Acyclic Stereoselection. 44. Diastereoselectivity in the Ortho Ester Claisen Rearrangement of Chiral Propargylic Alcohols. Use of β-Allenic Esters as Chiral Methylmalonaldehyde Synthons

Article abstract of DOI:10.1021/jo00255a014

The diastereoselectivity of the ortho ester Claisen rearrangement of chiral propargylic alcohols has been investigated for alcohols 6-12 (eq 3).The results of this study, summarized in Table II, show that aryl-substituted propargyl alcohols 11 and 12 react stereorandomly.However, alkyl-substituted propargyl alcohols 6-10 show a preference for formation of the 2S*, 4S* diastereomer, with stereoselectivity increasing with increasing steric bulk of R.In the most favorable case ( compound 10), a 95:5 mixture of diastereomeric products is produced.The diastereoselectivity of the process was established by the use of scalemic alcohols (R)-(+)-8, (S)-(-)-10, and (R)-(+)-10, which were obtained by resolution of the racemates ( Schemes II and III ).As shown in Scheme IV, (R)-(+)-8 and (S)-(-)-10 were each converted into the known acid (S)-(+)-28.Given the known relationship between the stereogenicity of a chiral propargylic alcohol and the chiral allene resulting from Claisen rearrangement, it may be deduced that (S)-8 and (R)-10 react via the derived E ketene acetals to give, preferentially, the 2S, 4S β-allenic esters.For the alkyl series, the results are explained by the mechanism (Scheme I) wherein the E and Z ketene acetals are in rapid equilibrium, with the E isomer reacting significantly more rapidly than the Z isomer.The observed effect of size of R on the stereoselectivity of the reaction is explained in terms of 1,3-interactions in the two alternative reacting conformations of the ketene acetal (Scheme I, E vs E').For propargyl alcohols 11 and 12, it is postulated that Claisen rearrangement is sufficientlyaccelerated by the aryl substituent that ketene acetal formation becomes the rate-limiting step; the observed 1:1 product ratios in these cases are believed to be a reflection of the ratio of double-bond isomers in the initial ketene acetal.It has been demonstrated that the ester and allenic functions may be manipulated independently, so that the chiral β-allenic esters may be used as " chiral methylmalonaldehyde " synthons.