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Synlett 2021; 32(04): 417-422
DOI: 10.1055/a-1274-2959
DOI: 10.1055/a-1274-2959
letter
Enantioselective Synthesis of Difluoroalkylated Isoindolinones via Chiral Spirocyclic Phosphoric Acid Catalyzed Mannich-Type Reaction
We appreciate the National Natural Science Foundation of China (22071213) for financial support.
Abstract
An enantioselective Mannich-type reaction of in situ generated cyclic ketimines with difluoroenoxysilanes catalyzed by chiral spirocyclic phosphoric acid has been developed. This methodology provides a facile route to difluoroalkyl-substituted chiral isoindolinones bearing a quaternary stereogenic center in high yields and up to 96% enantioselectivity.
Key words
enantioselective synthesis - Mannich-type reaction - chiral spirocyclic phosphoric acid - isoindolinone - difluoroenoxysilaneSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1274-2959.
- Supporting Information
Publication History
Received: 03 September 2020
Accepted after revision: 29 September 2020
Accepted Manuscript online:
29 September 2020
Article published online:
02 November 2020
© 2020. Thieme. All rights reserved
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References and Notes
- 1a Mikami K, Itoh Y, Yamanaka M. Chem. Rev. 2004; 104: 1
- 1b Ma J.-A, Cahard D. Chem. Rev. 2004; 104: 6119
- 1c O’Hagan D. Chem. Soc. Rev. 2008; 37: 308
- 1d Zhang C.-P, Chen Q.-Y, Guo Y, Xiao J.-C, Gu Y.-C. Chem. Soc. Rev. 2012; 41: 4536
- 1e Wang J, Sánchez-Roselló M, Aceña JL, del Pozo C, Sorochinsky AE, Fustero S, Soloshonok VA, Liu H. Chem. Rev. 2014; 114: 2432
- 1f Ma J.-A, Li S. Org. Chem. Front. 2014; 1: 712
- 1g Yang X, Wu T, Phipps RJ, Toste FD. Chem. Rev. 2015; 115: 826
- 1h Champagne PA, Desroches J, Hamel JD, Vandamme M, Paquin JF. Chem. Rev. 2015; 115: 9073
- 2a Erickson JA, McLoughlin JI. J. Org. Chem. 1995; 60: 1626
- 2b Jakeman DL, Ivory AJ, Williamson MP, Blackburn GM. J. Med. Chem. 1998; 41: 4439
- 2c Liu Y.-L, Yu J.-S, Zhou J. Asian J. Org. Chem. 2013; 2: 194
- 2d Ni C, Hu J. Chem. Soc. Rev. 2016; 45: 5441
- 3a Amii H, Kobayashi T, Hatamoto Y, Uneyama K. Chem. Commun. 1999; 1323
- 3b Schenck HA, Lenkowski PW, Choudhury-Mukherjee I, Ko S.-H, Stables JP, Patel MJ, Brown ML. Bioorg. Med. Chem. 2004; 12: 979
- 3c Decostanzi M, Campagne J.-M, Leclerc E. Org. Biomol. Chem. 2015; 13: 7351
- 3d Hu X.-S, Yu J.-S, Zhou J. Chem. Commun. 2019; 55: 13638
- 4a Hook DF, Gessier F, Noti C, Kast P, Seebach D. ChemBioChem 2004; 5: 691
- 4b Niida A, Tomita K, Mizumoto M, Tanigaki H, Terada T, Oishi S, Otaka A, Inui K, Fujii N. Org. Lett. 2006; 8: 613
- 4c Boyer N, Gloanec P, Nanteuil GD, Jubaulta P, Quiriona JC. Tetrahedron 2007; 63: 12352
- 4d Chu L, Zhang X, Qing F.-L. Org. Lett. 2009; 11: 2197
- 4e Poisson T, Belhomme MC, Pannecoucke X. J. Org. Chem. 2012; 77: 9277
