Highly Diastereo‐ and Enantioselective Reactions of Enecarbamates with Ethyl Glyoxylate To Give Optically Active syn and anti α‐Alkyl‐β‐Hydroxy Imines and Ketones

Abstract

The addition of enecarbamates to ethyl glyoxylate in the presence of a copper-diimine catalyst gives the corresponding imines in high yields with excellent enantioselectivities. Whereas E enecarbamates give anti adducts, syn adducts are obtained from Z enecarbamates. On the following pages, Kobayashi and co-workers describe this novel reaction and propose a concerted aza-ene-type reaction mechanism to explain the remarkable stereochemical outcome.

An Enamide‐Based Domino Reaction for a Highly Stereoselective Synthesis of Tetrahydropyrans

“…In general, the nucleophilic addition of enamides and enecarbamates to reactive electrophiles offers an attractive opportunity for the rapid construction of molecular complexity . Although reactions with highly electrophilic glyoxylic acid derivatives or activated ketones have been described (Scheme a), the addition of enamides to simple, non‐activated aldehydes has, to the best of our knowledge, not been reported so far. We envisioned that such a direct addition could open an attractive synthetic route to 1,3‐aminoalcohols (Scheme b).…”

Rapid Assembly of Molecular Complexity from Simple Enamides

“…We envisioned that such a reaction could provide a highly useful synthetic entry towards 1,3-aminoalcohols. However, only the addition of enamides to glyoxylic acid derivatives 9 or other activated ketones 10 has been described in the literature so far. access to all four diastereomers in 76-96% yield (isolated yield for the desired diastereomers) dr ranging from 85:15 to >98:2…”

Enamides: valuable organic substrates

“…The Kobayashi laboratory has since demonstrated the use of C 2 symmetric diamine ligands with a range of electrophiles and enamides as nucleophiles, promoted by Cu(II)-catalysts in conjunction with iminophosphonates for the enantioselective formation of phosphonic acid systems, 6 diazodicarboxylates for enantioselective a-aminations 7 and eventually demonstrated that some aldehydes (a-oxo aldehydes) will participate as useful electrophiles. 8 The Kobayashi group have once again demonstrated the synthetic utility of enamides in an enantioselective Michael reaction which forms, after hydrolysis, c-keto malonates in good yield and selectivity with an example displayed in Scheme 2. 9 Terada has reported that enamides are excellent substrates for chiral Brønsted acid promoted enantioselective additions to glyoxals.…”