Epoxidations of acyclic allylic alcohols

In the epoxidation of acyclic allylic alcohols (Scheme 6), the diastereoselectivity depends significantly on the substitution pattern of the substrate. The control of the threo selectivity is subject to the hydroxyl-group directivity, in which conformational preference on account of the steric interactions and the hydrogen bonding between the dioxirane oxygen atoms and the hydroxy functionality of the allylic substrate steer the favored 7r-facial... 

Allylic and cis-homoallylic alcohols are epoxidized readily, but frans-homoallylic and bishomoallylic alcohols react slowly, if at all. The stereoselectivity in the epoxidation of acyclic allylic alcohols is the same as and is comparable to that observed with r-BuOOH/VO(acac)2. The stereoselectivity in epoxidation of acyclic homoallylic alcohols is also the same but lower than that obtained with t-BuOOH/ VO(acac)2. Epoxidation of cyclic allylic alcohols proceeds more slowly and in lower yield than that of acyclic allylic alcohols. 

Epoxidation of acyclic allyl alcohols with peracid and Mo/TBHP displays an opposite stereospecificity to that for the V/TBHP system. Trimethylsilyl-substituted allylic alcohols give t/zreo-epoxyalcohols with MCPBA and erythro-alcohols with VO(acac)a-TBHP, with high stereoselectivity. In the stereospecific epoxidation of cis- and trans-allyl alcohols, formation of a transition state is assumed with the development of two H bonds between the hydrogen atom of the hydroxy group of the allyl alcohol and the oxygen of the peracid, and between the hydrogen of the peracid OH and the oxygen of the ether 10. An analysis of the diastereometric transition-state interactions for stereoselective epoxidation of acyclic allylic alcohols has been published. A conformational effect may be responsible for the unexpected cis major product in Eq. 2. 

WL Adam, A. K. Smerz, Solvent effects in the regio- aird diastereoselective epoxidations of acyclic allylic alcohols by dimethyldioxirane Hydrogen bonding as evidence for a dipolar transition state, J. Org. Chem. 61 (1996) 3506. 

W. Adam, C. M. Mitchell, C. R. Saha-Moller, Regio- and Diastereoselective Catalytic epoxidation of acyclic allylic alcohols with methyltrioxorhenium A mechanistic comparison with metal (peroxy and peroxo complexes) and nonmetal (peracids and dioxirane) oxidants, J. Org. Chem. 64 (1999) 3699. 

The development of Sharpless model was the result of a systematic investigation of the epoxidation reaction of a wide range of acyclic allylic alcohols [65], Two illustrative examples are shown below in Schemes 9.2 and 9.3. In the vanadium-catalyzed epoxidation of olefin 30, transition state 31 is believed to be favored. It includes an acute 0-C-C=C dihedral angle of 50° while at the same time, the dominant interactions are minimized (Scheme 9.2). In the epoxidation of 33 with a peracid, structure 34 incorporates an obtuse 0-C-C=C angle and concomitantly minimizes severe non-bonded A, j interactions (Scheme 9.3). 

Related catalytic enantioselective processes It is worthy of note that the powerful Ti-catalyzed asymmetric epoxidation procedure of Sharpless [27] is often used in the preparation of optically pure acyclic allylic alcohols through the catalytic kinetic resolution of easily accessible racemic mixtures [28]. When the catalytic epoxidation is applied to cyclic allylic substrates, reaction rates are retarded and lower levels of enantioselectivity are observed. Ru-catalyzed asymmetric hydrogenation has been employed by Noyori to effect the resolution of five- and six-membered allylic carbinols [29] in this instance, as with the Ti-catalyzed procedure, the presence of an unprotected hydroxyl function is required. Perhaps the most efficient general procedure for the enantioselective synthesis of this class of cyclic allylic ethers is that recently developed by Trost and co-workers, involving Pd-catalyzed asymmetric additions of alkoxides to allylic esters [30]. 

