Relative stabilities of transition states determine diastereocontrol in sulfur ylide additions onto chiral N‐sulfinyl imines

Abstract

Additions of methylphenylsulfonium methylide onto chiral non-racemic N-sulfinyl imines (R′-SO-N=CH-R, R′=t-butyl, R=protected diol), followed by ring closure, yield terminal aziridines with high diastereoselectivity. Control reactions have established that both N- and C- iminyl substituents impact product preference, and when properly matched, one addition product is selected almost exclusively. Using solution-phase density functional computational methods, minima and transition state searches have been performed to reveal the structural origins of the diastereoselectivity. Our computational findings indicate that ring closure is fast and irreversible, and consequently, the relative energies of the transition states for the competing Re/Si addition steps determine the product diastereomeric ratios. Analysis of addition transition state structures reveals the causes of selectivity as arising from the N- and C- iminyl substituents, and we identify the S (R) configuration of the N-sulfinyl sulfur atom as the dominant director of Si (Re) addition. The control attributed to the sulfur configuration is tied to an important favorable internal interaction between the sulfinyl oxygen and the iminyl hydrogen. The protected diol acts as a secondary director, owing to steric/electrostatic interactions with the approaching ylide.

Diastereoselective Synthesis of α-Quaternary Aziridine-2-carboxylates via Aza-Corey–Chaykovsky Aziridination of N-tert-Butanesulfinyl Ketimino Esters

“…Initially, we attempted to rationalize the observed stereoselectivity by invoking a six-membered ring chairlike transition state where the sodium cation coordinates the ylide oxygen and imine nitrogen. Since the final ring closure is fast and irreversible, the observed stereoselectivity was assumed to arise from the energy difference between the two diastereomeric betaine transition states . However, we felt this proposal did not adequately consider the electronic influence of the pendant α-ester on the transition state.…”