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Felkin–Anh is not enough
Author(s) -
Rosenberg Robert E.,
Kelly W. Jonathan
Publication year - 2015
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.3397
Subject(s) - chemistry , natural bond orbital , hydride , ab initio , nucleophile , aldehyde , ketone , conformational isomerism , transition state , computational chemistry , crystallography , ground state , ab initio quantum chemistry methods , stereochemistry , molecule , density functional theory , organic chemistry , catalysis , atomic physics , hydrogen , physics
The understanding of the electronic effects of the diastereoselective addition of a nucleophile to a polar substituted aldehyde or ketone is not complete, with several theories competing to explain the data. For numerous hydride reductions of 3‐X‐2‐butanones (X = F, Cl, Br), the selectivity for the major syn isomer is significantly and consistently higher for X = Br than for X = F. This result is rationalized as a shift in mechanism from Cornforth (X = F) to Felkin–Anh (X = Br). The experimental data is well modeled by ab initio calculations for the addition to these ketones by BH 3 , but not by other nucleophiles such as LiH or LiAlH 4 . The energetic ordering of the BH 3 transition states largely follows the trends for the ground state ketones. Here, consistent with electrostatic arguments, the anti orientation of the C―X and CO bonds is always lower in energy than the syn arrangement. The gauche conformer is intermediate between these two, becoming gradually lower in energy as X increases in size. The hyperconjugative interaction invoked by the Felkin–Anh model provides only a modest stabilization of the relevant transition states as judged by NBO analysis. Copyright © 2014 John Wiley & Sons, Ltd.