Oxazaborolidine Catalyst Research Articles

Metal-Free Enantioselective 1,4-Addition of Diarylphosphine Oxides to α,β-Unsaturated Carboxylic Esters.

The catalytic asymmetric conjugate addition of phosphorus nucleophiles to unsaturated compounds, catalyzed by metallic or nonmetallic catalysts, has been extensively developed. However, the enantioselective transformations involving α,β-unsaturated carboxylic esters for constructing chiral c-p bonds have been rarely reported, particularly in metal-free processes. In this study, we present a novel metal-free methodology for enantioselective 1,4-addition of diarylphosphine oxides to α,β-unsaturated carboxylic esters using classical chiral oxazaborolidine catalysts. Remarkably high yields and enantioselectivities were obtained for most of the products. Furthermore, these valuable chiral phosphorus esters serve as crucial intermediates that can be transformed into various derivatives including amides, acids, and alcohols in a single step.

Application of Oxazaborolidine Catalysts (CBS) on Enantioselective 1,4-Addition of Diarylphosphine Oxides to α,β-Unsaturated Thioesters.

Here, we report the first catalytic enantioselective 1,4-addition of diarylphosphine oxides to α,β-unsaturated thioesters. Importantly, the most common and commercial oxazaborolidine (CBS) was employed as a catalyst for its new application without being activated by strong protonic acids or Lewis acids and led to the chiral thioesters in excellent yields and enantioselectivities. Furthermore, this method features mild reaction conditions (room temperature and air-insensitive), good substrate tolerance, and easy scalability.

Robust Analytical Methods for Monitoring the Formation of a Chiral Oxazaborolidine Catalyst

Robust Analytical Methods for Monitoring the Formation of a Chiral Oxazaborolidine Catalyst

Insights into the origin of selectivity for [2+2] cycloaddition step reaction involved in the mechanism of enantioselective reduction of ketones with borane catalyzed by a B-methoxy oxazaborolidine catalyst derived from (–)-β-pinene: an HMDFT and combined topological ELF, NCI and QTAIM study

Insights into the origin of selectivity for [2+2] cycloaddition step reaction involved in the mechanism of enantioselective reduction of ketones with borane catalyzed by a B-methoxy oxazaborolidine catalyst derived from (–)-β-pinene: an HMDFT and combined topological ELF, NCI and QTAIM study

Understanding the origin of the enantioselectivity and the mechanism of the asymmetric reduction of ketimine generated from acetophenone with oxazaborolidine catalyst

The enantioselectivity of the oxazaborolidine-catalysed asymmetric reduction reaction of ketimine generated from acetophenone has been investigated by transition state theory at the hydride transfer step using DFT methods at the B3LYP/6-31G(d,p) level of theory. The obtained results indicate that the hydride attack at the Si face is more favourable than the Re one. Analyses of non-covalent interactions and molecular electrostatic potential indicate that the several favourable interactions at the Si hydrogen transfer mode are the origin of the enantioselectivity observed experimentally. Electron Localisation Function topological analysis indicates that the studied hydride transfer step takes place via a non-concerted three-stage mechanism.

Practical Enantioselective Reduction of Ketones Using Oxazaborolidine Catalysts Generated In Situ from Chiral Lactam Alcohols.

Oxazaborolidine catalyst (CBS catalyst) has been extensively used for catalytic borane reduction with a predictable absolute stereochemistry and high enantioselectivity. However, the use of isolated CBS catalyst sometimes has the drawback of low reproducibility due to the aging of the CBS catalyst during storage. Therefore, we investigated a more reliable and practical method for the reduction of a variety of ketones including challenging substrates, primary aliphatic ketones, α,β-enones, and trifluoromethyl ketones. This review surveys the developments in borane reduction using oxazaborolidine catalysts generated in situ from chiral lactam alcohols and borane.

