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Three new routes were established for the synthesis of biologically active murrayaquinone A and a new method was developed for synthesis of murrayanine from the same starting material as 4-hydroxy carbazole. During the synthetic course a few novel observation were recorded, which include two one pot reaction sequences and C–N bond cleavage by sodium cyanoborohydride.

A route to 3-arylpiperidines and 3-arylpyrrolidines involving radical 1,4- and 1,2-aryl migrations has been explored. For the piperidines, the first route requires a xanthate addition to an N-allylarylsulfonamide, followed by acetylation and treatment with lauroyl peroxide to give the corresponding 1,4-aryl transfer product. This compound can be converted into the desired piperidine derivative following acidic hydrolysis. For the second approach to piperidines, addition of an α-keto xanthate to olefins of type 14 causes 1,2-aryl migration leading to an α,β-unsaturated ester, which can be converted into a piperidine by the action of ammonia or a primary amine and sodium cyanoborohydride. Substituted 3-arylpyrrolidines can be obtained by simply starting with an α-amido substituted xanthate.

The synthesis of tryptophan analogs is reported in which the conformation has been constrained by formation of a seven-membered lactam. Boc-protected 2′-formyl tryptophan was obtained by SeO2 oxidation of Boc-tetrahydro-β-carboline-3-carboxylic acid. Reductive amination was performed with a variety of amines and amino acid esters using sodium cyanoborohydride, followed by ring closure to the target compounds. The constrained Trp derivative has been incorporated into the endomorphin-1 opioid peptide sequence to probe the bioactive conformation.

The condensation of 1,1′-bis(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline) with alkyl, aralkyl and aryl aldehydes, but not ketones, in ethanol or chloroform provides useful cyclic aminal [8-substituted 5,6,10,11,15b,15c-hexahydro-2,3,13,14-tetramethoxy-8H-imidazo[5,1-a:4,3-a′]diisoquinoline] intermediates that when subsequently treated with sodium cyanoborohydride in ethanol, followed by the addition of 2 M hydrochloric acid, gave monosubstituted N-alkyl 1,1′-bis(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline) derivatives in very high yields. The rates of the initial condensation with four different aldehydes were measured, and the entire sequence was successfully applied in one example to a ‘one-pot’ process; this signals a versatile route to differentially N-substituted 1,1′-bis(1,2,3,4-tetrahydroisoquinoline) derivatives.

The cascade 1,3-azaprotio cyclotransfer–1,3-dipolar cycloaddition reaction between ketoximes and divinyl ketone [or its equivalent bis(2-chloroethyl) ketone] affords high yields of substituted 1-aza-7-oxabicyclo[3.2.1]octan-4-ones and 1-aza-8-oxabicyclo[3.2.1]octan-4-ones where the cycloaddition regioselectivity is controlled by a judicious choice of experimental conditions. The N–O bonds in the products are reductively cleaved to form piperidones and perhydroazepinones and the ketone moiety undergoes stereoselective sodium cyanoborohydride reduction to afford anti-1-aza-7-oxa-4-hydroxybicyclo[3.2.1]octanes and anti-1-aza-8-oxa-4-hydroxybicyclo[3.2.1]octanes.

A general route to either cis- or trans-2,5-alkyl or aryl disubstituted tetrahydrofurans is described, using the nucleophilic addition of organolithium derivatives to tricyclic lactones, followed by a highly stereocontrolled acid-assisted reduction with sodium cyanoborohydride of the hemiketals formed. The stereoselectivity observed can be rationalized by the preferential approach of the hydride on the less hindered face of an oxonium ion intermediate.

The [2+2]-cycloaddition reactions of ketene diethyl acetal with methyl acrylate and acrylonitrile were optimized. Highly efficient ketal cleavage to either 2-cyano-1-cyclobutanone or 2-methoxycarbonyl-1-cyclobutanone was achieved using formic acid. Among the numerous reduction methods attempted, only sodium cyanoborohydride in acidic medium led successfully to the corresponding alcohols, but isolation of the desired products was not achievable. We show that the anomalous cyclobutanone chemistry is due to the acidic α-proton and the electron-withdrawing substituent in the α-position. Substitution of the α-proton by a methyl group results in a turnaround back to textbook chemistry.

