Reduction of ketones with borane

Other S/N ligands have been investigated in the enantioselective catalytic reduction of ketones with borane. Thus, Mehler and Martens have reported the synthesis of sulfur-containing ligands based on the L-methionine skeleton and their subsequent application as new chiral catalysts for the borane reduction of ketones." The in situ formed chiral oxazaborolidine catalyst has been used in the reduction of aryl ketones, providing the corresponding alcohols in nearly quantitative yields and high enantioselectivities of up to 99% ee, as shown in Scheme 10.60. 

They were applied as effective reagents for the asymmetric reduction of ketones with borane. 

Figure 1.27. Asymmetric reduction of ketones with borane catalyzed by oxazaborolidines.

The asymmetric reduction of ketones with borane or with NaBH4/Me3SiCl, catalysed by P-hydroxysulfoximines, afforded secondary alcohols in high yields with good enantioselectivities [241,242],... 

The use of chiral oxazaborolidines as catalysts for the enantioselective addition of alkynylboranes to aldehydes took place in a manner analogous to the asymmetric reduction of ketones with boranes mediated by proline-derived oxazaborolidines (Equation (127)).587 Addition of alkynylboranes to A-aziridinylimines provided a convenient method to prepare allenes from carbonyl compounds (Equation (128)).5... 

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. ... 

Reduction using boranes. A practical modification of the oxazaborolidine-catalyzed reduction of ketones with borane is to replace the trialkylborane component with trimethyl borate. For the reduction of (3-silyl and ( -stannyl enones the use of 80 is advocated. ... 

Reduction. Secondary alcohols with moderate ee values are obtained from the reduction of ketones with borane in the presence of such a complex. 

Reduction of ketones with borane. The basic principle for employing chiral... 

A new catalyst (46) (Figure 5) for asymmetric reduction of ketones with borane gives moderate to good enantioselectivities. It was designed to provide a Lewis basic site (the pyridyl nitrogen atom) in addition to the Lewis acidic site so that coordination of borane would enable intramolecular hydride delivery [structure (48)]. The success of this strategy was confirmed by the inferior enantioselectivity of the analogue (47), which has no Lewis basic site. ... 

Asymmetric reduction of prochiral ketones is one of most efficient method of the introduction of chirality in the synthesis of non-racemic biologically active compounds. Derived from chiral (S)-diphenyl prolinole the amino borate ester 1 has been prepared, fully characterized and used as highly effective catalyst for asymmetric reduction of ketons with borane. The optically pure alcohols 3 have been prepared using only 1 mol % of catalyst 1 in enantioselectivity up to 97%. 

Scheme 10.55 Borane reductions of ketones with p-hydroxy sulfoximine ligand.

Scheme 10.60 Borane reductions of ketones with L-methionine-derived S/N ligand.

Scheme 10.65 Ga-catalysed borane reductions of ketones with MTBH2 ligand.

Al complexes prepared in situ from Al[OCH(CH3)2]3 and two equivalents of (K)-BINAPHTHOL (9) and (i )-H8-BINAPHTHOL (10) promoted the enanti-oselective reduction of propiophenone with borane-dimethyl sulfide and gave the S alcohol in 83% and 90% ee, respectively (Scheme 7) [47]. The reaction was much slower and afforded a racemic product in the absence of Al[OCH(CH3)2]3 under otherwise identical conditions. The addition of a catalytic amount of Al(OC2H5)3 increased both the rate and enantioselectivity in the hydroboration of ketones with a chiral amino alcohol [48]. 

In 1979, Johnson reported the enantioselective reduction of ketones with stoichiometric amounts of optically active (1-hydroxy sulfoximine-borane complexes.131 Prochiral alkyl phenyl ketones (RCOPh) undergo enantioselective reduction with enantiomerically pure p-hydroxy sulfoximine borane complexes (301 and 302). These complexes are prepared by reaction of the corresponding P-hydroxy sulfoximine with borane at -78 °C. The structures 301 and 302 have been suggested for these complexes. In the case of the borane complex 301, the enantioselectivity increased as the steric bulk of the R substituent of the ketone (RCOPh) was decreased from IV to Me. The analogous reductions of methyl alkyl ketones (MeCOR) with these borane complexes were less enantioselective (3-27% ee).131... 

