Palladium-Catalyzed Double Carbopalladation/syn-Insertion Cascade toward a Pragmatic Synthesis of Aminated Polyheterocyclic 1,2-Benzothiazepine 1-Oxides

Abstract

A palladium-catalyzed tandem cyclization reaction was developed, which offers a pragmatic synthesis of aminated tetracyclic 1,2-benzothiazepine 1-oxides bearing a highly fused medium-sized cyclic unit. An acetyl (Ac) group was found to be the optimal protecting group for sulfoximines to reduce the nucleophilic ability of the N atom, thus efficiently suppressing the formation of intramolecular 5-exo-dig cyclization side products. The transformation proceeds through a double syn-carbopalladation/annulation sequence to construct the rigid tetracyclic carbo-heterocyclic framework with excellent chemoselectivity and regioselectivity.

Key words

palladium catalysis - carbopalladation - cascade reaction - polyheterocycles - 1,2-benzothiazepine 1-oxides - sulfoximines

• References

• 1 Bentley HR, McDermott EE, Pace J, Whitehead JK, Moran T. Nature 1950; 165: 150
• 2a Patrick M, Lars K. J. Med. Chem. 2020; 63: 14243
• 2b Mendonca MP, Robert AS. Org. Biomol. Chem. 2020; 18: 6429
• 2c Ghosh P, Ganguly B, Das S. Asian J. Org. Chem. 2020; 9: 2035
• 2d Han Y, Xing K, Zhang J, Tong T, Shi Y, Cao H, Yu H, Zhang Y, Liu D, Zhao L. Eur. J. Med. Chem. 2021; 209: 112885
• 3a Ghosh K, Rit R.-K, Ramesh E, Sahoo A. Angew. Chem. Int. Ed. 2016; 55: 7821
• 3b Mukherjee K, Grimblat N, Sau S, Ghosh K, Shankar M, Gandon V, Sahoo AK. Chem. Sci. 2021; 12: 14863
• 3c Cheng Y, Dong W, Parthasarathy K, Bolm C. Org. Lett. 2017; 19: 726
• 3d Sun Y, Cramer N. Angew. Chem. Int. Ed. 2018; 57: 15539
• 3e Rit R, Yadav M, Ghosh K, Shankar M, Sahoo A. Org. Lett. 2014; 16: 5258
• 4a Zhou T, Qian P, Li J, Zhou Y, Li H, Chen H, Shi B. J. Am. Chem. Soc. 2021; 143: 6810
• 4b Brauns M, Cramer N. Angew. Chem. Int. Ed. 2019; 58: 8902
• 4c Mi R, Chen H, Zhou X, Li N, Ji D, Wang F, Lan Y, Li X. Angew. Chem. Int. Ed. 2022; 61: e202111860
• 4d Langner M, Bolm C. Angew. Chem. Int. Ed. 2004; 43: 5984
• 4e Shen X, Zhang W, Ni C, Gu Y, Hu J. J. Am. Chem. Soc. 2012; 134: 16999
• 5a Shen X, Miao W, Ni C, Hu J. Angew. Chem. Int. Ed. 2014; 53: 775
• 5b Bolm C, Simic O. J. Am. Chem. Soc. 2001; 123: 3830
• 5c Frings M, Goedert D, Bolm C. Chem. Commun. 2010; 46: 5497
• 5d Koep S, Gais H.-J, Raabe G. J. Am. Chem. Soc. 2003; 125: 13243
• 6 Albrecht W, Laufer S, Selig R, Kloevekorn P, Praefke B. WO2020016243A1, 2020
• 7 Dillard R, Yen T, Stark P, Pavey D. J. Med. Chem. 1980; 23: 717
• 8 Artoszyk G, Dooley D, Barth H, Hartenstein J, Satzinger G. J. Pharm. Pharmacol. 1987; 39: 407

