The construction of heterocyclic compounds from activated cyclopropane derivatives offers an alternative strategy for the preparation of molecules that may be of interest from a structural or biological standpoint. Several newly developed methods provide access to densely functionalized heterocycles in a manner that can be considered useful for both diversity- and target-oriented synthetic approaches. This tutorial review focuses on the latter, describing recent developments and applications of cyclopropane ring-expansion reactions in natural product synthesis.
The first total synthesis of the indole alkaloid mersicarpine is reported. Key steps include a beta-dicarbonyl radical cyclization, as well as an oxidation of the benzopyrrole moiety to establish the masked 1,2-dicarbonyl functionality. An X-ray crystal structure and discussion of the 1H NMR behavior of the natural product are also presented.
Three into one will go! A three‐component coupling of a hydroxylamine, an aldehyde, and a cyclopropane diester provides the tetrahydro‐1,2‐oxazine scaffold necessary for completion of the first total synthesis of the natural product phyllantidine.
A stereodivergent synthesis of the [3.3.1] bicyclic core of edaxadiene was completed utilizing a key intramolecular oxidative ketone allylation. Significant discrepancies between the spectroscopic data obtained for the synthetic construct and the natural isolate raised questions about the structural assignment of edaxadiene. A subsequent structural reassignment was validated by completion of a total synthesis of the correct structure of the natural product.
[Chemical reaction: see text] Aldimines, generated in situ by the reaction of primary amines or anilines with aldehydes, undergo smooth reaction with various 1,1-cyclopropanediesters in the presence of catalytic Yb(OTf)3. The products are pyrrolidines in which the major diastereomer bears a cis relationship between substituents at the 2- and 5-positions. In most cases the diastereoselectivity is greater than 10:1.
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