Cyclizations sodium cyanoborohydride

The first total synthesis of 87 was published in 1990 (90TL1523). 5-Hydroxyindole (88) was mesylated and then reduced with sodium cyanoborohydride to give an indoline which was brominated to afford the bromoindoline 89 in good yield (Scheme 33). Cross-coupling with ortho-formyl boronic acid under Suzuki conditions, followed by air oxidation of the resulting cyclized product, followed by reduction of the lactam formed with excess Red-Al gave the target compound 87. 

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... 

Takano s group reported the first enantioselective total synthesis of (—)-anti-rhine as well (146). Chiral product 235 was prepared via a number of stereoselective reactions. Reductive condensation of 235 with tryptamine, using sodium cyanoborohydride at pH 6, supplied lactam 236, which was reduced by di-isobutylalminum hydride to hemiacetal 237. The latter could be cyclized to (-)-antirhine by simple acid treatment (146). 

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)). 

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). 

Generating tin hydride in situ by using a catalytic amount of tributyltin chloride and sodium cyanoborohydride [24] did not solve the problem. Although this method inherently produces the desired low concentration of n-BujSnH to promote cyclization over direct reduction of the starting material and reduces drastically the amount of tin residue, a displacement reaction between solvent and the benzylic hydroxyl group takes place. Eventually, the best method was the use of high dilution conditions at approximately 70 °C in benzene followed by the KF workup. 

Cyclohexanone (202) was converted to compound (203) whose transformation to cyclohexanone (204) was accomplished in three steps. It underwent cyclialkylation with boron trifluoride etherate affording the cyclized product (205) (R=R,=OMe) in 64% yield along with naphthalene (206) (R=Ri= H,H). Compound (205) on heating under reflux with DDQ in benzene produced ketone (207) whose tosylhydrazone on treatment with sodium cyanoborohydride afforded reduced product (208). Deprotection of the aryl methyl ethers and oxidation with ceric ammonium nitrate led to the formation of miltirone (197). 

In this cyclization reaction, as mentioned above, 3,4-dihydroquino-line 81 is generated as the initial product (Scheme 36). If this 3,4-di-hydroquinoline 81 could be reduced prior to the disproportionation, then 1,2,3,4-tetrahydroquinoIine 83a should be obtained. Accordingly, the cyclization of 80a was attempted in the presence of a reducing reagent, sodium cyanoborohydride (Na[BH3(CN)]), and 2-methyl-l,2,3,4-tetrahydroquinolin-8-ol (83a) was produced in 78% yield without the formation of quinoline 82a (Scheme... 

Ryu, Curran and their co-workers have achieved the fluorous hydroxymethyla-tion of organic halides using a catalytic quantity of a fluorous tin hydride [8] in the presence of sodium cyanoborohydride [10]. Interestingly, this fluorous reagent, as is usually the case for the related fluorous reactions [18], permits simple purification by a three-phase (aqueous/organic/fluorous) extractive workup. An example is given in Scheme 4-5. It should be noted that, unlike the cyclization-for-mylation sequence shown in the fourth equation in Scheme 4-3, the cyclization-hydroxymethylation sequence of the same substrate using a catalytic system was... 

Reductive cyclization has been used in a novel, recent synthesis of the alkaloids ( )-isoretronecanol (22) and ( )-trachelanthamidine (23) by Borch and Ho. Condensation of the dianion derived from methyl acetoacetate with Z-l,4-dichlorobut-2-ene, followed by cyclization with sodium meth-oxide yielded the cycloheptenone ester intermediate (32) (Scheme 2). Reductive amination of this ketoester with sodium cyanoborohydride and ammonium nitrate gave a mixture of the diastereoisomeric aminoesters 33 and 34. Oxidation with osmium tetroxide and periodate, followed by reductive cyclization, again using sodium cyanoborohydride, gave the two pyrrolizidine esters 35 and 36 in a ratio of 1 2 [gas-liquid chromatography (GLC) analysis]. The esters were separated by preparative layer chromatography, and lithium aluminum hydride reduction of the individual esters gave the two pyrrolizidine alkaloids 22 and 23. 

In the short synthesis of (-)-524 by Back and Nakajima, an efficient cyclization between the proline-derived chloroamine 556 and the alkynylsulfone 557 yielded the unsaturated indolizidine 558 (94%) (Scheme 71) (451). Stereoselective reduction of the conjugated double bond with sodium cyanoborohydride followed by cleavage of the sulfone with sodium in ammonia yielded a mixture of (-)-524 and the unsaturated analog 559. Catalytic hydrogenation ensured complete conversion of 559 into (- )-indolizidine 167B (524). 

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). 

Alkylation of 5-hydroxy-2-nitrobenzaldehyde with ethyl 4-bromobutyrate gave the ester (163) which was hydrolysed and converted to the amide (164). Reductive alkylation of the aldehyde group using glycine ethyl ester and sodium cyanoborohydride gave the nitro ester (165) which was hydrogenated and cyclized to lixazinone (166) Scheme 5.38.) [207-210]. 

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