Sodium cyanoborohydride acetals

The open-chain tautomers 24b and 25 of precursor incipient imidazolidine and perhydropyrimidine derivatives, which bear a six carbon transferable fragment, on acid-catalyzed reactions with tryptamine formed the diester 85. A similar reaction of 24a leads to quantitative formation of 86 and the reaction of 25 with tryptamine is appreciably faster than that of 24b. Sodium cyanoborohydride/acetic acid reduction of 85 was accompanied by intramolecular aminolysis to form piperidone 87. Its Bischler-Napieralski cyclization followed by borohydride reduction gave cis- and trara-isomers of indoloquinolizine ester 88, which on hydrolysis to acid and subsequent methylene lactam rearrangement gave methylene lactam 89. Its DIBAL reduction gave 18- or-deplancheine 84a (88T6187). 

Sodium cyanoborohydride-acetic acid and triethylsilane-trifluoroacetic acid have been found to be excellent reducing systems for oxime benzoates, providing a new general synthesis of O-acylhydroxylamines (Scheme 38). ... 

Reduction. Quinoline may be reduced rather selectively, depending on the reaction conditions. Raney nickel at 70—100°C and 6—7 MPa (60—70 atm) results in a 70% yield of 1,2,3,4-tetrahydroquinoline (32). Temperatures of 210—270°C produce only a slightly lower yield of decahydroquinoline [2051-28-7]. Catalytic reduction with platinum oxide in strongly acidic solution at ambient temperature and moderate pressure also gives a 70% yield of 5,6,7,8-tetrahydroquinoline [10500-57-9] (33). Further reduction of this material with sodium—ethanol produces 90% of /ra/ j -decahydroquinoline [767-92-0] (34). Reductions of the quinoline heterocycHc ring accompanied by alkylation have been reported (35). Yields vary widely sodium borohydride—acetic acid gives 17% of l,2,3,4-tetrahydro-l-(trifluoromethyl)quinoline [57928-03-7] and 79% of 1,2,3,4-tetrahydro-l-isopropylquinoline [21863-25-2]. This latter compound is obtained in the presence of acetone the use of cyanoborohydride reduces the pyridine ring without alkylation. 

Rather than preforming the a-amino ketimines to be reduced, it is often advantageous to form in situ the more reactive iminium ions from a-aminoketones and primary amines or ammonium salts in the presence of the reducing agent, e.g., sodium cyanoborohydride. Use of this procedure (reductive amination) with the enantiopure a-aminoketone 214 and benzylamine allowed the preparation of the syn diamines 215 with high yields and (almost) complete diastereoselectivities [100] (Scheme 32). Then, the primary diamines 216 were obtained by routine N-debenzylation. Similarly, the diamine 217 was prepared using ammonium acetate. In... 

The Hofmann degradation product 252 used for a synthesis of corynoline (254) was again a useful starting material for ( )-corydalic acid methyl ester (8). It was reduced with sodium cyanoborohydride to the trans derivative 10 as a major product, which was converted to 8 via acetal 268 and aldehyde 269 (143). 

The reactivity of these tricyclic compounds has been investigated in detail. Reaction of these with sodium cyanoborohydride in acetic acid reduces the imine double bonds to give the tetrahydro-derivatives, for example, 37 gives 39. Reaction of 37 with sodium methoxide results in the ring-opened sulfonate salt 40 re-acidification of this salt gives the corresponding sulfonic acid which cyclizes back to the tricycle 37. Further heating of the sulfonic acid... 

Richter utilized a reductive amination in their synthesis of the natural product (+)-hapalindole Q [294], Employing 10 equivalents of sodium cyanoborohydride and 40 equivalents of ammonium acetate in a methanol/THF mixture (150 °C, 2 min), the primary amine was obtained as a 6 1 mixture of diastereomers. Transformation to the isothiocyanate completed the total synthesis of (+)-hapalindole Q (Scheme 6.150). 

The diester 110 (E = CC Et) reacts with a mixture of trimethyltin chloride and sodium cyanoborohydride under AIBN catalysis to give the cyclopentane 111 as a 4 1 mixture of cis- and fraws-isomers. The products are destannylated to the acetals 112 by treatment with methanolic ceric ammonium nitrate (CAN). The 1,7-octadienyl derivative 113 was similarly converted into the cyclohexanes 114 (cis/trans = 1 1) (equation 60)67. 

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]. 

Thioamides were converted to aldehydes by cautious desulfurization with Raney nickel [1137, 1138] or by treatment with iron and acetic acid [172]. More intensive desulfurization with Raney nickel [1139], electroreduction [172], and reduction with lithium aluminum hydride [1138], with sodium borohydride [1140] or with sodium cyanoborohydride [1140] gave amines in good to excellent yields. 

Reduction Experiments. NEO (100-1000 pmole) was reacted with an excess (10-1000 equivalents) of sodium borohydride, sodium cyanoborohydride or Zn/acid in buffer at pH 8-10, 3-7 or 2-5 respectively. The borohydride and cyanoborohydride reductions were performed with and without added diglyme for 2-40 hours. The Zn was used with hydrochloric, acetic, phthalic or citric acid with... 

N-Methylation of vochysine (7) took place when it was treated with sodium cyanoborohydride in 30% HCHO and acetic acid (5). Additional methylation of OH groups was accomplished by refluxing with methyl iodide in acetone containing potassium carbonate (5). 

