CBS Catalyst Research Articles

Synthesis of (+)-goniopypyrone and (+)-goniotriol using Pd-catalyzed carbonylation

Syntheses of (+)-goniopypyrone and (+)-goniotriol isolated from Goniothalamus giganteus were achieved. The key steps involve Pd-catalyzed carbonylation for lactone ring formation and diastereoselective reduction of ynone using the (R)-CBS catalyst and borane dimethyl sulfide complex.

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.

Lewis Acids as Activators in CBS-Catalysed Diels-Alder Reactions: Distortion Induced Lewis Acidity Enhancement of SnCl4.

The effect of several Lewis acids on the CBS catalyst (named after Corey, Bakshi and Shibata) was investigated in this study. While (2) H NMR spectroscopic measurements served as gauge for the activation capability of the Lewis acids, in situ FT-IR spectroscopy was employed to assess the catalytic activity of the Lewis acid oxazaborolidine complexes. A correlation was found between the Δδ((2) H) values and rate constants kDA , which indicates a direct translation of Lewis acidity into reactivity of the Lewis acid-CBS complexes. Unexpectedly, a significant deviation was found for SnCl4 as Lewis acid. The SnCl4 -CBS adduct was much more reactive than the Δδ((2) H) values predicted and gave similar reaction rates to those observed for the prominent AlBr3 -CBS adduct. To rationalize these results, quantum mechanical calculations were performed. The frontier molecular orbital approach was applied and a good correlation between the LUMO energies of the Lewis acid-CBS-naphthoquinone adducts and kDA could be found. For the SnCl4 -CBS-naphthoquinone adduct an unusual distortion was observed leading to an enhanced Lewis acidity. Energy decomposition analysis with natural orbitals for chemical valence (EDA-NOCV) calculations revealed the relevant interactions and activation mode of SnCl4 as Lewis acid in Diels-Alder reactions.

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.

β-Hydroxyamide derivatives of salicylic acid as organocatalysts for enantioselective reductions of prochiral ketones

In order to find the most effective catalyst for the enantioselective reduction of a prochiral ketone, a series of novel β-hydroxyamide derivatives of salicylic acid and chiral amino alcohols were synthesized. Different substituted prochiral ketones have been reduced in high yield (up to 99%) and the corresponding secondary alcohols are formed with good enantiomeric excess (up to 86%). The mechanism of this type of catalyst can be explained by considering the reaction mechanism for the CBS catalyst.

ChemInform Abstract: Rational Electronic Tuning of CBS Catalyst for Highly Enantioselective Borane Reduction of Trifluoroacetophenone.

α,α,α-Trifluoroacetophenone (2), which is susceptible to noncatalytic reduction by BH3, could be reduced to chiral alcohol up to 90% ee by using electronically tuned-CBS catalyst (1) with BH3. The enantioselectivities highly correlated with the differential orbital energies between 1–BH3 adduct and 2, which were calculated by DFT method.

ChemInform Abstract: Enantioselective Synthesis of Optically Active Metolachlor via Asymmetric Reduction.

Abstract Optically active metolachlor was prepared by chloroacetylation of the corresponding amine obtained by asymmetric reduction of the requisite imine with the chiral hydrides, such as Itsuno's reagent ( 4 ), Corey's reagent ( 5 ) and K glucoride ( 6 ).

ChemInform Abstract: An Efficient Asymmetric Synthesis of Prostaglandin E1.

An asymmetric total synthesis of Prostaglandin E1 (5) has been achieved in a two-component coupling process. The chiral hydroxycyclopentenone 6 was readily available from furan with 96% ee. The key reaction step was a kinetic enzymatic resolution followed by an in situ inversion. A catalytic asymmetric reduction of the γ-iodo vinyl ketone 19 with the Corey CBS catalyst gave the ω-side chain 7 with >96% ee. Conjugate addition using the reaction with dilithiocyanocuprate followed by mild cleavage of the silyl protective groups and enzymatic hydrolysis of the methyl ester 22 gave (–)-PGE15in high yield.

