse range of oxygen heterocycles.
Here, we employed 3-aryl-2-nitroprop-2-enols in oxa-Michael-Michael reactions. Previously, 3-aryl-2-nitroprop-2-enols had been used as Michael acceptors with a subsequent acetalization/ketalization reaction to give enantiopure cyclic compounds (Scheme [1]).[8] For example, in 2009, Chandrasekhar and co-workers developed a domino Michael ketalization reaction of cyclohexanone with 3-aryl-2-nitroprop-2-enols to obtain bicyclic compounds.[8a] Later Ma and co-workers reported a synthesis of tetrahydropyrans through a domino Michael/acetalization reaction of pentanal with 3-aryl-2-nitroprop-2-enols.[8b] The groups of Vicario and Aleman independently reported the formation of cyclobutane-fused bicyclic hemiacetals by the dienamine-mediated reaction of enals with 3-aryl-2-nitroprop-2-enols.[8c] [d] The groups of Hong, Jørgensen, Enders, Zhao, and Chien reported Michael/hemiketalization reaction with various nucleophiles.[8e–i] However, there has been no report on the use of 3-aryl-2-nitroprop-2-enol as O-nucleophiles in organocatalytic asymmetric Michael reactions.[9]
Spiropyrazolones containing stereogenic cycloalkane/heterocycle and pyrazolone motifs have attracted attention because of their useful bioactivities in medicinal chemistry.[10] Accordingly, several organocatalytic methods have been developed to access structurally diverse spiropyrazolone derivatives.[4c] [11] However, there is an intrinsic challenge in the preparation of O-heterocycle-embedded spiropyrazolones and attaining a high enantioselectivity. We envisaged the use of 3-aryl-2-nitroprop-2-enols as reaction partners with unsaturated pyrazolones for the formation of novel spirotetrahydropyranopyrazolones.[12]
We started our investigation by performing a model reaction of the alkylidene pyrazolone 1a with 3-phenyl-2-nitroprop-2-enol (2a) in the presence of the quinine-derived bifunctional thiourea catalyst I in toluene at room temperature (Table [1]). To our delight, after one day, the oxa-Michael–Michael reaction progressed well to provide the spirotetrahydropyranopyrazolone 3a in 45% yield with a 4:1 diastereomeric ratio and an 85% enantiomeric excess of the major diastereomer (Table [1], entry 1). The relative configuration of 3a was determined by 2D NMR [for details, see the Supporting Information (SI)]. To improve the diastereo- and enantioselectivity, the bifunctional thiourea catalysts II and III were screened; however, the enantioselectivity was not enhanced, although a slight improvement in diastereoselectivity was observed with catalyst II (entries 2 and 3). Then, we turned our attention to the use of bifunctional squaramide catalysts[13] IV–VI in the reaction (entries 4–6). To our delight, the quinine-derived squaramide catalyst IV provided product 3a as a single diastereomer; however, the enantioselectivity was moderate (entry 4). A higher enantioselectivity and a moderate diastereoselectivity were achieved with catalyst V (entry 5). The cinchonidine-derived squaramide catalyst VI was also ineffective in the reaction (entry 6). We then speculated that the solvent might have an effect on the enantioselectivity. Gratifyingly, the enantioselectivity improved in dichloromethane solvent with both catalysts I and V, but the diastereoselectivity remained the same (entries 7 and 8). Finally, the best result was obtained with catalyst IV, and the product 3a was isolated as a single diastereomer in 55% yield with 98% ee (entry 9). Other solvents were also screened but no better result was achieved (for details, see SI).
a Reaction conditions: 1a (0.11 mmol), 2a (0.1 mmol), catalyst (10 mol%), solvent (0.4 mL), rt, 24 h.
b Isolated yield after column chromatography (silica gel).
c Determined by 1H NMR.
d For the major diastereomer, as determined by HPLC.
Having identified the best catalyst and reaction conditions, we examined the scope and generality of the reaction. Pleasingly, a single diastereomer was formed in all cases. Initially, we varied the alkylidene group of pyrazolone 1 (Table [2], entries 1–9). We were delighted to find that a range of electron-withdrawing and electron-donating groups could be incorporated in the ortho-, meta-, or para-position of the aryl group with good results.
