Boranes optically active

We further synthesized unsymmetrical MiniPHOS derivatives 13b (Scheme 13) [30]. Thus, enantioselective deprotonation of l-adamantyl(dimethyl)phos-phine-borane (74, R = 1 -Ad), followed by treatment with ferf-butyldichlorophos-phine or 1-adamantyldichlorophosphine, methylmagnesium bromide and bo-rane-THF complex afforded the optically active diphosphine-boranes 82b as a mixture with the corresponding raeso-diastereomer. Enantiomerically pure unsymmetrical MiniPHOS-boranes 82b were obtained by column chromatography on silica gel or separation by recycling preparative HPLC. 

P-Chirogenic diphosphine 19, which rhodium-chelate complex forms a seven-membered ring (rare case for P-stereogenic ligand), was also prepared in reasonable yield (68%) using the wide chemistry of secondary phosphine borane [37]. Deprotonation of the enantiomerically enriched ferf-butylmethylphos-phine-borane 88 (Scheme 15) followed by quenching with a,a -dichloro-o-xylene and recrystallization afforded optically active diphosphine-borane 89 (precursor of free phosphine 19). 

Scheme 17. Improved synthesis of optically active secondary phosphine-boranes...

New chiral oxazaborolidines that have been prepared from both enantiomers of optically active inexpensive a-pinene have also given quite good results in the asymmetric borane reduction of prochiral ketones.92 Borane and aromatic ketone coordinate to this structurally rigid oxazaborolidine (+)- or (—)-94, forming a six-membered cyclic chair-like transition state (Scheme 6-41). Following the mechanism shown in Scheme 6-37, intramolecular hydride transfer occurs to yield the product with high enantioselectivity. With aliphatic ketones, poor ee is normally obtained (see Table 6-9). 

Treatment of the optically active gem-borazirconocene alkanes with deuterium oxide followed by alkaline oxidation affords the corresponding optically active 1-deuterio primary alcohols. The enantiomeric excess of the resulting primary alcohols represents the diaster-eoselectivity of the asymmetric hydrozirconation (Scheme 7.13). Based on the cost and availability of optically active ligands, three types were explored monoterpenes, 1,2-diols, and 1,2-amino alcohols. Hydrozirconation of optically pure 1-alkenyl boranes 39 provided optically active 1,1-bimetallics 40. 

Addition of alane and borane to alkenes affords a host of alkylated alanes and boranes with various reducing properties (and sometimes bizarre names) diisobutylalane (Dibal-H ) [104], 9-borabicyclo[3.3.1]nonane (9-BBN) (prepared from borane and 1,5-cyclooctadiene) [705], mono- [106,107] and diiso-pinocampheylborane (B-di-3-pinanylborane) (both prepared from borane and optically active a-pinene) [108], isopinocampheyl-9-borabicyclo[3.3.1 Jnonane alias B-3-pinanyl-9-borabicyclo[3.3.1]nonane (3-pinanyl-9-BBN) (prepared from 9-borabicyclo [3.3.1]nonane and a-pinene) [709], NB-Enanthrane prepared from 9-borabicyclo[3.3.1]nonane and nopol benzyl ether) [770] and others. ... 

Reduction of a, -acetylenic ketones with chiral borane NB-Enanthrane prepared by addition of 9-borabicyclo[3.3.1]nonane to the benzyl ether of nopol yielded optically active acetylenic alcohols in 74-84% yields and 91-96% enantiomeric excess [770]. Another way to optically active acetylenic alcohols is reduction with a reagent prepared from lithium aluminum hydride and (2S, 3R)-( -I- )-4-dimethylamino-3-methy 1-1,2-dipheny 1-2-butanol. At —78° mainly R alcohols were obtained in 62-99% yield and 34-90% enantiomeric excesses [893]. 

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. 

A number of optically active allylic boron compounds have been used, including380 B-allylbis(2-isocaranyl)borane (28),381 E- and Z-crotyl-(/ ,/ )-2,5-dimethylborolanes (29),382... 

