Asymmetric Synthesis of 3,3-Disubstituted Isoindolinones Enabled by Organocatalytic Functionalization of Tertiary Alcohols

Abstract

An enantioselective intramolecular heterocyclization with in situ generated 3-hydroxyisoindolinone-derived N-acyliminium ions has been successfully accomplished. In the presence of a catalytic amount of a chiral phosphoric acid, functionalized 3,3-disubstituted isoindolinones bearing N-acyl-N,O-acetal moieties were obtained with good yields and a high level of stereocontrol (up to 98:2 er). This efficient method proceeds under mild conditions and exhibits broad scope with respect to both 3-hydroxyisoindolinones and hydroxyl partners.

Key words

N-acyliminium ion - chiral phosphoric acid - 3,3-disubstituted isoindolinones - N-acyl-N,O-acetal - enantioselective

• References

• 1a Gentry PR, Kokubo M, Bridges TM, Kett NR, Harp JM, Cho HP, Smith E, Chase P, Hodder PS, Niswender CM, Daniels JS, Conn PJ, Wood MR, Lindsley CW. J. Med. Chem. 2013; 56: 9351
• 1b Hardcastle IR, Liu J, Valeur E, Watson A, Ahmed SU, Blackburn TJ, Bennaceur K, Clegg W, Drummond C, Endicott JA, Golding BT, Griffin RJ, Gruber J, Haggerty K, Harrington RW, Hutton C, Kemp S, Lu X, McDonnell JM, Newell DR, Noble ME, Payne SL, Revill CH, Riedinger C, Xu Q, Lunec J. J. Med. Chem. 2011; 54: 1233

