Premium
Configurational stability of chiral lithiated cyclopropylnitriles: A density functional study
Author(s) -
Carlier Paul R.
Publication year - 2003
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.10222
Subject(s) - chemistry , deprotonation , racemization , enantioselective synthesis , asymmetric carbon , nitrile , transition state , ring (chemistry) , medicinal chemistry , lewis acids and bases , reagent , chiral auxiliary , carbon fibers , computational chemistry , stereochemistry , organic chemistry , catalysis , alkyl , ion , materials science , composite number , composite material
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/LiNH 2 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 β‐carbon of the cyclopropyl ring is predicted to significantly favor C ‐lithiation over N ‐lithiation, both kinetically and thermodynamically. Thus, chiral β‐Lewis base substituted cyclopropylnitriles may serve as precursors to chiral, configurationally stable organolithium reagents. Chirality 15:340–347, 2003. © 2003 Wiley‐Liss, Inc.