A Catalytic One-Pot Synthesis of Indolyl Cyclobutanones

Abstract

A general strategy for the synthesis of indolyl cyclobutanones via a tandem Brønsted acid catalyzed 2-hydroxycyclobutanone activation–indole nucleophilic addition has been exploited. The procedure leads to a wide range of 2- and 3-functionalized indole derivatives in good to high yields with broad substrate scope.

Key words

indoles - cyclobutanones - Brønsted acids - tandem reactions - catalysis

Publication History

Received: 14 September 2020

Accepted after revision: 30 October 2020

Article published online:
03 December 2020

• References

• 1a Gul W, Hamann MT. Life Sci. 2005; 78: 442
• 1b Klein-Júnior LC, Cretton S, Vander Heyden Y, Gasper AL, Nejad-Ebrahimi S, Christen P, Henriques AT. J. Nat. Prod. 2020; 83: 852
• 1c Tanifuji R, Minami A, Oguri H, Oikawa H. Nat. Prod. Rep. 2020; 37: 109
• 2a Humphrey GR, Kuethe JT. Chem. Rev. 2006; 106: 2875
• 2b Youn SW, Ko TY. Asian J. Org. Chem. 2018; 7: 1467
• 2c Kumar I, Kumar R, Sharma U. Synthesis 2018; 50: 2655
• 2d Santos Neto JS, Zeni G. Org. Chem. Front. 2020; 7: 155
• 3 Triggle DJ, Mitchell JM, Filler R. CNS Drug Rev. 1998; 4: 87
• 4 Zhu W, Bao X, Ren H, Da Y, Wu D, Li F, Yan Y, Wang L, Chen Z. Eur. J. Med. Chem. 2016; 115: 161
• 5 Anthes R, Benoit S, Chen C.-K, Corbett EA, Corbett RM, DelMonte AJ, Gingras S, Livingston RC, Pendri Y, Sausker J, Soumeillant M. Org. Process Res. Dev. 2008; 12: 178
• 6 Denya I, Malan SF, Enogieru AB, Omoruyi SI, Ekpo OE, Kapp E, Zindo FT, Joubert J. Med. Chem. Commun. 2018; 9: 357
• 7 Bogus SK, Kuzmin VS, Abramochkin DV, Suzdalev KF, Galenko-Yaroshevsky PA. J. Pharmacol. Sci. 2017; 133: 122
• 8 Fink SL, Vojtech L, Wagoner J, Slivinski NS. J, Jackson KJ, Wang R, Khadka S, Luthra P, Basler CF, Polyak SJ. Sci. Rep. 2018; 8: 8989
• 9a Papahatjis DP, Nikas S, Tsotinis A, Vlachou M, Makriyannis A. Chem. Lett. 2001; 192
• 9b Teng X, Degterev A, Jagtap P, Xing X, Choi C, Denu R, Yuan J, Cuny GD. Bioorg. Med. Chem. Lett. 2005; 15: 5039
• 9c Piccio P, Vonhoff S, Davidson K, Teh M.-T, Sugden D. J. Med. Chem. 2006; 49: 3509
• 10 Jandu KS, Barrett V, Brockwell M, Cambridge D, Farrant DR, Foster C, Giles H, Glen RC, Hill AP, Hobbs H, Honey A, Martin GR, Salmon J, Smith D, Woollard P, Selwood DL. J. Med. Chem. 2001; 44: 681
• 11 Bartolozzi A, Chen Z, Dines JA, Lo HY, Loke PL, Olague A, Riether D, Tye H, Wu L, Zindell RM. US20130196967A1, 2013
• 12 Zhang Y, Yu T, Liu B, Zhang X, Zhang S, Cheng C, Zhang J. WO2016037591A1, 2016
• 13 Goodacre SC, Labadie S, Li J, Liang J, Liao J, Ortwine DF, Ray NC, Wang X, Zbieg J, Zhang B. WO2017216279A1, 2017
• 14a Harmata M, Ying W, Hong X, Barnes CL. Synthesis 2008; 4: 594
• 14b Hu H, Wang Y, Qian D, Zhang Z.-M, Liu L, Zhang J. Org. Chem. Front. 2016; 3: 759
• 15 Turnu F, Luridiana A, Cocco A, Porcu S, Frongia A, Sarais G, Secci F. Org. Lett. 2019; 21: 7329
• 16a Martis A, Luridiana A, Frongia A, Arca M, Sarais G, Aitken DJ, Guillot R, Secci F. Org. Biomol. Chem. 2017; 15: 10053
• 16b Porcu S, Luridiana A, Martis A, Frongia A, Sarais G, Aitken DJ, Boddaert T, Guillot R, Secci F. Chem. Commun. 2018; 54: 13547
• 16c Porcu S, Demuro S, Luridiana A, Cocco A, Frongia A, Aitken DJ, Charnay-Pouget F, Guillot R, Sarais G, Secci F. Org. Lett. 2018; 20: 7699
• 16d Secci F, Porcu S, Luridiana A, Frongia A, Ricci PC. Org. Biomol. Chem. 2020; 18: 3684
• 17 N-Debenzylation of compound 4f was accomplished in a moderate yield (44%) by using NH₃/Li in THF at –78 °C, as reported in the Supporting Information.
• 18a Conia JM, Salaun J. Acc. Chem. Res. 1972; 5: 33
• 18b Barnier JP, Denis JM, Salaun J, Conia JM. Tetrahedron 1974; 30: 1397
• 18c Gembus V, Karmazin L, Pira S, Uguen D. Bull. Chem. Soc. Jpn. 2018; 91: 319
• 19 Brown HC, Morgan KJ, Chloupek FJ. J. Am. Chem. Soc. 1965; 87: 2137
• 20 Paquette LA, Hofferberth JE. Org. React. 2003; 62: 477