Enantioselective Cyclopropanation with α-Alkyl-α-diazoesters Catalyzed by Chiral Oxazaborolidinium Ion: Total Synthesis of (+)-Hamavellone B

Abstract

Chiral oxazaborolidinium ion-catalyzed asymmetric cyclopropanation of α- or α,β-substituted acroleins with α-alkyl-α-diazoesters has been developed. With this methodology, chiral functionalized cyclopropanes containing a quaternary stereogenic center were obtained with high to excellent enantioselectivities (up to >99% ee). The synthetic utility of optically enriched functionalized cyclopropane was demonstrated in the first total synthesis of (+)-hamavellone B, which establishes the absolute configuration of natural (+)-hamavellone B.

Catalytic Strategies for the Asymmetric Construction of Cyclic Frameworks with a Halogenated Tetrasubstituted Stereocenter

“…The desired products 59 can be obtained in moderate to good yield with excellent enantio‐ and diastereoselectivity (>20 : 1 dr, 91%–99% ee) through the Michael‐initiated ring‐closure cyclopropanation (Scheme ). The synthetic utility of the obtained enantioenriched functionalized cyclopropane was demonstrated in the first total synthesis of (+)‐hamavellone B …”

Asymmetric Synthesis of Enantioenriched 2‐Aryl‐2,3‐Dihydrobenzofurans by a Lewis Acid Catalyzed Cyclopropanation/Intramolecular Rearrangement Sequence

“…Recently, our group reported the catalytic asymmetric synthesis of cyclopropane through a Michael‐initiated ring‐closure reaction . Furthermore, we developed additional rearrangement reactions from in situ generated cyclopropanes to synthesize 2,5‐dihydrooxepin and cyclobutanone in the presence of a chiral oxazaborolidinium ion (COBI) as a Lewis acid catalyst.…”

Catalytic Enantioselective Synthesis of 2,5‐Dihydrooxepines

“…Among the α‐halogen‐substituted compounds, α‐bromoacrolein was the best substrate, providing 2,5‐dihydrooxepine 2 a in 82 % yield with 96 % ee (Table , entries 1–4). Asymmetric 2,5‐dihydrooxepine formation with alkyl or phenyl groups also proceeded with good enantiocontrol, although the yields were not as high (entries 5–8) . Interestingly, some α‐alkylacroleins required higher temperature for the retro‐Claisen rearrangement of the cis ‐FVC 1 to the 2,5‐dihydrooxepine 2 (entries 5–6).…”