Table 8. Optimum Reported Diastereoselectivities in the Epoxidation of Simple Acyclic Allylic Alcohols and Their Silylated Synthetic Equivalents...

As far as the epoxidation of enantiomerically pure acyclic allylic alcohols is concerned, the Katsuki-Sharpless enantioselective epoxidation process can be applied (see Section 4.5.2.4.1. and Houben-Weyl, Vol. E13/2, p 1219, and Table 148, pp 1226-1230). If matched substrate/ catalyst combinations are employed, many, otherwise unselective, epoxidations may be rendered highly diastereoselective. 

For acyclic allylic alcohols, very little a,p-unsaturated enone formation was observed besides epoxidation. Chemoselectivity was much less for cyclic allylic alcohols, for which oxidation of fhe allylic alcohol group competed significantly with epoxidation. In the case of 2-cyclohexenol as the substrate, the enone was even found to be the main product. A comparative sandwich POM-catalyzed epoxidation study of various (subsfifufed) cycloalkenols revealed that the enone versus epoxide chemoselectivity is controlled by the C=C-C-OH dihedral angle Ma in the allylic alcohol substrate. The more this dihedral angle deviates from fhe optimum C=C-C-OW dihedral angle otw for allylic acohol epoxidation, the more enone is formed (Fig. 16.5). 

Vanadium catalysts have found particular advantage for stereoselective epoxi-dations. Thus, the acyclic allylic alcohol 34 is oxidized with high selectivity using t-BuOOH and vanadium acetylacetonate, whereas with mCPBA a nearly equal mixture of the diastereomeric epoxides was produced (5.45). 

Epoxidation of Acyclic Alkenes. Stereoselective epoxidation of a series of allylic carbamate methyl esters (eq 34), homoallylic alcohols (eq 35), and acetates (eq 36) could be performed with good to excellent stereocontrol. It is believed that the directing effect of the carbamate protecting group plays an important role in dictating the level of stereocontrol. 

Walsh developed a highly enantio- and diastereoselective one-pot method for the efficient synthesis of acyclic epoxy alcohols and allylic epoxy alcohols [263]. This method took the advantage of a highly enantioselective C-C bond-forming reaction to set the initial chirality. The resulting allylic zinc alkoxide intermediate is then epoxidized in situ using either O2 or TBHP in the presence of a titanium... 

The identification of a fundamentally new reaction such as the asymmetric epoxidation of allylic alcohols substantively alters the landscape of chemical synthesis such discoveries not only augment the available tactics for synthesis, but they also impact on strategy. Sharpless and Masamune elegantly demonstrated how the asymmetric epoxidation of acyclic alcohols can be utilized to access all configurational isomers of i-hexoses as exemplified by the synthesis of r-Glucose (55) (Scheme 9.6) [77]. 

Andersson also showed that, in addition to meso-desymmetrization, kinetic resolution of some cyclic epoxides by use of the first-generation catalyst was also possible, giving both epoxides and allylic alcohols in good yields (Scheme 7.51) [108], Kozmin reported the effective use of the same catalyst in the desymmetrization of diphenylsilacyclopentene oxide. The resulting products could be used in the ster-eocontrolled syntheses of various acyclic polyols (Scheme 7.52) [109]. 

The subsequent epoxidation of these in situ formed allylic tertiary alcohols yielded the corresponding syn-e oxy alcohols with high levels of diastereo- and enantioselectivity, thus providing a novel one-pot asymmetric synthesis of acyclic chiral epoxyalcohols via a domino vinylation epoxidation reaction (Scheme 4.17). ... 

In acyclic secondary -allylic alcohols, epoxidation by the vanadium system shows opposite stereospecificity to that of peracid and molybdenum carbonyl-mediated epoxidation (see Scheme 6)22 The predominance of the erythro isomer in the former process is rationalized22 in terms of the energetically more favorable transition state (6, cf. 5) and in this context the mechanism has analogy in the epoxidation behavior of medium-ring cyclic allylic alcohols.23... 

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