Various prochiral olefins are hydroborated by Rh complexes of BINAP or DIOP in up to 96% optical yield (30h, 31). Oxidation of the products provides a convenient way to produce optically active alcohols. Reaction of styrene and catecholborane in the presence of a BINAP-Rh complex at low temperature forms, after oxidative workup, 1-phenylethyl alcohol in 96% ee (Scheme 11) (31). Double stereodifferentiation occurs in the BINAP-Rh catalyzed reaction of 4-methoxy-styrene and an ephedrine-derived chiral borane (32). 

The milder metal hydride reagents are also used in stereoselective reductions Inclusion complexes of amine-borane reagent with cyclodextrins reduce ketones to optically active alcohols, sometimes in modest enantiomeric excess [59] (equation 48). Diisobutylaluminum hydride modified by zmc broniidc-iV./V.A V -tetra-methylethylenediamine (TMEDA) reduces a,a-difluoro-(3-hydroxy ketones to give predominantly erythro-2,2-difluoro-l,3-diols [60] (equation 49). The threo isomers arc formed on reduction with aluminum isopropoxide... 

Asymmetric hydroboration of 1-phenyl-1,3-butadiene (95) catalyzed by Rh-BINAP gave the corresponding optically active 1,3-diol 155 with 72% ee [89,90] (Scheme 2.15). Palladium-MOP complex also exhibited catalytic activity for the asymmetric hydroboration of but-l-en-3-yne (156), giving an optically active allenyl borane 157 [91]. 

Subjecting boranes produced by asymmetric hydroboration to further reactions such as oxidation (see Section B2.1) leads to optically active products. For example, oxidation of the products of the reaction depicted in Figure B 1.5 gives (/ )-and (S)-2-methylbutan-l-ol in 21%e.e. in favour of the (R) enantiomer (Figure B1.6). (Note that this result reveals that the (+)-Ipc2BH preferentially attacks the upper face of 2-methyIbut-1 -ene.)... 

After the identification of aprepitant as a clinical candidate, Merck invested considerable process research toward an improved synthesis of aprepitant, which culminated in the elegant manufacturing process shown in Scheme 6.21,22 The key step relies on displacement of a trifluoroacetate from intermediate 48 by the optically active alcohol intermediate 49. The synthesis of 49 was accomplished via an oxazaborolidine-catalyzed borane reduction of the corresponding acetophenone. Although the displacement resulted in an almost equal mixture of the two diastereomers 50 and 51, the desired diastereomer 50 could be recovered in high yield by base-catalyzed equilibration of the mixture and crystallization. Addition of p-fluorophenyl magnesium bromide followed by hydrogenolysis afforded the key intermediate 40, which can be readily converted to 1 as detailed in the previous synthesis. 

Optically active TV-sulfonylamino alcohols derived from D-camphor or norephedrine were found to be efficient chiral ligands for the enantioselective allylboration of iV-silylimines (Equation (170)) 646-648 B-Allyl(diisopinocampheyl)borane allylated iV-diisobutylaluminum imines with 87% ee (Equation (171)).649,650... 

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... 

The (S)-prolinate-borane complex (5)-(22) reduces ketones to the corresponding alcohols with optical yields up to 50%. The asymmetric reduction of cyclic imines (24) with chiral sodium triacyloxyborohydride (S)-(23) was utilized to prepare optically active alkaloids (25) with optical yields up to 86% (eq 9). ... 

Silyl enol ethers react with aldehydes in the presence of chiral boranes or other additives " to give aldols with good asymmetric induction (see the Mukaiyama aldol reaction in 16-35). Chiral boron enolates have been used. Since both new stereogenic centers are formed enantioselectively, this kind of process is called double asymmetric synthesis Where both the enolate derivative and substrate were achiral, carrying out the reaction in the presence of an optically active boron compound ° or a diamine coordinated with a tin compound ° gives the aldol product with excellent enantioselectivity for one stereoisomer. Formation of the magnesium enolate anion of a chiral amide, adds to aldehydes to give the alcohol enantioselectively. 

Solid state reduction of alkyl aryl ketone 8 in an inclusion complex with the chiral host 10 with borane-ethylenediamine complex 2BH3-NH2CH2CH2NH2 gave optically active alcohol 9 in the optical and chemical yields summarized in Table 15-3 [7],... 

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