Sodium borodeuteride

Sodium borodeuteride (NaBD4) and lithium aluminum deuteride... 

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... 

Deuterioboration is one of the most important recent additions to the array of methods for saturating double bonds with deuterium. The easy accessibility of metal deuterides (lithium aluminum deuteride or sodium borodeuteride) facilitates the in situ preparation of deuteriodiborane which reacts with steroidal double bonds with a high degree of site and/or stereospecificity, depending on the location of the double bond. " ... 

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. 

Eujen and coworkers6-8 prepared trifluoromethylgermane-d3 for an infrared and Raman study, by treating trifluoromethyltriiodogermane with sodium borodeuteride in a phosphoric acid-d3-deuterium oxide mixture at room temperature (equation 7). 

The most commonly used method for synthesizing organotin hydrides with a hydrogen isotope bonded to the tin atom is to reduce the appropriate chlorostannanes with labelled hydride reagents, such as lithium aluminium deuteride or sodium borodeuteride. For example, tributylchlorostannane can be reduced with lithium aluminium deuteride42-45 or deuterated or tritiated sodium borohydride46 to give tributyltin deuteride and tritiated tributyltin hydride, respectively (equations 40 and 41). 

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). 

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. 

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,... 

SAMPLE SOLUTION (a) Sodium borodeuteride transfers deuterium to the carbonyl group of acetaldehyde, forming a C—D bond. 

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. 

Application of alumina-supported sodium borodeuteride under the reaction conditions described by Varma26 provided deuterated alcohols from aldehydes and ketones with a high degree of deuterium incorporation. The method is thus suitable for isotopic labelling procedures (Scheme 4.12)32. 

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. 

Keywords ketone, aldehyde, deuteriation, alumina, sodium borodeuteride, micro-wave irradiation, alcohol... 

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