A Direct Synthesis of Highly Substituted π-Rich Aromatic Heterocycles from Oxetanes

Angew Chem Int Ed Engl. 2017 Aug 21;56(35):10525-10529. doi: 10.1002/anie.201704119. Epub 2017 Jul 21.

Abstract

The ubiquitous use of π-rich five-membered heterocycles has driven the development of new methods for their synthesis for more than a century. Here, we disclose a general and reliable reaction manifold for the construction of highly substituted heterocycles through a facile Lewis-acid-catalyzed oxetane rearrangement. Notably, this methodology employs a keto-oxetane motif as a 1,4-dicarbonyl surrogate, which can be synthesized using robust alkylation or alkenylation reactions, and thus obviates the need to access 1,4-dicarbonyl compounds via umpoled starting materials. We harnessed this reactivity to generate a broad range of substituted furans and pyrroles, and extended this methodology to produce benzo-fused versions thereof.

Keywords: cyclization; furans; heterocycles; oxetanes; strained rings.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.