Sodium cyanoborohydride epoxide reduction

Oxirane cleavage. Isobe and co-workers effected the stereoselective reduction of 1 to 2 by sequential treatment of the epoxide with sodium cyanoborohydride in anhydrous HMPT and diborane in THF. The authors suggest that this reaction involves internal hydride transfer in the hypothetical intermediate 3. Reduction in DME or THF results in products with the opposite configuration at C7. 

We invoke 7c-stacking of the alkene with a phenyl moiety on the silicon protecting group (since this high degree of selectivity was only observed for TBDPS and not with TBS), in the precursor to explain this remarkable selectivity (Figure 1). Lewis acid induced reduction of the epoxide with sodium cyanoborohydride led regioselectively to the 1,3-diol (11) the hydride attacks the more substituted position via an S 2 mechanism. ... 

In contrast to the reductive cleavage of 1-methylcyclohexene epoxide with LiAlH4 or, better, with LiEtjBH to produce 1-methylcyclohexanol, reduction of the epoxide with sodium cyanoborohydride in the presence of boron trifluoride etherate furnishes cE-2-methylcyclohexanol. In this case, complexation of the epoxide oxygen with the Lewis acid BF3 now directs hydride addition to the more substituted carbon, which can better sustain the induced partial positive charge. 

The reductive ring opening of 330a with sodium cyanoborohydride/titanium tetrachloride in acetonitrile occurs with no ester reduction whatsoever to provide 421 in 83% yield. Subsequent conversion to the tosylate followed by reduction with lithium borohydride/lithium triethylborohydride affords in 61% yield the crystalline diol 422. Lithium aluminum hydride or sodium borohydride reduction of the tosylate of 421 fails to produce clean reductions to 422. Epoxide ring closure of 422 is achieved with two equivalents of sodium hydroxide in methanol to fiimish in 93% yield (2 S, 3i )-2-benzyloxy-3,4-epoxybutan-l-ol (423) [140] (Scheme 94). 

Squalene 2,3-epoxide has been isolated from the green alga Caulerpa prolifera. Oxidation of squalene with t-butyl hydroperoxide in the presence of Mo02(acac)2 and di-isopropyl (+)-tartrate gave the 2,3-epoxide (31%) with an induced asymmetry of about 14% in favour of the (35)-isomer. The ability of oxidosqualene cyclases to accept unnatural precursors has been further extended by the observation that lanosterol cyclase from rabbit liver converts the synthetic epoxide (1) into the jS-onocerin derivative (2). An authentic sample of (2) was prepared by sodium cyanoborohydride reduction of /3-onoceradione... 

The preparation of the CD building block was continued as follows. After reductive opening of the epoxide 91 with sodium cyanoborohydride, the resulting diol was converted into the bis-acetyl ester 92. Selective hydrolysis of the less sterically hindered ester was followed by conversion of the unprotected alcohol into the thiocarbonate. After deoxygenation via a Barton-McCombie reaction, the ensuing product 93 is set up for deprotection and oxidation to a key chiral CD intermediate for vitamin D synthesis. 

The reduction of alkyl hahdes has been important in many syntheses. Sodium cyanoborohydride in HMPA will reduce alkyl iodides, bromides, and tosylates selectively in the presence of ester, amide, nitro, chloro, cyano, alkene, epoxide, and aldehyde groups [118]. Tri-n-butyltin hydride will replace chloro, bromo, or iodo groups with hydrogen via a free radical chain reaction initiated by thermal decomposition of AIBN [119]. Other functionality such as ketones, esters, amides, ethers, and alcohols survive unchanged. The less toxic tris(trimethylsilyl) silane can be used similarly [120]. 

Cyanoborohydride and its modified reagents have been used for reductive dehalogenations. Thus, the combination of sodium or tetrabutylammonium cyanoborohydride, sodium or potassium 9-cyano-9-hydro-9-borabicyclo[3.3.1]nonanate [9-BBNCN] (2) or polymeric cyanoborane (3) in HMPA furnishes an efficient and mild system for the reduction of alkyl halides. The reagents are selective in that other functional groups, including ester, carboxylic acid, amide, cyano, alkene, nitro, sulfone, ketone, aldehyde and epoxide, are essentially inert under the reduction conditions thus, the reduction procedure is attractive for synthetic schemes which demand minimum damage to sensitive portions of the molecule. 

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