- 4f Liu Y.-L, Zhou J. Chem. Commun. 2012; 48: 1919
- 4g Yu J.-S, Liu Y.-L, Tang J, Wang X, Zhou J. Angew. Chem. Int. Ed. 2014; 53: 9512
- 4h Yu J.-S, Zhou J. Org. Biomol. Chem. 2015; 13: 10968
- 4i Yu J.-S, Liao F.-M, Gao W.-M, Liao K, Zuo R.-L, Zhou J. Angew. Chem. Int. Ed. 2015; 54: 7381
- 4j Wu Y.-B, Lu G.-P, Zhou B.-J, Bu M.-J, Wan L, Cai C. Chem. Commun. 2016; 52: 5965
- 4k Huang X, Zhang Y, Zhang C, Zhang L, Xu Y, Kong L, Wang Z.-X, Peng B. Angew. Chem. Int. Ed. 2019; 58: 5956
- 4l Hu X.-S, Ding P.-G, Yu J.-S, Zhou J. Org. Chem. Front. 2019; 6: 2500
- 4m Gao X, Chen R, Xiao Y.-L, Wan X.-L, Zhang X. Chem. 2019; 5: 2987
- 5a Yuan Z, Wei Y, Shi M. Chin. J. Chem. 2010; 28: 1709
- 5b Yuan Z, Mei L, Wei Y, Shi M, Kattamuri PV, McDowell P, Li G. Org. Biomol. Chem. 2012; 10: 2509
- 6 Kashikura W, Mori K, Akiyama T. Org. Lett. 2011; 13: 1860
- 7 Yu J.-S, Zhou J. Org. Chem. Front. 2016; 3: 298
- 8 Li J.-S, Liu Y.-J, Zhang G.-W, Ma J.-A. Org. Lett. 2017; 19: 6364
- 9a Blasko G, Gula DJ, Shamma M. J. Nat. Prod. 1982; 45: 105
- 9b Ferland J.-M, Demerson CA, Humber LG. Can. J. Chem. 1985; 63: 361
- 9c Maier L, Diel PJ. Phosphorus, Sulfur Silicon Relat. Elem. 1991; 57: 57
- 9d De Clercq E. J. Med. Chem. 1995; 38: 2491
- 9e Anzini M, Cappelli A, Vomero S, Giorgi G, Langer T, Bruni G, Romeo MR, Basile AS. J. Med. Chem. 1996; 39: 4275
- 9f Taylor EC, Zhou P, Jennings LD, Mao Z, Hu B, Jun J.-G. Tetrahedron Lett. 1997; 38: 521
- 9g Gotor V, Limeres F, García R, Bayod M, Brieva R. Tetrahedron: Asymmetry 1997; 8: 995
- 9h Zhuang Z.-P, Kung MP, Mu M, Kung H.-F. J. Med. Chem. 1998; 41: 157
- 9i Belliotti TR, Brink WA, Kesten SR, Rubin JR, Wustrow DJ, Zoski KT, Whetzel SZ, Corbin AE, Pugsley TA, Heffner TG, Wise LD. Bioorg. Med. Chem. Lett. 1998; 8: 1499
- 10a Yu X, Wang Y, Wu G, Song H, Zhou Z, Tang C. Eur. J. Org. Chem. 2011; 3060
- 10b Nishimura T, Noishiki A, Tsui GC, Hayashi T. J. Am. Chem. Soc. 2012; 134: 5056
- 10c Chen M.-W, Chen Q.-A, Duan Y, Ye Z.-S, Zhou Y.-G. Chem. Commun. 2012; 48: 1698
- 10d Nishimura T, Noishiki A, Ebe Y, Hayashi T. Angew. Chem. Int. Ed. 2013; 52: 1777
- 10e Zhou J.-Q, Sheng W.-J, Jia J.-H, Ye Q, Gao J.-R, Jia Y.-X. Tetrahedron Lett. 2013; 54: 3082
- 10f Nagamoto M, Yamauchi D, Nishimura T. Chem. Commun. 2016; 52: 5876
- 10g Suć J, Dokli I, Gredičak M. Chem. Commun. 2016; 52: 2071
- 10h Suneja A, Unhale RA, Singh VK. Org. Lett. 2017; 19: 476
- 10i Unhale RA, Molleti N, Rana NK, Dhanasekaran S, Bhandary S, Singh VK. Tetrahedron Lett. 2017; 58: 145
- 10j Zhou B, Li K, Jiang C, Lu Y, Hayashi T. Adv. Synth. Catal. 2017; 359: 1969
- 10k Glavač D, Gredičak M. Synlett 2017; 28: 889
- 10l Glavač D, Zheng C, Dokli I, You S.-L, Gredičak M. J. Org. Chem. 2017; 82: 8752
- 10m Unhale RA, Sadhu MM, Ray SK, Biswas RG, Singh VK. Chem. Commun. 2018; 54: 3516
- 10n Zhang L, Wu B, Chen Z, Hu J, Zeng X, Zhong G. Chem. Commun. 2018; 54: 9230
