Reduction Sodium borodeuteride

A one-pot, high-yielding synthesis of 1,2,3,4,6-penta-(9-acetyl-/ -D-( 1 -2H)glucopyranose (127) from tetra-O-acetyl-D-glucono-1,5-lactone (126) has been reported (172). Sodium borodeuteride reduction of 126, followed by in situ acetylation, gave the readily isolated and crystalline 127. The crystalline 2,4-dinitrophenyl 2,3,4,6-tetra-0-acetyl-/ -D-(l-2H)glucopyran-oside (128) was subsequently obtained from 127. 

The stereochemistry of the sulphur linkage to the ab quinolizidine ring of thiobinupharidine was deduced from the n.m.r. spectra of thio[6,6 - H2]bi-nupharidine (35b) and thio[6,6 - H2]nuphlutine-B (39a) obtained by sodium borodeuteride reduction of 6,6 -dihydroxythiobinupharidine (35c) and 6,6 -dihydroxythionuphlutine-B (39b) respectively (see Vol. 2 of these Reports). It was shown by parallel spectral and chemical studies that the relative stereochemistry at C-l(C-T), C-4(C-4 ), C-IO(C-IO ), and the CH2S group in thio-nuphlutine-B (39c) and thiobinupharidine (35a) are identical. Therefore, the... 

Deamination of N-deacetylated glycosamino-glycans followed by sodium borodeuteride reduction led to pseudo-disaccharides of 2,5-anhydro-D-mannitol or -D-talitol (from D-glucosamine and D-galact-osamine residues respectively) with attached glucuronic acid,... 

Reaction of an achiral reagent with a molecule exhibiting enantiotopic faces will produce equal quantities of enantiomers, and a racemic mixture will result. The achiral reagent sodium borodeuteride, for example, will produce racemic l-deM/eno-ethanol. Chiral reagent can discriminate between the prochiral faces, and the reaction will be enantioselective. Enzymatic reduction of acetaldehyde- -[Pg.106]

The reduction of the 16-keto function in kryptogenin (66) is a good example for the selectivity of sodium borodeuteride. The resulting 16a-di-16y -hydroxy analog (67) can then be cyclized to give a Iba-d -spirostane derivative (68). ... 

Thus, the reduction of tosylhydrazones with sodium borodeuteride in dioxane provides only monodeuterated analogs. For the insertion of two deuteriums it is necessary to first exchange the hydrazone proton and to carry out the reduction in aprotic or deuterated solvents. Under these conditions the reduction of the tosylhydrazone derivatives of 7- and 20-keto... 

The following general procedure has been used for the reduction of the tosylhydrazone derivatives of various steroidal ketones. A mixture of the tosylhydrazone (50 mg) and sodium borodeuteride (50 mg) in dry dioxane (3 ml) is heated under reflux for 2 hr, and then the excess deuteride is decomposed by the addition of a few drops of acetic acid. Ether is added and the resulting solution is washed with 2 N sodium bicarbonate solution and... 

Still has also carried out mechanistic experiments9 3 from which he could deduce that the major reduction pathway is by attack of hydride ion at the sulphur atom. This conclusion was deduced from the fact that reduction with sodium borodeuteride-aluminium oxide gave a sulphoxide that had only incorporated about 25% mole equivalent of deuterium on to a methyl carbon atom bound to the sulphur atom. The mechanistic pathway for direct reduction is outlined in equation (38), whereas the pathway whereby deuterium could be incorporated is portrayed in equation (39). These reactions support the proposed mechanism for the hydride reduction of sulphones as outlined in Section III.A.l, namely that attack at sulphur by hydride ions may occur, but will be competitive with proton abstraction in cases when the attack at sulphur is not facilitated. 

D-(l-2H)Glucopyranose was prepared (170) by direct reduction of D-glu-cono-1,5-lactone, in deuterium oxide solution, with sodium amalgam in the presence of phosphoric acid-rf3, or, alternatively, by reduction of the lactone tetrahydropyranyl derivative with sodium borodeuteride in tetrahydrofuran (171). 

Figure 5. Proposed structure of peak 9 in Figure 4 and its fragmentation pattern. Deuterium at C-l position was introduced during the reduction step with sodium borodeuteride.

The methylated D-galactose derivatives 66 and 67 were thereafter released by mild hydrolysis with acid. The product was reduced with sodium borodeuteride, the reduction product methylated with trideuteriomethyl iodide, and the ether analyzed. From the disappearance of the ethers derived from the uronic acid and the 2-substi-tuted L-rhamnose, and the appearance of the ethers 68 and 69, the... 

