With sodium cyanoborohydride

The reduction of 3,5-diphenylisoxazoline with sodium cyanoborohydride produced a mixture of isomeric 3,5-diphenylisoxazolidines. The H and NMR spectra were utilized to distinguish the isomers SOLAIOI). Sodium borohydride reductions likewise reduce isoxazolines to isoxazolidines (equation 56) (80JA4265). 

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. 

Reductive aziridine ring-opening with sodium cyanoborohydride has been described [74, 91]. In the presence of a catalytic amount of TsOH, compound 111 (Scheme 3.37) gave 112 in 68% yield on treatment with sodium cyanoborohydride [74, 91]. 

N,N-Dibenzyl (z -amino a-chloroketimines 202 can be prepared from the corresponding ketones, which in turn are available by the addition of chloromethyllithium to esters of natural cz-amino acids. Reduction of 202 with sodium cyanoborohydride directly afforded a-aminoalkyl-substituted aziridines 203 with high syn diastereoselectivity, which was only moderately affected by the size of the substituent [96] (Scheme 30). A complemen-... 

Scheme 32 Reductive amination of chiral a-aminoketones with sodium cyanoborohydride...

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 8-methyl-8,14-cycloberbine 364, derived from the protoberberine 324 via the betaine 363, was reduced with sodium borohydride or lithium aluminum tri-tert-butoxyhydride to give a diastereoisomeric mixture of cis-and trans-alcohols (7.8 1 or 1 7.8, respectively) (Scheme 64).t)n exposure to formaldehyde the mixture underwent N-hydroxymethylation and subsequent intramolecular substitution on the aziridine ring to give the oxazolidine 365. Removal of the hydroxyl group in 365 was accomplished by chlorination followed by hydrogenolysis with tributyltin hydride. Reductive opening of the oxazolidine 366 with sodium cyanoborohydride afforded ( )-raddeanamine (360), which has already been converted to ochotensimine (282) by dehydration. 

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... 

Schiff base interactions between aldehydes and amines typically are not stable enough to form irreversible linkages. These bonds may be reduced with sodium cyanoborohydride or a number of other suitable reductants (Chapter 2, Section 5) to form permanent secondary amine bonds. However, proteins crosslinked by glutaraldehyde without reduction nevertheless show stabilities unexplainable by simple Schiff base formation. The stability of such unreduced glutaraldehyde conjugates has been postulated to be due to the vinyl addition mechanism, which doesn t depend on the creation of Schiff bases. 

Derivatives of hydrazine, especially the hydrazide compounds formed from carboxylate groups, can react specifically with aldehyde or ketone functional groups in target molecules. Reaction with either group creates a hydrazone linkage (Reaction 44)—a type of Schiff base. This bond is relatively stable if it is formed with a ketone, but somewhat labile if the reaction is with an aldehyde group. However, the reaction rate of hydrazine derivatives with aldehydes typically is faster than the rate with ketones. Hydrazone formation with aldehydes, however, results in much more stable bonds than the easily reversible Schiff base interaction of an amine with an aldehyde. To further stabilize the bond between a hydrazide and an aldehyde, the hydrazone may be reacted with sodium cyanoborohydride to reduce the double bond and form a secure covalent linkage. 

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... 

Figure 7.11 Oxidation of glycoproteins with periodate, such as glycosylated antibodies, results in the formation of aldehyde groups that can be used for conjugation to dendrimers containing amine groups. Reductive amination with sodium cyanoborohydride results in coupling via secondary (or tertiary) amine bonds.

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.

Hapten molecules containing aldehyde residues may be crosslinked to carrier molecules by use of reductive animation (Chapter 3, Section 4). At alkaline pH values, the aldehyde groups form intermediate Schiff bases with available amine groups on the carrier. Reduction of the resultant Schiff bases with sodium cyanoborohydride or sodium borohydride creates a stable conjugate held together by secondary amine bonds. 

