Asymmetric intramolecular alpha-cyclopropanation of aldehydes using a donor/acceptor carbene mimetic

作者：Luo, Chaosheng; Wang, Zhen; Huang, Yong^*

来源：Nature Communications, 2015, 6(1): 10041.

DOI：10.1038/ncomms10041

• CATALYTIC ENANTIOSELECTIVE SYNTHESIS
• ALPHA,BETA-UNSATURATED ALDEHYDES
• ALKYLATION REACTIONS
• MICHAEL ADDITION
• KETONES
• FLUORINATION
• CHLORINATION
• CASCADE
• ACCESS
• ENYNES

Enantioselective alpha-alkylation of carbonyl is considered as one of the most important processes for asymmetric synthesis. Common alkylation agents, that is, alkyl halides, are notorious substrates for both Lewis acids and organocatalysts. Recently, olefins emerged as a benign alkylating species via photo/radical mechanisms. However, examples of enantioselective alkylation of aldehydes/ketones are scarce and direct asymmetric dialkylation remains elusive. Here we report an intramolecular alpha-cyclopropanation reaction of olefinic aldehydes to form chiral cyclopropane aldehydes. We demonstrate that an alpha-iodo aldehyde can function as a donor/acceptor carbene equivalent, which engages in a formal [2 + 1] annulation with a tethered double bond. Privileged bicyclo[3.1.0]hexane-type scaffolds are prepared in good optical purity using a chiral amine. The synthetic utility of the products is demonstrated by versatile transformations of the bridgehead formyl functionality. We expect the concept of using alpha-iodo iminium as a donor/acceptor carbene surrogate will find wide applications in chemical reaction development.

• 出版日期2015-12
• 单位北京大学深圳研究生院