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Regioselectivity in the Cu(I)-Catalyzed [4 + 2]-Cycloaddition of 2‑Nitrosopyridine with Unsymmetrical Dienes
journal contribution
posted on 2014-06-20, 00:00 authored by Anh T. Tran, Peng Liu, K. N. Houk, Kenneth M. NicholasThe 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.