Epoxides Regioselective reduction

In connection with the synthetic work directed towards the total synthesis of polyene macrolide antibiotics -such as amphotericin B (i)- Sharpless and Masamune [1] on one hand, and Nicolaou and Uenishi on the other [2], have developed alternative methods for the enantioselective synthesis of 1,3-diols and, in general, 1, 3, 5...(2n + 1) polyols. One of these methods is based on the Sharpless asymmetric epoxidation of allylic alcohols [3] and regioselective reductive ring opening of epoxides by metal hydrides, such as Red-Al and DIBAL. The second method uses available monosaccharides from the "chiral pool" [4], such as D-glucose. 

Another approach for the ring expansion of epoxides uses low-valent iron complexes which open epoxides under reductive conditions, as reported by Hilt et al. [106]. The iron complexes are reduced and after coordination of the epoxide to the iron center an electron transfer initiates the radical-type ring opening of the epoxide. Under formal insertion of an alkene, regioselective formation of tetrahy-drofurans was observed (Scheme 9.46). The reaction is applicable to a broad range of acceptor-substituted alkenes bearing another double or triple bond system in conjugation with the inserted carbon-carbon double bond. 

Scheme4.65. Regioselective reductive ring opening of epoxides substituted with electron-withdrawing groups [275-279],...

With chiral catalyst 47d regioselective reductive ring opening reactions of racemic epoxides can be achieved, For alkynyl epoxy ethers it leads to effective asymmetric 5-exo cyclization of one radical, but reduction of the other [161, 162]. 

Starting with picrotoxinin (1) Yoshikoshi developed an improved synthesis of ( )-picrotin (2). Epoxidation of picrotoxinin (1) with peracid at room temperature led to a 5 2 mixture of the epimeric epoxides. Regioselective cleavage of the epoxide was achieved with sodium phenylselenyl triethoxy boronate. Radical reduction of the phenyl selenides 414 with stannane completed this three-step sequence to picrotin (2) in 87% overall yield. 

Regioselective reduction of an epoxide. A key step in a short synthesis of (+)-muscarine (6) from the dibenzoate of 2,5-anhydro-D-glucitol (1) involves reduction of the epoxide 2. Use of SMEAH gives a 12 1 mixture of 3 and 4 use of LiAlH gives the same diols in the ratio 3 1. ... 

Regioselective reduction of epoxides Intramolecular hydrosilylation Stereoselectivity... 

Regioselective reduction of terminal epoxides.2 By appropriate choice of i-Bu2 AIH or 1-BU3AI, terminal epoxides can be reduced with marked regioselcctivity to the primary or the secondary alcohol. Alkyl-substituted epoxides are reduced by f-Bu2AIH mainly to a secondary alcohol, whereas use of i-BujAl favors rcduclion to the primary alcohol. This regioselcctivity is reversed in the case silyl-substitutcd epoxides. Phenyl-substituted epoxides are reduced by i-Bu3AI mainly to primary alcohols. Reduction of these epoxides to secondary alcohols is best effected with LiAIH4 in THF. 

Regioselective reduction of aryl-substituted epoxides with NaBHj is catalyzed by PdCl2 in the presence of moist alumina (H2O content, 19 wt%) in hexane. The selectivity in reduction of aryl-substituted epoxides was the same as with NaBILj and diborane. In addition, the alumina can be easily recovered and reused without further treatment. 

To convert enantiopure epoxides into secondary or tertiary alcohols, techniques for the regioselective reduction of epoxides are in demand. Again aluminum compounds have to be considered for chelation and complex formation. Being available as Lewis acids (e.g., DIBAH) as well as a nucleophile (e.g., Red-Al), they are particularly convenient for this endeavor. Their special properties come nicely into play in the reductive opening of epoxide 81 [27]. 

Ephng, G. A. and Wang, Q., Regioselective reduction of epoxides by electron transfer a photochemical approach,/. Chem. Soc., Chem. Commun., 1133, 1992. 

The Sharpless asymmetric epoxidation reaction has been utilized widely in total syntheses. Nicolaou investigated the combination of a Sharpless asymmetric epoxidation with a regioselective reduction of the resulting epoxide in an iterative manner as a general means to synthesize 1,3-skipped polyols [80]. The strategy was put into practice in the total synthesis of the antifungal agent amphotericin B (64, Scheme 9.7) [81]. 

Regioselectivity of C—C double bond formation can also be achieved in the reductiv or oxidative elimination of two functional groups from adjacent carbon atoms. Well estab llshed methods in synthesis include the reductive cleavage of cyclic thionocarbonates derivec from glycols (E.J. Corey, 1968 C W. Hartmann, 1972), the reduction of epoxides with Zn/Nal or of dihalides with metals, organometallic compounds, or Nal/acetone (seep.lS6f), and the oxidative decarboxylation of 1,2-dicarboxylic acids (C.A. Grob, 1958 S. Masamune, 1966 R.A. Sheldon, 1972) or their r-butyl peresters (E.N. Cain, 1969). 

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