Lithium Ephedrate-Mediated Addition of a Lithium Acetylide to a Ketone: Solution Structures and Relative Reactivities of Mixed Aggregates Underlying the High Enantioselectivities

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• 作者：Andrew Thompson ; Edward G. Corley ; Martha F. Huntington ; Edward J. J. Grabowski ; Julius F. Remenar ; and David B. Collum
• 刊名：Journal of the American Chemical Society
• 出版年：1998
• 出版时间：March 11, 1998
• 年：1998
• 卷：120
• 期：9
• 页码：2028 - 2038
• 全文大小：376K
• 年卷期：v.120,no.9(March 11, 1998)
• ISSN：1520-5126

文摘

Addition of lithium cyclopropylacetylide (RLi) toArCOCF₃ mediated by1(R),2(S)-R₂NCH(CH₃)CH(Ph)OLi (ROLi; R₂N = pyrrolidino) occurs with50:1 enantioselectivity (Thompson, A. S. et al.Tetrahedron.Lett. 1995, 36, 8937). Low-temperature⁶Li and ¹³C NMR spectroscopies reveallithium cyclopropylacetylidein THF to be a dimer-tetramer mixture and the lithium alkoxide to bea complex mixture of oligomers.Mixtures of RLi and ROLi in THF afford stoichiometry-dependentmixtures of 3:1, 2:2, and 1:3 mixed tetramers.The dramatic improvements in the stereochemistry of 1,2-additionscaused by aging the reaction at ambienttemperatures are shown to coincide with unusually slow aggregateequilibrations. ReactIR studies showedthat the previously detected requirement for 2 equiv of lithiumacetylide per ketone stems from autoinhibitionrather than from a proton abstraction of an NH moiety in the substrate.Semiempirical (MNDO) computationalstudies support a stereochemical model based upon 1,2-addition via aC₂ symmetric 2:2 mixed tetramer.