Sequential catalysis for stereoselective synthesis of complex polyketides

Abstract

This review presents recent advances in sequential catalytic methods developed in our group for the rapid and stereoselective synthesis of key structural features of complex polyketides. These include a novel domino reaction, based on a combination of a nucleophilic addition and a Tsuji-Trost reaction, an innovative sequence relying on an oxidative diyne cyclization and regioselective opening, as well as sequential cross coupling strategies. The design and scope of these methods are discussed and applications in complex target syntheses presented.

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

“…As part of our ongoing efforts to the design of novel tandem reactions for the synthesis of complex natural products [ 29 , 32 – 37 ], we have developed an innovative concept for heterocycles synthesis [ 26 – 31 ]. As shown in Scheme 1 , this approach that further advances and generalizes several individual reports by other groups [ 38 – 43 ], is based on a sequential nucleophilic addition and an intramolecular allylic substitution reaction.…”

“…Due to their intriguing structures in combination with the promising biological properties this class of bromopyrrole alkaloids has attracted great interest from synthetic chemists and a variety of elegant total syntheses has been reported [ 6 – 22 ]. Inspired by an innovative concept for heterocycles synthesis recently developed in our group [ 26 – 31 ], we became interested to devise a novel and a more versatile route to the central heterocyclic core of these marine metabolites. The method is based on a late-stage diversification strategy involving a Tsuji–Trost reaction of the urea-type joint precursor 5 .…”

Transition metal-free one-pot synthesis of nitrogen-containing heterocycles

“…The development of environmental, practical, and highly economic procedures for the preparation of heterocyclic compounds continues to be a challengining area for organic chemists [2]. One-pot synthetic pathways are remarkably advantageous to access diversely functionalized molecules which are useful as fine chemicals, chiral catalysts, ligands, drug candidates and drug intermediates [3][4][5][6].…”

A Personal Perspective on Organic Synthesis: Past, Present, and Future

“…Today, new catalytic concepts and activation of inert chemical bonds through unprecedented mechanistic pathways have received unparalleled attention, and this trend is expected to continue if not to intensify in the foreseeable future. Synergistic catalysis, cooperative catalysis, cascade catalysis, relay catalysis, shuttle catalysis, photoredox catalysis, biocatalysis, frustrated Lewis‐pair catalysis, just to name a few prominent recent examples. Notably, although the development of catalytic processes has remained the mainstream in the search for new and enhanced chemical reactivity and selectivity, growing understanding of the compatibility and cooperativity of individual reagent systems has enabled more sophisticated reagent blends to be developed.…”