title: Axial preferences in allylation reactions via the Zimmerman-Traxler transition state.
abstract: The reaction of a substituted allylmetal with a prostereogenic carbonyl compound can give rise to up to two racemic diastereomers (syn and anti). Classically, in such reactions, when pure E-isomers have afforded anti-selectivity and the Z-isomers exhibit syn-selectivity, researchers have used the empirical Zimmerman-Traxler model. In this model, chair-like transition states dominate over boat-like arrangements. The incoming aldehyde alkyl (aryl) residue occupies a pseudoequatorial rather than a pseudoaxial position to avoid potential 1,3-diaxial steric interactions. However, the reaction of γ,γ-disubstituted allylzinc species with carbonyl compounds generates two gauche interactions, which may result in a completely different stereochemical outcome. With these two gauche interactions, would a transition state in which the aldehyde substituent occupies a pseudoequatorial position or a pseudoaxial position be preferred? In this Account, we show that reaction of γ,γ-disubstituted allylzinc species with carbonyl compounds proceeds through a chair-like transition state and the substituent of the incoming aldehyde residue prefers to occupy a pseudoaxial position to avoid these two gauche interactions. Theoretical calculations on model systems support our experimental results. We have extended this new stereochemical outcome to describe the formation of α-alkoxyallylation of aldehydes through the formation of the rather uncommon (E)-γ,γ-disubstituted alkoxyallylzinc species. We also used this method to transform aromatic ketones and α-alkoxyaldehydes and ketones into functionalized adducts. In a one-pot reaction and using simple alkynes, three new carbon-carbon bonds and two to three stereogenic centers, including an all-carbon quaternary stereocenter could be created in acyclic systems. Because 1,3-diaxial interactions are now produced with the axial substituent, an increase in the substituent size on the zinc atom decreases the diastereoselectivity.
authors.affiliation: Mallat Family Laboratory of Organic Chemistry, Schulich Faculty of Chemistry, and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel.
authors.forename: Tom
authors.initials: T
authors.lastname: Mejuch
authors.forename: Noga
authors.initials: N
authors.lastname: Gilboa
authors.forename: Eric
authors.initials: E
authors.lastname: Gayon
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
authors.forename: Ilan
authors.initials: I
authors.lastname: Marek
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000475:Alkenes; D009942:Organometallic Compounds