VCD configuration of enantiopure/-enriched tetrasubstituted alpha-fluoro cyclohexanones and their use for epoxidation of trans-olefins.

The configurations of three enantiopure tetrasubstituted alpha-fluoro cyclohexanones (-)-5Ia, (-)-5IIa and (-)-6a were determined by VCD and proved to be (-)-(2S,5R)-5Ia, (-)-(2R,5R)-5IIa, and (-)-(2R,5R)-6a. The VCD study also identified the conformers populated in CDCl3 solution, including higher-energy gas-phase conformers with equatorial fluorine for 5Ia and 5IIa that are stabilized in CDCl3 solution. Used as catalysts for epoxidation of trans olefins (beta-methylstyrene, stilbene, methyl p-methoxy cinnamate) by oxone, it was found that (-)-5Ia is the most efficient for all trans olefins (providing, respectively, 62%, 90% and 66% ee) but that all three ketones provide high ee% with stilbene (78-90% ee). Moreover, the configurations predicted from the stereo outcome of the epoxidation reaction are identical to those determined by VCD.

Trans-diaryl epoxides: asymmetric synthesis, ring-opening, and absolute configuration.

Anthryl-phenyl, phenanthryl-phenyl, and naphthyl-phenyl trans-epoxides (1, 2, and 3, respectively) having enantiomeric purities of 95%, 99%, and 96% were synthesized from a diastereo and enantiopure sulfonium salt derived from Eliel's oxathiane. The determination of their (1R,2R) absolute configurations was achieved by application of the CD exciton chirality method using a Zn-porphyrin tweezer on the corresponding alcohols obtained after opening of these epoxides with LiAlH(4). The R-configuration at C2 of these epoxides, (-)-1, (+)-2, and (-)-3, is consistent with our previous results concerning asymmetric synthesis of monoaryl epoxides, cyclopropanes, and aziridines. The (1S,2R)-configuration of the cis isomer (when present) was also confirmed. Moreover, the agreement between the negative exciton chirality for conjugates of (S)-configuration predicted by molecular modeling and the observed CD spectra helps to clarify the relative steric size of phenyl and CH(2)-aryl (phenanthryl or anthryl), which is critical when the tweezer method is applied for absolute configurational assignment (phenyl = medium group; anthacenyl CH(2) and phenanthryl CH(2) = large group).

erythro-1-Naphthyl-1-(2-piperidyl)methanol: synthesis, resolution, NMR relative configuration, and VCD absolute configuration.

The erythro isomer of 1-naphthyl-1-(2-piperidyl)methanol 4, an efficient chiral modifier for asymmetric heterogeneous hydrogenation, was obtained as the major isomer (95%) in two steps while the threo isomer can be obtained as the major isomer (67%) in three steps. erythro-4 and threo-4 were resolved on a CHIRALCEL OD-RH column. It has been shown by VCD that the diastereomer determined as the erythro by NMR was indeed the erythro and that the first eluted (-)-enantiomer on CHIRALCEL OD-R or -RH columns has the (1R,2S) configuration. The VCD studies identify the presence of at least five conformers in CDCl(3) solution. Moreover, this (-)-(1R,2S) absolute configuration found by VCD is consistent with the expected stereo-outcome of catalytic hydrogenation of pyruvate into lactate, which supported the (+)-(1S,2R) assignment.

Epoxidation of p-methoxycinnamates using chiral dioxiranes derived from new trisubstituted halogenated cyclohexanones: enhanced efficiency of ketones having an axial halogen

Epoxidation of p-methoxycinnamates using substoichiometric amounts of chiral and enantiopure dioxiranes generated in situ from chiral trisubstituted chloro and fluoro cyclohexanones showed that ketones with an axial Cl or F were more efficient than ketones with an equatorial Cl or F, that increasing the steric hindrance in the alpha-position (isopropyl instead of methyl) decreased the efficiency, and that the alpha-fluoro ketone 5a (axial fluorine) was the most efficient (82% conversion and 46% ee in (-)-epoxide).