A Vinyl Cyclopropane Ring Expansion and Iridium‐Catalyzed Hydrogen Borrowing Cascade

• Published in: Angewandte Chemie International Edition 2020-07, Vol.59 (28), p.11339-11344
• Main Authors: Wübbolt, Simon, Cheong, Choon Boon, Frost, James R., Christensen, Kirsten E., Donohoe, Timothy J.
• Format: Article
• Language: English
• Subjects: Alcohols; Aldehydes; catalysis; Communication; Communications; cyclopentane; Cyclopropane; Electron transfer; hydrogen borrowing; Iridium; Ketones; Organic compounds; Oxidation; rearrangement; Single electrons; Stereoselectivity; Substitutes
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202003614

A vinyl cyclopropane rearrangement embedded in an iridium‐catalyzed hydrogen borrowing reaction enabled the formation of substituted stereo‐defined cyclopentanes from Ph* methyl ketone and cyclopropyl alcohols. Mechanistic studies provide evidence for the ring‐expansion reaction being the result of a cascade based on oxidation of the cyclopropyl alcohols, followed by aldol condensation with the pentamethyl phenyl‐substituted ketone to form an enone containing the vinyl cyclopropane. Subsequent single electron transfer (SET) to this system initiates a rearrangement, and the catalytic cycle is completed by reduction of the new enone. This process allows for the efficient formation of diversely substituted cyclopentanes as well as the construction of complex bicyclic carbon skeletons containing up to four contiguous stereocentres, all with high diastereoselectivity. A vinyl cyclopropane/cyclopentene rearrangement process has been embedded in an iridium‐catalyzed hydrogen borrowing reaction, enabling the formation of substituted, stereo‐defined cyclopentanes containing up to four contiguous stereogenic centres—all from reaction of pentamethylphenyl (Ph*) methylketone and a variety of cyclopropyl alcohols.