γ-Chloro-α-(N-alkylimino)esters were reduced by sodium cyanoborohydride in methanol in the presence of acetic acid with complete selectivity to give rise to either γ-chloro-α-(N-alkylamino)esters (reaction at 0°C) or 1-alkyl-3,3-dimethylazetidine-2-carboxylic esters (reaction at reflux). The isolable γ-chloro-α-(N-alkylamino)esters are suitable sources for 1-(N-alkylamino)-2,2-dimethylcyclopropane-1-carboxylic esters via base-induced 1,3-dehydrochlorination, while the former substrates as transient species undergo 1,4-dehydrochlorination to the corresponding azetidines. The latter process was used for the synthesis of 3,3-dimethylazetidine-2-carboxylic acid, a new non-proteinogenic sterically hindered α-amino acid, via hydrogenolysis of methyl 1-benzyl-3,3-dimethylazetidine-1-carboxylate and subsequent acidic hydrolysis. Reduction of alkyl 4-chloro-3,3-dimethyl-α-(N-alkylimino)butanoates with lithiumaluminiumhydride in diethyl ether afforded 1-alkyl-3,3-dimethyl-2-(hydroxymethyl)-azetidines.

Reaction of the bromoketals 3, 7a-g and 11 with tri-n-butyltin chloride and sodium cyanoborohydride in the presence of a catalytic amount of AIBN furnished the ethers 5, 8a-g and 13 via a tandem sequence comprising of a radical cyclisation reaction and tri-n-butylhalostannane and sodium cyanoborohydride mediated reductive demethoxylation of the resulting cyclic ketals.

The Stille coupling of 9-2-[bis(2-propoxy)phosphonylmethoxy]ethyl-6-chloropurines with 1-(ethoxyvinyl)tributyltin afforded 6-(1-ethoxyvinyl)purine derivatives. Their acid hydrolysis gave 6-acetylpurine derivatives that after reductive amination using various primary and secondary amine hydrochlorides and sodium cyanoborohydride followed by deprotection afforded the title N-substituted 6-(1-aminoethyl)-9-(2-phosphonomethoxyethyl)purine derivatives.

A range of 1-phenyloxiranemethanamines has been prepared and their reactions with sodium cyanoborohydride under boron triflouride catalysis have been investigated. In general the products were the corresponding 2-amino-3-phenylpropan-1-ols derived from Lewis acid-mediated ring opening of the epoxide in an aza-Payne manner and benzylic reduction of the intermediate aziridinium species.

Secondary and tertiary amines are prepared from α-aminonitriles by selective reductive cleavage of the cyanide moiety. The α-aminonitriles in this case, function as “masked” imine or iminium ions and are “unmasked” by mercury (II) in the presence of sodium cyanoborohydride to obtain the reduced product. Secondary amines may be prepared indirectly from primary amines in good yield without danger of over alkylation.

Refluxing 3-(2-azidoethyl)-3-[3,4-(methylenedioxy)phenyl]cyclohex-1-ene ( 2 ) in toluene for 24 hours afforded 3a-[3,4-methylenedioxy)phenyl]-3,3a,4,5,6,7-hexahydro-2 H -indole ( 12 ) in quantitative yield. This reaction proceeds by intramolecular 1,3-dipolar cycloaddition of the azide onto the alkene followed by loss of nitrogen from the triazoline intermediate to give an imine. Reduction of the imine 12 with sodium cyanoborohydride in acetic acid/THF gave (3aR ∗ , 7aR ∗ )-3a-[3,4-methylenedioxy)phenyl]-2,3,3a,4,5,6,7,7a-octahydroindole ( 13 ). Warming 13 with Eschenmoser's salt provided (±)-crinane ( 1 ). The synthesis of (±)-crinane ( 1 ) from cyclohexenone was accomplished in 8 steps in 23% overall yield.

A regiospecific reduction of quinolines (and 1,10-phenanthroline) into the corresponding 1,2,3,4-tetrahydro derivatives using a combination of sodium cyanoborohydride and boron trifluoride etherate in refluxing methanol is described. Under the same conditions indole and acridine reduced to the corresponding dihydroderivatives, whereas acyl group transfer from oxygen to nitrogen atom is also noticed in the case of 8-acyloxyquinolines.

The stereochemical course of reductions of iminium ions with sodium cyanoborohydride and sodium triacetoxyborohydride was examined within the context of model studies directed toward the synthesis of the quinolizidine alkaloid clavepictine A. Conformational preferences of the iminium ion and and effective size of the reducing agent were shown play a role in determining reduction stereochemistry.

A convenient, mild and simple procedure, employing sodium cyanoborohydride in the presence of either catalytic or stoichiometric amount of boron trifluoride etherate in dry THF, for the reductive cleavage of the acetals and ketals is described.

The one-pot preparation of hindered 1,2-diarylethylamines 3 and 4 and ethylenenamides 5 is achieved via sodium cyanoborohydride reduction and acylation of the deoxybenzoin imines 2 , respectively. A new methodology for the synthesis of 3-arylisoquinolinium salts by the Bischler-Napieralski reaction of 1,2-diarylethylenenamides and their transformation into 12-methyl substituted benzo[c]phenanthridines has been developed.

