Regioselectivity in the Cu(I)-Catalyzed [4 + 2]-Cycloaddition of 2-Nitrosopyridine with Unsymmetrical Dienes

Abstract

The thermal (uncatalyzed) and Cu(I)-catalyzed reactions of 2-nitrosopyridine (PyrNO) with the dienes 1,3-pentadiene, E,E-2,4-hexadienol, and 1-phenylbutadiene are investigated experimentally and computationally. The uncatalyzed reactions of the first two dienes occur with low regioselectivity, while the latter proceeds with complete proximal selectivity. Using the M06/6-311+G(d,p)-SDD method, various concerted transition states for the reactions of 2-nitrosopyridine with (E)-1,3-pentadiene and 1-phenylbutadiene were computed. In quantitative agreement with the experimental findings, (a) no energy difference (0.0 kcal/mol) is found between the most stable transition states, endo-prox-anti and endo-dist-anti, in the pentadiene/PyrNO reaction, leading to nearly equal amounts of prox and dist cycloadducts, and (b) the proximal transition state is strongly favored (by 3.7 kcal/mol) over the distal for the highly selective phenylbutadiene/PyrNO reaction. The regioselectivity of the pentadiene/PyrNO reaction is improved markedly (90:10 dist/prox) when catalyzed by Cu(CH3CN)4(+); (diimine)2Cu(+) catalysts increase selectivity for the proximal product (55-65%). Modest effects of the catalyst nature on regioselectivity are observed in the sorbyl alcohol and 1-phenylbutadiene reactions. The relative affinity of an equilibrating set of (diimine)2Cu(+) complexes for the prox and dist cycloadducts, assessed by ESI-MS, is marginally correlated with the prox/dist product regioselectivity produced by the corresponding catalysts. Transition states in the Cu(CH3CN)4(+)- and Cu(diimine)2(+)-catalyzed reactions are located that account for the observed regioselectivities. Coordination effects on the regioselectivity are derived from FMO orbital interactions and the extent of electron transfer between the Cu center and the coordinated nitroso and diene units.

Generating Skeletal Diversity and Complexity from Boron‐Substituted 1,3‐Dienes and Enophiles

“…To extend the scope of the ene reactions of dienyl boronates, we then examined the reactivity of 1a towards other enophiles. 2‐Nitrosopyridine, prepared according to the method of Taylor et al, has already been used to react with a variety of substituted alkenes to give the corresponding ene products, while 1,3‐dienes afforded the corresponding 3,6‐dihydro‐ 2H ‐1,2‐oxazines . In our case, we also observed a unique [4+2] cycloaddition/ring contraction sequence in methanol or ethyl acetate and 3‐methyl‐1‐(2‐pyridyl)‐pyrrole 5 was only detected by 1 H NMR with respective conversions of 43 and 14 % after 16 h. With 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP), the reaction is much faster, with 78 % conversion after 3.5 h, and the formation of the ene product 6 was mainly observed (Scheme ).…”

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

“…This was demonstrated by Miller in both higher temperature and Cu(I)-mediated hetero-Diels–Alder reactions of a chiral ligand with nitroso-heteroarene reactants [91]. Nicholas and co-workers investigated the thermal (uncatalyzed) and Cu(I)-catalyzed reactions of 2-nitrosopyridine with various dienes [92]. …”

Theoretical Calculations on the Mechanism of Enantioselective Copper(I)-Catalyzed Addition of Enynes to Ketones

“…As THF was used as the solvent in the actual experiments [67], the latter calculations in the actual system were carried out with a dielectric constant ε = 7.43 for the solvent THF. For evaluating the solvent effects, the free energies were calculated at the M06/6-311+G(d,p) [60,75] level and added to the gas phase free energy to obtain the Gibbs energy in THF (G solv ) at 298.15 K. Unless otherwise stated, G solv is used in the discussion and the energy levels refer to the G solv scale.…”