Hydroxamic acid, alcohol epoxidation

Metal alkoxides undergo alkoxide exchange with alcoholic compounds such as alcohols, hydro-xamic acids, and alkyl hydroperoxides. Alkyl hydroperoxides themselves do not epoxidize olefins. However, hydroperoxides coordinated to a metal ion are activated by coordination of the distal oxygen (O2) and undergo epoxidation (Scheme 1). When the olefin is an allylic alcohol, both hydroperoxide and olefin are coordinated to the metal ion and the epoxidation occurs swiftly in an intramolecular manner.22 Thus, the epoxidation of an allylic alcohol proceeds selectively in the presence of an isolated olefin.23,24 In this metal-mediated epoxidation of allylic alcohols, some alkoxide(s) (—OR) do not participate in the epoxidation. Therefore, if such bystander alkoxide(s) are replaced with optically active ones, the epoxidation is expected to be enantioselective. Indeed, Yamada et al.25 and Sharp less et al.26 independently reported the epoxidation of allylic alcohols using Mo02(acac)2 modified with V-methyl-ephedrine and VO (acac)2 modified with an optically active hydroxamic acid as the catalyst, respectively, albeit with modest enantioselectivity. 

The development of transition metal mediated asymmetric epoxidation started from the dioxomolybdcnum-/V-cthylcphcdrinc complex,4 progressed to a peroxomolybdenum complex,5 then vanadium complexes substituted with various hydroxamic acid ligands,6 and the most successful procedure may now prove to be the tetroisopropoxyltitanium-tartrate-mediated asymmetric epoxidation of allylic alcohols. 

SCHEME 60. Optically active hydroxamic acid ligands for the vanadium-catalyzed asymmetric epoxidation of allylic alcohols,... 

Prior to the usage of the Ti-based catalytic system , the Sharpless group had reported their first asymmetric epoxidation of allylic alcohols using a combination of VO(acac)2/ TBHP and the chiral hydroxamic acid 67 (ee < 50%) or derivatives (ee 80%) ". In 1999, Yamamoto and coworkers described an improvement of this oxidation protocol, ee values up to 94%, by using hydroxamic acids derived from binaphthol, 68 being the... 

With a twist on the Sharpless asymmetric epoxidation protocol, Yamamoto and co-workers <99JOC338> have developed a chiral hydroxamic acid (17) derived from binaphthol, which serves as a coordinative chiral auxiliary when combined with VO(acac)j or VO(i-PrO)j in the epoxidation of allylic alcohols. In this protocol, triphenylmethyl hydroperoxide (TiOOH) provides markedly increased enantiomeric excess, compared to the more traditional t-butyl hydroperoxide. Thus, the epoxidation of E-2,3-diphenyl-2-propenol (18) with 7.5 mol% VO(i-PiO)3 and 15 mol% of 17 in toluene (-20 °C 24 h) provided the 2S,3S epoxide 19 in 83% ee. 

The asymmetric epoxidation of allylic alcohols with cumene hydroperoxide or rerf-butyl hydroperoxide (TBHP) was first examined by using chiral amino alcohol-Mo complexes 45) and V complexes with chiral hydroxamic acid ligands (Scheme 20) 46). The highest optical yields were 33% with geraniol and 50% with 2-phenylcinnamyl alcohol. Combined use of VO(acac)2 and a hydroxamic acid derived from proline led to 80% optical yield with 2-phenylcinnamyl alcohol 47). 

The asymmetric epoxidation of homoallylic alcohols has continued to be a problematic area. A potential solution has recently been published <07JA286 07T6075>. The use of bis-hydroxamic acid 1 as a chiral ligand for a vanadium catalyst has provided both excellent yields and enantioselectivity. This method works well with both cis- and trans-alkenes. 

R. C. Michaelson, R. E. Palermo, K. B. Sharpless, Chiral hydroxamic acids as ligands in the vanadium catalyzed asymmetric epoxidation of allylic alcohols by tert-butyl hydroperoxide, /. Am. Chem. Soc. 99 (1977) 1990. 

When bomeol or camphor is heated with solid potassium hydroxide to 250-280 °C, ring cleavage of the bicyclic system occurs and the product, campholic acid 68, can be isolated in high yield65-67. Thus, (-)-borneol gives ( + )-campholic acid [( + )-68], which has been used as the hydroxamic acid derivative as a chiral ligand for a vanadium catalyst in the enantioselective epoxidation of allylic alcohols (Section D.4.5.2.4.). 

Yamamoto took a similar approach for the epoxidation of allyUc and homoallyhc alcohols (Schane 4.20). This process employed chiral hydroxamic acid ligand 101 to induce stereocontrol and VO(OtPr)3 to serve as the Lewis acid [49]. ( )-HomoaIlyhc alcohol 102 was converted to epoxide 103... 

SCHEME 34.15. Asymmetric epoxidation of allyl alcohols 54 leading to enantioenriched epoxides 56 mediated by vanadium(V) catalysts with a chiral hydroxamic acid ligand 55 and t-butyl hydroperoxide as a terminal oxidant. 

The retrosynthetic analysis proposed by Yamamoto et is based on the asymmetric epoxidation of a homoallylic alcohol 58 obtained from (5)-limonene (Scheme 34.16). The (5)-homoallyl alcohol 58 was epoxidized diastereoselectively using hydroxamic acid 59 as ligand to give the corresponding epoxy alcohol 60 with 84% yield and 90% de. 

Hoshino Y, Yamamoto H. Novel a-amino acid-based hydroxamic acid hgands for vanadium-catalyzed asymmetric epoxidation of aUylic alcohols. J. Am. Chem. Soc. 2000 122 10452-10453. 

SCHEME 35.6. Asymmetric epoxidation of homoallylic alcohols catalyzed by vanadium-chiral-hydroxamic-acid complexes. 

General experimental procedure for Yamamoto epoxidation of homoallylic alcohols To a mixture of hydroxamic acid 21 (0.02 mmoi) and toiuene (0.25 mL) at room temperature was added VO(0/-Pr)3 (0.01 mmol). The mixture was stirred at room temperature for 8hours. After that time, 88% cumene hydroperoxide (1.5 mmol) was added, followed by homoallyhc alcohol (l.Ommol). The reaction mixture was stirred for 24 hours and then quenched by the addition of trimethyiphos-phite (1.5 mmol). The mixture was extracted with ethyi acetate. The combined organic layers were dried over Na2S04, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gei to give the desired epoxide. 

Yamamoto has studied a variety of readily available, chiral hydroxamic-acid based ligands, which have proven effective in vanadium-catalyzed enantioselective epoxidations of allylic (Equation 14) [84, 85] and homoallylic alcohols (Equation 15) [86], as well as in molybdenumunfunctionalized olefins [87], For example, treatment of 74 and 77 with tert-BuOOH and 1 mol % vanadium catalyst 75 furnished epoxides 76 and 78 in 97 and 91 % ee, respectively [85]. 

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