A Novel Asymmetric Synthesis of the Core Octadienoic Acid Unit of Cryptophycins from (R)-2,3-O-Cyclohexylideneglyceraldehyde

Abstract

A facile asymmetric synthesis of the octadienoic acid unit of cryptophycins was developed starting from (R)-2,3-O-cyclohexylideneglyceraldehyde. The key steps of the synthesis are the stereocontrolled generation of the required asymmetric centers through (i) a gallium-mediated highly diastereoselective crotylation of the glyceraldehyde in [bmim][Br], (ii) a stereoselective allylation with allyltributylstannane, and (iii) an enantioselective Grignard addition to an a-oxygenated aldehyde.

Bi-mediated allylation of aldehydes in [bmim][Br]: a mechanistic investigation

“…The metal-mediated Barbier-type allylation of aldehydes has drawn considerable attention, because the resultant homoallylic alcohols are versatile intermediates for natural product synthesis [1–7]. The reaction, carried out in organic solvents, water, mixed solvent systems and room temperature ionic liquids (RTILs) is also ideal for probing in situ formation of different allylmetal species in solution, their stability and reactivity towards electrophiles [8–10].…”