title: Transition State Gauche Effects Control the Torquoselectivities of the Electrocyclizations of Chiral 1-Azatrienes.
abstract: Hsung et al. have reported a series of torquoselective electrocyclizations of chiral 1-azahexa-1E,3Z,5E-trienes that yield functionalized dihydropyridines. To understand the origins of the torquoselectivities of these azaelectrocyclizations, we modeled these electrocyclic ring closures using the M06-2X density functional. A new stereochemical model that rationalizes the observed 1,2 stereoinduction emerges from these computations. This model is an improvement and generalization of the "inside-alkoxy" model used to rationalize stereoselectivities of the 1,3-dipolar cycloaddition of chiral allyl ethers and emphasizes a stabilizing hyperconjugative effect, which we have termed a transition state gauche effect. This stereoelectronic effect controls the conformational preferences at the electrocyclization transition states, and only in one of the allowed disrotatory electrocyclization transition states is the ideal stereoelectronic arrangement achieved without the introduction of a steric clash. Computational experiments confirm the role of this effect as a stereodeterminant since substrates with electropositive groups and electronegative groups have different conformational preferences at the transition state and undergo ring closure with divergent stereochemical outcomes. This predicted reversal of stereoselectivity for the ring closures of several silyl substituted azatrienes have been demonstrated experimentally.
authors.forename: Ashay
authors.initials: A
authors.lastname: Patel
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Vella
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, and Department of Chemistry, University of Wisconsin , Madison, Wisconsin 53705, United States.
authors.forename: Zhi-Xiong
authors.initials: ZX
authors.lastname: Ma
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, and Department of Chemistry, University of Wisconsin , Madison, Wisconsin 53705, United States.
authors.forename: R P
authors.initials: RP
authors.lastname: Hsung
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D001372:Aza Compounds / Q000737:chemistry*; D003500:Cyclization; D004563:Electrochemistry; D008958:Models, Molecular; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D001372:Aza Compounds