Initially, various para-substituents were checked, and products 3b and 3c containing a 4-tert-butyl and a 4-trifluoromethyl group, respectively, were isolated in good yields and high enantioselectivities (Table [2], entries 2 and 3). Then pyrazolones 1d–g containing various meta-substituted aryl groups were employed and gave satisfactory outcomes (entries 4–7). To our delight, the meta-methoxy-substituted pyrazolone 1e delivered the corresponding product 3e in 42% yield and 99% ee (entry 5). Halo substitution was also tolerated, and product 3f was obtained in 86% ee (entry 6). Pyrazolone 1g containing a 3-trifluormethyl group also reacted smoothly to deliver product 3g in 37% yield and 91% ee (entry 7). Our method was also suitable for pyrazolones containing ortho-substituents; high enantioselectivities were obtained for products 3h and 3i containing an ortho-tolyl and an ortho-anisyl group, respectively (entries 8 and 9). We then turned our attention to an examination of N-aryl substitution of the pyrazolone motif. Pyrazolone 1j containing a 4-bromophenyl substituent was prepared and employed in the reaction. A smooth conversion was detected and product 3j was isolated in 45% yield with 83% ee (entry 10). Unfortunately, the reaction did not proceed cleanly when the phenyl group in nitroolefin 2a was replaced by other aryl groups, and complex mixtures were obtained.
a Reaction conditions: 1a (0.11 mmol), 2a (0.1 mmol), IV (10 mol%), CH2Cl2 (0.4 mL), rt, 24 h.
b Isolated yield after column chromatography (silica gel).
c Determined by 1H NMR.
d Determined by chiral HPLC.
In summary, we have developed an efficient organocatalytic cascade oxa-Michael–Michael reaction for the first catalytic asymmetric synthesis of spirotetrahydropyranopyrazolones. We also report the first use of 3-aryl-2-nitroprop-2-enols as O-nucleophiles in enantioselective catalysis. The reaction furnished the products in acceptable yields and with perfect diastereomeric ratios as well as good to excellent enantioselectivities. Given the high pharmaceutical importance of spiropyrazolones our method might be applicable to a shortened preparation of these compounds.
#
Conflict of Interest
The authors declare no conflict of interest.
Acknowledgment
We thank CIF, the Indian Institute of Technology Guwahati, and the North East Centre for Biological Sciences and Healthcare Engineering (NECBH), IIT Guwahati, for the provision of instrumental facilities.
Supporting Information
- Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-1938-1243.
- Supporting Information
-
References and Notes
- 1a Nising CF, Bräse S. Chem. Soc. Rev. 2008; 37: 1218