- 10o Kang Z, Zhang D, Shou J, Hu W. Org. Lett. 2018; 20: 983
- 10p Feng F.-F, Li J.-S, Li S, Ma J.-A. Adv. Synth. Catal. 2019; 361: 4222
- 11a Munoz SB, Krishnamurti V, Barrio P, Mathew T, Prakash GK. S. Org. Lett. 2018; 20: 1042
- 11b Barrio P, Ibáñez I, Herrera L, Román R, Catalán S, Fustero S. Chem. Eur. J. 2015; 21: 11579
- 12a Xu F, Huang D, Han C, Shen W, Lin X, Wang Y. J. Org. Chem. 2010; 75: 8677
- 12b Xu F, Huang D, Lin X, Wang Y. Org. Biomol. Chem. 2012; 10: 4467
- 12c Huang D, Xu F, Lin X, Wang Y. Chem. Eur. J. 2012; 18: 3148
- 12d Li X, Zhao Y, Qu H, Mao Z, Lin X. Chem. Commun. 2013; 49: 1401
- 12e Huang D, Li X, Xu F, Li L, Lin X. ACS Catal. 2013; 3: 2244
- 12f Shen X, Wang Y, Wu T, Mao Z, Lin X. Chem. Eur. J. 2015; 21: 9039
- 12g Lou H, Wang Y, Jin E, Lin X. J. Org. Chem. 2016; 81: 2019
- 12h Xie E, Rahman A, Lin X. Org. Chem. Front. 2017; 4: 1407
- 12i Rahman A, Xie E, Lin X. Org. Biomol. Chem. 2018; 16: 1367
- 12j Wang L, Zhong J, Lin X. Angew. Chem. Int. Ed. 2019; 58: 15824
- 12k Luo J, Zhang T, Wang L, Liao G, Yao Q.-J, Wu Y.-J, Zhan B.-B, Lan Y, Lin X.-F, Shi B.-F. Angew. Chem. Int. Ed. 2019; 58: 6708
- 12l Zhan B.-B, Wang L, Luo J, Lin X.-F, Shi B.-F. Angew. Chem. Int. Ed. 2020; 59: 3568
- 12m Rahman A, Lin X. Org. Biomol. Chem. 2018; 16: 4753
- 13a Čorić I, Müller S, List B. J. Am. Chem. Soc. 2010; 132: 17370
- 13b Müller S, Webber MJ, List B. J. Am. Chem. Soc. 2011; 133: 18534
- 13c Xu B, Zhu S.-F, Xie X.-L, Shen J.-J, Zhou Q.-L. Angew. Chem. Int. Ed. 2011; 50: 11483
- 13d Chen Z.-L, Wang B.-L, Wang Z.-B, Zhu G.-Y, Sun J.-W. Angew. Chem. Int. Ed. 2013; 52: 2027
- 13e Wu J, Wang Y.-M, Drljevic A, Rauniyar V, Phipps RJ, Toste FD. Natl. Acad. Sci. U.S.A. 2013; 110: 13729
- 13f Wang S.-G, You S.-L. Angew. Chem. Int. Ed. 2014; 53: 2194
- 13g Zhang Y, Zhao J, Jiang F, Sun S, Shi F. Angew. Chem. Int. Ed. 2014; 53: 13912
- 13h Gobé V, Guinchard X. Chem. Eur. J. 2015; 21: 8511
- 13i Rong Z, Zhang Y, Chua RH. B, Pan H, Zhao Y. J. Am. Chem. Soc. 2015; 137: 4944
- 13j Rubush DM, Morges MA, Rose BJ, Thamm DH, Rovis T. J. Am. Chem. Soc. 2012; 134: 13554
- 13k Li S, Zhang J.-W, Li X.-L, Cheng D.-J, Tan B. J. Am. Chem. Soc. 2016; 138: 16561
- 13l Lin J, Dong X, Li T, Jiang N, Tan B, Liu X. J. Am. Chem. Soc. 2016; 138: 9357
- 13m Zhu G, Bao G, Li Y, Sun W, Li J, Hong L, Wang R. Angew. Chem. Int. Ed. 2017; 56: 5332
- 13n Lin J.-S, Wang F.-L, Dong X.-Y, He W.-W, Yuan Y, Chen S, Liu X.-Y. Nat. Commun. 2017; 8: 14841
- 13o Wang F.-L, Dong X.-Y, Lin J.-S, Zeng Y, Jiao G.-Y, Gu Q.-S, Guo X.-Q, Ma C.-L, Liu X.-Y. Chem. 2017; 3: 979
- 13p Zhang L, Zhang J, Ma J, Cheng D.-J, Tan B. J. Am. Chem. Soc. 2017; 139: 1714
- 13q Qian D, Chen M, Bissember AC, Sun J. Angew. Chem. Int. Ed. 2018; 57: 3763
- 13r Zhang J.-W, Xu J.-H, Cheng D.-J, Shi C, Liu X.-Y, Tan B. Nat. Chem. 2018; 10: 58
