Synthesis of Benzo-Fused Cycloheptanones from Cyclobutanol Derivatives by a C–C Cleavage/Cross-Coupling/Enolate Arylation Sequence

Abstract

Herein, we describe a convergent method for the synthesis of benzo-fused cycloheptanones from cyclobutanol derivatives and 1,2-dihaloarene electrophiles. The inherent ring strain of the cyclobutanol coupling partner is leveraged to drive a Pd-catalyzed C–C cleavage/cross-coupling. A subsequent intramolecular enolate arylation results in the formation of the benzo-fused seven-membered carbocycle in a one-pot sequence. A range of electronically diverse 1,2-dihaloarene electrophiles as well as various substituted cyclobutanols were investigated as cross-coupling partners.

Key words

C–C cleavage - Pd-catalyzed cross-coupling - benzocycloheptanones - cyclobutanols - 1,2-dihaloarenes - one-pot synthesis

• References

• 1 Battaglia R, De Bernardi M, Mellerio GF. G, Vidari G, Vita-Finsi P. J. Nat. Prod. 1980; 43: 319
• 2 Simmons EM, Sarpong R. Nat. Prod. Rep. 2009; 26: 1195
• 3 Jin P, Zheng G, Yuan X, Ma X, Feng Y, Yao G. Bioorg. Chem. 2021; 111: 104870
• 4 Fan Y.-Y, Zhang X.-R, Zheng C.-Y, Li Y, Yue J.-M. Tetrahedron 2024; 152: 133841
• 5 Kagan HB, Riant O. Chem. Rev. 1992; 92: 1007
• 6 Morgan TD. R, LeBlanc LM, Ardagh GH, Boyd RJ, Burnell DJ. J. Org. Chem. 2015; 80: 1042
• 7 Li H, Wu J. Synthesis 2015; 47: 22
• 8 Geis O, Schmalz H.-G. Angew. Chem. Int. Ed. 1998; 37: 911
• 9 Reisman SE, Nani RR, Levin S. Synlett 2011; 2437
• 10 Hudlicky T, Fan R, Reed JW, Gadamasetti KG. Org. React. 1992; 41: 1
• 11 Smith PA. S, Baer DR. Org. React. 1960; 11: 157
• 12 Pellissier H. Adv. Synth. Catal. 2018; 360: 1551
• 13 Yin Z, He Y, Chiu P. Chem. Soc. Rev. 2018; 47: 8881
• 14 Zhang R, Xia Y, Dong G. Angew. Chem. Int. Ed. 2021; 60: 20476
• 15 Paulisch TO, Mai LA, Strieth-Kalthoff F, James MJ, Henkel C, Guldi DM, Glorius F. Angew. Chem. Int. Ed. 2022; 61: e202112695
• 16 Xing Z, Fang B, Luo S, Xie X, Wang X. Org. Lett. 2022; 24: 4034
• 17 Jain R, Sponsler MB, Coms FD, Dougherty DA. J. Am. Chem. Soc. 1988; 110: 1356
• 18 Shi Z, Lu L, Lu P. Org. Lett. 2024; 26: 5353
• 19 Bhosale VA, Nigríni M, Dračínský M, Císařová I, Veselý J. Org. Lett. 2021; 23: 9376
• 20 Sietmann J, Tenberge M, Wahl JM. Angew. Chem. Int. Ed. 2023; 62: e202215381
• 21 Andersh B, Murphy DL, Olson RJ. Synth. Commun. 2000; 30: 2091
• 22 Kogashi K, Matsuno T, Sato S, Isobe H. Angew. Chem. Int. Ed. 2019; 58: 7385
• 23 Sanz R, Castroviejo MP, Fernández Y, Fañanás FJ. J. Org. Chem. 2005; 70: 6548
• 24 Menzel K, Dimichele L, Mills P, Frantz DE, Nelson TD, Kress MH. Synlett 2006; 1948
• 25 Li C.-M, Geng H.-C, Li M.-M, Xu G, Ling T.-J, Qin H.-B. Nat. Prod. Bioprospect. 2013; 3: 117
• 26 Chen T, Peng R, Hu W, Zhang F.-M. Org. Biomol. Chem. 2016; 14: 9859