Asymmetric Synthesis Using Tartrate Ester Modified Allylboronates. 2. Single and Double Asymmetric Reactions with Alkoxy-Substituted Aldehydes

Article abstract of DOI:10.1021/jo00300a032

The reactions of tartrate allylboronates 1a and 1b with a series of chiral and achiral alkoxy-substituted aldehydes are described.It is shown that conformationally unrestricted α- and β-alkoxy aldehyde substituents have a significant, negative impact on the stereoselectivity of the asymmetric allylborations.For example, α-alkoxy aldehydes 25-27 and β-alkoxy aldehydes 28-30 undergo asymmetric allylborations with 1 in only 56-59percent and 63-66percent ee, respectively, while the reactions of 1 and aliphatic aldehydes such as decanal or cyclohexane-carboxaldehyde proceed in 86-87percent ee under the same conditions.Evidence of reduced stereoselection is also apparent in the double diastereoselectivity data reported in Table I and Scheme I for the asymmetric allylborations of chiral β-alkoxy aldehydes 16 and 19 and chiral α-alkoxy aldehyde 22.In contrast, chiral aldehydes containing alkoxy groups that are conformationally constrained by incorporation in rings, as in glyceraldehyde acetonide 4,4-deoxythreose ketal 7, and α,β-epoxy aldehydes 10 and 13, are excellent allylboration substrates, with diastereoselection in the cases of 4 and 7 being significantly greater than that obtained with simpler achiral substrates.A model that rationalizes this "alkoxy effect" is presented.Specifically, it is inferred that the observed trends in stereoselection are not steric in origin, but rather that unfavorable lon pair/lone pair interactions occur between the tartrate ester carbonyl and alkoxy substituents particularly of conformationally unconstrained aldehyde substrates (e.g., 16, 19, 22, 25-30) that results in diminished reaction stereoselection (see transition structures 58 and 61).For substrates with conformationally constrained alkoxy substituents , e.g. 4 and 7, favorable lone pair/dipole interactions between the tartrate ester carbonyl and the backside of the β-alkoxy C-O bond leads to increased stabilization of the favored transition state (see transition structures 59 and 60) and hence to increased reaction diastereoselection.A simple method for the analysis of the average diastereofacial selectivity of a chiral reagent in a pair of double asymmetric reactions is also presented.This analysis, which is independent of the intrinsic diastereofacial bias of the chiral aldehyde, enables one to make direct comparisons of the relative diastereoselectivities of a range of chiral substrates with a given chiral reagent (or vice versa).In this way, double diastereoselcetivity data are easily analyzed to determine if the chiral reagent/chiral substrate pair is "well behaved" compared to typical achiral substrate reference systems, thereby providing insight into the structural features that influence reaction stereoselectivity.