Axial preferences in allylation reactions via the Zimmerman-Traxler transition state

Tom Mejuch, Noga Gilboa, Eric Gayon, Hao Wang, K. N. Houk, Ilan Marek

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1659-1669
Number of pages11
JournalAccounts of Chemical Research
Issue number7
StatePublished - 16 Jul 2013

All Science Journal Classification (ASJC) codes

  • General Chemistry


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