Why is the reaction of ethyl (2‐cyanoacetyl)carbamate with ethyl orthoformate highly stereoselective?

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.