| Abstract
| - The boron-mediated aldol reactions of certain types of β-alkoxy methyl ketone show remarkably highlevels of stereoinduction with achiral aldehydes, leading preferentially to 1,5-anti related stereocenters.Given the low levels of asymmetric induction usually observed in acetate aldol reactions, this is of greatsynthetic utility and has been used successfully in the total synthesis of a number of polyketide naturalproducts. We have investigated the effects of the alkoxy protecting group (OMe, OPMB, PMP acetal,tetrahydropyran, and OTBS) present in the boron enolate on the level and sense of remote 1,5-stereoinduction, using density functional theory calculations (B3LYP/6-31G**). Our predictions ofdiastereoselectivity from comparison of the competing aldol transition structures are in excellent qualitativeand quantitative agreement with experimentally reported values. We conclude that the boron aldol reactionsof unsubstituted boron enolates proceed via boat-shaped transition structures in which a stabilizing formylhydrogen bond exists between the alkoxy oxygen and the aldehyde proton. It is this interaction that leadsto preferential formation of the 1,5-anti adduct, by minimizing steric interactions between the β-alkylgroup and one of the ligands on boron. In the case of silyl ethers, the preference for this internal hydrogenbond is not observed due to the size of the protecting group and the electron-poor oxygen atom thatdonates electron density into the adjacent silicon atom. We show that this stereochemical model is alsoapplicable in rationalizing the 1,4-syn stereoselectivity of boron aldol reactions involving certain α-chiralmethyl ketones. These detailed results may be summarized as a conformational diagram that can be usedto predict the sense of stereoinduction.
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