Synthesis of (−)‐Hebelophyllene E: An Entry to Geminal Dimethyl‐Cyclobutanes by [2+2] Cycloaddition of Alkenes and Allenoates

AbstractThe first synthesis of hebelophyllene E is presented, along with assignment of its previously unknown relative configuration through synthesis of epi‐ent‐hebelophyllene E. Development of a catalytic enantioselective [2+2] cycloaddition of alkenes and allenoates provides access to the required chiral geminal dimethylcyclobutanes. Key to its success is the identification of a novel oxazaborolidine catalyst which promotes the cycloaddition in high enantioselectivities with good functional‐group tolerance (9 examples, up to 97:3 e.r.). Thus, a late‐stage cycloaddition using a fully functionalized alkene, followed by a diastereoselective reduction allows a concise entry to this class of natural products.

Synthesis of (-)-Hebelophyllene E: An Entry to Geminal Dimethyl-Cyclobutanes by [2+2] Cycloaddition of Alkenes and Allenoates.

The first synthesis of hebelophyllene E is presented, along with assignment of its previously unknown relative configuration through synthesis of epi-ent-hebelophyllene E. Development of a catalytic enantioselective [2+2] cycloaddition of alkenes and allenoates provides access to the required chiral geminal dimethylcyclobutanes. Key to its success is the identification of a novel oxazaborolidine catalyst which promotes the cycloaddition in high enantioselectivities with good functional-group tolerance (9 examples, up to 97:3 e.r.). Thus, a late-stage cycloaddition using a fully functionalized alkene, followed by a diastereoselective reduction allows a concise entry to this class of natural products.

Catalytic Asymmetric Cycloadditions of Silyl Nitronates Bearing α-Aryl Group.

1,3-Dipolar cycloadditions of 2-alkylacroleins or atropaldehyde with triisopropylsilyl nitronates bearing an α-aryl group produced 3-aryl-2-isoxazolines having a chiral quaternary center in up to 94% ee and up to 88% yield with the aid of Corey's oxazaborolidine catalyst. Specifically, the TIPS nitronate with an α-(p-methoxyphenyl) group gave mainly the 2-isoxazolines having an all-carbon quaternary center.

New Oxazaborolidine Catalysts for the Diels–Alder Reaction

A new axially chiral oxazaborolidine catalyst has been developed. This catalyst consists of a chiral boronic acid and an easily modifiable achiral amino alcohol. It could be applied to a Diels–Alder reaction to give the corresponding adduct with good enantioselectivity. Additionally, the bis(oxazaborolidine) catalyst, bearing two Lewis acidic centers enabled a Diels–Alder reaction with higher enantioselectivity.

ChemInform Abstract: Enantioselective Desymmetrization of Glutarimides Catalyzed by Oxazaborolidines Derived from cis‐1‐Amino‐indan‐2‐ol.

Enantioselective reductive desymmetrization of glutarimides has been achieved employing an oxazaborolidine catalyst derived from cis-1-amino-indan-2-ol. The reaction was found to proceed through a stereoablative process that upgraded the enantioselectivity of an intermediate hydroxy-lactam. The reaction was generally tolerant of a number of substituents in the 4-position, giving enantiomeric excesses of greater than 82%.

Enantioselective Desymmetrization of Glutarimides Catalyzed by Oxazaborolidines Derived from cis-1-Amino-indan-2-ol.

Enantioselective reductive desymmetrization of glutarimides has been achieved employing an oxazaborolidine catalyst derived from cis-1-amino-indan-2-ol. The reaction was found to proceed through a stereoablative process that upgraded the enantioselectivity of an intermediate hydroxy-lactam. The reaction was generally tolerant of a number of substituents in the 4-position, giving enantiomeric excesses of greater than 82%.

ChemInform Abstract: Catalytic Asymmetric Synthesis of Isoxazolines from Silyl Nitronates.

AbstractThe utility of this method is demonstrated in a synthesis of (R)‐(+)‐tanikolide (XI).

ChemInform Abstract: An Oxazaborolidine‐Based Catalytic Method for the Asymmetric Synthesis of Chiral Allylic Alcohols.