Rational electronic tuning of CBS catalyst for highly enantioselective borane reduction of trifluoroacetophenone

α,α,α-Trifluoroacetophenone (2), which is susceptible to noncatalytic reduction by BH(3), could be reduced to chiral alcohol up to 90% ee by using electronically tuned-CBS catalyst (1) with BH(3). The enantioselectivities highly correlated with the differential orbital energies between 1-BH(3) adduct and 2, which were calculated by DFT method.

The “Corey's Reagent,” 3,5-di-tert-butyl-1,2-Benzoquinone, as a Modifying Agent in the Synthesis of Fluorescent and Double-Headed Nucleosides

A new method for the synthesis of fluorescent nucleosides has been developed. It has been shown that a reaction of benzoquinone with aminopropenyl group at C-5-position of 2′-deoxyuridine or 2′-deoxycytidine and aminopropynyl group at the C-7-position of 8-aza-7-deazaadenosine under extremely mild conditions affords conjugated benzoxazole derivatives of nucleosides, which possess strong fluorescent properties. In a similar reaction 5′-amino-5′-deoxy-nucleosides form double-headed nucleoside derivatives with benzoxazole attached at C-4′-position.

Convenient One-Pot Synthesis of N-Substituted 3-Trifluoroacetyl Pyrroles

A new one-pot strategy for the synthesis of a series of new N-substituted 3-trifluoroacetyl pyrroles is presented. These compounds were obtained by the reaction of 3-trifluoroacetyl-4,5-dihydrofuran with primary amines, which generated 1,1,1-trifluoro-3-(2-hydroxyethyl)-4-alkylaminobut-3-en-2-one intermediates. In most cases these intermediates were not stable enough to be isolated. Thus, in the same reaction vessel they were directly submitted to oxidation with PCC (Corey's reagent) to furnish 1,1,1-trifluoro-3-(2-ethanal)-4-alkylaminobut-3-en-2-ones, which under reflux underwent intramolecular cyclization to give the desired N-substituted 3-trifluoroacetyl pyrroles, in moderate yields. All of these pyrroles were tested against pan-susceptible Mycobacterium tuberculosis H37Rv and clinical isolates INH- and RMP-resistant strain and some of these compounds showed significant in vitro antimicrobial activity.

The Mg‐Oppenauer Oxidation as a Mild Method for the Synthesis of Aryl and Metallocenyl Ketones

Magnesium alkoxides undergo a hydride-transfer oxidation with benzaldehyde as the oxidant. This magnesium variant of the Oppenauer oxidation was used for the synthesis of polyfunctional biaryl ketones. LiCl was found to promote this reaction by enhancing the solubility of magnesium alkoxides. This mild oxidation method was especially useful for preparing ketones bearing a metallocenyl unit as well as various new ferrocenyl ketones and tricarbonylchromium complexes. This last class of ketones was reduced with the CBS catalyst (CBS=Corey-Bakshi-Shibata, diphenyl oxazaborolidine) to chiral benzhydrol complexes with high enantioselectivity enabling an asymmetric synthesis of electron-rich or -poor benzhydryl alcohols (up to 94 % ee).

Preparation of New Chiral Building Blocks: Highly Enantioselective Reduction of Prochiral 1,3-Cycloalkanediones Possessing a Methyl Group and a Protected Hydroxymethyl Group at Their C2 Position with Baker's Yeast or CBS Catalyst

Highly enantioselective reduction of five-, six-, seven-, and eight-membered prochiral 1,3-cycloalkanediones possessing a methyl group and a protected hydroxymethyl group at their C2 position with baker's yeast or CBS catalyst and a new efficient and general method for preparing the 1,3-cycloalkanediones have been developed. These baker's yeast mediated reductions were found to produce corresponding ketols with high optical purity (>99% ee) and high yield. All of the prepared ketols and their derivatives, chiral building blocks, have been fully characterized, and their absolute configurations have been determined. These compounds would be useful for the convergent synthesis of complex natural products.

A model for double asymmetric induction in the stereocontrolled reduction of glycosyl alpha-ketoesters with oxazaborolidines.

