Tetramethylammonium triacetoxyborohydride

Sodium or tetramethylammonium triacetoxyborohydride has become the reagent of choice for diastereoselective reduction of P-hydroxyketones to antidiols. Trialkylborohydrides, eg, alkaH metal tri-j -butylborohydrides, show outstanding stereoselectivity in ketone reductions (39). 

Tetramethylammonium triacetoxyborohydride gives anft -l,3-diols from (3-hydroxy ketones.136 These reactions are thought to occur by a rapid exchange that introduces the hydroxy group as a boron ligand. 

Syn stereoselectivity in reduction of acylic chiral ketoxime ethers of type 91 (equation 63) can be obtained using bulky tetramethylammonium triacetoxyborohydride that produces FeUdn-type products with high selectivity . Reaction of a-tolylsulfinylketoximes 92 (equation 64) with L-Selectride also results in syn products 93. 

Evans DA, Chapman KT et al (2002) Directed reduction of P-hydroxy ketones employing tetramethylammonium triacetoxyborohydride. J Am Chem Soc 110 3560-3578... 

In the synthesis of RK-397 (18), Denmark and Fujimori prepared an anft -diol using the Evans-Chapman-Carreira protocol5 (Scheme 4.2f). The (3-hydroxy ketone 21, obtained by a diastereoselective boron aldol reaction between 19 and 20, was reduced with tetramethylammonium triacetoxyborohydride to afford the anti-diol derivative 22 in greater than 19 ldiastereoselectivity. 

The best results are obtained with tetramethylammonium triacetoxyborohydride and the best conditions appear to be — 40 °C in acetic acid/acetonitrile (1 1) for several hours. The selectiv-ities are generally very satisfactory. It is notable, though perhaps not surprising, that the reaction of 9,10-s>7t-10-benzyloxymethoxy-9-hydroxy-2,2-diinethyl-1-phenylsulfonyl-3,7-un-decancdione is regioselective (see last entry in table above). 

An interesting variant on this method is the use of a newly created hydroxy group to direct the reduction of a second carbonyl group. Thus the diketone 3-phenylpropyl 7-hydroxy-8-methyl-3,5-dioxononanoate was treated with tetramethylammonium triacetoxyborohydride in acetic acid at ambient temperature to give a mixture of isomeric triols in which the anti,anti-isomer comprised 85% of the total43. 

After TBS protection, methanolysis of the dioxolenone liberates the heptanoic acid ester 950. Stereocontrolled reduction of the -keto function furnishes either syn or anti diols depending on the hydride reagent employed. Diethylmethoxyborane-sodium borohydride gives syn-d o 952 as a single isomer in 86% yield, whereas tetramethylammonium triacetoxyborohydride produces a mixture of anti and yw-diols 953 and 952 (ratio anti syn = 10 1) in 85% yield [173] (Scheme 129). 

Sodium triacetoxyborohydride can reduce aldehydes selectively in the presence of ketones. However, a- and -hydroxy-ketones are reduced with this reagent. The reduction occurs stereoselectively to give predominantly the anti diol product. The reagent tetramethylammonium triacetoxyborohydride Me4NBH(OAc>3 has shown excellent selectivity for this transformation (7.88). Exchange of one of the acetoxy groups for the alcohol is thought to proceed stereoselective intramolecular transfer of hydride. 

Related Reagents. Cerium(III) Chloride Nickel Boride Potassium Triisopropoxyborohydride Sodium Cyanoboro-hydride Sodium Triacetoxyborohydride Cobalt Boride Lithium Borohydride Lithium Aluminium Hydride Zinc Borohydride Tetramethylammonium Triacetoxyborohydride. 

Tetramethylammonium triacetoxyborohydride [109704-53-2] M 263.1, m 93-98", 96.5-98. If impure, wash it with freshly distilled Et20 and dry it overnight in a vacuum to give a free flowing powder. Check H NMR, and if still suspect prepare it freshly from Me4NBH4 and AcOH in CgH6 and store it away from moisture [Banus et al. J Am Chem Soc 74 2346 1952, Evans Chipman Tetrahedron Lett 27 5939 1986. It is an IRRITANT and MOISTURE SENSITIVE. 

Some more significant changes at C-13 have also been made. Thus Georg and her coworkers prepared 13-epitaxol from baccatin III (43). The key to their strategy was the stereoselective reduction of 4-deacetyl-13-oxo-7-(triethylsilyl)baccatin III (2.2.1) with tetramethylammonium triacetoxyborohydride, which gave a 13-epibaccatin derivative which was converted to the taxol analog 2.2.2. This product was essentially inactive in a tubulin-assembly assay. 

Deoxy-sugars have also been constructed from noncarbohydrate starting materials. One-carbon extension of the L-lactate derivative (59) gave dithioacetal (60) from which various 4-deoxy-L-threose and -erythrose derivatives were synthesised. Tetramethylammonium triacetoxyborohydride has been used to selectively reduce -hydroxy-ketones to anti-1.3-diols. as in the conversion of ketones (61) and (62) to diol (63) and triol (64),... 

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