Cross Couplings of Cinnamates to Benzo‐Fused Oxanorbornadienes

• Published in: Asian journal of organic chemistry 2023-08, Vol.12 (8), p.n/a
• Main Authors: Cheng, Chung‐Hsuan, Hsueh, Han‐Hsuan, Jian, Shi‐Jie, Chen, Chien‐Tien
• Format: Article
• Language: English
• Subjects: 7-oxa-norbornene; [3+2] cyclization; Additives; Asymmetry; Carbonyls; Catalysis; Charcoal; Couplings; exo-specific; fused indanes; Optical activity; Organic chemistry; Palladium; Pd-catalyzed; Substitutes
• ISSN: 2193-5807; 2193-5815
• DOI: 10.1002/ajoc.202300255

Potential exo‐specific [3+2] cascade cyclizations between o‐Br‐substituted cinnamates (CM−Br) and benzo‐fused 7‐oxa‐norbornadiene (Bz‐OND) by Pd‐mediated catalysis were explored both in racemic and asymmetric methods. A systematic study on Pd(II) catalysts, silane additives, carbonate bases, solvents, chiral diphosphines within a reaction temperature range of 60–80 °C were carried out. The best combination was between methyl o‐Br‐cinnamate and Bz‐OND catalyzed by Pd(OAc)2/dppf and /DM‐BINAP, respectively, in CH3CN at 80 °C. The desired racemic and optically active Bz‐OND‐fused indanes bearing 1‐carbonylmethylidene (CBM) unit were thus afforded in 95 % and 71 % yields and with enantioselectivities of up to 43 % ee. The optimal asymmetric recipe can be applied to alkyl, aryl cinnamates, 4‐substituted, and 5‐substituted o‐bromo‐cinnamates. Exclusive hydrogenations from the exo‐face of the CBM alkene units can be readily done by Pd(0)/charcoal in EtOAc, affording the product complementary to the direct Rh(I)‐catalyzed cyclization. A systematic study of phosphine ligands, solvents, o‐bromo‐cinnamate esters was carried out for the [3+2] cyclization with benzo‐fused 7‐oxa‐norbornadiene (Bz‐OND). The best scenario involved the use of Pd(OAc)2 and dppf or DM‐BINAP ligand, leading to highly Z‐selective synthesis of indane‐fused Bz‐OND with (RO2C)methylidene units. The target products were furnished with ee of up to 43 %.