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

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.