Lithium Salts of Conformationally Constrained and Restricted Chiral Allylic α-Sulfonyl Carbanions − A Joint Study of their Structures, Dynamics, and Stereoselectivities

Abstract

The structures of the lithium salts of the chiral bicyclic allylic α-sulfonyl carbanions 3−5, each possessing a norbornane skeleton and a tert-butyl group at the S atom, have been studied by 1H, 13C, 6Li, and 6Li,1H HOESY NMR spectroscopy, cryoscopy, and X-ray crystal structure analysis. Because of their relatively high endo-exo isomerization barriers, the Cα−S endo and exo diastereomers of 3−5 could be observed by NMR spectroscopy at −30 °C to −50 °C in [D8]THF. The endo diastereomer is the preferred equilibrium species under these conditions, as shown by 1H,1H HOESY experiments. Carbanion salt 3 has endo-exo isomerization barriers of ΔG#270 = 13.1±0.1 kcal/mol and 12.6±0.1 kcal/mol, while the 7-benzhydrylidene-substituted carbanion salt 5 has barriers of ΔG#288 = 13.5±0.1 kcal/mol and 13.3±0.1 kcal/mol. Cryoscopy and 6Li NMR spectroscopy of 5 in THF at −100 °C to −108 °C revealed the formation of dimers and monomers in a ratio of approximately 2:1. NMR spectroscopy of 3−5 at −90 °C to −105 °C allowed observation of the dimers and monomers of which the anions have endo conformations and also of which the anions adopt exo conformations. The NMR spectroscopic results for 3−5 are compatible with monomeric and dimeric CIPs, featuring planar allylic moieties and allylic stabilization by delocalization of the negative charge. 6Li,1H-HOESY examination of the mixture of the monomers and dimers of endo-5 and exo-5 in [D8]THF at room temperature gave only evidence for coordination of the Li atom to the O atom(s) in the CIPs. The NMR spectroscopic results for 3 were corroborated by X-ray crystal structure analysis of the monomer exo-3·PMDETA, which features (i) an essentially planar anionic C(2) atom, (ii) the exo conformation, (iii) the typical Cα−S conformation, also allowing for a stabilizing nC−σ*StBu interaction, and (iv) a single O−Li bond, but no C−Li bond. Upon treatment of the endo and exo sulfones 9, 10, and 12 with nBuLi at very low temperatures, the corresponding endo and exo carbanion salts endo-3−5 and exo-3−5, respectively, were selectively generated as mixtures of monomers and dimers, the reactions of which with electrophiles were studied. Deprotonation of the exo and endo sulfones with nBuLi proceeds stereoselectively, the exo sulfone preferentially giving the endo anion and vice versa. The diastereomeric endo and exo carbanion salts 3−5 each react with reactive electrophiles at the anionic C(2) atom syn to the sulfonyl O atoms, giving the corresponding substituted endo and exo sulfones, respectively, with significant degrees of asymmetric induction. Reactions of the endo and exo diastereomers of 3−5 with CF3COOD and MeOCH2I were faster than their endo-exo isomerization and approached kinetic quenching, while those with MeI and allyl iodide were slower, approaching the Curtin−Hammett limit and preferentially giving the exo sulfones. Deprotonation-deuteration experiments of the 7-oxa-sulfone endo-11 showed that the corresponding 7-oxa-substituted carbanion salts endo-6 and exo-6 not only can be generated at low temperatures but may also, despite their tendency to rearrange, be converted into the corresponding 7-oxa-sulfones on treatment with reactive electrophiles.