Cycloaddition Reactions of a Nitrogen-Substituted Oxyallyl Cation with Cyclopentadiene and Substituted Furans. Reaction Conditions, Diastereoselectivity, Regioselectivity, and Transition State Modeling

Abstract

An investigation of the cycloaddition reactions of a nitrogen-substituted oxyallyl cation is presented. The nitrogen-substituted oxyallyl cation, M+-1 (M+ = H+ or Li+), can be generated from the dibromide 2 using either CF3CH2OH/Et3N or LiClO4/CH3CN/Et3N. These oxyallyl cations were found to undergo [4 + 2] cycloaddition reactions with furan, cyclopentadiene, 2-methylfuran, and 2-methoxyfuran. The diastereo- and regioselectivities in these reactions were found to be positively influenced by the presence of Li+. Reaction of M+-1 with the 2-substituted furans led to primarily those adducts arising from endo addition (as was observed with the unsubstituted dienes) and which had the 2-substituent syn to the bromine. Consideration of the frontier molecular orbitals of the reacting species (Li+-1 and 2-substituted furans calculated at the PM3 semiempirical level of theory) led to the conclusion that FMO theory does not explain the regiochemistry observed in this process, although the relative electrophilicity of M+-1 (M+ = H+ or Li+) could be rationalized. Transition structure modeling was consistent with empirical observations in that it predicted an endo addition of furan to Li+-1 via a stepwise reaction. Calculation of the reaction coordinate for this nonconcerted process predicted a ΔH rxn ∼ −50 kcals/mol and ΔH act ∼ +11 kcal/mol, with the second bond-forming process having a ΔH act ∼ +1.7 kcal/mol.

Stereoselectivities and Regioselectivities of (4 + 3) Cycloadditions Between Allenamide-Derived Chiral Oxazolidinone-Stabilized Oxyallyls and Furans: Experiment and Theory

“…Walters 5 generated nitrogen-substituted oxyallyl intermediates from the α,α’-dihalide 3 , by treatment with either Et 3 N in trifluoroethanol or Et 3 N/LiClO 4 in acetonitrile. Both reacted with 2-methylfuran or 2-methoxyfuran to give predominantly anti adducts ( 4b ).…”

(4+3) Cycloaddition Reactions of Nitrogen‐Stabilized Oxyallyl Cations

“…16 In all cases, the anti regiochemistry ( 19a and 19b ) was favored having the phthalimide and furan substituent on opposite sides of the cycloadduct. A small amount of the exo (extended) 17 product was obtained in each case.…”

“…16,23,24 However, there have been few systematic studies concerning the regioselectivity of oxyallyls and the influence of substituents on the diene. 3e,23 Furthermore, there had not been any coherent let alone predictive model reported for the regioselectivities in (4 + 3) cycloadditions.…”

“…4a,16,26,36. In contrast, nitrogen-substituted oxyallyl cations are a distinct class of oxyallyl displaying ambiphilic properties and thus, are truly stabilized oxyallyl cations.…”

“…The use of nitrogen-stabilized oxyallyl cations with unsymmetrical dienes in (4 + 3) cycloadditions has been reported to provide high levels of regioselectivity in many cases. [16,23,24] However, there have been few systematic studies concerning the regioselectivity of oxyallyls and the influence of substituents on the diene. [3e, 23] Furthermore, there had not been any coherent let alone predictive model reported for the regioselectivities in (4 + 3) cycloadditions.…”