Application as a Component of an Asymmetric Catalyst. Amino alcohol (1) has proven to be a highly versatile ligand for use in asymmetric catalysts for a series of reactions. One of the most comprehensively studied uses is as an ox-azaborolidine derivative such as 8 for the asymmetric control of the reduction of ketones by borane. Although its use was first described with stoichiometric levels of 1 being employed for the reduction of both ketones and oximes, development of the system has delivered a catalytic method requiring only 5-10 mol % catalyst. Enantiomeric excesses of over 85% and as high as 96% have been achieved for a range... 

One of the most powerful asymmetric catalytic reductions of ketones is borane reduction with oxazaborolidine catalyst [92, 93]. Various types of polymer-supported chiral amino alcohols have been prepared and used for the formation... 

New stereogenic centres from prochiral units in planar molecules Enantiotopic and diastereotopic groups Asymmetric Reduction of Unsymmetrical Ketones Asymmetric boron or aluminium hydrides Asymmetric reduction by boranes Reduction of ketones with Ipc2BCl (DIP-Chloride ) Asymmetric Electrophiles... 

Since the first asymmetric reduction of ketones with chiral borohydrides by Itsuno et al. [ 1 ], a number of studies on the asymmetric reduction of ketones with chiral borane reagents have been demonstrated [2]. Corey s oxazaborolidines are some of the most successful reagents [3 ]. The effect of fluorine substituents was examined in the asymmetric reduction of acetophenone with LiBH4 by the use of chiral boronates (73) obtained from substituted phenyl boronic acid and tartaric acid [4]. Likewise, 3-nitro, fluorine, and trifluoromethyl groups on the 3- or 4-position provided enhanced stereoselection (Scheme 5.20). 

Table 1. Optically Active Secondary Alcohols by Selective Borane Reduction of Ketones with Oxazaborolidine Catalysis...

Table 2. Acetylenic Secondary Alcohols by Reduction of Ketones with Alpine-Borane...

Table 3. Secondary Alcohols by Reduction of Ketones with Alpine-Borane (Methods A. B) or ( fDiisopino-campheylchloroborane (Method C)...

Enantioselective reduction of ketones with a borane complex The complex (2). obtained by reaction of BH, THF or BH3 S(CH3)2 with 1 at 25°, is an effective catalyst... 

Corey et al. [4] have investigated enantioselective reduction of ketones with THF-BHa and (5 )-diphenyl prolinol-borane adduct as catalyst. They further introduced modification of oxazaborolidines in which R = CH3, n-butyl as catalyst 1 and used along with other boranes as reducing agents (Scheme 1). The catalysts 1 are known as CBS catalysts and... 

H. Sakuraba, N. Inomata, Y. Tanaka, Asymmetric reduction of ketones with crystalline cyclodextrin complexes of amine-boranes, J. Org. Chem., 1989, 54, 3482. 

If we first consider purely organic systems, one can mention the asymmetric reduction of ketmies with borane promoted by a chiral oxazaborolidine 1 developed by Corey, Bakshi, and Shibata (CBS reduction. Scheme 1) [13,14]. In this system, the nitrogen atom of the oxazaborolidine serves as Lewis base and coordinates BH3 thus improving its nucleoplulicity, while the endocyclic boron atom acts as the Lewis acid and activates the ketone toward the reduction. This seminal work constimtes an early example of metal-free catalysis and shows that cooperative effects can emerge from ambiphilic Lewis acid/base catalytic system. 

Similar to the reduction of aldehydes, reduction of ketones with Alpine-Borane also involves two competing reaction pathways, a bimolecular -hydride elimination process (cyclic mechanism) affording optically active product [6], and a dehydroboration-reduction sequence yielding racemic product [2] (Scheme 26.1). 

Enantioselective Reduction of Ketones with Polymeric (S)-Prolinol-Borane Reagent, J. Chem. Soc., Perkin Trans. 1, (1984) 2887-2893. 

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