ABNO‐Catalyzed Aerobic Oxidative Synthesis of 2‐Substituted 4H‐3,1‐Benzoxazines and Quinazolines

Abstract

A new transition‐metal‐free 9‐azabicyclo[3.3.1]nonan‐N‐oxyl (ABNO) catalyzed aerobic oxidative synthesis of 2‐substituted 4H‐3,1‐benzoxazines and quinazolines has been developed through cascade reaction of aldehydes with 2‐aminobenzyl alcohols and 2‐aminobenzylamines, respectively. Under the optimal reaction conditions, the two kinds of heterocycles were obtained in 72–97 % isolated yield.

Divergent Synthesis of Quinazolines Using Organocatalytic Domino Strategies under Aerobic Conditions

“…These may be summarized as follows: (i) the reaction delivered the desired product 3a when peroxides were used as oxidants (Table , entries 1–3 and 5); (ii) the formation of the desired product 3a decreased drastically when the reaction was carried out under a nitrogen atmosphere (Table , entry 11), and a small amount of product 3a was formed when the reaction was carried out under aerobic conditions in absence of catalyst using MeCN and DMSO as solvent (Table , entries 13 and 14); (iii) the reaction delivered the desired product 3a in the presence of all the pyridine derivatives used as catalysts under aerobic conditions (Table , entries 1–5). On the basis of our experimental observations and literature evidence,[30b], a plausible mechanism is given in Scheme . We expect that intermediate 4 is formed by a condensation reaction between 1a and 2a .…”

“…= 100–102 °C (lit. [30b] 100–101 °C). 1 H NMR (400 MHz, [D 6 ]DMSO): δ = 9.71 (s, 1 H, 4‐H), 8.57 (d, 3 J = 9 Hz, 2 H, 12‐H), 8.18 (d, 3 J = 7.96 Hz, 1 H, 8‐H), 8.08–8.02 (m, 2 H, 5‐H and 7‐H), 7.75 (t, 3 J = 7.5 Hz, 1 H, 6‐H), 7.56–7.57 (m, 3 H, 13‐H, and 14‐H) ppm.…”

“…The use of large excesses of nonrenewable, hazardous, and toxic oxidants may restrict the applicability of these protocols. More recently, organocatalytic approaches to synthesis have been recognized . These approaches rely on 9‐azabicyclo[3.3.1]nonan‐ N ‐oxyl (ABNO), (2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO), and rose Bengal as green organocatalytic systems .…”

“…More recently, organocatalytic approaches to synthesis have been recognized . These approaches rely on 9‐azabicyclo[3.3.1]nonan‐ N ‐oxyl (ABNO), (2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO), and rose Bengal as green organocatalytic systems . The methods mentioned above and some other reported methods are useful, and have found extensive applications in synthesis; however, the development of more general and practical approaches based on organocatalysis is highly desirable.…”

“…These approaches rely on 9‐azabicyclo[3.3.1]nonan‐ N ‐oxyl (ABNO), (2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO), and rose Bengal as green organocatalytic systems . The methods mentioned above and some other reported methods are useful, and have found extensive applications in synthesis; however, the development of more general and practical approaches based on organocatalysis is highly desirable. As part of our ongoing research into the development of new catalytic approaches, limiting the use of excess amounts of reagents, we aimed to investigate an alternative protocol for the synthesis of these scaffolds using easy‐to‐operate synthetic tools.…”