Diastereoselective synthesis epoxides

The (partial) description of the synthesis and coupling of the five fragments starts with the cyclohexyl moiety C —C. The first step involved the enantio- and diastereoselective harpless epoxidation of l,4-pentadien-3-ol described on p. 126f. The epoxide was converted in four steps to a d-vinyl d-lactone which gave a 3-cyclohexenecarboxylate via Ireland-CIaisen rearrangement (cf. p. 87). Uncatalysed hydroboration and oxidation (cf. p. 131) yielded the desired trans-2-methoxycyclohexanol which was protected as a silyl ether. The methyl car-... 

Epoxidative lactonization.1 This reaction can be used for a diastereoselective synthesis of 5-hydroxyalkylbutanolides (3) from (E)- and (Z)-4-alkenoic acids (1). Thus epoxidation of (E)-l results in an epoxide (2) that in the presence of acid is converted into erythro-i. In contrast, (Z)-l is converted into threo-3. Yields are essentially quantitative. 

Scheme 14.2 (a) Enantio- vs. (b) Concept of the diastereoselective synthesis, (c) diastereoselective epoxidation. 

With the proper choice of reaction conditions, diastereoselective synthesis of a-allenic alcohols 69 and 70 from propargylic epoxide 68 was achieved [80, 81], With RMgBr and 5 mol% of CuBr/2PnBu3, anti allenic alcohols 69 are obtained with up to 100% diastereoselectivity. On the other hand, syn allenic alcohols 70 can be prepared with 88-96% diastereoselectivity with RMgCl, Me3SiCl and 5mol% CuBr (Scheme 3.36). 

Highly diastereoselective dioxirane epoxidations have been widely employed in organic synthesis. For example, in the total synthesis of epothilone B, an important antitumor agent , the required epoxide was obtained in good yield and diastereoselectivity by DMD oxidation (equation 7) . ... 

Asymmetric sulfur-ylide-type epoxidation is an excellent tool for enantioselective and diastereoselective synthesis of epoxides. By use of Aggarwal-type methodology a broad range of aromatic, enolizable, and base-sensitive aldehydes can be converted into the desired epoxides. In addition to an excellent diastereomeric ratio, the optimized organocatalytic systems of this sulfur-ylide-type epoxidation also... 

Nagase, T., Kawashima, T., and Inamoto, N., Diastereoselective synthesis of 2.3-epoxyalkylphospho-nates and phosphinates by epoxidation, Chem. Lett., 1655, 1985. 

Sun BE, Hong R, Kang YB, Deng L (2009) Asymmetric Total Synthesis of (-)-Plicatic Acid via a Highly Enantioselective and Diastereoselective Nucleophilic Epoxidation of Acyclic Trisubstitued Olefins. J Am Chem Soc 131 10384... 

A diastereoselective synthesis of a-tocopherol 87 features a Shi epoxidation with ent-2 and a carefully controlled intramolecular epoxide opening cyclization for the formation of the chromanol ring. Good conversion and high enantioselectivity have been achieved in the epoxidation step. ... 

The remarkable stereospecificity of TBHP-transition metal epoxidations of allylic alcohols has been exploited by Sharpless group for the synthesis of chiral oxiranes from prochiral allylic alcohols (Scheme 76) (81JA464) and for diastereoselective oxirane synthesis from chiral allylic alcohols (Scheme 77) (81JA6237). It has been suggested that this latter reaction may enable the preparation of chiral compounds of complete enantiomeric purity cf. Scheme 78) ... 

The past thirty years have witnessed great advances in the selective synthesis of epoxides, and numerous regio-, chemo-, enantio-, and diastereoselective methods have been developed. Discovered in 1980, the Katsuki-Sharpless catalytic asymmetric epoxidation of allylic alcohols, in which a catalyst for the first time demonstrated both high selectivity and substrate promiscuity, was the first practical entry into the world of chiral 2,3-epoxy alcohols [10, 11]. Asymmetric catalysis of the epoxidation of unfunctionalized olefins through the use of Jacobsen s chiral [(sale-i i) Mi iln] [12] or Shi s chiral ketones [13] as oxidants is also well established. Catalytic asymmetric epoxidations have been comprehensively reviewed [14, 15]. 

This synthesis is shown in Scheme 13.59. Two enantiomerically pure starting materials were brought together by a Wittig reaction in Step C. The aldol addition in Step D was diastereoselective for the anti configuration, but gave a 1 1 mixture with the 6S, 1R-diastereomer. The stereoisomers were separated after Step E-2. The macrolactonization (Step E-4) was accomplished by a mixed anhydride (see Section 3.4.1). The final epoxidation was done using 3-methyl-3-trifluoromethyl dioxirane. 

Another illustration of the use of such a biocatalytic approach was the synthesis of either enantiomer of a-bisabolol, one of these stereoisomers (out of four) which is of industrial value for the cosmetic industry. This approach was based on the diastereoselective hydrolysis of a mixture of oxirane-diastereoiso-mers obtained from (R)- or (S)-limonene [68]. Thus,starting from (S)-hmonene, the biohydrolysis of the mixture of (4S,81 S)-epoxides led to unreacted (4S,8S)-epoxide and (4S,8i )-diol. The former showed a diastereomeric purity (> 95%) and was chemically transformed into (4S,8S)-a-bisabolol. The formed diol... 

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