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

The thermal (uncatalyzed) and Cu­(I)-catalyzed reactions of 2-nitrosopyridine (PyrNO) with the dienes 1,3-pentadiene, <i>E</i>,<i>E</i>-2,4<i>-</i>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 <i>proximal</i> selectivity. Using the M06/6-311+G­(d,p)–SDD method, various concerted transition states for the reactions of 2-nitrosopyridine with (<i>E</i>)-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, <i>endo-prox-anti</i> and <i>endo-dist-anti,</i> in the pentadiene/PyrNO reaction, leading to nearly equal amounts of <i>prox</i> and <i>dist</i> cycloadducts, and (b) the <i>proximal</i> transition state is strongly favored (by 3.7 kcal/mol) over the <i>distal</i> for the highly selective phenylbutadiene/PyrNO reaction. The regioselectivity of the pentadiene/PyrNO reaction is improved markedly (90:10 <i>dist</i>/<i>prox</i>) when catalyzed by Cu­(CH<sub>3</sub>CN)<sub>4</sub><sup>+</sup>; (diimine)<sub>2</sub>­Cu<sup>+</sup> catalysts increase selectivity for the <i>proximal</i> 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)<sub>2</sub>­Cu<sup>+</sup> complexes for the <i>prox</i> and <i>dist</i> cycloadducts, assessed by ESI-MS, is marginally correlated with the <i>prox</i>/<i>dist</i> product regioselectivity produced by the corresponding catalysts. Transition states in the Cu­(CH<sub>3</sub>CN)<sub>4</sub><sup>+</sup>- and Cu­(diimine)<sub>2</sub><sup>+</sup>-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.