Abstract The enantioselective reduction of a broad range of prochiral α,β-unsaturated ketones 1a – 1y using the oxazaborolidine-based catalyst providing chiral allylic alcohols 2a – 2y with both high enantioselectivity and chemoselectivity is described. The optimum reaction conditions were found using the oxazaborolidine catalysts prepared in situ from the chiral amino alcohols and borane reagents. Various chiral amino alcohols 4a – 4f were screened for this one-pot asymmetric reduction of α,β-enones. Amino alcohol 4a [( R )-DPP] and trimethylboroxine catalyze this asymmetric reduction in toluene at −20 °C within 0.5–2 h in a highly efficient manner. The synthesized chiral allylic alcohols 2a – 2y are new compounds, which are valuable intermediates in the preparation of new ligands and in the synthesis of several natural molecules.

Catalytic Asymmetric Synthesis of Isoxazolines from Silyl Nitronates.

1,3-Dipolar cycloadditions of triisopropylsilyl nitronates and 2-alkylacroleins produced isoxazolines bearing a chiral quaternary center in high yields and enantioselectivities with the aid of a chiral oxazaborolidine catalyst. One chiral isoxazoline product was converted to (R)-(+)-Tanikolide in 9 steps in a total yield of 43%.

An oxazaborolidine-based catalytic method for the asymmetric synthesis of chiral allylic alcohols

The enantioselective reduction of a broad range of prochiral α,β-unsaturated ketones 1a–1y using the oxazaborolidine-based catalyst providing chiral allylic alcohols 2a–2y with both high enantioselectivity and chemoselectivity is described. The optimum reaction conditions were found using the oxazaborolidine catalysts prepared in situ from the chiral amino alcohols and borane reagents. Various chiral amino alcohols 4a–4f were screened for this one-pot asymmetric reduction of α,β-enones. Amino alcohol 4a [(R)-DPP] and trimethylboroxine catalyze this asymmetric reduction in toluene at −20°C within 0.5–2h in a highly efficient manner. The synthesized chiral allylic alcohols 2a–2y are new compounds, which are valuable intermediates in the preparation of new ligands and in the synthesis of several natural molecules.

Effect of BF3 on the enantioselective reduction of trifluoromethyl ketones using a chiral lactam alcohol with borane

The addition of BF3·THF to an oxazaborolidine catalyst prepared in situ from chiral lactam alcohol 2 and borane enhanced the enantioselectivities (up to 90% ee) and yield (up to 91%) during the reduction of reactive trifluoromethyl ketones at room temperature.

Asymmetric synthesis of α-chiral hydroxyalkylphosphines by a catalytic enantioselective reduction of acylphosphines.

Enantioselective reduction of acylphosphines, after precomplexation with borane, proceeded smoothly in the presence of a chiral oxazaborolidine catalyst and catecholborane. α-Hydroxyalkylphosphine products were obtained as phosphine-borane complexes in good yield and enantioselectivity. One of the products of the enantioselective reduction was successfully applied as an optically active phosphine ligand for asymmetric catalysis after suitable derivatization.

Enantioselective Catalytic Desymmetrization of Maleimides by Temporary Removal of an Internal Mirror Plane and Stereoablative Over-reduction: Synthesis of (R)-Pyrrolam A

A highly enantioselective (>95% ee) strategy to affect the desymmetrization of a maleimide has been performed by temporary attachment to an anthracene template followed by asymmetric reduction with an oxazaborolidine catalyst. A stereoablative over-reduction process was partially responsible for the high levels of enantioselectivity. Exemplification of the strategy by stereoselective functionalization and retro-Diels-Alder reaction provided the natural product pyrrolam A.

Enantioselective Reduction of Prochiral Ketones with NaBH4/Me2SO4/(S)-Me-CBS

The enantioselective reduction of prochiral ketones with NaBH4/Me2SO4/(S)-Me-CBS is described. Borane is generated in situ via the reaction of NaBH4 with Me2SO4 in tetrahydrofuran, which is as efficient as the commercial one. Such in situ–generated borane reagent was applied to reduce prochiral ketones in the presence of chiral oxazaborolidine catalyst directly. The corresponding chiral secondary alcohols were obtained with excellent enantiomeric excesses (93–99% ee) and good to excellent yield (80–99%).