Harnessing the TEMPO-Catalyzed Aerobic Oxidation for Machetti–De Sarlo Reaction toward Sustainable Synthesis of Isoxazole Libraries

A practical synthesis of isoxazole/isoxazoline
derivatives via
Machetti–De Sarlo reaction under sustainable conditions has
been accomplished. This protocol involves the use of readily available
2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) to catalyze
the cyclocondensation of primary nitroalkanes with alkynes/alkenes
to afford a library of isoxazole/isoxazoline products. From an eco-benign
perspective, notable advantages of this method are as follows: (i)
water as the solvent, (ii) air as the oxidant, (iii) transition metal-free,
(iv) no base required, (v) no toxic byproduct, (vi) no need of solvent
extraction, (vii) diverse substrate scope, (viii) high chemical yields,
(ix) excellent chemo- and regioselectivity, (x) short reaction time,
(xi) gram-scale synthesis, (xii) extension to heterogeneous version,
and (xiii) catalyst recyclability. For these reasons, the developed
method is appropriate for safe laboratory use and can be expected
to inspire the progress of TEMPO-based organocatalysis for the preparation
of isoxazole/isoxazoline moieties in an environmentally benign fashion.