2.3- epoxy alcohol derivatives

Ohno, H. Hiramatsu, K. Tanaka, T. Asymmetric construction of quaternary carbon centers by Ti-mediated stereospecific allylation of 2,3-epoxy alcohol derivatives. Tetrahedron Lett. 2004, 45, 75-78. 

Bromohydrins. A highly regioselective ring opening of 2,3-epoxy alcohol derivatives to give products having a vic-diol pattern is mediated by MejSiBr-SnBr (6 examples, 68-99%). 

Carvone-derived 2,3-epoxy alcohol derivatives (317) have been found to rearrange with stereoselective formation of ring-contracted ketones (318) in a process where the stereochemical result seems to be independent of epoxide configuration. On the basis of this study, the authors concluded that the rearrangement of tetrasubstituted cyclic epoxy alcohol derivatives remains a transformation for which both regiose-lectivity and stereochemical outcome are difficult to predict. New solid acid catalysts based on silica-supported zinc triflate have been prepared for use in the rearrangement of a-pinene oxide to campholenic aldehyde. ... 

Scheme 8.45 Suzuki-Tsuchihashi rearrangement of epoxy alcohol derivatives.

In Holton s and Wender s work, the total synthesis was achieved by sequentially forming the AB ring through the fragmentation of epoxy alcohols derived from (—)-camphor and a-pinene. Nicolau s, Danishefsky s, and Kuwa-jima s total syntheses involved B ring closure connecting the A and C rings, whereas in Mukaiyama s synthesis, the aldol reaction was extensively applied to construct the polycyclic system. 

A limited number of allylic alcohols of the (2,3Z)-disubstituted type have been subjected to asymmetric epoxidation. With one exception, the C-2 substituent in these substrates has been a methyl group, the exception being a f-butyl group [38]. The (3Z)-substituents have been more varied, as illustrated by structures 61-64, which show the epoxy alcohols derived from the corresponding allylic alcohol substrates. 

Benedetti F, Magnan M, Miertus S, Norbedo S, Parat D, Tossi A, Stereoselective synthesis of non symmetric dihydroxyethylene dipeptide isosteres via epoxy alcohols derived from alpha-amino acids. Bioorg. Med. Chem. Lett., 9 3027-3030, 1999. 

Both saturated (50) and unsaturated derivatives (51) are easily accepted by lipases and esterases. Lipase P from Amano resolves azide (52) or naphthyl (53) derivatives with good yields and excellent selectivity. PPL-catalyzed resolution of glycidyl esters (54) is of great synthetic utiUty because it provides an alternative to the Sharpless epoxidation route for the synthesis of P-blockers. The optical purity of glycidyl esters strongly depends on the stmcture of the acyl moiety the hydrolysis of propyl and butyl derivatives of epoxy alcohols results ia esters with ee > 95% (30). 

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

As well as the Payne rearrangement, 2,3-epoxy alcohols and some of their derivatives show some other interesting rearrangement procedures that often constitute key steps in syntheses of complex molecules. 

In a formal synthesis of fasicularin, the critical spirocyclic ketone intermediate 183 was obtained by use of the rearrangement reaction of the silyloxy epoxide 182, derived from the unsaturated alcohol 180. Alkene 180 was epoxidized with DMDO to produce epoxy alcohol 181 as a single diastereoisomer, which was transformed into the trimethyl silyl ether derivative 182. Treatment of 182 with HCU resulted in smooth ring-expansion to produce spiro compound 183, which was subsequently elaborated to the desired natural product (Scheme 8.46) [88]. 

In a different type of reaction, alkenes are photooxygenated (with singlet O2, see 14-8) in the presence of a Ti, V, or Mo complex to give epoxy alcohols formally derived from allylic hydroxylation followed by epoxidation, for example, ... 

Although the Sharpless asymmetric epoxidation is an elegant method to introduce a specific defined chirality in epoxy alcohols and thus, in functionalized aziridines (see Sect. 2.1), it is restricted to the use of allylic alcohols as the starting materials. To overcome this limitation, cyclic sulfites and sulfates derived from enantiopure vfc-diols can be used as synthetic equivalents of epoxides (Scheme 5) [12,13]. 

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