- 1b Nising CF, Bräse S. Chem. Soc. Rev. 2012; 41: 988
- 1c Hu J, Bian M, Ding H. Tetrahedron Lett. 2016; 57: 5519
- 2a Wang Y, Du D.-M. Org. Chem. Front. 2020; 7: 3266
- 2b Ahmad T, Ullah N. Org. Chem. Front. 2021; 8: 1329
- 2c Biswas A, Ghosh A, Shankdhar R, Chatterjee I. Asian J. Org. Chem. 2021; 1345
- 3a Zhu Y, Li X, Chen Q, Su J, Jia F, Qiu S, Ma M, Sun Q, Yan W, Wang K, Wang R. Org. Lett. 2015; 17: 3826
- 3b Saha P, Biswas A, Molleti N, Singh VK. J. Org. Chem. 2015; 80: 11115
- 3c Zheng W, Zhang J, Liu S, Yu C, Miao Z. RSC Adv. 2015; 5: 91108
- 3d Zhao K, Zhi Y, Shu T, Valkonen A, Rissanen K, Enders D. Angew. Chem. Int. Ed. 2016; 55: 12104
- 3e Tang C.-K, Feng K.-X, Xia A.-B, Li C, Zheng Y.-Y, Xu Z.-Y, Xu D.-Q. RSC Adv. 2018; 8: 3095
- 3f Roy S, Pradhan S, Kumar K, Chatterjee I. Org. Chem. Front. 2020; 7: 1388
- 3g Dalpozzo R, Mancuso R. Symmetry 2019; 11: 1510
- 4a Asano K, Matsubara S. Org. Lett. 2012; 14: 1620
- 4b Liu Y, Jun A, Paladhi S, Song C.-E, Yan H. J. Am. Chem. Soc. 2016; 138: 16486
- 4c Mondal B, Maity R, Pan SC. J. Org. Chem. 2018; 83: 8645
- 4d Mondal B, Pan SC. Adv. Synth. Catal. 2018; 360: 4348
- 4e Mondal B, Balha M, Pan SC. Asian J. Org. Chem. 2018; 7: 1788
- 5 McGarraugh PG, Johnston RC, Martínez-Muñoz A, Cheong PH.-Y, Brenner-Moyer SE. Chem. Eur. J. 2012; 18: 10742
- 6 Corbett MT, Johnson JS. Chem. Sci. 2013; 4: 2828
- 7a Orue A, Uria U, Roca-López D, Delso I, Reyes E, Carrillo L, Merino P, Vicario JL. Chem. Sci. 2017; 8: 2904
- 7b Reyes E, Talavera G, Vicario JL, Badía D, Carrillo L. Angew. Chem. Int. Ed. 2009; 48: 5701
- 8a Chandrasekhar S, Mallikarjun K, Pavankumarreddy G, Rao KV, Jagadeesh B. Chem. Commun. 2009; 4985
- 8b Wang Y, Zhu S, Ma D. Org. Lett. 2011; 13: 1602
- 8c Talavera G, Reyes E, Vicario JL, Carrillo L. Angew. Chem. Int. Ed. 2012; 51: 4104
- 8d Parra A, Reboredo S, Alemán J. Angew. Chem. Int. Ed. 2012; 51: 9734
- 8e Hong B.-C, Lan D.-J, Dange NS, Lee G.-H, Liao J.-H. Eur. J. Org. Chem. 2013; 2472
- 8f Cruz Cruz D, Mose R, Villegas Gómez C, Torbensen SV, Larsen MS, Jørgensen KA. Chem. Eur. J. 2014; 20: 11331
- 8g Urbanietz G, Atodiresei I, Enders D. Synthesis 2014; 46: 1261
- 8h Parellaa R, Jakkampudi S, Arman H, Zhao JC.-G. Adv. Synth. Catal. 2019; 361: 208
- 8i Akula PS, Wang Y.-J, Hong B.-C, Lee G.-H, Chein S.-Y. Org. Lett. 2021; 23: 4688
- 9 For an achiral noncatalytic reaction, see: Gudise VB, Settipalli PC, Reddy EK, Anwar S. Eur. J. Org. Chem. 2019; 2234
- 10a Chande MS, Barve PA, Suryanarayan V. J. Heterocycl. Chem. 2007; 44: 49
- 10b Schlemminger I, Schmidt B, Flockerzi D, Tenor H, Zitt C, Hatzelmann A, Marx D, Braun C, Kuelzer R, Heuser A, Kley H.-P, Sterk GJ. WO 2010055083, 2008
