Theoretical Study of Diastereoselective NHC-Catalyzed Cross-Benzoin Reactions between Furfural and N-Boc-Protected α-Amino Aldehydes

J Org Chem. 2019 Nov 1;84(21):13565-13571. doi: 10.1021/acs.joc.9b01821. Epub 2019 Oct 7.

Abstract

The mechanism and origins of syn and anti selectivity of cross-benzoin reactions between furfural and α-amino aldehydes, catalyzed by a triazolium-based NHC, were investigated using density functional theory calculations. N-Boc-α-amino aldehydes were found to react with anti selectivity, while N-Bn-N-Boc-α-amino aldehydes react with syn selectivity. We find that the anti product is more thermodynamically favored than the syn product for reactions with N-Boc-α-amino aldehydes, and that the formation of the syn product for reactions involving N-Bn-N-Boc-α-amino aldehydes is kinetically favored. The switch in selectivity is a result of an intramolecular hydrogen bond in the N-Boc-α-amino aldehyde, whereas switching to N-Bn-N-Boc-α-amine removes the hydrogen bond. The steric and electronic interactions in the transition state are rationalized by a Felkin-Anh model.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't