Science of Synthesis

Hodgson, D. M.; Humphreys, P. G., Science of Synthesis, (2008) 36, 652.

A route to enantiopure allylic alcohols involves the enzymatic resolution of their racemic mixtures.[‌361‌] Typically, one of the enantiomers undergoes preferential acetylation, although there are examples of oxidation of one enantiomer to an enone.[‌362‌] A major drawback of this method is that the yield is constrained to 50%, an unacceptable fact when working with complex allylic alcohols. Although dynamic kinetic methods utilizing tandem enzymatic and metal-mediated (catalyzed) resolutions can be employed to afford single enantiomers from racemic mixtures,[‌363‌–‌365‌] these reactions will not be considered here as they only give access to enantioenriched allylic esters, not allylic alcohols. Another difficulty with enzymatic resolutions of racemic allylic alcohols is the absence of predictive models that allow the selection of the correct enzyme. Hence screening with a wide variety of enzymes is usually required in order to obtain satisfactory levels of enantiomeric purity.[‌366‌] Nonetheless, if a simple, bulky allylic alcohol is resolved on a large scale then it can provide a chiral building block for subsequent syntheses. Inexpensive and effective enzymes for the resolution of certain allylic alcohols include Pseudomonas lipases in the presence of excess vinyl acetate. One of the advantages of these enzymes is that they can be used in organic hydrocarbon solvents, which alleviates any solubility problems associated with aqueous media.[‌367‌] A variety of alkylated and arylated allylic alcohols ‌170‌ can be resolved in this way to give single enantiomers ‌171‌, along with the corresponding acetates ‌172‌ formed from their antipodes that act as substrates for the enzymes (‌Scheme 79‌).[‌367‌,‌368‌] Unfortunately, Z-disubstituted allylic alcohols are unsatisfactory substrates for these lipases and give poor levels of enantiomeric excess (ca. 60% ee).

‌Meeeee 88‌ Meeeeeeee Meeeeeeeee ee Meeeeee Meeeeeee[‌888‌]

Meeeeeeeeeee Meeeeeeee

(M)-8-Meeeeeeee-8-ee-8-ee (‌888‌, M8 = Me; M8 =Me; M8 = M); Meeeeee Meeeeeeee:[‌888‌]

M Meeeeeeeeee eeeeeee eeeeee (888 ee, 8.8 eeee eeeee) eee eeeee ee e eeeeeee eeeeeeeeee ee eeeeee 8-Å eeeeeeeee eeeeee (888 ee) ee eeeeee (88 eM) ee ee. Meeeeee eeeeeeeee eeeee eeeeeee (888 ee) eee 8-eeeeeeeee-8-ee-8-ee (‌888‌, M8 = Me; M8 = Me; M8 = M; 888 ee) eeee eeeee eee eee eeeeeeeee eeeeeee eee eeeeeee eee 8 e. Mee eeeeeee eee eeeeeeee, eee eeee eee eeeeeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Meeeee eeeeeeeeeeeeee (eeeeee eee, eeeeee/eeeeeee 88:8 ee 8:8) ee eee eeeeeee eeeee eeee eee eeeeeee ‌888‌ (M8 = Me; M8 = Me; M8 = M), eeeeeeee ee eee eeeee eeeeeeee; eeeee: 88 ee (88%); >88% ee; [α]M88 +88.8 (e 8.88, MMMe8).

References