- 10c Schmidt B, Scheufler C, Volz J, Feth MP, Hummel R.-P, Hatzelmann A, Zitt C, Wohlsen A, Marx D, Kley H.-P, Ockert D, Heuser A, Christians JA. M, Sterk GJ, Menge WM. P. B. WO 2008138939, 2010
- 11a Mondal S, Mukherjee S, Yetra SR, Gonnade RG, Biju AT. Org. Lett. 2017; 19: 4367
- 11b Yang W, Sun W, Zhang C, Wang Q, Guo Z, Mao B, Liao J, Guo H. ACS Catal. 2017; 7: 3142
- 11c Leng H.-J, Li Q.-Z, Zeng R, Dai Q.-S, Zhu H.-P, Liu Y, Huang W, Han B, Li J.-L. Adv. Synth. Catal. 2018; 360: 229
- 11d Tang C.-K, Zhou Z.-Y, Xia A.-B, Bai L, Liu J, Xu D.-Q, Xu Z.-Y. Org. Lett. 2018; 20: 5840
- 11e Meninno S, Mazzanti A, Lattanzi A. Adv. Synth. Catal. 2019; 361: 79
- 11f Lu H, Zhang HX, Tan C.-Y, Liu J.-Y, Wei H, Xu P.-F. J. Org. Chem. 2019; 84: 10292
- 11g Tan CY, Lu H, Zhang J.-L, Liu J.-Y, Xu P.-F. J. Org. Chem. 2020; 85: 594
- 11h Chauhan P, Mahajan S, Enders D. Chem. Commun. 2015; 51: 12890
- 11i Liu S.-Y, Bao X.-Z, Wang B.-M. Chem. Commun. 2018; 54: 11515
- 11j Xie X, Xiang L, Peng C, Han B. Chem. Rec. 2019; 19: 2209
- 12a Franz AK, Hanhan NV, Ball-Jones NR. ACS Catal. 2013; 3: 540
- 12b Rios R. Chem. Soc. Rev. 2012; 41: 1060
- 12c Nakazaki A, Kobayashi S. Synlett 2012; 23: 1427
- 13a Malerich J, Hagihara K, Rawal V. J. Am. Chem. Soc. 2008; 130: 14416 . For reviews, see
- 13b Alemán J, Parra A, Jiang H, Jørgensen KA. Chem. Eur. J. 2011; 17: 6890
- 13c Chauhan P, Mahajan S, Kaya U, Hack D, Enders D. Adv. Synth. Catal. 2015; 357: 253
- 13d Rouf A, Tanyeli C. Curr. Org. Chem. 2016; 20: 2996
- 13e Zhao B.-L, Li J.-H, Du A.-M. Chem. Rec. 2017; 17: 994
- 14 4-Methyl-9-nitro-2,6,10-triphenyl-7-oxa-2,3-diazaspiro[4.5]dec-3-en-1-one (3a); Typical ProcedureAn oven-dried round-bottomed flask was charged with pyrazolone 1 (17.9 mg, 0.1 mmol), enol 2 (28.8mg, 0.11 mmol), and catalyst IV (10 mol%). CH2Cl2 (0.4 mL) was added and the mixture was stirred at rt for 1 d until the reaction was complete (TLC). The mixture was then concentrated and purified directly by column chromatography [silica gel, hexane–EtOAc (8%)] to give a yellowish sticky solid; yield 24.3 mg (55%, 98% ee).HPLC [Chiralpak IF, hexane–i-PrOH (85:15), 1.0 mL/min, λ = 220 nm]: t major = 20.99 min, t minor = 17.90 min. 1H NMR (500 MHz, CDCl3): δ = 7.27 (t, J = 4.6 Hz, 4 H), 7.26–7.22 (m, 5 H), 7.19 (t, J = 8.0 Hz, 3 H), 7.11 (d, J = 8.0 Hz, 2 H), 7.07 (t, J = 7.4 Hz, 1 H), 5.68 (dt, J = 12.3, 7.2 Hz, 1 H), 4.77 (s, 1 H), 4.69–4.60 (m, 3 H), 2.33 (s, 3 H). 13C NMR (126 MHz, CDCl3): δ = 171.7, 156.5, 136.9, 135.0, 133.0, 129.3, 129.0, 128.9, 128.7, 128.4, 127.6, 126.2, 125.8, 120.1, 81.7, 78.7, 68.4, 64.1, 45.9, 16.96. HRMS (ESI): m/z [M + H]+ calcd for C26H24N3O4: 442.1761; found: 442.1750.