Thus, glycoproteins such as HRP, GO, or most antibody molecules can be activated for conjugation by brief treatment with periodate. Crosslinking with an amine-containing protein takes place under alkaline pH conditions through the formation of Schiff base intermediates. These relatively labile intermediates can be stabilized by reduction to a secondary amine linkage with sodium cyanoborohydride (Figure 20.8). 

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. 

REDUCTION OF ALKYL HALIDES AND TOSYLATES WITH SODIUM CYANOBOROHYDRIDE IN HEXAMETHYL-PHOSPHORAMIDE (HMPA) A. 1-IODODECANE TO n—DECANE B. 1-DODECYL TOSYLATE TO n-DODECANE, 53, 107 REDUCTION OF KETONES BY USE OF TOSYLHYDRAZONE DERIVATIVES ANDROSTAN-17 0—OL, 52, 122 REDUCTIVE AMINATION WITH SO-... 

This lengthy procedure requiring protection and deprotection of the hydroxy group can be circumvented by preparing the 3-hydroxy derivatives in 60-65% yield by the straightforward reduction of the corresponding 3-oxo derivatives with sodium cyanoborohydride (Scheme 9) [15,16]. 

Synthesis of a C(8)-C(18) segment of the larger fragment of lb using the same basic strategy is depicted in Scheme 25. Here, hydroxy ketone 176 was subjected to syn-selective (dr of crude product=90 10) reductive amination [42] with sodium cyanoborohydride and benzylamine followed by tetrahydro-oxazine formation using aqueous formaldehyde. The resulting heterocycle 182 was then converted to unsaturated ester 184 by successive desilylation, oxidation, and entirely (Z)-selective Horner-Wadsworth-Emmons olefination. Re-... 

REDUCTIVE AMINATION WITH SODIUM CYANOBOROHYDRIDE N,N-DIMETHYLCYCLOHEXYL-... 

A combined reductive amination sequence has been developed as a useful way of synthesizing amines, with sodium cyanoborohydride as the reducing agent of choice. This complex metal hydride is a less reactive version of sodium... 

Vinylamines (enamines) are reduced by alane, mono- and dichloroalane to saturated amines, and hydrogenolyzed to amines and alkenes [710]. Reduction is favored by dichloroalane while hydrogenolysis is favored by alane. Alane, chloroalane and dichloroalane gave the following results with -N-pyrrolidinylcyclohexene V-pyrrolidinylcyclohexane in 13, 15 and 22% yield, and pyrrolidine and cyclohexene in 80, 75 and 75% yields, respectively [710]. Saturated amines were also obtained by treatment of enamines with sodium borohydride [711], with sodium cyanoborohydride [103, 712] (Procedure 22, p. 210) and by heating for 1-2 hours at 50-70° with 87% or 9S% formic acid (yields 37-89%) [320]. 

Reduction of unsaturated ketones to unsaturated alcohols is best carried out Nit v complex hydrides. a,/3-Unsaturated ketones may suifer reduction even at the conjugated double bond [764, 879]. Usually only the carbonyl group is reduced, especially if the inverse technique is applied. Such reductions are accomplished in high yields with lithium aluminum hydride [879, 880, 881, 882], with lithium trimethoxyaluminum hydride [764], with alane [879], with diisobutylalane [883], with lithium butylborohydride [884], with sodium boro-hydride [75/], with sodium cyanoborohydride [780, 885] with 9-borabicyclo [3.3.1]nonane (9-BBN) [764] and with isopropyl alcohol and aluminum isopro-... 

Ketones containing triple bonds in the a,)3-positions are reduced to the corresponding unsaturated alcohols with sodium cyanoborohydride or tetra-butylammonium cyanoborohydride in 64-89% yields [780]. Thus 4-phenyl-3-butyn-2-one gave 4-phenyl-3-butyn-2-ol [780]. If the same ketone was converted to its p-toluenesulfonylhydrazone and this was reduced with bis benzyloxy)borane, 1-phenyl-1,2-butadiene was obtained in 21% yield [786]. 

---