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Why is the reaction of ethyl (2‐cyanoacetyl)carbamate with ethyl orthoformate highly stereoselective?
Author(s) -
Sung Kuangsen,
Lin MingChi,
Huang PinMei,
Zhuang BoRen,
Sung Robert,
Wu RuRong
Publication year - 2005
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.979
Subject(s) - chemistry , steric effects , isodesmic reaction , stereoselectivity , triethyl orthoformate , carbamate , medicinal chemistry , stereochemistry , organic chemistry , catalysis , molecule
The reaction of ethyl (2‐cyanoacetyl)carbamate ( 1 ) with ethyl orthoformate in the presence of acetic anhydride is highly stereoselective and only E ‐ethyl (2‐cyano‐3‐ethoxyacryloyl)carbamate ( E ‐ 2 ) is isolated. The reaction is thermodynamically controlled and the product distribution depends on the relative stability between E ‐ 2 and Z ‐ 2 . Both the resonance stabilization of 1.47 kcal mol −1 and the steric hindrance of 2.28 kcal mol −1 in favour of E ‐ 2 contribute to the relative stability (3.75 kcal mol −1 ) between Z ‐ 2 and E ‐ 2 , which is calculated from four isodesmic reactions, and this is the reason why the reaction of compound 1 with ethyl orthoformate is highly stereoselective. The electron‐withdrawing ability of some substituents was evaluated. The sequence of π‐accepting ability is C(O)NHC(O)OEt > C(O)NH 2 > CN and the sequence of σ‐accepting ability is CN > C(O)NHC(O)OEt > C(O)NH 2 . Copyright © 2005 John Wiley & Sons, Ltd.