An Experimental and Computational Approach to Understanding the Reactions of Acyl Nitroso Compounds in [4 + 2] Cycloadditions

  • J Org Chem. 2015 Oct 2;80(19):9518-34. doi: 10.1021/acs.joc.5b01470.
Duangduan Chaiyaveij  1 ,  Andrei S Batsanov  2 ,  Mark A Fox  2 ,  Todd B Marder  3 ,  Andrew Whiting  2
Affiliations
  • 1. Chemistry Department, Faculty of Science and Technology, Thammasat University Rangsit Campus , Khlongluang, Pathumthani 12120, Thailand.
  • 2. Centre for Sustainable Chemical Processes, Department of Chemistry, Durham University, Science Laboratories , South Road, Durham DH1 3LE, United Kingdom.
  • 3. Institut für Anorganische Chemie, Julius-Maximilians-Universität Würzburg , Am Hubland, 97074 Würzburg, Germany.
PMID: 26340265 DOI: 10.1021/acs.joc.5b01470
Abstract

Catalytic aerobic oxidation of phenyl hydroxycarbamate 1 and 1-hydroxy-3-phenylurea 2 using CuCl2 and 2-ethyl-2-oxazoline in methanol gave acyl nitroso species in situ, which were trapped in nitroso-Diels-Alder (NDA) reactions with various dienes to afford the corresponding cycloadducts in high yields (90-98%). Competing ene products were also present for dienes containing both alkene π-bonds and allylic σ-bonds, and the ene yields are higher with 1 than with 2. The use of the chiral hydroxamic acid, (R)-1-hydroxy-3-(1-phenylethylurea) 3 (same conditions) gave NDA cycloadducts in high yields (97-99%) with no ene product from 2,3-dimethyl-1,3-butadiene. NDA cycloadducts were not obtained from Other hydroxamic acid analogues [RCONHOH (R = PhCH2 4; Ph(CH2)2 5; Ph(CH2)3 6; Ph(CH2)4 7; Ph 8; 2-pyridyl 9; 3-pyridyl 10] with various dienes using copper-oxidation but rather were obtained using sodium periodate, resulting in variable NDA yields (13-51%) from hydroxamic acids 1-10 with cyclohexa-1,3-diene and 2,3-dimethyl-1,3-butadiene (several cycloadducts characterized by X-ray crystallography). The NDA and nitroso-ene reaction pathways of nitroso intermediates with dienes were mapped by DFT computations (B3LYP/6-31G*), which showed that the acyl nitroso species are super-reactive and that activation energies in the NDA processes are lower than the isomerization barriers between some cis- and trans-butadienes.

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