Sodium cyanoborohydride reduction with

Glutaraldehyde is the most popular b/s-aldchydc homobifunctional crosslinker in use today. Flowever, a glance at glutaraldehyde s structure is not indicative of the complexity of its possible reaction mechanisms. Reactions with proteins and other amine-containing molecules would be expected to proceed through the formation of Schiff bases. Subsequent reduction with sodium cyanoborohydride or another suitable reductant would yield stable secondary amine... 

Another route to the formation of a hydrazide on a surface is to use an aldehyde-containing particle (such as HEMA/acrolein copolymers) and subsequently modify the aldehydes to form hydrazone linkages with bis-hydrazide compounds, which then can be stabilized by reduction with sodium cyanoborohydride (Chapter 2, Section 5). The resulting derivative contains terminal hydrazides for immobilization of carbonyl ligands (see Figure 14.18). 

Figure 14.21 Aldehyde-particles can be reacted with amine-containing proteins or other molecules to form intermediate Schiff bases, which can be stabilized by reduction with sodium cyanoborohydride.

Reduction of the Oximino Fragment in Substituted 5,6-Dihydro-4H-Oxazines Catalytic hydrogenation of substituted dihydro-477-oxazines (552), as well as their reduction with sodium cyanoborohydride (553), were studied in sufficient detail and were used in several total syntheses. However, the use of silylation of six-membered cyclic nitronates enables the synthesis of previously unknown dihydrooxazines containing functionalized substituents at the C-3 and C-4 atoms from easily available precursors. 

The use of C-furfuryl nitrones by Merino and co-workers (201) as latent carboxylate functionality (see Section 1.7) has inspired the development of an analogous C-thiazolyl nitrone. Thus, after reaction of this dipole with acrylate esters, the authors take advantage of the thiazolyl-to-formyl synthetic equivalence to reveal aldehyde functionality after reduction with sodium cyanoborohydride. 

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... 

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. 

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... 

Reduction of alkyl halides and tosylates. - Reduction with sodium cyanoborohydride in HMPT provides a rapid and selective removal of iodo. bromo, and tosyloxy groups in high yield. Thus 1-iododecane can be reduced in thi.s way to n-deeane in... 

Primary alcohols can be reduced to hydrocarbons in two steps conversion into the iodide with triphenyl phosphite methiodide (methyltriphenoxyphosphonium iodide, 1, 1249 2. 446 ), followed by reduction with sodium cyanoborohydride in HMPT. 

This method is superior to the reduction of quinazolin-4-ones to 3,4-dihydroquinazolines with lithium aluminum hydride.Similarly, compounds 8 (R, as above), which are resistant to both methods, are reduced to, V-dialkyl-3,4-dihydroquinazolin-2-amines 9 by first being converted in situ to their imino chlorides on treatment with phosphoryl chloride, followed immediately by reduction with sodium cyanoborohydride." ... 

NBH, in the presence of carboxylic acids. Reduction with sodium cyanoborohydride gives reduction but no alkylation under similar conditions. The reduction of 5-nitroisoquinoline produced dihydroiso-quinoline (27) or tetrahydroisoquinoline (28) with NBH in acetic acid, depending on the solvent and temperatures employed. 

SCHEME 7.48 Lactol reduction with sodium cyanoborohydride. 

Lhommet and co-workers synthesized (- )-436 by the route shown in Scheme 66 [422). Wittig-Homer reaction between the 2,5-rrans -disubstituted pyrrolidine aldehyde 509, made from (S)-pyroglutamic acid [423), and the protected keto-phosphonate 510 introduced all the skeletal carbon atoms of the target. Simultaneous hydrogenation and //-deprotection of enone 511 gave the aminoketone 512, which spontaneously formed the bicyclic enamine 513 in 98% yield when exposed to trifluoroacetic acid—apparently the first time that such an intermediate has actually been isolated en route to indolizidines. Reduction with sodium cyanoborohydride in acidic medium acid produced a diastereomeric mixture (92 8) of (- )-436 and (+ )-437. The former was isolated in 84% yield after chromatography on silica gel. The overall yield of this 15-step sequence was 8% based on (S)-pyroglutamic acid. 

Thus, Cid and Pombo-Villar have also described the synthesis of (-)-a-skytanthine (201) and (+)-epi-dihydrotecomanine (202) from the common intermediate 200 (195). Treatment of200with (4-toluenesulfonyl)hydrazide and in situ reduction with sodium cyanoborohydride afforded the piperi-done 203 in 44% yield. Debenzylation with Li-NH3 followed by reduction of the lactam 204 [which is formally an aza-analog of (+)-isoiridomyrmecin (205)] with UAIH4 gave 206, and iV-methylation under Eschweiler-Clarke conditions afforded (-)-a-skytanthine (201) (Scheme 12) (195). 

Although Schiff base formation can be performed with amine groups, the low stability of the bond in aqueous conditions makes hydrazide a better alternative. Hydrazides can be introduced on the sensor surface via reaction of hydrazine or carbohydrazine to carboxylic groups after activation with EDC/NHS (Fig. 11) [32]. The hydrazide-aldehyde bond forms rapidly and is relatively stable in neutral to alkaline conditions, but disintegrates slowly in acidic buffers. If necessary, the bond can be further stabilized by reduction with sodium cyanoborohydride at pH 4. 

The aziridine (67), formed by irradiation of berberine betaine, on treatment with formaldehyde, gives the base (68), which on reduction with sodium cyanoborohydride affords a cis-glycol that is... 

E)-l-Chloro-3-(N,N-dimethylamino)-1-arylprop-l-enes are conveniently prepared from aryl chloropropeniminium salts by reduction with sodium cyanoborohydride.75 Those iminium salts also undergo 1,2-addition of Grignard reagents (Scheme 32). N,N-Dialkylaminomethyl arenes can be obtained by the reaction of... 

Oxidation of Sephadex G-50 or Enzacryl polyacetal using periodate affords aldehydic pol5nners with which the primary amino groups of the amino acid moieties in aminoacyl-tRNA form Schiff bases, and coupling is rendered irreversible by reduction with sodium cyanoborohydride. Hence, only the amino-acylated tRNA molecules in a mixture are retained, and the tRNA may subsequently be released by washing with ammonium bicarbonate buffer, thus affording a convenient method for the separation of isoacceptor tRNA species. ... 

The use of an alcohol rather than water as the nucleophilic solvent will lead to formation of an ether, and is a simple variation of oxymercuration.243,246 Donaldson s synthesis of the C3-C15 segment of phorboxazole, pyrone 312 was treated with mercuric acetate in methanol.247 Subsequent reduction with sodium cyanoborohydride (sec. 4.5.D) gave a 69% yield of 313 with high selectivity. The intramolecular... 

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