Catalytic hydrogenation of the unstable pyrroles (281a-c), which are prepared by heating the 1,4-diketones (280a-c) with an excess of ammonium carbonate at 120°C, gives 2,5-dialkylpyrrolidines (lOa-c) (cis trans = 85 15, 85% conversion) (Scheme 25) 133). Reductive amination of 1,4-diketones (282b,f,h,i) with ammonium acetate and sodium cyanoborohydride produces 2,5-dialkylpyr-rolidines (10b,f,h,i) identical to natural products in 50-90% yields. Each pyrrolidine is an approximately 1 1 mixture of cis and trans isomers (Scheme 26) 25,138). 

The overall carbon-nitrogen framework was confirmed by synthesis. Reductive amination of the triketone (336) (429) with sodium cyanoborohydride and ammonium acetate formed a mixture of four isomeric pyrrolizidines. Pure sam-... 

Stractures of 3-alkyl-5-methylindolizidines, found in thief ants, Solenopsis species (Table II), arrived at by gas chromatographic and mass spectral analysis were confirmed by coinjection and direct comparison with the synthetic sample. Indolizidine 15a from S. conjurata exhibits characteristic peaks at miz 152 (M — CHj) and 138 (M — C2H5, a base peak) as well as a parent peak at m/z 167 in the mass spectram. It corresponds to an isomer of 3-ethyl-5-methylindolizidine (15) which was prepared as a mixture of four stereoisomers by reductive amination of triketone 391 with ammonium acetate-sodium cyanoborohydride and sodium borohydride (Scheme 47). 

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... 

The synthesis of a triptan with a chiral side chain begins by reduction of the carboxylic acid in chiral 4-nitrophenylalanine (15-1). The two-step procedure involves conversion of the acid to its ester by the acid chloride by successive reaction with thionyl chloride and then methanol. Treatment of the ester with sodium borohy-dride then afford the alanilol (15-2). Reaction of this last intermediate with phosgene closes the ring to afford the oxazolidone (15-3) the nitro group is then reduced to the aniline (15-4). The newly obtained amine is then converted to the hydrazine (15-5). Reaction of this product with the acetal from 3-chloropropionaldehyde followed by treatment of the hydrazone with acid affords the indole (15-6). The terminal halogen on the side chain is then replaced by an amine by successive displacement by means of sodium azide followed by catalytic reduction of the azide. The newly formed amine is then methylated by reductive alkylation with formaldehyde in the presence of sodium cyanoborohydride to afford zolmitriptan (15-7) [15]. 

Dialkylpyrrolidines. These compounds can be prepared by reductive amination of 1,4-diketones with sodium cyanoborohydride and ammonium acetate (4, 448-449). 1-Pyrrolines are usually formed also, but they can be reduced to pyrrolidines by NaBH4 in a second step.1... 

MacrocycBc lactams. Two key steps in a synthesis of the polyamine alkaloid dihydroperiphylline (4) involve ring expansion of the cyclic imino ether 1 by reaction with the /3-lactam 2 to form 3. Sodium cyanoborohydride in acetic acid reduces 3 in high yield to 4, probably by way of intermediates a and b.2... 

Indolines are produced in good yield from 1-benzenesulfonylindoles by reduction with sodium cyanoborohydride in TFA at 0°C (Equation 5) (89TL6833). If acyl groups are present at C-2 or C-3 in the substrate, they are reduced to alkyl groups. Indole is also reduced to 2,3-dihydroindole by sodium cyanoborohydride and acetic acid or triethylamineborane and hydrochloric acid. An alternative method for preparing indolines involves treatment of indoles with formic acid (or a mixture of formic acid and ammonium formate) and a palladium catalyst (82S785). Reduction of the heterocyclic ring under acidic conditions probably involves initial 3-protonation followed by reaction with hydride ion. 

Oxidation of 8-hydroxymethyl-2-isopropyl-l 1 //-pyrido[2,l-b]quinazolin-11-one with pyridinium chlorochromate in methylene chloride gave the 8-carboxaldehyde, which was converted into its 8-aminomethyl derivatives by reacting with amines followed by reduction of the Schiff bases with sodium cyanoborohydride in acetic acid (87JOC2469). 

Hydrogen chloride in diethyl ether at room temperature was added to a mixture of 7 [34] (1.00 g, 2.16 mmol) and sodium cyanoborohydride (1.70 g, 27.0 mmol) in tetrahydrofuran (30 mL, distilled from LiAlH ) containing 3-A molecular sieves, until the evolution of gas biased. Use of TLC [silica gel, light petroleum (bp 40-60°)/ethyl acetate 5 1] after 5 min, PrHcated complete reaction. The mixture was diluted with CHjClj (50 mL) and water, [filtered, and the solution was extracted with water and then with saturated aqueous... 

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... 

Dichloro-2,2-difluoroethylene, 105 (Diethylamino)sulfur trifluoride, 110 Reduction reactions (see also Deoxygenation, Reductive. . . ) of acetals and ketals Dibromoalane, 237 Diisobutylaluminum hydride, 237 Triethylsilane-Tin(IV) chloride, 237 of acetates and other esters to alkanes Nickel boride, 197 Triphenylsilane, 334 of acyl halides to alcohols Sodium cyanoborohydride-Tin(II) chloride, 280... 

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