Sulfide, crotyl phenyl oxidation

The titanium- ate complexes of a-methoxy allylic phosphine oxides, generated in situ by reaction of the corresponding lithium anion and Ti(0-i-Pr)4, condense with aldehydes exclusively at the a-position to produce homoallylic alcohols in a diastereose-lective fashion. The overall result is the three-carbon homologation of the original aldehyde, and this protocol has been used in a synthesis of (-)-aplysin-20 from nerolidol. The titanium- ate complex produced by reaction of the chiral lithium anion of an ( )-crotyl carbamate with Ti(0- -Pr)4 affords -y-condensation products (homoaldols) on reaction with aldehydes. Allyl anions produced by the reductive metalation of allyl phenyl sulfides condense with a,p-unsaturated aldehydes in a 1,2-manner at the more substituted (a) allyl terminus in the presence of Ti(0-i-Pr)4. 1,2-Addition of dialky Izincs to a,p-unsaturated aldehydes can be achieved with useful levels of enantiocontrol when the reaction is conducted using a chiral titanium(IV) catalyst in the presence of Ti(0- -Pr)4 (eq 20). Higher ee values are observed when an a-substituent (e.g. bromine) is attached to the substrate aldehyde, but a -substituent cis-related to the carbonyl group has the opposite effect. 

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