Peter S. Diez, G. C. Micalizio
May 21, 2012
Citations
0
Influential Citations
17
Citations
Journal
Angewandte Chemie
Abstract
Over the last thirty years, substantial advances in stereoselective synthesis have enabled the preparation of exquisitely complex and therapeutically valuable polyketide-derived natural products.[1] While impressive, these accomplishments are typically composed of multistep sequences that are required to manage the reactivity of synthetic intermediates in the course of iterative chain growth (i.e. protecting/functional group manipulations and carbonyl redox chemistry). This is particularly evident in synthesis strategies for deoxypropionate-containing natural products (Figure 1). Reduced polypropionate architecture is found in natural products that possess a broad range of biological properties and, as such, has been the target of numerous studies in stereoselective synthesis.[2] A variety of iterative synthetic strategies to deoxypropionates have been described that can be characterized in one of two ways: (1) Those that forge single C–C bonds in the iterative chain elongation process (i.e. methods based on sequential enolate alkylation,[3] SN2’ chemistry,[4] and carbonyl olefination/asymmetric hydrogenation),[5] and (2) those that proceed by constructing 2 C–C bonds in the course of chain elongation (i.e. methods based on asymmetric carbometalation/oxidation/carbonyl olefination,[6] and stereoselective 1,4-addition/carbonyl olefination[7]).[8, 9] While these iterative synthesis strategies to deoxypropionates are powerful and stereochemically flexible, they uniformly suffer from the requirement of long sequences of chemical transformations to construct a complex deoxypropionate chain and, as such, suffer from poor step-economy (3–4 steps required for 2-carbon chain elongation).[10]