For reviews, see:
For reviews, see:
For selected recent examples, see:
For a review, see:
For selected recent examples, see:
For reviews, see:
For reviews on asymmetric synthesis of spiro compounds, see:
For initial report, see:
Corresponding Author
Publication History
Received: 30 May 2021
Accepted after revision: 07 September 2021
Accepted Manuscript online:
07 September 2022
Article published online:
28 September 2022
© 2021. Thieme. All rights reserved
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References and Notes
- 1a Nising CF, Bräse S. Chem. Soc. Rev. 2008; 37: 1218
- 1b Nising CF, Bräse S. Chem. Soc. Rev. 2012; 41: 988
- 1c Hu J, Bian M, Ding H. Tetrahedron Lett. 2016; 57: 5519
- 2a Wang Y, Du D.-M. Org. Chem. Front. 2020; 7: 3266
- 2b Ahmad T, Ullah N. Org. Chem. Front. 2021; 8: 1329
- 2c Biswas A, Ghosh A, Shankdhar R, Chatterjee I. Asian J. Org. Chem. 2021; 1345
- 3a Zhu Y, Li X, Chen Q, Su J, Jia F, Qiu S, Ma M, Sun Q, Yan W, Wang K, Wang R. Org. Lett. 2015; 17: 3826
- 3b Saha P, Biswas A, Molleti N, Singh VK. J. Org. Chem. 2015; 80: 11115
- 3c Zheng W, Zhang J, Liu S, Yu C, Miao Z. RSC Adv. 2015; 5: 91108
- 3d Zhao K, Zhi Y, Shu T, Valkonen A, Rissanen K, Enders D. Angew. Chem. Int. Ed. 2016; 55: 12104
- 3e Tang C.-K, Feng K.-X, Xia A.-B, Li C, Zheng Y.-Y, Xu Z.-Y, Xu D.-Q. RSC Adv. 2018; 8: 3095
- 3f Roy S, Pradhan S, Kumar K, Chatterjee I. Org. Chem. Front. 2020; 7: 1388
- 3g Dalpozzo R, Mancuso R. Symmetry 2019; 11: 1510
- 4a Asano K, Matsubara S. Org. Lett. 2012; 14: 1620
- 4b Liu Y, Jun A, Paladhi S, Song C.-E, Yan H. J. Am. Chem. Soc. 2016; 138: 16486
- 4c Mondal B, Maity R, Pan SC. J. Org. Chem. 2018; 83: 8645
- 4d Mondal B, Pan SC. Adv. Synth. Catal. 2018; 360: 4348
- 4e Mondal B, Balha M, Pan SC. Asian J. Org. Chem. 2018; 7: 1788
- 5 McGarraugh PG, Johnston RC, Martínez-Muñoz A, Cheong PH.-Y, Brenner-Moyer SE. Chem. Eur. J. 2012; 18: 10742
- 6 Corbett MT, Johnson JS. Chem. Sci. 2013; 4: 2828
- 7a Orue A, Uria U, Roca-López D, Delso I, Reyes E, Carrillo L, Merino P, Vicario JL. Chem. Sci. 2017; 8: 2904
- 7b Reyes E, Talavera G, Vicario JL, Badía D, Carrillo L. Angew. Chem. Int. Ed. 2009; 48: 5701
- 8a Chandrasekhar S, Mallikarjun K, Pavankumarreddy G, Rao KV, Jagadeesh B. Chem. Commun. 2009; 4985
- 8b Wang Y, Zhu S, Ma D. Org. Lett. 2011; 13: 1602
- 8c Talavera G, Reyes E, Vicario JL, Carrillo L. Angew. Chem. Int. Ed. 2012; 51: 4104
- 8d Parra A, Reboredo S, Alemán J. Angew. Chem. Int. Ed. 2012; 51: 9734
- 8e Hong B.-C, Lan D.-J, Dange NS, Lee G.-H, Liao J.-H. Eur. J. Org. Chem. 2013; 2472
- 8f Cruz Cruz D, Mose R, Villegas Gómez C, Torbensen SV, Larsen MS, Jørgensen KA. Chem. Eur. J. 2014; 20: 11331
- 8g Urbanietz G, Atodiresei I, Enders D. Synthesis 2014; 46: 1261
- 8h Parellaa R, Jakkampudi S, Arman H, Zhao JC.-G. Adv. Synth. Catal. 2019; 361: 208
- 8i Akula PS, Wang Y.-J, Hong B.-C, Lee G.-H, Chein S.-Y. Org. Lett. 2021; 23: 4688
- 9 For an achiral noncatalytic reaction, see: Gudise VB, Settipalli PC, Reddy EK, Anwar S. Eur. J. Org. Chem. 2019; 2234
- 10a Chande MS, Barve PA, Suryanarayan V. J. Heterocycl. Chem. 2007; 44: 49
