Sodium Borohydride - A Versatile Reducing Agent

Biographical Sketches

Li Zhenjiang was born in Urumqi, Xinjiang, China. He received his BSc (Chemistry) degree from Lanzhou University, China and MSc (Polymer) degree from East China University of Science and Technology, China. He is currently working towards his PhD under the supervision of Profs. Ouyang Pingkai and Shi Yuhu at Nanjing University of Technology. His research interests include asymmetric synthesis of unusual amino acids and green nano-materials based on montmorillonite.

Introduction

<P>The use of alkali metal borohydrides as reducing agents in organic chemistry is well documented since the pioneering work by H. C. Brown and colleagues. [1] After its first application in carbonyl reduction, [2] sodium borohydride has been widely used as an economical and mild reducing agent in the reduction of carbonyl and related compounds as well as other unsaturated compounds. [3] Suitable substrates [4] included conjugated carbonyl compounds, alkoxysulfonium salts, nitro compounds, carboxylic acids and esters, sulfonate esters, alkyl halides, nitriles, and amides. It was observed that the reducing activity was influenced by solvents and metal ions, [5] and can be finely adjusted by Lewis acid mediation. [6] Reduction in acidic media [7] was investigated extensively. Sodium borohydride (NaBH₄) is commercially available as a white crystalline powder with moderate hygroscopic property. It can be used as solution in lower alcohols, or in glymes for elevated temperature. In neutral and acidic water, NaBH₄ hydrolyzes to afford hydrogen gas, but a basic aqueous solution of NaBH₄ is stable and useful in the lab.</P>

Abstracts

<TD VALIGN="TOP"> (A) Enantioselective reduction of prochiral ketones by NaBH₄ and chiral amino alcohols led to optically active alcohols. The chiral oxazaborolidine-catalyzed reduction (CBS) [8a] of ketones was an important method for secondary chiral alcohol synthesis. Jiang [8b] has shown that (S)-a,a-diphenylpyrrolidinemethanol catalyzed the NaBH₄ reduction of achiral ketone to afford the chiral alcohol with excellent ee and almost quantitative yield. A similar chiral auxiliary was employed in the reduction of the carbonyl group of a,b-unsaturated ketones. [8c] At the chiral interface of an amphiphilic dendrimer, alcohols were obtained in high ee by reduction of the corresponding prochiral ketones. [8d] </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> (B) Polymer reagents are useful in NaBH₄ reduction. Quaternary ammonium-functionalized cross-linked polyacrylamide was used as a solid-liquid phase transfer catalyst in the reduction of carbonyl compounds with NaBH₄. [9a] The resin proved to be efficient in carbonyl reduction and highly regioselective in a,b-unsaturated ­aldehyde and ketone reduction. A new combination system of Amberlyst-15(H⁺)-NaBH₄-LiCl [9b] facilitated the reduction of oximes and hydrazones to the corresponding amines and hydrazines. </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> (C) A highly stereoselective reduction of g-oxo-a-amino acids by NaBH₄ in the presence of a catalytic amount of manganese(II) chloride gives syn-g-hydroxy-a-amino acids. [10] In most reported cases, the dr is higher than 97:3. </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> (D) A combination of NaBH₄ and a catalytic amount of indium(III) chloride in acetonitrile reduces exclusively the a,b carbon-carbon double bond in a,b,g,d-unsaturated diaryl ketones, dicarboxylic ­esters, cyanoesters, and dicyano compounds. [11a] The same system reduces selectively the carbon-carbon double bonds in activated conjugated alkenes. [11b] </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> (E) A practical procedure for the catalytic reduction of nitriles to Boc amines [12a] has been developed; it is neither air- nor moisture-sensitive, and is easily worked up. Nitro compounds, [12b] imines, [12c] and azides [12d] are reduced by Lewis acid-assisted NaBH₄ to afford amines. </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> (F) Reduction of the ester group in Baylis-Hillman adducts by NaBH₄ is facilitated by the secondary hydroxyl group present at the b-position. This method is efficient for the preparation of ­substituted propane-1,3-diols. [13] </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> (G) NaBH₄ in combination with Lewis acids is effective in the ­selective deprotection or cleavage of certain protective groups. A room-temperature deprotection method for trityl amines, trityl ethers, and trityl thioethers was reported. [14a] An efficient and chemoselective deprotection of prenyl ethers of phenols and alcohols with ZrCl₄/NaBH₄ in CH₂Cl₂ was achieved in high yields. [14b]
Reagents: 1. TFA, H₂O; 2. HgHal₂/TFA, H₂O; 3. HgHal₂/TFA, H₂O, NaBH₄; 4. TFA, H₂O, NaBH₄; 5. Hg(OAc)₂/AcOH, H₂O, HgCl₂/MeCN, H₂O; 6. NaBH₄/MeCN; 7. HgHal₂/MeCN, NaBH₄; 8. i. 7 and ii. NaBH₄; 9. HCl/MeCN, H₂O. </TD><TD VALIGN="TOP">

</TD>

References

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