For selected examples, see:
• 9a Ma Y, Guo C, Zhao Q, Zhang J, Chen X. Green Chem. 2018; 20: 2953
• 9b Li S, Shan S, Liu L, Wang R, Yang Y, Li J, Wei J. Org. Lett. 2020; 22: 7470
• 9c Wu C, Huang R, Zhang M, Chen Z. J. Org. Chem. 2020; 85: 841
• 9d Li L, Li Y, Zhao Z, Luo H, Ma Y. Org. Lett. 2019; 21: 5995
• 9e Kong X, Lin X, Chen L, Chen Y, Wang W, Xu B. ChemSusChem 2021; 14: 3277
• 9f Nie R, Lai R, Lv S, Xu Y, Guo L, Wang Q, Wu Y. Chem. Commun. 2019; 55: 11418
• 9g Bachon A, Hermann A, Bolm C. Chem. Eur. J. 2019; 25: 5889
• 9h Yu H, Li Z, Bolm C. Angew. Chem. Int. Ed. 2018; 57: 12053
• 9i Huang J, Huang Y, Wang T, Huang Q, Wang Z, Chen Z. Org. Lett. 2017; 19: 1128
• 9j Xie H, Lan J, Gui J, Chen F, Jiang H, Zeng W. Adv. Synth. Catal. 2018; 360: 3534
• 9k Wang Z, Wei L, Cheng Z, Xia J, Chen Z. Chin. Chem. Lett. 2021; 32: 2756
• 9l Wen J, Tiwari DP, Bolm C. Org. Lett. 2017; 19: 1706
• 9m Cheng Y, Bolm C. Angew. Chem. Int. Ed. 2015; 54: 12349
• 9n He F, Xie S, Yao Y, Wu J. Chin. Chem. Lett. 2020; 31: 3065
• 9o Dong WR, Wang L, Parthasarathy K, Pan FF, Bolm C. Angew. Chem. Int. Ed. 2013; 52: 11573
• 10 Shi P, Tu Y, Wang C, Kong D, Ma D, Bolm C. Org. Lett. 2020; 22: 8842
• 11 Wen J, Cheng H, Raabe G, Bolm C. Org. Lett. 2017; 19: 6020
• 12a Aher Y, Lade D, Pawar A. Chem. Commun. 2018; 54: 6288
• 12b Li J, Li H, Fang D, Liu L, Han X, Sun J, Li C, Zhou Y, Ye D, Liu H. J. Org. Chem. 2021; 86: 15217
• 12c Huang G, Shan Y, Yu J, Pan C. Org. Biomol. Chem. 2021; 19: 10085
• 12d Huang J, Liu F, Du F, Zeng L, Chen Z. Green Synth. Catal. 2022; in press
• 13 Dai L, Yuan J, Wu C, Chen Z. Chem. Commun. 2021; 57: 4271
• 14a Zhou H, Chen W, Chen Z. Org. Lett. 2018; 20: 2590
• 14b Chen X, Zhou H, Chen Z. Org. Chem. Front. 2019; 6: 3415
• 15a Figueiredo R, Suppo J, Campagne J. Chem. Rev. 2016; 116: 12029
• 15b Shi Q, Liao Z, Liu Z, Wen J, Li C, He J, Deng J, Cen S, Cao T, Zhou J, Zhu S. Nat. Commun. 2022; 13: 4402
• 15c Chen L, Chen K, Zhu S. Chem 2018; 4: 1208
• 16a Wan Y, Fang G, Chen H, Deng X, Tang Z. Eur. J. Med. Chem. 2021; 226: 113837
• 16b Xiong Y, Du F, Zeng L, Chen Z. Chin. Chem. Lett. 2023; 34: 107569

For selected reviews, see:
• 17a Hu Y, Zhao Y, Wan B, Chen Q. Chem. Soc. Rev. 2021; 50: 2582
• 17b Luo J, Chen G, Chen S, Yu J, Li Z, Liu Y. ACS Catal. 2020; 10: 13978
• 17c Chen Y, Qian P, Ye L. Chem. Soc. Rev. 2020; 49: 8897
• 17d Lynch C, Sripada A, Wolf C. Chem. Soc. Rev. 2020; 49: 8543
• 17e Hong F, Ye L. Acc. Chem. Res. 2020; 53: 2003
• 17f Wang X, Yeom H, Fang L, He S, Ma Z, Kedrowski BL, Hsung RP. Acc. Chem. Res. 2014; 47: 560
• 18 Yao B, Wang Q, Zhu J. Angew. Chem. Int. Ed. 2013; 52: 12992
• 19 CCDC 2180915 (3a) 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/structures
• 20a Harmata M, Rayanil K, Gomes MG, Zheng P, Calkins NL, Kim S, Fan Y, Bumbu V, Lee DR, Wacharasindhu S, Hong X. Org. Lett. 2005; 7: 143
• 20b Barthelemy A, Anselmi E, Le T, Vo-Thanh G, Guillot R, Miqueu K, Magnier E. J. Org. Chem. 2019; 84: 4086
• 21a Wang H, Luo Y, Zhu B, Wu J. Chem. Commun. 2012; 48: 5581
• 21b Luo Y, Wu J. Chem. Commun. 2011; 47: 11137