Sodium cyanoborohydride tosylates

REDUCTION OF ALKYL HALIDES AND TOSYLATES WITH SODIUM CYANOBOROHYDRIDE IN HEXAMETHYL-PHOSPHORAMIDE (HMPA) A. 1-IODODECANE TO n—DECANE B. 1-DODECYL TOSYLATE TO n-DODECANE, 53, 107 REDUCTION OF KETONES BY USE OF TOSYLHYDRAZONE DERIVATIVES ANDROSTAN-17 0—OL, 52, 122 REDUCTIVE AMINATION WITH SO-... 

REDUCTION OF ALKYL HALIDES AND TOSYLATES WITH SODIUM CYANOBOROHYDRIDE IN HEXAMETHYLPHOS-PHORAMEDE (HMPA) ... 

B. Reduction of 1-Dodecyl Tosylate to n-Dodecane. In a dry 200-ml. three-necked flask equipped exactly as described in Section A are placed 50 ml. of hexamethylphosphoramide (HMPA), 1-dodecyl tosylate (6.80 g., 0.0201 mole) (Note 8), and sodium cyanoborohydride (5.02 g., 0.080 mole) (Note 3). The solution is stirred at 80° for 12 hours (Note 9), then diluted with 50 ml. of water, and extracted with three 60-ml. portions of hexane. The hexane solution is washed twice with water, dried over anhydrous magnesium sulfate, and then concentrated at reduced pressure with a rotary evaporator. Distillation of the residue through a short-path apparatus (Note 5) (Cautionl foaming) affords 2.49-2.64 g. (73-78%) of w-dodecane, b.p. 79-81° (3.75 mm.) na4D 1.4217 (lit.,3 n20d 1.4219) (Note 7). 

The large excess of sodium cyanoborohydride is recommended for the reduction of tosylates. Use of reduced molar excesses led to substantially lower yields. For example, a 3 1 cyanoborohydride to tosylate ratio afforded less than 60% yield of product at 80° for 5 hours, while a 1.5 1 excess gave only 52% yield at 70° for 8 hours. 

These preparations that illustrate the use of sodium cyanoborohydride in hexamethylphosphoramide as an effective, selective, and convenient procedure for the reduction of alkyl halides and tosylates is essentially the same as previously described.8 The very mild reducing ability of sodium cyanoborohydride makes the method particularly valuable when other functional groups are present in the molecule... 

Reduction of alkyl halides and tosylates. - Reduction with sodium cyanoborohydride in HMPT provides a rapid and selective removal of iodo. bromo, and tosyloxy groups in high yield. Thus 1-iododecane can be reduced in thi.s way to n-deeane in... 

Sodium borohydride is usually ineffective for removing tosylate. Sodium cyanoborohydride, lithium aluminum hydride or possibly lithium borohydride (or NaBH4 + metal salts) are better choices to accomplish this transformation. This is a poor choice... 

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). 

A method for the conversion of carbonyl compounds into the corresponding hydrocarbons involves reduction of the derived toluene-p-sulfonyl (tosyl) hydra-zones with sodium cyanoborohydride in acidic dimethylformamide (DMF). The reaction is specific for aliphatic carhonyl compounds aromatic compounds are normally unaffected. The tosyl hydrazone need not be isolated but can be prepared and reduced in situ. For example, the ketone 97 was reduced to the alkane 98 (7.89). 

Tosylhydrazones (32) are reduced in high yield to the corresponding tosyl-hydrazines by sodium cyanoborohydride in acidic media. High stereoselectivity results from reductions of (32) where R is a group capable of complexing with organometallic reagents (Scheme 32). 

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]. 

More recently sodium cyanoborohydride (NaBHjCN) has been reported to be effective in reducing primary, secondary, and tertiary halides and tosylates. 

---