Observation of a Transient Intermediate in Soai's Asymmetric Autocatalysis: Insights from ~1H NMR Turnover in Real Time

摘要

The amplifying asymmetric autocatalysis of alkylzinc addition to aldehydes discovered by Soai and co-workers in 1995 remains the only effective example of this genre, despite widespread continuing interest in asymmetric amplification, primarily in the context of studies probing the origin of biological homochirality. The autocatalytic process is highly circumscribed, being effective only within a narrowly defined regime: only 2-substituted pyrimidin-5-als such as 1 function as reactant and only di-isopropylzinc 2 functions as reagent. The active catalyst is thought to be a higher-order alkoxide species derived from alkoxide 3 and is normally generated in situ from the alcohol 4. Significant advances in the period since the initial discovery include absolute asymmetric synthesis,amplification from extremely low to high levels of enantiomer excess, and initiation by diverse chiral entities or by isotopically chiral promoters. Kinetic and spectroscopic studies have provided much information about the nature of the autocatalytic process, and kinetic and computational modeling have contributed to our understanding. To date, however, neither experimental observations of intermediate species, nor evidence of the nature of the catalytic entity, have been reported. Hence the molecular mechanisms by which amplifying autocatalysis occur are not yet properly understood.