Allyltitanates in Stereospecific Additions to Chiral δ-Lactol:  Efficient Enantioselective Route to a Potential Precursor of the C1−C9 Portion of Tylonolide

The Hoppe reaction, which is an allylation reaction of aldehydes using an optically active titanated crotyl carbamate intermediate generated from the corresponding N,N-diisopropyl crotyl carbamate with n-BuLi/(−)-sparteine, was in most cases applied to achiral aldehydes. In this work an extension of this reaction is reported using a racemic γ-alkoxy allyltitanate (17) and an optically active aldehyde (16) to deliver in good yield the anti adduct 18 as the major isomer. When the corresponding δ-lactol 24 was used in place of aldehyde 16, the anti adduct 25 was obtained in 94% yield as the only product. Structural modifications effected on 25 delivered aldehyde 28 which was in turn submitted to a second allylation reaction in the presence of the optically active titanated crotyl carbamate 2, prepared as described by Hoppe from crotyl carbamate 1, to conduct to compound 29 in 80% yield. This derivative corresponds to a potential precursor of the C1−C9 portion of Tylonolide, aglycon of Tylosin (4).