Zinc cyanoborohydride

Zinc cyanoborohydride [KOI, LDl] is formed by reaction of ZnClj in diethylether with a solution of NaCNBHj in this solvent [KOI] or by the reaction of Znl2 with NaCNBH3 in CHjClj [LDl]. 

Many borohydrides are highly unstable and have to be used as freshly prepared ethereal solutions. However there are instances where the polymer-supported versions are more stable e. g. an Amberlyst anion exchange resin supported borohydride and cyanoborohydride [61], polyvinylpyridine supported zinc borohydride [62] and the corresponding zirconium borohydride [63]. Such compounds, in their labeled forms, should turn out to be very useful. 

The double bond in indole and its homologs and derivatives is reduced easily and selectively by catalytic hydrogenation over platinum oxide in ethanol and fluoroboric acid [456], by sodium borohydride [457], by sodium cyanoborohydride [457], by borane [458,459], by sodium in ammonia [460], by lithium [461] and by zinc [462]. Reduction with sodium borohydride in acetic acid can result in alkylation on nitrogen giving JV-ethylindoline [457]. 

Ketoester 208 derived from l-(2-nitrophenyl)-lH-pyrrole and ethyl oxalyl chloride can be selectively reduced at the keto group with zinc iodide and sodium cyanoborohydride. Further reduction of the nitro group and cyclization to lactam 209 has been accomplished by treatment with stannous chloride in refluxing ethanol (Scheme 43 (2003BMCL2195)). 

Reduction of the unstable alcohol 116 is achieved using sodium cyanoborohydride in the presence of zinc iodide to produce the saturated compound 117 <2001SM(119)99> (Equation 30). 

Esters of racemic pyrazolidine-3-carboxylic acid (5-azaproline, 16) are obtained by a two-step reaction via addition of diazomethane to acrylic acid esters to form the corresponding dihydropyrazoline derivatives, which are converted into the desired pyrazolidine-3-carb-oxylic acid derivative by hydrogenation over palladium on charcoal,11621 or by reduction with sodium cyanoborohydride,[164l or with zinc in acetic acid. Details are given in Table 6J1651... 

Sodium borohydride, 278 Sodium cyanoborohydride-Zinc iodide, 280 of epoxides... 

Tributyltin hydride, 316 Zinc iodide, 280 From alkyl halides Lithium aluminum hydride-Ceri-um(III) chloride, 159 Palladium catalysts, 230 Sodium cyanoborohydride-Tin(II) chloride, 280 From alkyl sulfonates Lithium triethylborohydride, 153 From thiols... 

From carbonyl groups Sodium cyanoborohydride-Zinc iodide, 280 From thioketals Lithium aluminum hydride-Bis-(cyclopentadienyl)nickel, 158 From arenesulfonylhydrazones Sodium borohydride, 278 Sodium cyanoborohydride-Zinc iodide, 280... 

Sodium borohydride-Palladium chloride. Sodium borohydride-Rhodium(lII) chloride. Sodium borohydride-Tin(II) chloride. Sodium cyanoborohydride. Sodium 9-cyano-9-hydrido-9-borabicyclo[3.3.1]nonane. Sodium dithionite. Sodium hydride-Sodium t-amyl oxide-Zinc chloride. Sodium trimethoxyborohydride. Tetra-/i-butylammonium borohydride. Tetra-n-butylammonium cyanoborohydride. Tetra-n-butylammonium octahydrotriborate. Tri-n-butyltin hydride. Triethoxy silane. Triisobutylaluminum-Bis(N-methyl-salicyclaldimine)nickel. Zinc borohydride. REDUCTIVE CYCLIZATION Cobaloximc(I). 

Zinc-modified cyanoborohydride (the exact nature of the reagent is not clear), generated from Na(CN)BH3 and zinc chloride in a 2 1 ratio, is a selective reducing agent. In methanol, reduction of tertiary enamines proceeded smoothly and the corresponding amines could be isolated in good yields119 (Scheme 88). 

A mixture of sodium cyanoborohydride (0.11 mmol) and zinc chloride (0.05 mmol) in 2 ml methyl alcohol was added to a solution containing the Step 2 product (0.05 mmol) and 4-(4-fluorophenyl)piperidine (0.05 mmol) dissolved in 2 ml methyl alcohol, then stirred overnight at ambient temperature. The mixture was concentrated and the residue treated with 3 ml saturated NaHC03 solution and 5 ml CH2C12. The layers were separated and the organic component poured into an SCX cartridge, then washed four times with 2 ml methyl alcohol. It was then eluted twice with 2 ml 2 M methyl alcohol/ammonia, concentrated, and the product was isolated in 70% yield as a colorless solid. 

Fentanyl and its analogs are made from TV-substituted-4-piperidones [i.e., from the same intermediates of the reversed esters of pethidine (p. 266)]. These ketones condense with aniline under the influence of catalysts such as toluene-p-sulfonic acid(2) and zinc chloride(18) to give Schiff bases, which are reduced to diamines 4 by NaBH4 or LAH. Recently, the direct conversion of 4-piperidones to 4-anilino derivatives 4 has been achieved by reductive amination with aniline and sodium cyanoborohydride (NaBH3CN).(19) The diamines are acylated with propionic anhydride. 

Zinc-modified cyanoborohydride, prepared from anhydrous zinc chloride and sodium cyanoborohy-dride in the ratio 1 2 in ether, selectively reduced aldehydes and ketones but not acids, anhydrides, esters and tertiary amides. In methanol the reactivity paralleled the unmodified reagent. Zinc and cadmium borohydrides form solid complexes with DMF, which may prove to be convenient sources of the reducing agents.Aromatic and a,p-unsaturated ketones were reduced much more slowly than saturated ketones, so chemoselective reduction should be possible. 

A zinc-modifled cyanoborohydride reagent, prepared in situ by the reaction of sodium borohydride with zinc chloride in ether, reduces tertiary halides in high yields, whereas primary and secondary halides remain intact. Similar reactivity is observed with lithium 9,9-di-n-butyl-9-borabicyclo[3.3.1]-nonanate (4), as shown in equation (5). ... 

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