Asymmetric Borane Reduction Of Ketones Research Articles

Chiral Aminoalcohols and Squaric Acid Amides as Ligands for Asymmetric Borane Reduction of Ketones: Insight to In Situ Formed Catalytic System by DOSY and Multinuclear NMR Experiments.

A series of squaric acid amides (synthesized in 66–99% isolated yields) and a set of chiral aminoalcohols were comparatively studied as ligands in a model reaction of reduction of α-chloroacetophenone with BH3•SMe2. In all cases, the aminoalcohols demonstrated better efficiency (up to 94% ee), while only poor asymmetric induction was achieved with the corresponding squaramides. A mechanistic insight on the in situ formation and stability at room temperature of intermediates generated from ligands and borane as possible precursors of the oxazaborolidine-based catalytic system has been obtained by 1H DOSY and multinuclear 1D and 2D (1H, 10/11B, 13C, 15N) NMR spectroscopy of equimolar mixtures of borane and selected ligands. These results contribute to better understanding the complexity of the processes occurring in the reaction mixture prior to the possible oxazaborolidine formation, which play a crucial role on the degree of enantioselectivity achieved in the borane reduction of α-chloroacetophenone.

Enantioselective borane reduction of ketones catalyzed by tricyclic 1,3,2-oxazaborolidines

Two novel tricyclic 1,3,2-oxazaborolidines were synthesized in seven steps from methyl Boc-l-pyroglutamate. They are characterized by an ortho- and peri-fused 5/5/6-ring system with the B–N bond forming one ring junction. In the asymmetric borane reduction of ketones, the B-alkoxy bridged derivative permits excellent enantioselectivities of up to 98% ee and its activity is comparable to that of the standard CBS catalyst. The closely related, B-alkyl bridged derivative is less enantioselective and less active, as determined by competition experiments.

ChemInform Abstract: Effect of Borane Source on the Enantioselectivity in the Enantiopure Oxazaborolidine‐Catalyzed Asymmetric Borane Reduction of Ketones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Unexpected influence and its origin in rationally tuning the electronic effect of catalysts in the asymmetric borane reduction of ketones

Rationally tuning the electronic effect of catalysts is one of the most important strategies to improve stereoselectivity in asymmetric catalysis. ( S)-2-aryl-3,1,2-oxazaborobicyclo[3.3.0]octanes, which can be considered as electronically tuned ( S)-2-phenyl-3,1,2-oxazaborobicyclo[3.3.0]octane, were prepared and evaluated in the asymmetric borane reduction of ketones. An unexpected influence of the electronic effect of catalysts on the enantioselectivity was observed and attributed to the catalyst dimerization that was further confirmed experimentally. The unsuccessful tuning is accounted for by assuming that hydride transfer in the catalytic cycle is the rate-determining step in the reduction catalyzed by B-aryl catalysts.

Effect of borane source on the enantioselectivity in the enantiopure oxazaborolidine‐catalyzed asymmetric borane reduction of ketones

AbstractThe effect of borane source on enantioselectivity in the enantiopure oxazaborolidine‐catalyzed asymmetric borane reduction of ketones has been investigated by using (S)‐3,1,2‐oxazaborobicyclo[3.3.0]octane and (S)‐7,3,1,2‐thiaxazaborobicyclo[3.3.0]octane as catalysts. The results indicate that the enantioselective order of different borane sources is borane–dimethyl sulfide < borane–N,N‐diethylaniline < borane–THF for the asymmetric reduction of a ketone under the same conditions. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:740–746, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20370

Effect of the Secondary Reduction on the Enantioselectivity and Function of Additives in the Chiral Oxazaborolidine‐Catalyzed Asymmetric Borane Reduction of Ketones

AbstractThe secondary reduction in the direct and oxazaborolidine‐catalyzed asymmetric borane reduction of ketones was investigated by the use of GC/MS tracing titration and control experiments. The results indicate that the secondary reduction affects the enantioselectivity only in noncoordinated solvents at low temperature and not under the usual catalytic reduction conditions because the intermediate alkoxyborane is unstable and quickly converts to borane and dialkoxyborane. The function of an alcohol additive in the asymmetric borane reduction of ketones is to consume excess borane in the reduction system thus inhibiting noncatalytic reduction, which leads to increased enantioselectivity in the catalytic reduction.

Structurally Well-Defined, Recoverable C3-Symmetric Tris(β-hydroxy phosphoramide)-Catalyzed Enantioselective Borane Reduction of Ketones

[reaction: see text] A series of new chiral C(3)-symmetric tris(beta-hydroxy phosphoramide) ligands have been synthesized via the reaction of trisphosphoramide ester and Grignard reagents. The catalytic asymmetric borane reduction of ketones with these new C(3)-symmetric chiral tris(beta-hydroxy phosphoramide)s was investigated. Structurally well-defined, recoverable ligand 1d is an efficient catalyst for the enantioselective borane reduction of both electron-deficient and electron-rich ketones, and high enantioselectivities were achieved (up to 98% ee).

( S)-2-Aryl-4,4-diphenyl-3,1,2-oxazaboro[3.3.0]octanes: Efficient catalysts for the asymmetric borane reduction of electron-deficient ketones

The obvious influence of electronic effects of ketones on the enantioselectivities was observed previously in the oxazaborolidine-catalyzed asymmetric borane reduction of ketones. On the basis of the catalytic reduction mechanism, the electronic effect of organocatalysts, B-aryl-substituted oxazaborolidines, was tuned rationally to improve the enantioselectivities of the electron-deficient ketones in the reduction. The results indicate that all B-aryloxazaborolidines show excellent enantioselectivities for the electron-deficient ketones. This indicates that B-aryloxazaborolidines show better enantioselectivities than B-unsubstituted and B-methoxy-substituted oxazaborolidines for the electron-deficient ketones.

