Designing Reactions with Post-Transition-State Bifurcations: Asynchronous Nitrene Insertions into C–C σ Bonds

Abstract

Principles for designing reactions with post-transition-state bifurcations are laid out and applied to the design of a reaction that combines nitrene addition with alkyl-shifting events, leading to polycyclic structures with distinct bicyclic frameworks. A dynamics-based model for selectivity control of this type of reaction is presented. SUMMARYDiscoveries of chemical reactions with potential energy surfaces with posttransition-state bifurcations are increasing in frequency. Although such potential energy surface features are often discovered accidentally, we demonstrate here that they can be designed rationally. We describe a process for designing such reactions and apply it to the design of a nitrene addition/alkyl-shift reaction with a post-transition state bifurcation. We examine substituent effects on this reaction and propose a dynamics-based model for selectivity control.

Chirality without Stereoisomers: Insight from the Helical Response of Bond Electrons

“…[27,29] Future work could include application to chiral selectivity during a chemical reaction, in particular for the design of reactions with post-transition state bifurcations (PTSB) where an asynchronous nitrene insertion into CÀ C σ bonds can be used to modulate the product sensitivity. [53] Further work could include the determination of the C helicity for molecules with multiple chiral centers: each dominant torsional bond associated with a separate chiral center would be considered independently. Treating the chiral centers independently is possible because obtaining the C helicity requires constraining the corresponding torsional dihedral angle, allowing the remaining atoms and molecular electronic density distribution to relax to an energetic minimum in response.…”

Natural reaction orbitals for characterizing electron transfer responsive to nuclear coordinate displacement

“…The NRO analysis is also examined for the 1,2-alkyl shift/ nitrene addition. 53 Fig. 17 shows the energy profile and the sum of squared singular values of U (1) VO , K k k F 2 ; along the IRC calculated at the B3LYP/6-311++G(d,p) level.…”

Bifurcating reactions: distribution of products from energy distribution in a shared reactive mode

“…see Table S5). The studied reactions cover a broad spectrum of reactions, featuring a rich set of bifurcating pericyclic processes (1-12, 23-34, 47-48), 14,43,44,45,46,47,48,49,50,51,52,53,54,55,56 nitrene insertions (35)(36)(37)(38), 57 rearrangement and fragmentation reactions (13-16, 39), 13,58,59,60 the branching in nucleophilic additions and substitutions (17-22, 46), 11,61 and solvent-dependent isomeric Pummerer rearrangements (40-44). 12 Page 11 of 35 Chemical Science…”