Configurational stability of chiral lithiated cyclopropylnitriles: A density functional study
Configurational stability of chiral lithiated cyclopropylnitriles: A density functional study
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DOI：
10.1002/chir.10222
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发表时间：
2003-05-05
期刊：
影响因子：
2
通讯作者：
Carlier, PR
中科院分区：
文献类型：
--
作者：
Carlier, PR
Chiral, configurationally stable lithiated nitriles would be valuable intermediates for asymmetric carbon-carbon bond-forming reactions. To gain insight into the design of such species, Walborsky's attempted enantioselective deprotonation/trapping reactions of a chiral cyclopropylnitrile were studied computationally up to the MP2 (fc) / 6-31+G* and B3LYP/6-31+G* levels. Investigation of cyclopropylnitrile/LiNH2 deprotonation transition structures demonstrated a significant (20-23 kcal/mol) kinetic preference for N-lithiation, and a facile (4-6 kcal/mol barrier) "conducted tour" racemization pathway for the N-lithiated nitrile product. Addition of a model directing group (formyl) to the beta-carbon of the cyclopropyl ring is predicted to significantly favor Glithiation over N-lithiation, both kinetically and thermodynamically. Thus, chiral beta-Lewis base substituted cyclopropylnitriles may serve as precursors to chiral, configurationally stable organolithium reagents.