The reduction of tosylhydrazones can also be performed with sodium borodeuteride in boiling methanol or dioxane, but the mechanism of this reaction (in boiling dioxane at least) is radically different from that of the lithium aluminum deuteride reductions.82 With sodium borohydride the first step is apparently hydride attack on the carbon atom of the C=N bond which is probably concerted with the elimination of the tosylate anion (110 - 111). Migration of the hydrogen from nitrogen to C-3 in (111) concerted with expulsion of nitrogen, provides the corresponding methylene derivative (100).82... 

Reduction of Steroidal Tosylhydrazones with Sodium Borodeuteride... 

The reduction of unsaturated-ketohexosyl purines has been thoroughly studied.52 53 In particular, in the case of the unsaturated 2 -keto-nucleosides 61a, 61b, and 63, a mechanism of the reduction by metal hydride was established53 by study of the n.m.r. spectra of the different deoxynucleosides obtained by the action of sodium borohydride in deu-terated solvents and of sodium borodeuteride in nondeuterated solvents. The reduction of both 7-(3-0-acetyl-4,6-dideoxy-L-g(i/cm>-hex-3-eno-pyranosyl-2-ulose)theophylline (61a) and its 6-chloropurine relative 61b in methanol led, respectively, to 7-(2-0-acetyl-4,6-dideoxy-/ -L-xi/fo-hexopyranosyl)theophylline (90a) and (2-0-acetyl-4,6-dideoxy-/ -L-xi/fo-hexopyranosyl)-6-chloropurine (90b) having OH-2 equatorial,... 

Borohydrides normally do not attack carbon-carbon multiple bonds, and thus, a, 3-unsaturated imines (1-aza-1,3-butadienes) are reduced only at their C=N bond, under both thermal and microwave conditions. However, the corresponding (1-aza-1,3-butadiene)tricarbonyliron(O) complexes show a totally different reactivity under the same conditions, and a simultaneous reduction of both C=N and C=C takes place if microwave irradiation is applied25. When the reaction was performed with sodium borodeuterid, 1,2,3-trideutero, secondary amines were obtained. In contrast to their behaviour under microwave conditions, these complexes were totally inert to reduction by NaBH4 under thermal conditions (Scheme 4.7)25. 

A formal synthesis of L-[6-3H]ascorbic acid was achieved when D-glucurono-6,3-lactone was reduced to L-[6-3H]gulono-l,4-lactone with sodium borotritide.354 L-Gulono-1,4-lactone has been converted into 1 by several routes (see Section III,7b,c). Starting with methyl o-xylo-2-hexulosonate, and following the method shown in Scheme 17, L-(5-2H)ascorbic acid was prepared by reduction of 121 with sodium boro-deuteride.547,548,587 In a related, but shorter, synthesis, sodium D-threo-2,5-hexodiulosonate was reduced with sodium borodeuteride to a mixture of keto-acids (see Section III,9d), which was esterified. By fractional recrystallization, methyl L-xylo-2-hexulosonate was obtained, and this was then converted598 into (5- H)l. 

A triflate group undergoes ready reduction by sodium borohydride. The reaction has been applied to the preparation of methyl 2,3,6-tri-0-benzyl-4-deoxy-a-D-xy/o-hexopyranoside. By using sodium borodeuteride, the 4-deoxy-a-d-(4- 2H)-galactopyranoside was obtained.93... 

The reaction course of the reductive photocyclization of enamides in Scheme 17 was firmly established by the experiments using deuterated reagents (75). When enamide 14 was irradiated in the presence of sodium borodeuteride in acetonitrile-methanol (10 1) solution, the isolated product 15 in 93% yield was deuterated at the 3 position, whereas irradiation in the presence of sodium borohydride in acetonitrile-deuterium methoxide solution afforded lactam 16, deuterated in the benzene ring as shown in Scheme 18 (55). 

The main limitation of the use of partially methylated alditol acetates for the characterization of methylated sugars lies in the structural symmetry that may exist when the primary hydroxyl group (0-5 in pentoses and 0-6 in hexoses) is not etherified. This difficulty, however, can be overcome by introducing deuterium at C-1 by reduction of the sugar with sodium borodeuteride. 

Sodium amalgam reduction of organomercurials in alkaline deuterium oxide gives products with stereospecific retention during the replacement of mercury by deuterium [71]. This was shown in the reduction of cw-8-acetoxymercuri- (Ila) and c75-8-chloromer-curidibenzobicylo[2.2.2]octadien-7-ol acetates (Ilb), /ra/75-8-chloromercuridibenzobicy-clo[2.2.2]octadien-7-ol, and some norbornyl derivatives. Reduction of these compounds with sodium borodeuteride gave products without stereospecific deuterium incorporation [71]. 

These results were confirmed by carrying out the reduction with sodium borodeuteride and deuteromethanol. The C-5 proton originates from the... 

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