Amino alcohol-borane complex

In 1969, Fiaud and Kagan[U1 tested ephedrine boranes but achieved only 3.6-5% enantiomeric excess in the reduction of acetophenone. Itsuno et a/.[121 reported in 1981 an interesting enantioselective reduction of a ketone using an amino alcohol-borane complex as a catalyst. Buono[131 investigated and developed the reactivity of phosphorus compounds as ligands in borane complexes for asymmetric hydrogenation. 

Scheme 13) (35). This high selectivity can be obtained with the 1 2 amino alcohol-borane reagent, however, the 1 1 reagent is less reactive and affords only low stereoselectivity (36). The continuous-flow reaction using a polymer-bound amino alcohol provides evidence for the catalytic nature of the reduction with respect to the chiral ancillary. The reduction is accelerated by the presence of the amino alcohol-borane adduct, and the product is not bound to the complex. 

The most successful of the Lewis acid catalysts are oxazaborolidines prepared from chiral amino alcohols and boranes. These compounds lead to enantioselective reduction of acetophenone by an external reductant, usually diborane. The chiral environment established in the complex leads to facial selectivity. The most widely known example of these reagents is derived from the amino acid proline. Several other examples of this type of reagent have been developed, and these will be discussed more completely in Section 5.2 of part B. 

Nonmetallic systems (Chapter 11) are efficient for catalytic reduction and are complementary to the metallic catalytic methods. For example lithium aluminium hydride, sodium borohydride and borane-tetrahydrofuran have been modified with enantiomerically pure ligands161. Among those catalysts, the chirally modified boron complexes have received increased interest. Several ligands, such as amino alcohols[7], phosphino alcohols18 91 and hydroxysulfoximines[10], com-plexed with the borane, have been found to be selective reducing agents. 

High stereoselectivities (94-100 %) are attained in the reduction of aromatic ketones by use of a new chiral borane complex with (S)-2-amino-3-methyl-l,l-diphenylbutan-l-ol,(S-68) readily prepared in two steps from (S)-valine, in an experimentally convenient procedure961. (S)-Valine methyl ester hydrochloride was converted with excess of phenylmagnesium bromide into (S-68). The same treatment of (R)-valine gave (R-68). In a typical asymmetric reduction the reagent, prepared from (S-68) and borane, and the ketone (69) in tetrahydrofuran were kept at 30 °C for some hours. The corresponding alcohols were obtained in high optical purity. (S-68) could be recovered to more than 80% without racemization 96). 

Enantioselective reduction of jS-keto nitriles to optically active 1,3-amino alcohols has been carried out in one step using an excess of borane-dimethyl sulfide complex as a reductant and a polymer-supported chiral sulfonamide as a catalyst with moderate to high enantioselectivity (Figure 3.11). The facile and enantioselective method to prepare optically active 1,3-amino alcohols has been used to prepare 3-aryloxy-3-arylpropylamine type antidepressant drugs, for example (l )-fluoxetine. 

Organometallic compounds asymmetric catalysis, 11, 255 chiral auxiliaries, 266 enantioselectivity, 255 see also specific compounds Organozinc chemistry, 260 amino alcohols, 261, 355 chirality amplification, 273 efficiency origins, 273 ligand acceleration, 260 molecular structures, 276 reaction mechanism, 269 transition state models, 264 turnover-limiting step, 271 Orthohydroxylation, naphthol, 230 Osmium, olefin dihydroxylation, 150 Oxametallacycle intermediates, 150, 152 Oxazaborolidines, 134 Oxazoline, 356 Oxidation amines, 155 olefins, 137, 150 reduction, 5 sulfides, 155 Oxidative addition, 5 amine isomerization, 111 hydrogen molecule, 16 Oxidative dimerization, chiral phenols, 287 Oximes, borane reduction, 135 Oxindole alkylation, 338 Oxiranes, enantioselective synthesis, 137, 289, 326, 333, 349, 361 Oxonium polymerization, 332 Oxo process, 162 Oxovanadium complexes, 220 Oxygenation, C—H bonds, 149... 

The steric bulk of the silyl groups in acylsilanes influences their asymmetric reduction to give chiral secondary alcohols by borane complexed with )-2-amino-3-... 

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]. 

Free oxazaborolidine (16), by itself, will not reduce ketones. Furthermore, (16) is not particularly stable, reacting with moisture (H2O), air (O2), unreacted amino alcohol, other alcohols, or, depending on the substituents, with itself to form various dimers. This instability is due to the strain of a partial double bond between nitrogen and boron (eq 4). Formation of the oxazaborolidine-borane complex (17) tends to release some of this strain. As such, (16) and (17) are generally prepared and used in situ without isolation in many cases, they have not been fully characterized. ... 