Experimental diastereoselectivities for the stereocontrolled reduction of glycosyl alpha-ketoesters into the corresponding alpha-hydroxyesters have recently been reported with unexpected results. The process is catalyzed by a chiral oxazaborolidine derivative (the so-called CBS catalyst) and represents the key step in the synthesis of glycosyl alpha-amino acids synthons, a class of compounds that allow preparation of natural glycopeptides analogues exhibiting potential therapeutic relevance. Good to very good diastereomeric excesses have been obtained for a series of reactions with different glucidic derivatives, but surprisingly, the major product obtained does not correspond to that predicted by using Corey's model. In the present work, we carry out a theoretical investigation of these reactions at the density functional level. Separated effects from the catalyst and from the glucidic derivative have been computed to rationalize the observed diastereoselectivities and the double asymmetric induction.

Preparation of New Chiral Building Blocks via Asymmetric Catalysis.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Preparation of new chiral building blocks via asymmetric catalysis

Highly enantio- and stereoselective preparation of some new chiral building blocks with baker's yeast or the CBS catalyst is described.

A practical kinetic resolution of 4-acetyl[2.2]paracyclophane

The kinetic resolution of 4-acetyl[2.2]paracyclophane has been realized by borane reduction in the presence of a CBS catalyst. The structure of the two diastereomeric alcohol products has been established. The ketone was recovered in more than 99% e.e. at 69% conversion.

Enantioselective reduction of 3,3-dimethyl butanone-2 with borane catalyzed by oxazaborolidine. Part 1. Quantum chemical computations on the structures and properties of catalyst and catalyst–borane–ketone adducts

In the present paper, the ab initio molecular orbital computations of the enantioselective reduction of 3,3-dimethyl butanone-2 with borane catalyzed by chiral oxazaborolidine (the CBS catalyst) are performed by means of the Hartree–Fock method at the 6-31G ∗ basis sets and the structures and properties of the oxazaborolidine catalyst and the catalyst–borane–3,3-dimethyl butanone-2 adducts are studied. Chiral oxazaborolidine is of a twisted chair structure and reacts with borane to form the catalyst–borane adduct whose formation reaction is exothermic. The formation of the catalyst–borane adduct causes the B BH3–H BH3 bond in the borane moiety to be weakened considerably. The catalyst–borane adduct reacts with 3,3-dimethyl butanone-2 to generate the catalyst–borane–3,3-dimethyl butanone-2 adducts. The catalyst–borane–3,3-dimethyl butanone-2 adducts have two stable structures. One is of a twisted boat structure and the other of a twisted chair structure. The formation of the catalyst–borane–3,3-dimethyl butanone-2 adducts results in a great increase in the carbonyl bond length in the 3,3-dimethyl butanone-2 moiety. In addition, there is a quite weak interaction between C CO and H BH3 in the catalyst–borane–3,3-dimethyl butanone-2 adducts. These results are beneficial to the hydride transfer from the BH 3 moiety to the carbonyl carbon of 3,3-dimethyl butanone-2.

An Efficient Asymmetric Synthesis of Prostaglandin E1

An asymmetric total synthesis of Prostaglandin E1 (5) has been achieved in a two-component coupling process. The chiral hydroxycyclopentenone 6 was readily available from furan with 96% ee. The key reaction step was a kinetic enzymatic resolution followed by an in situ inversion. A catalytic asymmetric reduction of the γ-iodo vinyl ketone 19 with the Corey CBS catalyst gave the ω-side chain 7 with >96% ee. Conjugate addition using the reaction with dilithiocyanocuprate followed by mild cleavage of the silyl protective groups and enzymatic hydrolysis of the methyl ester 22 gave (–)-PGE15in high yield.

An Efficient Asymmetric Synthesis of Prostaglandin E1

An asymmetric total synthesis of Prostaglandin E1 (5) has been achieved in a two-component coupling process. The chiral hydroxycyclopentenone 6 was readily available from furan with 96% ee. The key reaction step was a kinetic enzymatic resolution followed by an in situ inversion. A catalytic asymmetric reduction of the γ-iodo vinyl ketone 19 with the Corey CBS catalyst gave the ω-side chain 7 with >96% ee. Conjugate addition using the reaction with dilithiocyanocuprate followed by mild cleavage of the silyl protective groups and enzymatic hydrolysis of the methyl ester 22 gave (–)-PGE15in high yield.