“…Addition of Lewis Acids. Researchers at Merck have used additives to achieve a high degree of enantioselectivity in the oxazaborolidine-catalyzed ketone reduction …”
When stabilized BH(3-)THF (BTHF) was added to a mixture of ketone and tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaborole (MeCBS-ozaxaborolidine, MeCBS) catalyst 1, low enantioselectivities resulted. Several relative rate experiments showed that a borohydride species in BTHF catalyzed the nonselective borane reduction of ketones, effectively competing with enantioselective MeCBS reduction of ketones, lowering the overall selectivity of the reaction. Improved enantioselectivities in the reaction are obtained by reversing the mode of addition (ketone to BTHF and catalyst), lowering the concentration of NaBH(4) stabilizer in the BTHF solution (87-95% ee) and increasing the concentration or addition rate of BTHF. Decreased reaction temperature and increased catalyst loading only slightly improved the selectivity of the reaction. Upon reaction parameter optimization, simultaneous addition of substrate and BTHF to MeCBS catalyst stabilizer resulted in the highest overall enantioselectivities (96% ee) and diminished the effect of the borohydride. Alternatively, the addition of Lewis acids such as BF(3-)THF to the reaction mixture effectively destroyed the NaBH(4) stabilizer in BTHF solutions, restoring the enantioselectivity to acceptable levels.
“…Addition of Lewis Acids. Researchers at Merck have used additives to achieve a high degree of enantioselectivity in the oxazaborolidine-catalyzed ketone reduction …”
When stabilized BH(3-)THF (BTHF) was added to a mixture of ketone and tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaborole (MeCBS-ozaxaborolidine, MeCBS) catalyst 1, low enantioselectivities resulted. Several relative rate experiments showed that a borohydride species in BTHF catalyzed the nonselective borane reduction of ketones, effectively competing with enantioselective MeCBS reduction of ketones, lowering the overall selectivity of the reaction. Improved enantioselectivities in the reaction are obtained by reversing the mode of addition (ketone to BTHF and catalyst), lowering the concentration of NaBH(4) stabilizer in the BTHF solution (87-95% ee) and increasing the concentration or addition rate of BTHF. Decreased reaction temperature and increased catalyst loading only slightly improved the selectivity of the reaction. Upon reaction parameter optimization, simultaneous addition of substrate and BTHF to MeCBS catalyst stabilizer resulted in the highest overall enantioselectivities (96% ee) and diminished the effect of the borohydride. Alternatively, the addition of Lewis acids such as BF(3-)THF to the reaction mixture effectively destroyed the NaBH(4) stabilizer in BTHF solutions, restoring the enantioselectivity to acceptable levels.
“…To date, the system that can provide high selectivity, even in alkyl cases, is based on oxazaborolidines 68 (Scheme 56). 33,236,[307][308][309][310][311][312][313][314][315][316][317][318] The proposed mechanism for the reduction is summarized in Scheme 57. 308,309,[319][320][321][322][323][324][325] Other oxazaborolidines, such as 69-72, are also excellent catalysts for the asymmetric reduction of ketones to secondary alcohols.…”
Section: B As Ligandsmentioning
confidence: 99%
“…The reduction of carbonyl compounds has been the most successful for this class of ligands. To date, the system that can provide high selectivity, even in alkyl cases, is based on oxazaborolidines 68 (Scheme ). ,,− 56 …”
Section: B As Ligandsmentioning
confidence: 99%
“…Other oxazaborolidines, such as 69 − 72 , are also excellent catalysts for the asymmetric reduction of ketones to secondary alcohols. − ,,,,− Oxazaborole−boranes give high degrees of asymmetric reduction with dialkyl ketones and are stable and amenable to scale up, as do terpene-based oxazaborolidines, although enantioselectivity is not as high with the latter . The addition of triethylamine to oxazaborolidine-catalyzed reactions has been shown to increase enantioselectivity, especially in dialkyl ketones …”
“…Investigations into the mechanism of the catalytic asymmetric reduction were also conducted [2,3]. Some researchers have paid much attention to the factors that affect the enantioselectivity in the asymmetric reduction, such as the structure [1,2,4], the stability [2a,5] and the loading amount [2a,5a,6] of catalysts, the type [7] and amount [2a,6c] of borane sources, the order and rate of the addition of a ketone or a borane complex into a reductive system [1d,6c], the reduction temperature [5d,6c,8], the solvent [5a,6c,7a,d], the additive [8g, 9,10], the secondary reduction [9a,11], the stabilizer in borane [12], the electronic effects of both ketones [4a,5a,10,13,14] and catalysts [4a,10,14], the kinetics of the asymmetric reduction [15], etc. Although some investigators have referred that different enantioselectivities could be observed with different borane sources [7], all of them evaluated the effect at about room temperature.…”
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