Chiral modification is not limited to boronate and aluminate complexes. Boranes or alanes are partially decomposed with protic substances such as chiral amines, alcohols or amino alcohols to form useful reagents for enantioselective reduction of carbonyl compounds. For example, reduction of acetophenone with borane modified with the amines (65) to (67) gives (5)-l-phenylethyl alcohol with 3.5-20%... 

These complexes are more stable than the borane complexes with diethylether or MejS. They are soluble in water and alcohols and stable in the presence of acetic acid. Their decomposition requires the action of a strong acid or decomplexation by an amino alcohol. 

Supported borane amino alcohol complexes and other supported Lewis acids... 

Boranes other than those based on a-pinene are particularly useful in allylic transfer to imines to make single enantiomers of unsaturated amines. One good combination is an allylboron compound 80 complexed with an /V-sulfonyl amino alcohol such as 78, derived from nor-ephedrine (see chapter 23) with an /V-silyl imine such as 81. The unsaturated amines 82 are formed in good... 

A variety of optically active amines and amino alcohols have been used as chiral auxiliaries for borane reductions. With few exceptions9, early results gave poor to modest asymmetric induction. For example, a variety of amino alcohols derived from a-amino acids gave reduction products of up to 60% ee1U. These reagents presumably used one equivalent of borane per mole of amino alcohol. In 1983 it was shown that the ratio of borane to amino alcohol was important and that two equivalents of borane were required for maximum asymmetric induction. It was postulated that an amino-borane complex of an oxazaborolidinc was involved in the reduction11. 

Treatment of the amino alcohol with borane provides the oxazaborolidine catalyst, which presumably complexes with borane to provide the reducing agent. 

If the chiral amino alcohol is incorporated into polystyrene, a chiral polymeric reducing agent is obtained. Acetophenone O-methyloxime was reduced by such a polymeric borane complex to give optically active 1-phenylethylamine with 99% ee35 36 With borane-tetrahydrofuran and 1 mol% of the chiral amino alcohol (lS,3S,5S)-(a,a-diphenyl)hydroxymethyl-2-azabicy-clo[3.3.0]octane (7), (7 )-1-phenylethylamine can be synthesized from acetophenone O-methyloxime in 64% yield with 17% ee37. 

By similar reduction procedures, amino alcohols can be derived from almost every amino acid. (S)-Valinol [(S)-4], (S)-leucinol [(S)-5], and (S -zm-leucinol [(S) ] are prominent examples of these compounds. A detailed procedure for the reduction of (S)-valine to (S)-valtnol by borane-dimethyl sulfide/boron trifluoride-diethyl ether complex has been reported6, as well as details on the preparation of (5)-leucinol2 and (S)-/m-leucinol ... 

Indeed, by immobilization of optically active a- or )0-amino alcohols on cross-linked polystyrenes as in 6a-d, utilization of chiral borane complexes becomes feasible. These functionalized polymers were incorporated into simple columns and enantioselective reductions of aldehydes and ketones were performed. Thus, reduction of acetophenone with a borane complex prepared from 6d yielded optically active (-)-l-phenyl-2-propanol in high optical yield (>99% ee) [31]. In addition, the flow system also served for continuous regeneration of the immobilized complex. Injection of borane and valerophenone into the column, which was loaded with polymer 6a, was followed by collection of fractions every 30 min. The individual batches of collected 1-phenylpentanol were analyzed and the enantiomeric excess was determined to be 87,93, and 91% for three batches [32]. 

Amine borane complexes, 142-143 Amines, 210, 211 Amino acid esters, 81 Amino acids, 393-394 BOC-Amino acids, 5 7 B-Amino alcohols, 210, 211 Aminoalkylation, 184... 

One of the more widely used solutions to this challenge is the chiral borohydride analogue invented by Itsuno in Japan and developed by Corey, Bakshi, and Shibata. It is based on a stable boron heterocycie made from an amino alcohol derived from proline (see the box below for the synthesis), and is known as the CBS catalyst after its developers. The active reducing agent is generated when the heterocycie forms a complex with borane. Only catalytic amounts (usually about 10%) of the boron heterocycie are needed because borane is sufficiently reactive to reduce ketones only when complexed with the nitrogen atom. The rest of the borane just waits until a molecule of catalyst becomes free. 

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