Axial Preferences in Allylation Reactions via the Zimmerman-Traxler Transition State

作者：Mejuch Tom; Gilboa Noga; Gayon Eric; Wang Hao; Houk K N; Marek Ilan^*

来源：Accounts of Chemical Research, 2013, 46(7): 1659-1669.

DOI：10.1021/ar4000532

The reaction of a substituted allylmetal with a prostereogenic carbonyl compound can give rise to up to two racemic diastereomers (syn and ant. 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 gamma,gamma-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? %26lt;br%26gt;In this Account, we show that reaction of gamma,gamma-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 alpha-alkoxyallylation of aldehydes through the formation of the rather uncommon (E)-gamma,gamma-disubstituted alkoxyallylzinc species. We also used this method to transform aromatic ketones and alpha-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.

• 出版日期2013-7-16