Background: Acylnitroso intermediates are considered as highly reactive and useful transient
that have been used to synthesize a broad class of biological active compounds and synthetic
drugs. Although there are some reported methods for the generation of these intermediates, but still
challenge for mild and environmental benign protocol. Herein, we report the facile in situ synthesis of
acylnitroso intermediates and their efficient hetero Diels-Alder (HDA) and ene reactions.
Methods: Acylnitroso intermediates were readily obtained by hydrogen peroxide oxidation of hydroxamic
acids catalyzed by Cu(I)-, Ir(I)- or Ru(II)-complexes and easily reacted with symmetric and
asymmetric conjugated dienes beside their reaction with different alkenes which converted to biological
Results: The resulted acylnitroso intermediates were efficiently afforded the hetero Diels-Alder cycloadducts
in the presence of cyclopentadiene, cyclohexadiene or α-terpinene in high yields along with
good regioselectivity for the later. In case of N-dienyl lactams, the cycloadducts were formed in the
yield up to 89% with complete regioselectivity. In the presence of optically active N-dienyl pyroglutamates,
diastereoisomers were formed in high yields with up to 72 de. In addition, the transient acylnitroso
species were trapped with alkene to form the ene product in yield up to 95 %. As an interesting
transformation, the halocyclization of the ene products gave substituted oxazolidone in 77% yield
which considered as one of the effective antimicrobial and antibiotic compounds.
Conclusion: In a brief, we introduce a mild and effective route to deliver acylnitroso intermediates in
situ by using environmentally benign, cost effective, and non-toxic hydrogen peroxide oxidant catalyzed
by Cu(I)-, Ir(I)- or Ru(II)-complexes. Good to excellent yields, regio- and diastereoselectivity
were obtained by trapping these intermediates in symmetric and asymmetric HDA and ene reactions.
Interestingly, the ene products easily transformed to potent drugs.