Enantioselective synthesis of A 3′-dephenylcryptophycin synthon

An enantioselective synthesis of tert-butyl (5 S,6 R)-( E)-5- tert-butyldimethylsilyloxy-6-methyl-2,7-octadienoate, a precursor for the synthesis of the antimitotic macrolides cryptophycin A and arenastatin A (cryptophycin-24), is presented. The key step in the reaction sequence features a crotyl boration that sets both stereocenters that become the C16 hydroxyl and C1′ methyl in the cryptophycins. Homologation of the terminal olefin via a Heck reaction is presented. An enantioselective synthesis of a cryptophycin-1 precursor is presented. The key step in the reaction sequence features a crotyl boration, setting the chiral centers at C1′ and C16.