Direct Measurement of the Rate of Interconversion of Zirconaaziridine Enantiomers

Abstract

The insertion of enantiopure C2-symmetric diphenylethylene carbonate into the Zr-C bonds of zirconaaziridines leads to the asymmetric synthesis of amino acid methyl esters. Because the zirconaaziridine enantiomers interconvert, the reaction is a dynamic kinetic resolution (DKR). The efficiency of the DKR (the ratio of the two diastereomeric products) is determined by the balance between the rate of enantiomer interconversion and the rate of insertion; slow addition of the inserting enantiopure carbonate is often required to maximize the stereoselectivity. For a case when enantiomer interconversion is fast, its rate constant kinv has been determined by NMR line broadening; for a case when interconversion is slow, k(inv) has been determined by computer simulation of the formation of the diastereomeric products as a function of time; for several intermediate cases, k(inv) has been determined by making the zirconaaziridine enantioenriched and monitoring its racemization by CD spectroscopy. The observed k(inv) is independent of [THF], implying that interconversion occurs with THF coordinated. Interconversion presumably occurs via an achiral intermediate, either a rapidly inverting (via an eta1-N structure) eta3-azaallyl hydride or an eta1-imine. As addition of THF slows insertion without affecting enantiomer interconversion, it produces a more efficient DKR without slow addition of the enantiopure carbonate.