One-Pot Tandem Assembly of Amides, Amines, and Ketones: Synthesis of C4-Quaternary 3,4- and 1,4-Dihydroquinazolines

A multicomponent tandem assembly
procedure for the synthesis of
diverse C4-quaternary 3,4-dihydroquinazolines from amides, amines,
and ketones has been developed. The one-pot reaction involves successive
triflic anhydride mediated amide dehydration, ketimine addition, and
Pictet–Spengler-like cyclization processes and affords products
in up to 92% yield. Conversion of 3,4-dihydroquinazolines to the corresponding
1,4-dihydroquinazolines via a two-step N1 dealkylation and regioselective
N3 functionalization protocol, including computational rationale for
the observed regioselectivity, is also described.