Cyanoborohydride reaction with alcohols

Sodium cyanoborohydride. reductive ami nation with, 931 Sodium cyclamate, LP50 of, 26 Sodium hydride, reaction with alcohols, 605... 

Schkeryantz and Pearson (59) reported a total synthesis of ( )-crinane (298) using an intramolecular azide-alkene cycloaddition (Scheme 9.59). The allylic acetate 294 was first subjected to an Ireland-Claisen rearrangement followed by reduction to give alcohol 295, which was then converted into the azide 296 using Mitsunobu conditions. Intramolecular cycloaddition of the azide 296 in refluxing toluene followed by extrusion of nitrogen gave the imine 297 in quantitative yield. On reduction with sodium cyanoborohydride and subsequent reaction with... 

Aldehydes and ketones are unaffected by sodium cyanoborohydride in neutral solution, but they are readily reduced to the corresponding alcohol at pH = 3-4 by way of the protonated carbonyl group. By previous exchange of the hydrogens of the borohydride for deuterium or tritium, by reaction with D2O or tritiated water, an efficient and economical route is available for deuteride or tritiide reduction of aldehydes and ketones. 

Chemical reduction of aromatic aldehydes to alcohols was accomplished with lithium aluminum hydride [5i], alane [770], lithium borohydride [750], sodium borohydride [757], sodium trimethoxyborohydride [99], tetrabutylam-monium borohydride [777], tetrabutylammonium cyanoborohydride [757], B-3-pinanyl-9-borabicyclo[3.3.1]nonane [709], tributylstannane [756], diphenylstan-nane [114], sodium dithionite [262], isopropyl alcohol [755], formaldehyde (crossed Cannizzaro reaction) [i7i] and others. 

Consequently, by choosing proper conditions, especially the ratios of the carbonyl compound to the amino compound, very good yields of the desired amines can be obtained [322, 953]. In catalytic hydrogenations alkylation of amines was also achieved by alcohols under the conditions when they may be dehydrogenated to the carbonyl compounds [803]. The reaction of aldehydes and ketones with ammonia and amines in the presence of hydrogen is carried out on catalysts platinum oxide [957], nickel [803, 958] or Raney nickel [956, 959,960]. Yields range from low (23-35%) to very high (93%). An alternative route is the use of complex borohydrides sodium borohydride [954], lithium cyanoborohydride [955] and sodium cyanoborohydride [103] in aqueous-alcoholic solutions of pH 5-8. 

Redox catalysis with antibodies was first described for the reduction of resazu-rin using sulfite [43] and for heme-based peroxidase activity [44]. Concerning reactions relevant to preparative synthesis, Schultz and coworkers have described an elegant regio- and enantio-selective reduction of ketone 25 a with cyanoborohydride giving enantioselectively keto-alcohol 26 using an antibody... 

With strong protic acids, the regiochemistry of the reductive cleavage reverses to give the benzyl ether of the less hindered alcohol. One of the few metal hydrides that can withstand the harshly acidic conditions of the reaction is sodium cyanoborohydride. When used in large excess, it will reduce benzylidene acetals in the presence of anhydrous HG [Scheme 3.61] -or trifluoro-methanesulfonic acid. The excess is required because the sodium cyanoborohydride is consumed under the reaction conditions at an appreciable rate. More convenient reaction conditions were described by DeNinno and co-workers in which the benzylidene acetal is reductively cleaved using triethylsilane in the presence of trifluoroacetic acid [Scheme 3.62]. ... 

Reactions.—New systems for the reduction of alkyl halides to alkanes include mixtures of lithium aluminium hydride with transition-metal chlorides (such as Ni or Co" chlorides) and some complex metal hydrides of copper, especially the THF-soluble Li4CuHs. Details of the application of sodium cyanoborohydride to the reduction of halides (and sulphonate esters) in dipolar aprotic solvents have been published. Virtually all other functional groups are inert to this convenient, mild, and efficient system, which has been used to develop a one-pot deoxygenation of primary alcohols (Scheme 39) via the iodides. The alternative cyanoborohydride reagents (55) and the polymeric (56) are also discussed. ... 

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. 

---