Open AccessAsymmetric Induction in C-Alkylation of Tropane-Derived Enamines: Congruence Between Computation and Experiment
Author(s) -
Yifei Li,
Kelvin E. Jackson,
Andrew Charlton,
Ben Le Neve-Foster,
Asma Khurshid,
Heinrich-K. A. Rudy,
Amber L. Thompson,
Robert S. Paton,
David M. Hodgson
Publication year - 2017
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.7b01954
Subject(s) - chemistry , asymmetric induction , alkylation , tropane , robustness (evolution) , quantum chemical , computational chemistry , stereochemistry , enantioselective synthesis , organic chemistry , molecule , catalysis , biochemistry , gene
Quantum chemical studies of C-ethylation of 1-methyl- and 1,4,4-trimethyl-tropane-derived enamines predict good (89:11 er, B3LYP) and high (98:2 er, B3LYP) levels, respectively, of asymmetric induction in the resulting α-alkylated aldehydes. The non-racemic tropanes were synthesized using Mannich cyclization strategies (Robinson-Schöpf and by way of a Davistype N-sulfinyl amino bisketal, respectively), and ethylation of the derived enamines was found to support the predicted sense and magnitude of asymmetric induction (81:19 er and 95:5 er, respectively). A comparison of several computational methods highlights the robustness of predicted trends in enantioselectivity, enabling theory to guide synthesis