Alcohols product mixtures from borane

In a soluble polymer strategy comparable to resin-capture [145], Janda reported a MeO-PEGsooo-supported dialkyl borane reagent (31) that was used in the purification of a solution-phase library of y9-amino alcohols [146]. Purification was achieved by simply adding (31) to the crude reaction mixture followed by subsequent precipitation of the polymer with diethyl ether to give polymer-supported 1,3,2-oxazaboroU-dine (32) (Scheme 5.2). The /9-amino alcohol product could then be released from the soluble support by treatment with acid. In a two-step synthetic strategy that is readily amendable to automation, the isolation of a small library of /9-amino alcohols was accomplished with all compounds obtained in >80% purity. 

The addition of allylic boron reagents to carbonyl compounds first leads to homoallylic alcohol derivatives 36 or 37 that contain a covalent B-O bond (Eqs. 46 and 47). These adducts must be cleaved at the end of the reaction to isolate the free alcohol product from the reaction mixture. To cleave the covalent B-0 bond in these intermediates, a hydrolytic or oxidative work-up is required. For additions of allylic boranes, an oxidative work-up of the borinic ester intermediate 36 (R = alkyl) with basic hydrogen peroxide is preferred. For additions of allylic boronate derivatives, a simpler hydrolysis (acidic or basic) or triethanolamine exchange is generally performed as a means to cleave the borate intermediate 37 (Y = O-alkyl). The facility with which the borate ester is hydrolyzed depends primarily on the size of the substituents, but this operation is usually straightforward. For sensitive carbonyl substrates, the choice of allylic derivative, borane or boronate, may thus be dictated by the particular work-up conditions required. 

An alternative access was achieved by alkylation of the a-diphenylphosphino acetaldehyde SAMP hydrazone 95, yielding the hydrazone products 96 in good yields (60-63%) and good diastereomeric excesses (die = 68-71%) as EjZ mixtures, from which the major diastereomer was separated and purified by preparative HPLC. Ozonolysis and in-situ reduction with the borane-dimethyl sulfide complex of the aldehydes generated gave the air-stable borane-protected 2-diphenylphosphino alcohols 97 in good yields (67-83%). Reaction with DABCO afforded the unprotected 2-phosphino alcohols 98 in very good yields (85-91%) and excellent enantiomeric excesses (ee > 96%) (Scheme 1.1.27). 

Devaky and Rajasree have reported the production of a polymer-bound ethylenediamine-borane reagent (63) (Fig. 41) for use as a reducing agent for the reduction of aldehydes.87 The polymeric reagent was derived from a Merrifield resin and a 1,6-hexanediol diacrylate-cross-linked polystyrene resin (HDODA-PS). The borane reagent was incorporated in the polymer support by complexation with sodium borohydride. When this reducing agent was used in the competitive reduction of a 1 1 molar mixture of benzaldehyde and acetophenone, benzaldehyde was found to be selectively reduced to benzyl alcohol. 

The product from Step 3 (0.0775 mol) was dissolved in 90 ml THE and borane/dimethyl sulfide added drop wise. The mixture was stirred at ambient temperature for 8 hours and 23.5 ml ethyl alcohol added. The mixture was evaporated to dryness, the residue re-dissolved in EtOAc, washed, dried, and the product isolated after re-crystallization in isopropanol, mp = 128 °C. 

The product from Step 1 was dissolved in 150 ml THE, cooled to —20°C, 2M borane dimethylsulfide (110 mmol) dissolved in THE added, and the mixture refluxed 3 hours. The mixture was re-cooled to —20°C, 72 ml methyl alcohol added and stirred one hour at ambient temperature. Thereafter, 16.4 ml 1M HCl in diethyl ether was added, the solution concentrated, and the residue partitioned between CH2Cl2/THF/water, 3 1 1. The pH was adjusted to 10 with NaHC03, the aqueous layer saturated with NaCl, and extracted with CH2CI2/THF, 3 1. The combined organic layers were dried, concentrated, and purified by flash chromatography on silica gel using chloroform with a methyl alcohol gradient of 3-10%. The material was further purified by crystallization in EtOAc and the product isolated. 

The product from Step 1 (35.0mmol) was dissolved in 100 mlTHF,borane THF(52.5 mmol) added over 90 minutes, the mixture stirred 30 minutes under ice cooling, and then 4 hours at ambient temperature. Thereafter, 5 ml ethyl alcohol was added, the mixture stirred 5 minutes, followed by the addition of 13 ml 6M borane THF. The mixture was stirred 20 minutes under ice cooling, 3 hours at ambient temperature, poured into water, and extracted with EtOAc. The organic layer was washed with brine, dried, and concentrated. The residue was purified by chromatography on silica gel using n-hexane/EtOAc, 70 30 to 60 40. The two products, N-t-butoxycarbony l-spiro[(2-hydroxy )indane-1,4Cpiperidine] and N-t-butoxycarbonyl-spiro[(3-hydroxy)indane-1,4 -piperidine] were isolated in 55% and 40% yields, respectively. H-NMR, IR, and MS data supplied. 

Hydrogen generation catalysts can also be prepared by reduction of precious metals salts. For example, a catalyst has been prepared in the vicinity of poly(N-vinyl-2-pyrrohdone) by alcohol co-reduction of two metal ions in ethanol/water mixture. Pt-Ru bimetaUic catalyst system had a hydrogen production rate of9884 Lmin mol from ammonia borane. Moreover, the turn over frequency value was observed as 308 mol H min. ... 

Some effort has been expended in attempting to determine the effect of changes in steric bulk around the site of reduction. As shown in Equation 9.17, the reduction of bicyclo[2.2.1]heptan-2-one with both borane (B2H6) in oxacyclopentane (THF) and lithium aluminum hydride (LLAIH4) in ether (CH3CH2OCH2CH3) yields a mixture of endo- and exo-bicyclo[2.2.1]heptan-2-ols. Despite the different pathways (yide supra) by which borane (B2H6) and lithium aluminum hydride (LiAlHi) function, the endo-product predominates in both cases because delivery of hydride from the exo-direction (leading to endo-alcohol) is sterically preferred. 

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