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-1,3,5-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 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 of substituent achieved without the introduction of a steric clash. Computational experiments confirm the role of this effect as a stereodeterminant, since substrates with electropositive groups like a silyl substituent 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 closure of a silyl-substituted azatriene has been demonstrated experimentally.

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“…This confirmed the results of Blanchard et al [12] . Hyperconjugative effects [13] and Sn−F interactions were proposed to explain the stereochemical role of the β‐fluoride.…”

The stereoselectivities of tributyltin hydride-mediated reductions of 5-bromo-d-glucuronides tol-iduronides are dependent on the anomeric substituent: syntheses and DFT calculations

“…The first factor is a stereoelectronic effect recently termed the 'transition state gauche effect' by Houk, Hsung and co-workers. 40 This effect depends on hyperconjugative interactions between the σ* orbital associated with the newly-forming C-H bond, and groups on adjacent atoms. The C-H σ* orbital acts as a σ acceptor.…”

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“…TS2 [41] . In TS1, favorable hyperconjugative interaction between C−H bond and ring oxygen lone pair is observed.…”

“…The stereoelectronic phenomenon termed as 'transition state gauche effect' is employed to explain the preference of TS1 over TS2. [41] In TS1, favorable hyperconjugative interaction between CÀ H bond and ring oxygen lone pair is observed. Whereas, in TS2, this interaction is between CÀ H and CÀ O bond, which points toward a weaker hyperconjugative interaction.…”