Catalytic Asymmetric Vinylogous Aldol Reaction Of Conjugated Silyl Diene Ether

Vinylogous Mukaiyama Aldol (VMA) reaction, the variant of general aldol process, is widely employed as a versatile C-C bond forming tool in synthetic chemistry. Recent progresses in both diastereoselective and enantioselective version have produced remarkable achievements in synthesis of stereochemically complex structures. The vast majority of vinylogous aldol reaction employ silyl dienolates derived from β-ketoesters as aldol donors as their addition to carbonyl compounds gives the optically pure δ-hydroxyl-β-ketoesters, versatile building blocks in synthesis of natural products and commercial drugs. At the meantime, few attention has been paid to the simple α,β-unsaturated ester derived silyl dienes, although their addition to aldehyde would deliver δ-hydroxyl α,β-unsaturated esters, potential intermediate with respect to natural products such as Callipeltoside A and Dactylolide.Previously our group reported a novel BINOL-Ti complex assisted by LiCl (BTHL), designed on the strategy of combined acids, effectively promote the asymmetric vinylogous aldol reaction of Brassard’s dienes with various aldehydes. We propose that the combination of the two Lewis acids would provide reinforced Lewis acidity while the reorganized conformation forms a better chiral indcution. Considering the similarity between Brassard’s diene and simple α,β-unsaturated esters derived silyl diene, we reason that this kind of silyl diene ether could be well adopted under the BTHL system.In this paper, we will describe our accomplishment on the asymmetric vinylogous aldol reaction between aromatic aldehydes, heterocyclic aldehydes, aliphatic aldehydes and three a, β-unsaturated silyl diene ethers, especially3-methyl silyl diene ether, catalyzed by the (R)-BTHL system affording the chiral derived δ-hydroxyl α,β-unsaturated esters exclusively in good yields with excellent enantioselectivities (83-99%ee) under mild conditions. Nonlinear Effect (NLE) experiments and the role of in situ generated isopropyl alcohol experiments were then carried out to gain preliminary insight into the structure of the active catalytic species and the mechanism of the catalytic process.