For selected reviews, see:
• 2a Awasthi A, Singh M, Rathee G, Chandra R. RSC Adv. 2020; 10: 12626
• 2b Chen L, Zou YX. Adv. Synth. Catal. 2021; 363: 4159
• 2c Gao W, Chen MW, Ding Q, Peng Y. Chem. Asian J. 2019; 14: 1306
• 2d Topolovčan N, Gredičak M. Org. Biomol. Chem. 2021; 19: 4637
• 2e Basson AJ, McLaughlin MG. Tetrahedron 2022; 114: 132764
• 2f Wu P, Nielsen TE. Chem. Rev. 2017; 117: 7811
• 3a Yu X, Lu A, Wang Y, Wu G, Song H, Zhou Z, Tang C. Eur. J. Org. Chem. 2011; 2011: 892
• 3b Rong MY, Li JS, Zhou Y, Zhang FG, Ma JA. Org. Lett. 2020; 22: 9010
• 3c Fang K, Huang W, Shan C, Qu J, Chen Y. Org. Lett. 2021; 23: 5523
• 3d Peter C, Geoffroy P, Miesch M. Org. Chem. Front. 2018; 5: 566
• 3e Unhale RA, Sadhu MM, Ray SK, Biswas RG, Singh VK. Chem. Commun. 2018; 54: 3516
• 3f Fang F, Hua G, Shi F, Li P. Org. Biomol. Chem. 2015; 13: 4395
• 3g Aranzamendi E, Sotomayor N, Lete E. J. Org. Chem. 2012; 77: 2986
• 3h Feng F, Li J, Li S, Ma J. Adv. Synth. Catal. 2019; 361: 4222
• 3i Yu X, Wang Y, Wu G, Song H, Zhou Z, Tang C. Eur. J. Org. Chem. 2011; 2011: 3060
• 3j Zhang H, Wang Y, Xie Y, Zhu Z, Shi F, Tu S. J. Org. Chem. 2014; 79: 7141
• 3k Glavač D, Zheng C, Dokli I, You S, Gredičak M. J. Org. Chem. 2017; 82: 8752
• 4a Zhang L, Wu B, Chen Z, Hu J, Zeng X, Zhong G. Chem. Commun. 2018; 54: 9230
• 4b Unhale RA, Sadhu MM, Singh VK. Org. Lett. 2022; 24: 3319
• 4c He Y, Cheng C, Chen B, Duan K, Zhuang Y, Yuan B, Zhang M, Zhou Y, Zhou Z, Su Y, Cao R, Qiu L. Org. Lett. 2014; 16: 6366
• 5a Suc J, Dokli I, Gredicak M. Chem. Commun. 2016; 52: 2071
• 5b Rajshekhar AU, Nagaraju M, Nirmal KR, Sivasankaran D, Subhrajyoti B, Vinod KS. Tetrahedron Lett. 2017; 58: 145
• 5c Eitzinger A, Otevrel J, Haider V, Macchia A, Massa A, Faust K, Spingler B, Berkessel A, Waser M. Adv. Synth. Catal. 2021; 363: 1955
• 6 Suneja A, Unhale RA, Singh VK. Org. Lett. 2017; 19: 476
• 7 Sikoraiová J, Marchalín Š, Daïch A, Decroix B. Tetrahedron Lett. 2002; 43: 4747
• 8a Romo D, Meyers AI. Tetrahedron Lett. 1991; 47: 9503
• 8b Groaning MD, Meyers AI. Tetrahedron Lett. 2000; 56: 9843
• 9 For review on the progress towards the synthesis of N-acyl-N,O-acetals, see: Ma, X.; Shao, F.; Hu, X.; Liu, X. Synthesis 2022, 54 1203; and references therein.
• 10a Wang H, Kowalski MD, Lakdawala AS, Vogt FG, Wu L. Org. Lett. 2015; 17: 564
• 10b Ziegler RE, Desai BK, Jee JA, Gupton BF, Roper TD, Jamison TF. Angew. Chem. Int. Ed. 2018; 57: 7181
• 11 Li H, Belyk KM, Yin J, Chen Q, Hyde A, Ji Y, Oliver S, Tudge MT, Campeau L.-C, Campos KR. J. Am. Chem. Soc. 2015; 137: 13728
• 12a Jing K, Wang XN, Wang GW. J. Org. Chem. 2019; 84: 161
• 12b Romo D, Romine JL, Midura W, Meyers AI. Tetrahedron Lett. 1990; 46: 4951
• 12c Allin SM, Northfield CJ, Page MI, Slawin AM. Z. Tetrahedron Lett. 1997; 38: 3627
• 13a Allin SM, James SL, Martin WP, Smith TA. D. Tetrahedron Lett. 2001; 42: 3943
• 13b Olsen DK, Torian BE, Morgan CD, Braun LL. J. Org. Chem. 1980; 45: 4049
• 14a Kim H, Lim W, Im D, Kim DG, Rhee YH. Angew. Chem. Int. Ed. 2012; 51: 12055
• 14b Nguyen NH, Nguyen QH, Biswas S, Patil DV, Shin S. Org. Lett. 2019; 21: 9009
• 14c Vellalath S, Coric I, List B. Angew. Chem. Int. Ed. 2010; 49: 9749
• 15a Maryanoff BE, Zhang H.-C, Cohen JH, Turchi IJ, Maryanoff CA. Chem. Rev. 2004; 104: 1431
• 15b Lanke V, Marek I. Chem. Sci. 2020; 11: 9378
• 15c Gualandi A, Rodeghiero G, Cozzi PG. Asian J. Org. Chem. 2018; 7: 1957
• 16a Pan Y, Jiang Q, Rajkumar S, Zhu C, Xie J, Yu S, Chen Y, He Y.-P, Yang X. Adv. Synth. Catal. 2021; 363: 200
• 16b Chen L, Yin X.-P, Wang C.-H, Zhou J. Org. Biomol. Chem. 2014; 12: 6033
• 17 Zhang C, Gao Q, Li M, Wang J, Yu C, Mao B. Org. Lett. 2021; 23: 3949
• 18a Brak K, Jacobsen EN. Angew. Chem. Int. Ed. 2013; 52: 534
• 18b Phipps RJ, Hamilton GL, Toste FD. Nat. Chem. 2012; 4: 603
• 18c Lacour J, Moraleda D. Chem. Commun. 2009; 7073
• 19a Čorić I, List B. Nature 2012; 483: 315
• 19b Čorić I, Sreekumar V, List B. J. Am. Chem. Soc. 2010; 132: 8536
• 20 CCDC 2161973 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures