INVERSE ELECTRON DEMAND DIELS-ALDER REACTIONS OF N-SULFONYL ALPHA,BETA-UNSATURATED IMINES - A GENERAL-APPROACH TO IMPLEMENTATION OF THE 4-PI PARTICIPATION OF 1-AZA-1,3-BUTADIENES IN DIELS-ALDER REACTIONS

Full details of a study of the inverse electron demand Diels-Alder reactions of N-sulfonyl-1-aza-1,3-butadienes are described. The alpha,beta-unsaturated N-sulfonylimines proved accessible through clean, homolytic rearrangement of in situ generated oxime O-sulfinyl compounds or through direct condensation of sulfonamides with alpha,beta-unsaturated aldehydes. Thermal- or pressure-promoted [4 + 2] cycloaddition reactions of the N-sulfonyl-1-aza-1,3-butadienes with electron-rich olefins generally provided a single cycloadduct derived from predominant (greater-than-or-equal-to 20:1) cycloaddition through an endo transition state. The complementary C3 addition of an electron-withdrawing substituent to the N-sulfonyl-1-aza-1,3-butadienes substantially accelerated their participation in the LUMO(diene)-controlled Diels-Alder reactions and such reactions may be conducted at 25-degrees-C. Characteristic of a concerted [4 + 2] cycloaddition reaction, the reactions were found to proceed with full preservation of the dienophile olefin stereochemistry, to exhibit little solvent dependency on the [4 + 2] cycloaddition rate, trans 1,2-disubstituted dienophiles were shown to be more reactive than cis 1,2-disubstituted dienophiles, and the cis versus trans 1,2-disubstituted dienophiles were shown to exhibit a preferential pressure-induced rate acceleration. In addition, the noncomplementary C2 or C4 addition of an electron-withdrawing substituent to the N-sulfonyl-1-aza-1,3-butadienes accelerated the azadiene participation in LUMO(diene)-controlled Diels-Alder reactions (25-degrees-C) that maintain the regioselectivity and endo diastereoselectivity of the parent azadienes and that display characteristics consistent with concerted [4 + 2] cycloaddition reactions. Computational studies support the observed endo diastereoselectivity that may be derived from a pronounced, stabilizing secondary orbital interaction. However, the unusually high endo diastereoselectivity (greater-than-or-equal-to 20:1) suggests this may only be part of the origin of the cycloaddition selectivity. It is suggested that the endo [4 + 2] cycloaddition transition state in which the lone pair on nitrogen and the sigma-C-O bond of the dienophile lie trans periplanar further benefits from a n-sigma* stabilization in a manner analogous to the product ground-state conformation (anomeric effect).