A New Synthetic Route to Acylnitroso Intermediates and Their Applications in HDA and Ene Reactions

Author(s): Ahmad Fakhruddin, Abdel-Moneim Abu-Elfotoh*, Kazutaka Shibatomi, Seiji Iwasa

Journal Name: Letters in Organic Chemistry

Volume 15 , Issue 3 , 2018

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Graphical Abstract:


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 active products.

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.

Keywords: Acylnitroso intermediates, diels-alder reactions, HDA, hydrogen peroxide, ruthenium, Iridium.

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Article Details

Year: 2018
Published on: 07 February, 2018
Page: [196 - 205]
Pages: 10
DOI: 10.2174/1570178614666170710101309
Price: $65

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