- 13s Li J.-T, Kong M, Qiao B.-K, Lee R, Zhao X.-W, Jiang Z.-Y. Nat. Commun. 2018; 9: 2445
- 13t Zhang J, Yu P.-Y, Li S.-Y, Sun H, Xiang S.-H, Wang J, Houk KN, Tan B. Science 2018; 361: eaas8707
- 13u Lin J.-S, Li T.-T, Liu J.-R, Jiao G.-Y, Gu Q.-S, Cheng J.-T, Guo Y.-L, Hong X, Liu X.-Y. J. Am. Chem. Soc. 2019; 141: 1074
- 14a Akiyama T, Itoh J, Yokota K, Fuchibe K. Angew. Chem. Int. Ed. 2004; 43: 1566
- 14b Uraguchi D, Terada M. J. Am. Chem. Soc. 2004; 126: 5356
- 14c Akiyama T, Itoh J, Fuchibe K. Adv. Synth. Catal. 2006; 348: 999
- 14d Akiyama T. Chem. Rev. 2007; 107: 5744
- 14e Terada M. Chem. Commun. 2008; 4097
- 14f Adair G, Mukherjee S, List B. Aldrichimica Acta 2008; 41: 31
- 14g You S.-L, Cai Q, Zeng M. Chem. Soc. Rev. 2009; 38: 2190
- 14h Terada M. Synthesis 2010; 1929
- 14i Rueping M, Kuenkel A, Atodiresei I. Chem. Soc. Rev. 2011; 40: 4539
- 14j Parmar D, Sugiono E, Raja S, Rueping M. Chem. Rev. 2014; 114: 9047
- 15 General Procedure for the Reaction of 3-Hydroxyisoindolin-1-ones 1 with Difluoroenoxysilanes 2 To a mixture of 3-hydroxyisoindolin-1-ones 1 (0.05 mmol) and catalyst (S)-4e (0.005 mmol, 10 mol%) in toluene (0.5 mL) was added difluoroenoxysilanes 2 (0.1 mmol, 2 equiv). After stirring at 0 °C for 48 h, the residue was then purified by flash column chromatography with ethyl acetate/petroleum ether (1:4, v/v) on silica gel to give the desired product 3. 3-(1,1-Difluoro-2-oxo-2-phenylethyl)-3-phenylisoindolin-1-one (3a) White solid; mp 167–169 °C; 87% yield; 92% ee, determined by HPLC (Daicel Chiralcel OD-H column (250 × 4.6 mm), n-hexane/i-PrOH = 80:20, 0.8 mL/min, 254 nm; t major = 8.176 min, t minor = 7.063 min); [α]D 20 +143.2 (c 0.34, CH2Cl2). 1H NMR (400 MHz, DMSO-d 6): δ = 10.03 (s, 1 H), 8.02 (d, J = 7.6 Hz, 1 H), 7.87–7.78 (m, 4 H), 7.71–7.39 (m, 9 H). 13C NMR (100 MHz, DMSO-d 6): δ = 188.19 (dd, J = 30.8, 27.6 Hz), 168.95, 143.52 (d, J = 3.8 Hz), 135.59, 134.49, 132.64, 132.37, 131.53, 129.67, 128.74, 128.56, 127.01, 125.69, 123.17, 120.12, 117.46, 114.84, 68.39 (t, J = 25.8 Hz). 19F NMR (376 MHz, DMSO-d 6): δ = –99.44 (d, J = 268.9 Hz, 1 F), –102.12 (d, J = 268.9 Hz, 1 F). IR (film): ν = 3432, 3054, 2970, 1701, 1266, 739, 704 cm–1. HRMS (EI-TOF): m/z calcd for C22H15F2NO2: 363.1071; found: 363.1071.
- 16 Procedure for the 2 mmol Scale Reaction To a mixture of 3-hydroxyisoindolin-1-one 1a (450 mg, 2.0 mmol) and catalyst (S)-4e (0.2 mmol, 10 mol%) in toluene (40 mL) was added difluoroenoxysilane 2e (1.22 g, 4.0 mmol, 2 equiv). After stirring at 0 °C for 72 h, the solvent was removed under vacuo. The residue was then purified by flash column chromatography with ethyl acetate/petroleum ether (1:4, v/v) on silica gel to give the desired product 3q in 62% yield with 90% ee. Recovery of catalyst 4e was achieved after acidification of the relevant fractions as described previously (122 mg, 92%).
