Reductions enantioselective, sodium borohydride

Although sodium borohydride cannot reduce unactivated pyrimidines, it can reduce the polarized C=N bonds in dihydropyrimidines to their tetrahydro derivatives. For example, the reduction of the dihydropyrimidinone 537 can be performed enantioselectively with sodium borohydride to give the tetrahydropyrimidinone 538 in 85% yield <199608201 >. 

A cobalt complex containing this type of ligand is effective in the sodium borohydride-mediated enantioselective reduction of a variety of a,/ -unsaturated carboxylates. As can be seen from Scheme 6-8, in the presence of a catalytic amount of a complex formed in situ from C0CI2 and chiral ligand 11, reduction proceeds smoothly, giving product with up to 96% ee. The chiral ligand can easily be recovered by treating the reaction mixture with acetic acid. 

The applications of sodium acyloxyborohydrides, formed from sodium borohydrides in carboxylic acid media, are reviewed. ° Useful reviews of the stereoselective reduction of endocyclic C=N compounds and of the enantioselective reduction of ketones have appeared. ... 

A different approach to enantiotopic group differentiation in bicyclic anhydrides consists of their two-step conversion, first with (/ )-2-amino-2-phcnylethanol to chiral imides 3, then by diastereoselective reduction with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) to the corresponding chiral hydroxy lactames 4, which may be converted to the corresponding lactones 5 via reduction with sodium borohydride and cyclization of the hydroxyalkyl amides 101 The overall yield is good and the enantioselectivity ranges from moderate to good. Absolute configurations of the lactones are based on chemical correlation. 

Similarly to the case of amino acids, hydroxy acids can also be deracemized by combining an enantioselective oxidation with a non-enantioselective reduction with sodium borohydride. For example, the group of Soda has reported the transformation of DL-lactate into D-lactate in >99% (Scheme 5.38) [78]. 

High enantioselectivities (up to 94%) are obtained in the sodium borohydride reduction of aliphatic ketones using a tartaric acid-derived boronic ester (TarB-N02) as a chiral catalyst. A mechanism (Scheme 14) involving an acyloxyborohydride intermediate has been postulated.319... 

With sodium borohydride and catalytic amounts of titanyl acetoacetonate, a,fi-unsaturated carbonyl compounds give allyl alcohols regioselectively, whereas a-diketones and acyloins are reduced to vicinal diols.325 Enantioselectivities in the reduction of acetophenone, catalysed by 1,3,2-oxazaborolidones, have been examined using the AM1-SCF MO method. The optimized geometries, thermal enthalpies, and entropies of R and S transition states in the stereo-controlling steps of the reduction have been obtained.326... 

A diphenylprolinol derivative, having hydrophobic perfluoroalkyl phase tags, has been synthesized and used as a pre-catalyst to generate in situ a fluorous oxaz-aborolidine catalyst for the reduction of prochiral ketones with borohydride. The system afforded high enantioselectivities and the pre-catalyst is easily separated and recycled.272 Reduction of enantiopure A-p-toluenesulfinyl ketimines derived from 2-pyridyl ketones with sodium borohydride affords A-p-toluenesulfinylamines with good yields and diastereoselectivities.273... 

Enantioselective reduction of ketones.1 Sodium borohydride aged with L-tar-taric acid can effect enantioselective reduction of ketones bearing an a-substitueut... 

In 1993, Bolm reported that these reactions could be performed using catalytic quantities (10 mol%) of the chiral P-hydroxy sulfoximine.132 The enantiomeric purities of the product alcohols ranged from 52% (1-indanone) to 93% (PhCOCHjOSiRj). In many cases the enantiomeric purities were enhanced using sodium borohydride as reductant in the presence of chlorotrimethylsilane.133 These methods have been extended to the asymmetric reductions of imines.134 /V-SPh-substituted imines gave the highest enantioselectivities and these reductions proceeded in the same stereochemical sense as the reductions of ketones. 