Influences of Electronic Effects and Anions on the Enantioselectivity in the Oxazaborolidine‐Catalyzed Asymmetric Borane Reduction of Ketones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Rationale on the Abnormal Effect of Temperature on the Enantioselectivity in the Asymmetric Borane Reduction of Ketones Catalyzed by L‐Prolinol

AbstractThe effect of temperature on the enantioselectivity of the oxazaborolidine‐catalyzed asymmetric borane reduction of ketones was investigated in the presence of (5S)‐3‐oxa‐1‐aza‐2‐borabicyclo[3.3.0]octane (=(3aS)‐tetrahydro‐1H,3H‐pyrolo[1,2‐c][1,3,2]oxazaborole; 1a) and its 2‐methoxy derivative (1b) as catalysts, which were synthesized from L‐prolinol with borane and trimethyl borate, respectively. The results indicate that the two catalysts induce a different temperature‐dependent enantioselectivity. The enantioselectivity of the B‐unsubstituted (5S)‐3‐oxa‐1‐aza‐borabicyclo[3.3.0]octane (1a) increases with increasing temperature, while its B‐methoxy‐substituted derivative 1b shows the highest enantioselectivity at ca. 50°. (5S)‐3‐Oxa‐1‐aza‐2‐borabicyclo[3.3.0]octane (1a) is more likely to dimerize than its 2‐methoxy derivative 1b. The conversion rates of L‐proline to L‐prolinol in the presence of different amounts of borane were also determined in this study.

Influences of electronic effects and anions on the enantioselectivity in the oxazaborolidine-catalyzed asymmetric borane reduction of ketones.

The influence of electronic effects on the enantioselectivity of the oxazaborolidine-catalyzed asymmetric borane reduction of ketones has been observed and investigated with use of para-substituted acetophenones and propiophenones with a variety of functional groups and B-unsubstituted and B-methoxyoxazaborolidines derived from (S)-2-(diphenylhydroxymethyl)pyrrolidine with borane and trimethyl borate as catalysts in toluene and THF. The results indicate that Hammett linear free energy electronic effects on the enantioselectivity in the asymmetric reduction were observed and rationalized. Tuning electronic effects of the catalyst can improve the enantioselectivity in the reduction. Another interesting finding to be noted is that anions heavily affect the enantioselectivity, especially for the B-methoxy catalyst, because of their coordination with the boron atom in the catalysts.

Effect of Temperature on the Enantioselectivity in the Oxazaborolidine‐Catalyzed Asymmetric Reduction of Ketones. Noncatalytic Borane Reduction, a Nonneglectable Factor in the Reduction System.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Preparation of highly optically pure homochiral sulfide-containing alcohols via oxazaborolidine-catalyzed asymmetric borane reduction of ketones.

Highly optically pure homochiral 1-(4-alkylthiophenyl) alcohols were prepared efficiently and practically via the oxazaborolidine-catalyzed asymmetric borane reduction of prochiral ketones in toluene at 25 degrees C. The coordination of the sulfur atom in the ketones to the boron atom in the catalyst and borane can be inhibited under these reduction conditions.

Effect of temperature on the enantioselectivity in the oxazaborolidine-catalyzed asymmetric reduction of ketones. Noncatalytic borane reduction, a nonneglectable factor in the reduction system.

The effect of temperature on the enantioselectivity of the oxazaborolidine-catalyzed asymmetric borane reduction of ketones has been investigated carefully using alkyl aryl ketones with a variety of functional groups and a B-methoxyoxazaborolidine derived from trimethyl borate and (S)-alpha,alpha-diphenylprolinol as a catalyst. The reductions were carried out over a range of temperatures in THF and toluene with or without the catalyst. The reductive rates increase along with increasing reaction temperature with or without the catalyst by determining the conversion of the ketones to alcohols by GC analysis. However, the rates of the catalytic reductions increase faster than those without the catalyst. The results indicate that the noncatalytic borane reduction is an important factor to the enantioselectivity in the reduction. The highest enantioselectivities were usually obtained between 20 and 30 degrees C in the asymmetric reduction.

ChemInform Abstract: Asymmetric Borane Reduction of Ketones Promoted by Menthopyrazole—ZnCl2 Complex.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Reaction of a chiral oxygen–sulfur paired bidentate ligand with nickel and iron boride: asymmetric borane reduction of ketones

An α-thio alcohol derived from camphor is anchored to nickel boride provided the nickel surface atoms have been passivated. The resulting heterogeneous catalyst affords moderate enantioselectivity in the reduction of acetophenone.

Asymmetric borane reduction of ketones promoted by menthopyrazole‐zncl2 complex

AbstractThe enantioselective reduction of ketones was accomplished by borane in the presence of pyrazole derivatives, particularly 2‐methoxymethyl‐3‐phenyl‐1‐menthopyrazole (8). The catalysis of zinc chloride makes it possible to lower the reaction temperature below 0 °C, and to promote enantioselectivity.

ChemInform Abstract: Asymmetric Borane Reduction of Ketones Catalyzed by N‐Hydroxyalkyl‐l‐menthopyrazoles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Application of MerCO as a Chiral Catalyst in Asymmetric Synthesis: Asymmetric Borane Reduction of Ketones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Application of MerCO as a chiral catalyst in asymmetric synthesis: asymmetric borane reduction of ketones

The borane reduction of aryl methyl ketones catalyzed by MerCO [(1 R,2 S,3 R)-3-mercaptocamphan-2-ol] produced 1-aryl ethyl alcohols in 92% e.e. at 50°C in toluene. Significant temperature and solvent effects were observed in this reaction.