- 17 Procedure for the Synthetic Transformation of 3j To a solution of 3j (0.15 mmol, 95% ee) in THF (2.0 mL) was added NaOH (0.3 mmol, 2.0 equiv) at room temperature. The mixture was stirred until full consumption of 3j for 7 h, and then quenched by water, followed by extraction using DCM, and then dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (eluting with ethyl acetate/petrolem ether, 1:2) to afford 6 as white solid. 3-(Difluoromethyl)-3-(m-tolyl)isoindolin-1-one (6) White solid; mp 165–168 °C; 99% yield; 95% ee, determined by HPLC (Daicel Chiralcel AD-H column (250 × 4.6 mm), n-hexane/i-PrOH = 70:30, 0.8 mL/min, 254 nm; t major = 10.131 min, t minor = 6.871 min); [α]D 20 +156.2 (c 0.46, CH2Cl2). 1H NMR (400 MHz, DMSO-d 6): δ = 9.69 (s, 1 H), 7.76 (dd, J = 16.8, 7.5 Hz, 2 H), 7.66 (t, J = 7.4 Hz, 1 H), 7.57 (t, J = 7.3 Hz, 1 H), 7.48 (s, 2 H), 7.32 (t, J = 7.9 Hz, 1 H), 7.19 (d, J = 7.3 Hz, 1 H), 6.96 (t, J = 54.4 Hz, 1 H), 2.32 (s, 3 H). 13C NMR (100 MHz, DMSO-d 6): δ = 169.37, 144.38, 138.05, 136.41, 132.30, 131.63, 129.42, 129.01, 128.68, 126.58, 123.97, 123.28 (d, J = 8.7 Hz), 117.81, 115.36, 112.91, 67.54, 21.11. 19F NMR (376 MHz, DMSO-d 6): δ = –125.16 (d, J = 273.4 Hz, 1 F), –127.96 (d, J = 273.4 Hz, 1 F). IR (film): ν = 3427, 3199, 3054, 2986, 1707, 1265, 1075, 741, 705 cm–1. HRMS (EI-TOF): m/z calcd for C16H13F2NO 273.0965; found: 273.0966. Procedure for the Synthetic Transformation of 3q A solution of benzyl bromide (0.24 mmol) in DMF (2.0 mL) was cooled to 0 °C. The mixture was charged with portion wise addition of NaH (0.24 mmol) at the same temperature. To the reaction mixture was then slowly added a cooled (0 °C) solution of 3q (0.2 mmol) in DMF (2.0 mL). Reaction mixture was allowed to stir for 3 h at room temperature. Upon completion of the reaction, the mixture was quenched with saturated aqueous NH4Cl solution, and the solvent was removed in vacuo. The resulting aqueous solution was extracted with DCM, and then dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (eluting with ethyl acetate/petrolem ether, 1:50) to afford 7 as colorless oil. 2-Benzyl-3-[2-(4-bromophenyl)-1,1-difluoro-2-oxoethyl]-3-phenylisoindolin-1-one (7) Colorless oil; 88% yield; 94% ee, determined by HPLC (Daicel Chiralcel OD-H column (250 × 4.6 mm), n-hexane/i-PrOH = 99:1, 0.8 mL/min, 254 nm; t major = 8.990 min, t minor = 10.179 min); [α]D 20 +73.0 (c 0.33, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 8.07 (d, J = 7.7 Hz, 1 H), 7.97 (d, J = 7.8 Hz, 2 H), 7.92–7.82 (m, 2 H), 7.60–7.39 (m, 5 H), 7.38–7.26 (m, 8 H), 5.38 (d, J = 12.2 Hz, 1 H), 5.13 (d, J = 12.2 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 172.05, 151.94, 149.30, 137.34, 135.83, 134.27, 131.61, 130.93, 130.24, 129.88, 129.76, 129.61, 129.47, 129.40, 126.95, 122.55, 71.68. 19F NMR (376 MHz, CDCl3): δ = –101.67, –102.34, –103.19, –103.85. IR (film): ν = 3054, 2985, 1695, 1624, 1575, 1351, 1265, 739, 704, 440 cm–1. HRMS (EI-TOF): m/z calcd for C29H20BrF2NO2: 531.0645; found: 531.0641.
- 18a Ge S.-Z, Chaładaj W, Hartwig JF. J. Am. Chem. Soc. 2014; 136: 4149
- 18b Wu Y.-B, Lu G.-P, Zhou B.-J, Bu M.-J, Wan L, Cai C. Chem. Commun. 2016; 52: 5965
- 19 Banik SM, Medley JW, Jacobsen EN. Science 2016; 353: 51
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