Stereocontrol Mechanism in Asymmetric Synthesis with a Chiral Tether

Abstract

When a prochiral reactant and a reagent element are connected through 2,4-pentanediol (PD), a reaction species generated from the reagent moiety reacts internally with the reactant moiety. Applicable combinations of the two moieties extend in a wide range, and selectivities in their reactions are very high to give essentially optically pure compounds after elimination of the PD tether. Although selectivities with the PD tether are too high to measure their temperature dependency, other lower analogues like a 1,3-butanediol tether resulted in an imperfect stereoselectivity, and it showed almost no temperature dependency. The low temperature dependency of a sufficiently high stereoselectivity means that the selectivity is governed by the entropy term at the transition states. The advantage of this entropy-controlled mechanism is revealed in a flash vacuum pyrolysis (FVP) performed at 250-350° C. The origin of the differential activation entropy was deduced from some intramolecular reaction rates measured for different tethers. By this analysis, it was disclosed that strict stereocontrol with two methyl groups on the PD tether must be attributable to acceleration of one diastereomeric process and deceleration of the other by the entropy term.