Lewis Acid Catalyzed Formal (3+2)‐Cycloaddition of Bicyclobutanes with Ketenes

Design, synthesis and application of benzene bioisosteres have attracted a lot of attention in the past 20 years. Recently, bicyclo[2.1.1]hexanes have emerged as highly attractive bioisosteres for ortho‐ and meta‐substituted benzenes. Herein we report a mild, scalable and transition‐metal‐free proto...

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Bibliographic Details
Published in:	Angewandte Chemie International Edition Vol. 62; no. 34
Main Authors:	Radhoff, Niklas, Daniliuc, Constantin G, Studer, Armido
Format:	Journal Article
Language:	English
Published:	Weinheim Wiley Subscription Services, Inc 01-08-2023
Edition:	International ed. in English
Subjects:	Benzene Butane Cycloaddition Functional groups Hexanes Ketenes Ketones Lewis acid Substitutes
Online Access:	Get full text
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Summary:	Design, synthesis and application of benzene bioisosteres have attracted a lot of attention in the past 20 years. Recently, bicyclo[2.1.1]hexanes have emerged as highly attractive bioisosteres for ortho‐ and meta‐substituted benzenes. Herein we report a mild, scalable and transition‐metal‐free protocol for the construction of highly substituted bicyclo[2.1.1]hexan‐2‐ones through Lewis acid catalyzed (3+2)‐cycloaddition of bicyclo[1.1.0]‐butane ketones with disubstituted ketenes. The reaction shows high functional group tolerance as documented by the successful preparation of various 3‐alkyl‐3‐aryl as well as 3,3‐bisalkyl bicyclo[2.1.1]hexan‐2‐ones (26 examples, up to 89 % yield). Postfunctionalization of the exocyclic ketone moiety is also demonstrated.
ISSN:	1433-7851 1521-3773
DOI:	10.1002/anie.202304771