Chain elongation, polypropionate synthesis

Vogel and co-workers have used 1 as double chain elongation synthon in their synthesis of long chain polypropionate fragments (eq 48). Their approach is based on an one-pot reaction cascade which involves hetero-Diels-Alder addition of electron-rich l-alkoxy-3-acyloxy-l,2-dienes (e.g., 25) to sulfur dioxide, subsequent ionization into zwitterionic intermediates (e.g., 26), then reaction of the latter with allylsilanes. The final step of this sequence is the retro-ene desulfinylation of an intermediate allylsilyl sulfinate (e.g., 27) to produce useful synthetic intermediates containing two more stereogenic centers (e.g., 28). 

SCHEME 22.50. Convergent synthesis of complicated polypropionates fragments through one-pot, dissymmetrical, two-directional chain elongation. 

Exner CJ, Turks M, Fonquerne F, Vogel P. Concise synthesis of complicated polypropionates through one-pot disymmetri-cal two-directional chain elongation. Chem. Eur. J. 2011 17 4246 253. 

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

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