Asymmetric epoxidation of homoallylic alcohols. Synthesis of (-)-.gamma.-amino-.beta.-(R)-hydroxybutyric acid (GABOB)

Abstract

Asymmetric epoxidation of seven homoallylic alcohols using the Ti(0-t-Pr)4, (+)or (-)-diethyl tartrate, and ferf-butyl hydroperoxide system is described. Enantiomeric purities range from 23% to 55%. Interestingly, the enantiofacial selection is opposite that observed for allylic alcohols. Characteristics of the reaction and product isolation are discussed. Synthetic utility is demonstrated by the synthesis of the title compound in three steps from epoxy alcohol lb.

Asymmetric 1,4-additions to 5-alkoxy-2(5h)-furanones

“…Several important applications of optically active 3,4-epoxy-1-butanol have been recently described for instance the synthesis of all four stereoisomers of the insect pheromones of Paresvespula vulgaris L. 6 This is further illustrated by the asymmetric synthesis of (-)-γ-amino-β-(R)-hydroxybutyric acid ((-)-GABOB), an antiepileptic and hypotensive drug, in 49% enantiomeric excess via (R)-4. 3 Both enantiomers of these products are now readily available using the asymmetric synthesis procedures described here. In conclusion we have synthesized new multifunctional C4-chiral synthons and have found an efficient route to enantiomerically pure (R)-and (S)-3,4-epoxy-1-butanol.…”

Enantioselective synthesis of epoxides via Sharpless epoxidation of alkenylsilanols

“…Since the atomic radius of silicon is considerably larger than that of carbon, it seems that the stereoelectronic requirement in the epoxidation step may be sufficiently flexible to accommodate the increased bond length of Si-0 and Si-C bonds in the alkenylsilanol. This is to be contrasted with the epoxidation of homoallylic alcohols where the enantioselectivity was found to be poor (19). Furthermore, the face selection in the epoxidation of homoallylic alcohol is opposite from that observed for allylic alcohols (19) and alkenylsilanols.…”

“…This is to be contrasted with the epoxidation of homoallylic alcohols where the enantioselectivity was found to be poor (19). Furthermore, the face selection in the epoxidation of homoallylic alcohol is opposite from that observed for allylic alcohols (19) and alkenylsilanols. This suggests that the facial selection is governed less by the distance between the double bond and the hydroxy group than by the relative angle of the two functionalities.…”

“…The crude product was therefore used directly for the following step without purification. Compound ( -) -I ,2-Epo.r,.heptcr11e (19) A solution of compound 18 (0.10 g, 0.52 mmol) and tetraethylammonium fluoride hydrate (1.2 g, 3.5 mmol) in acetonitrile (2 mL) was stirred at 60°C for 6 h. The mixture was partitioned between water and pentane-ether (20: 1) solutions. The organic phase was dried (MgSO,) and the solvent removed by careful distillation.…”

Optically active chlorohydrins as chiral C3 and C4 building units: Microbial resolution and synthetic applications

“…Also, optically active CHB and BN are key compounds for the syntheses of L-carnitine and L-GABOB. 11,12 We have been studying microbial conversion of halogenated compounds and have isolated several unique microorganisms with novel stereoselective dehalogenase and stereoselective assimilating activity. [13][14][15] By using this microbial resolution we have succeeded in producing highly optically active DCP, CPD, EP, and GLD.…”