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

• DOI: 10.1021/acs.joc.0c01308
• Publication Date: 2020-08-07T22:38:39Z
• Authors: Molly V. Campbell; Alexei V. Iretskii; R. Adam Mosey
• Keywords: Cyclization; Stereoisomerism; Amines; Ketones; Amides; 01 natural sciences; 0104 chemical sciences

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.