- 10b Schlemminger I, Schmidt B, Flockerzi D, Tenor H, Zitt C, Hatzelmann A, Marx D, Braun C, Kuelzer R, Heuser A, Kley H.-P, Sterk GJ. WO 2010055083, 2008
- 10c Schmidt B, Scheufler C, Volz J, Feth MP, Hummel R.-P, Hatzelmann A, Zitt C, Wohlsen A, Marx D, Kley H.-P, Ockert D, Heuser A, Christians JA. M, Sterk GJ, Menge WM. P. B. WO 2008138939, 2010
- 11a Mondal S, Mukherjee S, Yetra SR, Gonnade RG, Biju AT. Org. Lett. 2017; 19: 4367
- 11b Yang W, Sun W, Zhang C, Wang Q, Guo Z, Mao B, Liao J, Guo H. ACS Catal. 2017; 7: 3142
- 11c Leng H.-J, Li Q.-Z, Zeng R, Dai Q.-S, Zhu H.-P, Liu Y, Huang W, Han B, Li J.-L. Adv. Synth. Catal. 2018; 360: 229
- 11d Tang C.-K, Zhou Z.-Y, Xia A.-B, Bai L, Liu J, Xu D.-Q, Xu Z.-Y. Org. Lett. 2018; 20: 5840
- 11e Meninno S, Mazzanti A, Lattanzi A. Adv. Synth. Catal. 2019; 361: 79
- 11f Lu H, Zhang HX, Tan C.-Y, Liu J.-Y, Wei H, Xu P.-F. J. Org. Chem. 2019; 84: 10292
- 11g Tan CY, Lu H, Zhang J.-L, Liu J.-Y, Xu P.-F. J. Org. Chem. 2020; 85: 594
- 11h Chauhan P, Mahajan S, Enders D. Chem. Commun. 2015; 51: 12890
- 11i Liu S.-Y, Bao X.-Z, Wang B.-M. Chem. Commun. 2018; 54: 11515
- 11j Xie X, Xiang L, Peng C, Han B. Chem. Rec. 2019; 19: 2209
- 12a Franz AK, Hanhan NV, Ball-Jones NR. ACS Catal. 2013; 3: 540
- 12b Rios R. Chem. Soc. Rev. 2012; 41: 1060
- 12c Nakazaki A, Kobayashi S. Synlett 2012; 23: 1427
- 13a Malerich J, Hagihara K, Rawal V. J. Am. Chem. Soc. 2008; 130: 14416 . For reviews, see
- 13b Alemán J, Parra A, Jiang H, Jørgensen KA. Chem. Eur. J. 2011; 17: 6890
- 13c Chauhan P, Mahajan S, Kaya U, Hack D, Enders D. Adv. Synth. Catal. 2015; 357: 253
- 13d Rouf A, Tanyeli C. Curr. Org. Chem. 2016; 20: 2996
- 13e Zhao B.-L, Li J.-H, Du A.-M. Chem. Rec. 2017; 17: 994
- 14 4-Methyl-9-nitro-2,6,10-triphenyl-7-oxa-2,3-diazaspiro[4.5]dec-3-en-1-one (3a); Typical ProcedureAn oven-dried round-bottomed flask was charged with pyrazolone 1 (17.9 mg, 0.1 mmol), enol 2 (28.8mg, 0.11 mmol), and catalyst IV (10 mol%). CH2Cl2 (0.4 mL) was added and the mixture was stirred at rt for 1 d until the reaction was complete (TLC). The mixture was then concentrated and purified directly by column chromatography [silica gel, hexane–EtOAc (8%)] to give a yellowish sticky solid; yield 24.3 mg (55%, 98% ee).HPLC [Chiralpak IF, hexane–i-PrOH (85:15), 1.0 mL/min, λ = 220 nm]: t major = 20.99 min, t minor = 17.90 min. 1H NMR (500 MHz, CDCl3): δ = 7.27 (t, J = 4.6 Hz, 4 H), 7.26–7.22 (m, 5 H), 7.19 (t, J = 8.0 Hz, 3 H), 7.11 (d, J = 8.0 Hz, 2 H), 7.07 (t, J = 7.4 Hz, 1 H), 5.68 (dt, J = 12.3, 7.2 Hz, 1 H), 4.77 (s, 1 H), 4.69–4.60 (m, 3 H), 2.33 (s, 3 H). 13C NMR (126 MHz, CDCl3): δ = 171.7, 156.5, 136.9, 135.0, 133.0, 129.3, 129.0, 128.9, 128.7, 128.4, 127.6, 126.2, 125.8, 120.1, 81.7, 78.7, 68.4, 64.1, 45.9, 16.96. HRMS (ESI): m/z [M + H]+ calcd for C26H24N3O4: 442.1761; found: 442.1750.
For reviews, see:
For reviews, see:
For selected recent examples, see:
For a review, see:
For selected recent examples, see:
For reviews, see:
For reviews on asymmetric synthesis of spiro compounds, see:
For initial report, see:
