Oxirane reduction stereochemistry

The stereochemistry of the first step was ascertained by an X-ray analysis [8] of an isolated oxazaphospholidine 3 (R = Ph). The overall sequence from oxi-rane to aziridine takes place with an excellent retention of chiral integrity. As the stereochemistry of the oxirane esters is determined by the chiral inductor during the Sharpless epoxidation, both enantiomers of aziridine esters can be readily obtained by choosing the desired antipodal tartrate inductor during the epoxidation reaction. It is relevant to note that the required starting allylic alcohols are conveniently prepared by chain elongation of propargyl alcohol as a C3 synthon followed by an appropriate reduction of the triple bond, e. g., with lithium aluminum hydride [6b]. 

Epoxidation of oxonine 93 with dimethyldioxirane, followed by reduction with diisobutylaluminium hydride (DIBAL-H), resulted in a separable mixture of alcohols 95 and 96, and the side product 94 (Scheme 16). Each of the isomers was submitted to Swern oxidation and sequential stereoselective reduction with L-selectride to achieve desired stereochemistry of the products 97 and 98. Formation of the side product 94 was explained by Lewis acidity of DIBAL-H and confirmed by treatment of oxirane derived from 93 with another Lewis acid, AlMe3, to produce oxocine aldehyde 99 in 35% isolated yield <1997CL665>. Similar oxidative synthetic sequence was utilized for the synthesis of functionalized oxonines as precursors of (-l-)-obtusenyne <1999JOG2616>. 

The past decade has also seen the publication of many articles on the catalytic reduction of oxiranes. An account of the mechanism and stereochemistry of the hydrogenolysis is presented in various reviews and papers discussed in the next section. A review that appeared recently on the reduction of oxiranes to alcohols covers all of these methods. 

The mechanism and stereochemistry of the reduction with metal hydride has been dealt with in many articles. It may be stated in general that the structure of the oxirane and the nature of the reducing agent exert great effects on the rate and pathway of the reaction. 

Acetylation and reduction with sodium borohydride of (106a) led to (109) dehydrated to (110). Lithium aluminium hydride reduction of the oxiran ring of (110) afforded the tertiary alcohol (111) identical to N-isobutyrylbuxaline F, isolated from Buxus balearica whereby structure and stereochemistry were established. 

Opposite regioselectivity to that of regular metal hydride reductions has been observed in the NaBH4 reductions of oxiranes in the presence of triethylamine under photochemical conditions (hydride attacks the more highly substituted carbon) <92CC1133>. Diborane (B2H6) likewise tends to reduce oxiranes at the sterically more hindered oxirane carbon the mechanism and stereochemistry of the diborane reduction in connection with aliphatic oxiranes has been studied <82H(l8)28l>. 

The phosphonate epoxide (28) has been prepared in 58% yield from the trimethylsilyl ether (26) via fluoride-ion-induced cyclization of the intermediate (27) (Scheme 1). The stereochemistry of bromohydrin (31), which yields the oxiran (33) after sequential reduction and treatment with a base, has been proved by the use of a novel oxidative bromocarbonation (Scheme 2). Enol (29) of known stereochemistry is converted into the cyclic bromo-carbonate (32) (79%) upon treatment of the lithium alkoxide of (29) with dry CO2 followed by Br2. Since (32), on treatment with base, gives... 

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