Reduction using catecholborane

The third approach to obtain diarylmethylpiperazine derivatives uses the highly stereospecific chiral oxazaborolidine-catalyzed reduction, using catecholborane as the reductant of the 4-bromobenzophenone chromium tricarbonyl complex, as described by Corey and Helal [59], followed by the stereospecific displacement of the hydroxyl benzyl group by the /V-substituted-piperazine [44]. As outlined in Scheme 2, Delorme et al. [44] used this approach for the enantioselective synthesis of compound 31, (+)-4-[ (aS)-a-(4-benzyl-l-piperazinyl)benzyl]-lV,lV-diethylben-zamide. Lithiation of the readily available benzene chromium tricarbonyl with n-BuLi in the presence of TMEDA in THF at —78 °C, followed by addition of... 

Reactions using catecholborane proceed smoothly in toluene (Scheme 16) (40). The utility of catalytic hydroboration of ketones has been demonstrated by the efficient enantioselective synthesis of a series of biologically active compounds (41). Scheme 17 shows some compounds prepared by using this method. Enantioselective reduction of trichloro-methyl ketones is a general route to a-amino acids and a-hydroxy esters it also allows ready synthesis of a precursor to the carbonic anhy-drase inhibitor MK-0417 (42). 

These products are biologically significant as some of these phosphonates have been observed to be potent inhibitors of proteolytic enzymes such as rennin and HIV protease. Stereoselective reduction of aminoketophosphonates using catecholborane provides a facile access to these biologically important molecules. 

An analogous approach was used in a stereoselective synthesis of /Tamino-a-hydroxy phosphonates [33]. Reduction of corresponding a-keto phosphonate substrates with borane-dimethylsulfide complex aided by oxazaborolidine catalysis afforded a mixture of diastereomers, but significant diastereoselectiv-ity was achieved using catecholborane as the reductant in toluene at -60 °C. 

The use of catecholborane as reductant can avoid the side reaction caused by BHj. The catecholborane procedure functions well at -78 °C in toluene. Chiral allylic alcohols were obtained in >95% yield with high ees [35]. Cyclic enones are also reduced enantioselectively to give chiral cyclic allylic alcohols by using catecholborane as reductant [35]. 

The catalytic reduction of trifluoromethyl ketones was successfully realized by using catecholborane as reductant. In the case of the reduction of anthryl trifluoromethyl ketone, one recrystallization of the crude (i )-alcohol (94% ee) afforded the enantiopure carbinol [35]. Trichloromethyl ketones were also reduced... 

For ketone reduction with catecholborane, chiral titanium alkoxide species prepared from (j-PrO)4Ti and diol 67 have been used. ... 

Tosylhydrazones are reduced to the corresponding methylene derivatives using catecholborane. It has been demonstrated that monodeuteriated products are obtained on conducting the reduction in the presence of D2O or MeOD. "... 

Enantioselective reduction of ketones has been carried out using catecholborane and a BINOL-derived phosphoric acid the latter is suggested to be a pre-catalyst, with B-NMR evidence for the formation of a phosphoryl catechol borate as active catalyst. ... 

The corresponding A-butyloxazaborolidine is also frequently used as a catalyst. The enantioselectivity and reactivity of these catalysts can be modified by changes in substituent groups to optimize selectivity toward a particular ketone.150 Catecholborane can also be used as the reductant.151... 

Another approach to (R)-(-)-phoracantholide I (245) used a ring enlargement of cyclohexanone (255) which had been alkylated with chiral synthon 256 (Scheme 14) [206]. Thus, compound 257 was prepared in 35% yield on a 7-g scale by alkylation of cyclohexanone with chiral 256. Cyclization with Am-berlyst A-15 provided enol ether 258 that was directly submitted to ruthenium tetroxide oxidation to give oxolactone 259 in a 47% yield. Reduction of the latter with catecholborane via its tosylhydrazone afforded (R)-(-)-phoracan-tholide I (245) in 31% yield. 

Alkynes are reactive toward hydroboration reagents. The most useful procedures involve addition of a disubstituted borane to the alkyne. This avoids the complications which occur with borane that lead to polymeric structures. Catecholborane is a particularly useful reagent for hydroboration of alkynes.168 Protonolysis of the adduct with acetic acid results in reduction of the alkyne to the corresponding Z-alkene. Oxidative workup with hydrogen peroxide gives ketones via enol intermediates. 

This adduct can be prepared, stored, and used as a stoichiometric reagent if so desired.97 Catecholborane can also be used as the reductant.98... 

Reaction of achiral and chiral bis(oxazolines) (BOX) with catecholborane (CATBH) provides boron-BOXate complexes that can be used as catalysts in the enantioselective reduction of ketones. It has been shown that asymmetric transfer of the hydride ion from the boron atom of CATBH to the prochiral carbonyl is the rate-determining step of the catalytic reaction.314... 

Catecholborane is a versatile reducing reagent, a mild and convenient alternative to the classical (Clemmensen, using acids and Wolff-Kishner, using bases) reduction procedure of tosylhydrazones. Regiospecific isomerization occurs during the reduction of a,(3-unsaturated carbonyl derivatives often leading to unique alkenes (Eqs. 134 and 135) 222-223> and allenes (Eq. 136) 224). 

Several novel catalysts in which borohydride is complexed with a difiinctional chiral ligand have been developed and used for the enantioselective reduction of prochiral ketones to chiral alcohols. Corey-Bakshi-Shibatareduction (CBS reduction) is an organic reaction which reduces ketones enantioselectively into alcohols by using chiral oxazaborolidines and BHs-THF or catecholborane as stoichiometric reductants (CBS reagent, 1.64) (also see Chapter 6, section 6.4.2). 

Enantioselective Ketone Reduction. After the pioneering work of Itsuno et al., Corey s group isolated the 1,3,2-oxazaborolidine derived from chiral a,a-diphenyl-2-pyrrolidinemethanol (2) and applied it (and also other related B-alkyl compounds) to the stereoselective reduction of ketones with borane-tetrahydrofuran, borane-dimethyl sulfide (BMS) or catecholborane.It was named the CBS method (after Corey, Bakshi, and Shibata). Since then, the CBS method has become a standard and has been extensively used, specially for aromatic and a,p-unsaturated ketones, not only in academic laboratories but also in industrial processes. ... 

Alcohols 3-8, obtained by the reduction of the corresponding ketones with equimolar amounts of BMS and are obtained with high ees (ee values given are obtained using 0.1 equiv of (R)-1). Enantioselectivity is excellent (often similar or only slightly lower than those reported in the CBS reduction) for aromatic and hindered methyl ketones, (e.g. 3-5) and is also good for linear and a-monobranched enones (e.g. 7 and 8), but lower for linear methyl ketones like 2-octanone (6). In should be noted that in the reduction of unsaturated ketones, the time of addition is critical (the optimum being around 15-20 min) in order to avoid concomitant olefin hydroboration. In sharp contrast to the CBS process, the use of catecholborane (instead of BMS) or alternative solvents proved to be detrimental. 

The asymmetric total synthesis of prostaglandin Ei utilizing a two-component coupling process was achieved in the laboratory of B.W. Spur. The hydroxylated side-chain of the target was prepared via the catalytic asymmetric reduction of a y-iodo vinyl ketone with catecholborane in the presence of Corey s CBS catalyst. The reduction proceeded in 95% yield and >96% ee. The best results were obtained at low temperature and with the use of the B-n-butyl catalyst. The 6-methyl catalyst afforded lower enantiomeric excess and at higher temperatures the ee dropped due to competing non-catalyzed reduction. 

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