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. 2010 Jul 14;132(27):9335-40.
doi: 10.1021/ja1009162.

Origins of stereoselectivity in the trans Diels-Alder paradigm

Robert S Paton  1 , Joel L Mackey, Woo Han Kim, Jun Hee Lee, Samuel J Danishefsky, K N Houk
Affiliations

Origins of stereoselectivity in the trans Diels-Alder paradigm

Robert S Paton et al. J Am Chem Soc. .

Abstract

The regioselectivity and stereoselectivity aspects of the Diels-Alder/radical hydrodenitration reaction sequence leading to trans-fused ring systems have been investigated with density functional calculations. A continuum of transition structures representing Diels-Alder and hetero-Diels-Alder cycloadditions as well as a sigmatropic rearrangement have been located, and they all lie very close in energy on the potential energy surface. All three pathways are found to be important in the formation of the Diels-Alder adduct. Reported regioselectivities are reproduced by the calculations. The stereoselectivity of radical hydrodenitration of the cis-Diels-Alder adduct is found to be related to the relative conformational stabilities of bicyclic radical intermediates. Overall, the computations provide understanding of the regioselectivities and stereoselectivities of the trans-Diels-Alder paradigm.

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Figures

Figure 1
Figure 1
Transition structures and adducts for the cycloaddition of 2,3-dimethyl-1,3-butadiene and 1-nitrocyclohexene. Selected distances shown in Å, B3LYP/6-31G(d) relative free energies, with M06-2X/6-31G(d) in parentheses, shown in kcal/mol.
Figure 2
Figure 2
Summary of the low energy transition structures leading to the formation of the DA adduct.
Figure 3
Figure 3
Transition structures for the cycloadditions of isoprene and 1-nitrocyclohexene. Selected distances shown in Å, B3LYP/6-31G(d) relative free energies, with M06-2X/6-31G(d) in parentheses, in kcal/mol.
Figure 4
Figure 4
[3,3]-Sigmatropic rearrangement transition structures in the cycloaddition of isoprene and 1-nitrocyclohexene. Selected distances shown in Å, B3LYP/6-31G(d) relative free energies, with M06-2X/6-31G(d) in parentheses, in kcal/mol.
Figure 5
Figure 5
Solvent effects on the energetics of the cycloadditions of 1,3-butadiene and 1-nitrocyclohexene. Selected distances shown in Å, B3LYP/6-31G(d) relative free energies in kcal/mol, compared with implicit CPCM values in parentheses and gas-phase values in italics.
Figure 6
Figure 6
Bicyclic radicals and connecting transition structure, and hydrogen transfer TSs and dehydrodecalin products in the cycloaddition of 2,3-dimethyl-1,3-butadiene and 1-nitrocyclohexene. Selected distances shown in Å, UB3LYP/LANL2DZ relative free energies, UM06-2X/LANL2DZ in parentheses, in kcal/mol.
Figure 7
Figure 7
6,5-Bicyclic radicals and connecting transition structure, and hydrogen transfer TSs and bicyclic products in the cycloaddition of 2,3-dimethyl-1,3-butadiene and 1-nitrocyclopentene. Selected distances shown in Å, UB3LYP/LANL2DZ relative free energies, UM06-2X/LANL2DZ in parentheses, in kcal/mol.
Scheme 1
Scheme 1
The trans Diels-Alder paradigm involving a cis-dienophile.
Scheme 2
Scheme 2
Cycloadditions of 1-nitrocyclohexene and hydrocarbon dienes. MW = microwave irradiation.
Scheme 3
Scheme 3
Diels-Alder (DA) and hetero-Diels-Alder (HDA) cycloadditions of nitroalkenes.
Scheme 4
Scheme 4
Radical hydrodenitration of the DA adduct to yield trans-fused decalins.
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