Regio- and stereoselectivity of the formation of 1,3-oxazolidines in the reaction of l-ephedrine with phenylglyoxal. Unexpected rearrangement of 2-benzoyl-3,4-dimethyl-5-phenyl-1,3-oxazolidine to 4,5-dimethyl-3,6-diphenylmorpholin-2-one.

Asymmetric Synthesis of Chiral 1,2-Amino Alcohols and Morpholin-2-ones from Arylglyoxals

“…However, there is a knowledge gap in the preparation of isomeric structures, i.e., those with a chiral nitrogen-substituted carbon. In search of a practical method for the synthesis of aryl amino alcohols, we were inspired by the work of Polyak who reported a transformation of arylglyoxals into morpholinones . This method is characterized by unusual mildness and utilizes 1,2-amino alcohols that, when exposed to aryl glyoxals and a Brønsted acid, undergo a rearrangement into morpholinones.…”

Catalytic Enantioselective Synthesis of Morpholinones Enabled by Aza-Benzilic Ester Rearrangement

“…The reaction of arylglyoxals with vicinal amino alcohols leading to 2-acyloxazolidines is well-known. , It has also been observed that these oxazolidines isomerize to morpholinones upon prolonged storage or under acidic conditions . This latter reaction has been exploited by the Merck group for the synthesis of 3-(4-fluorophenyl)­morpholin-2-one, a key building block for the synthesis of aprepitant, and has recently been generalized by the group of Walczak for the diastereoselective synthesis of C-substituted morpholinones using chiral vicinal amino alcohols as reactants (Scheme a) .…”

Arylglyoxals in Synthesis of Heterocyclic Compounds

“…By treatment of PG-hydrate with l -ephedrine 589 under different conditions such as in the presence of 4 Å MS in ether at 20 °C or 4 Å MS in EtOH at 20 °C or Amberlyst-15 in refluxing toluene, regiospecifically, 2-benzoyloxazolidine 590 was obtained with a quantitative yield via condensation of 589 with the more reactive aldehyde group of PG. 2-Benzoyloxazolidine 590 was obtained as two diastereomers, which rearranged to 4,5-dimethyl-3,6-diphenylmorpholin-2-one 591 at ambient temperature after 12 days (Scheme ) …”