Hydrogenation of acrylic acid esters with high enantioselectivity has usually been accomplished with difficulty. The enantioselective reduction of a,p-unsaturated carboxylates with sodium borohydride in the presence of cobalt-semicorrin complexes has been achieved in up to 96% ee (equation 14). The (Eland (Z)-isomers each afford products of opposite configuration, and the isolated double bonds remain un-touched. ... 

Pfaltz et al. performed enantioselective reduction of a,P-imsatuxated esters by sodium borohydride in ethanol in the presence of semicorrin I6-C0CI2 catalyst (Scheme 11), with some enantioselectivities reaching 96% ee [58b]. 

Only a few chiral catalysts based on metals other than rhodium and ruthenium have been reported. The titanocene complexes used by Buchwald et al. [109] for the highly enantioselective hydrogenation of enamines have aheady been mentioned in Section 3.4 (cf. Fig. 32). Cobalt semicorrin complexes have proven to be efficient catalysts for the enantioselective reduction of a,P-unsaturated carboxylic esters and amides using sodium borohydride as the reducing agent [ 156, 157]. Other chiral cobalt complexes have also been studied but with less success... 

The highly enantioselective hydride reduction of the di-imine of entry 2.6 was accomplished with sodium borohydride and sub-stoichiometric amounts of a chiral amino alcohol as catalyst [24]. 

Although the catalytic asymmetric borane reductions mentioned above are a powerful tool to obtain highly enantio-enriched alcohols, these require the use of a rather expensive and potentially dangerous borane complex. Sodium borohydride and its solution are safe to handle and inexpensive compared to borane complexes. Thus sodium borohydride is one of the most common industrial reducing agents. However its use in catalytic enantioselective reductions has been limited. One of the most simple asymmetric catalysts is an enantiopure quaternary armnonium salt that acts as phase-transfer catalyst. For instance, in the presence of the chiral salt 81 (Fig. 9), sodium borohydride reduction of acetophenone gave the secondary alcohol in 39% ee [124]. The polymer-supported chiral phase-transfer catalyst 82 (Fig. 10) was developed for the same reduction to give the alcohol in 56% ee [125]. 

Our enantioselective approach to cleomeolide began by controlled dithioketalization [86] of optically pure Wieland-Miescher ketone [87] in order to distinguish between the two carbonyl groups. The best means uncovered for the homologation of 161 to the cis-dimethyl ketone 163 involved 162 as an intermediate (Scheme XIX). The action of (methoxymethylene)triphenylphos-phorane on 161 afforded a 7 1 cis/trans mixture of isomers, which were easily separated after sodium borohydride reduction to the primary carbinols. The major component underwent reductive conversion to 163 very smoothly. 

One of the limitations of the Warren s adaptation of Homer-Wittig olefina-tion, the failure of the (Z)-selective route when the alkene has a branched chain substituent, has now been overcome. Reduction of the p-ketophosphonates carrying a-branches, e.g. (112) and (113), with sodium borohydride and cerium chloride gives excellent a / -stereoselectivity and hence (Z)-alkene on base-induced elimination. Enantioselective synthesis of both jy -(115) and anti- ll) P-hydroxy-phosphine oxides has been achieved with up to 90% e.e. through two separate approaches. The jyn-isomer was obtained by reduction of the corresponding ketone (114), while the anti-isomer is the product of the reaction of the oxazolidine substituted aldehyde (116) with lithiated diphenylmethyl-phosphine oxide (Scheme 10). A new, highly stereoselective approach to trisubstituted alkenes has been reported. Cerium(III) chloride-promoted... 

The enantioselective synthesis of monoprotected fra 5-2,5-pyrrolidine dialcohol 1119, a potentially useful intermediate for the construction of pyrrolizidine alkaloids, uses ( S)-malic acid as the chiral source and radical cyclization to fabricate the heterocycle (Scheme 164) [236]. The crucial intermediate 1112 is prepared from acetonide 454b by a Mitsunobu reaction of 1110 with oxazolidine-2,4-dione, resulting in inversion of configuration at the hydroxyl-bearing carbon. Reduction of the 4-carbonyl group of heterocycle 1111 with sodium borohydride followed by dehydration of the resulting alcohol furnishes 1112. 

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