LITHIUM EPHEDRATE-MEDIATED ADDITION OF A LITHIUM ACETYLIDE TO A KETONE - SOLUTION STRUCTURES AND RELATIVE REACTIVITIES OF MIXED AGGREGATES UNDERLYING THE HIGH ENANTIOSELECTIVITIES

Addition of lithium cyclopropylacetylide (RLi) to ArCOCF3 mediated by 1(R),2(S)-R2NCH(CH3)CH(Ph)OLi (ROLi; R2N = pyrrolidino) occurs with 50 :1 enantioselectivity (Thompson, A. S. et al. Tetrahedron. Lett. 1995, 36, 8937). Low-temperature Li-6 and C-13 NMR spectroscopies reveal li thium cyclopropylacetylide in THF to be a dimer-tetramer mixture and t he lithium alkoxide to be a complex mixture of oligomers. Mixtures of RLi and ROLi in THF afford stoichiometry-dependent mixtures of 3:1, 2: 2, and 1:3 mixed tetramers. The dramatic improvements in the stereoche mistry of 1,2-additions caused by aging the reaction at ambient temper atures are shown to coincide with unusually slow aggregate equilibrati ons. ReactIR studies showed that the previously detected requirement f or 2 equiv of lithium acetylide per ketone stems from autoinhibition r ather than from a proton abstraction of an NH moiety in the substrate. Semiempirical (MNDO) computational studies support a stereochemical m odel based upon 1,2-addition via a C-2 symmetric 2:2 mixed tetramer.