The oxidation of several 4-substituted catechols in aqueous solution, pH7 in the presence of aniline results in the formation of 4,5-dianilino-1,2-benzoquinone 2 and the anil of 2 , ( 3 ). The C-4 substituent is efficiently cleaved and mechanisms are proposed to account for this phenomenon based on HPLC and GC studies and the formation of N-methylaniline when these reactions were performed in the presence of sodium cyanoborohydride. The evidence suggests that the initial step involves the addition of aniline to the catechol C-4 side chain.

Theα-oxoketene dithioacetals 1 are shown to undergo conjugate 1,4-reduction in highly regio- and chemoselective manner with sodium borohydride in acetic acid to afford the corresponding β-oxodithioacetals 5 in good yields. These results have been rationalized according to HSAB principle in terms of 'hard soft affinity inversion' concept. The reduction of 1 with sodium cyanoborohydride also proceeds in 1,4-conjugate addition-elimination manner to afford the corresponding vinylogous thiolesters 6 in good yields.

Fortimicin B ( 2 ) has been converted to 6'- epi -fortimicin B 5 and 6'- epi -fortimicin A 4 both of which have the same diaminosugar moiety as that present in gentamicin C 2 3 . The syntheses of the 6'- epi -fortimicins and their antibacterial activities are reported. Although reductive amination of 1,2'-di-N-benzyloxycarbonyl-6'-oxo-fortimicin B-4,5-carbamate 17 with sodium cyanoborohydride and ammonium acetate in methanol gave a mixture of 1,2'-di-N-benzyloxycarbonyl-6'- epi -fortimicin B-4,5-carbamate 18 and 1,2'-di-N-benzyloxycarbonylfortimicin B-4,5-carbamate 14 , attempted reduction of 1,2'-di-N-benzyloxycarbonyl-6'-iminofortimicin B-4,5-carbamate 16 , under identical conditions gave only recovered imine. The significance of these results relative to the mechanism of the reductive amination of carbonyl compounds with sodium cyanoborohydride and amine salts is discussed.

A novel synthesis of 11,12-dimethoxyabieta-8,11,13-triene ( 4 ), involving the biomimetic cyclization of allylic alcohol 5 is described. This represents a formal total synthesis of taxodione ( 1 ), a tumor-inhibitory diterpenoid quinone methide. Treatment of the sodium salt of 8 with allyl bromide gave a 91% yield of allyl ether 19 which readily underwent a Claisen rearrangement to give (after methylation with dimethyl sulfate) the dimethoxy olefin 21 in 90% yield. Hydroboration with disiamylborane, followed by oxidative work-up gave alcohol 17 in 98% yield. Oxidation with Collins' reagent afforded 22 in 83% yield. which, upon treatment with isopropenylmagnesium bromide, gave allylic alcohol 23 in 91% yield. Conversion of 23 into chloro ketone 25 was readily effected in 80% yield via a chloro ketal Claisen rearrangement. This substance afforded epoxide 26 in 94% yield when treated with isopropenyllithium. Reduction of 26 with lithium in liquid ammonia gave the desired substrate 5 in 93% yield. When 5 was treated with trifluoroacetic acid in methylene chloride at ca −45° for 45 min, a 90% yield of the desired tricyclic material 6 was obtained. Conversion of 6 to dl -11,12-dimethoxy-abieta-8,11,13-triene ( 4 ) was effected in 59% yield by ruthenium tetroxide oxidation (to give 30 ) followed by sodium cyanoborohydride reduction of the corresponding tosylhydrazone of 30 . Resolution of 30 involved the separation of the diastereomeric ketals 31 . Conversion of d - 30 into d -11,12-dimethoxyabieta-8,11,13-triene ( 4 ) was effected in the aforementioned manner used in the dl -series.

The structure of alamaridine (1) a novel benzopyridoquinolizine alkaloid, was established by spectral data. However, its stereochemistry could only be determined now by a total synthesis involving the key cyclisation of an 1-methyl-2-pyridylmethyl-3,4-dihydroisoquinolinium salt 19a in presence of pivaloyl chloride and triethylamine. O-Benzyldehydroalamaridine thus formed was reduced by sodium cyanoborohydride and then deprotected to obtain alamaridine (1) and 5-epi-alamaridine (26). Isoalamaridine (27) and its 5-epimer (28) were also synthesised following the same route.

Sodium cyanoborohydride reduction of benzothiazolium 1 and Δ2-thiazolinium 2 cations give benzothiazolines 3 and thiazolidines 5 alongwith [[ o -(disubstituted amino) phenyl] and 2-(dialkylamino)ethyl]thio]boranecarbonitriles ( N - B ) 4 and 6 . Because of the heterocyclic structures formed through N→ B coordination and consequent chirality, the latter species constitute mixtures of two diastereomers which are exceptionally stable to acid and base.