Asymmetric Morita Baylis Hillman Reaction Research Articles

Engineering the simply asymmetric Morita–Baylis–Hillman reactions in a sodium phosphate buffer system: from enzyme‐ to proline‐catalyzed transformation

AbstractBACKGROUNDThe Morita–Baylis–Hillman (MBH) reaction is an important carbon–carbon bond‐forming reaction. However, most MBH reactions suffer disadvantages such as high amounts of catalyst and hazardous solvents, long reaction time, low reactivity and selectivity. In this study, simple, cost‐effective and eco‐friendly asymmetric MBH reactions are developed.RESULTSFollowing our previous study that the commercial Candida antarctica lipase B (lipase CalB)‐catalyzed MBH reaction can be activated by introducing an amide compound as a co‐catalyst, the recombinant lipase CalBs (rCalBs) with polyamino acid tails are first attempted to be used in the same MBH reaction, but unfortunately chiral MBH products are not obtained. Enoate reductase (ER) is found to give asymmetric transformation of the MBH reaction with a conversion of 36.9% and enantiomeric excess (e.e.p) of 6.8% when other enzyme resources are expanded. According to the observation that the surface amino acids of ER may be key factors in achieving the MBH reaction, single amino acids are subsequently selected to catalyze the MBH reactions, and the reverse configuration of (R)‐ and (S)‐MBH products with e.e.p of 63.9% and 62.1% for single l‐proline‐ and d‐proline‐catalyzed MBH reactions are reached only in 4 h, respectively.CONCLUSIONProline can afford the asymmetric MBH reaction in a sodium phosphate buffer only in 4 h without the help of the other co‐catalyst in our study, which is superior to those reported. The study aims to introduce a novel phenomenon observed from enzyme‐catalyzed to proline‐catalyzed MBH reactions. © 2022 Society of Chemical Industry (SCI).

Highly Efficient Asymmetric Morita–Baylis–Hillman Reaction Promoted by Chiral Aziridine-Phosphines

Continuing our research on the use of organophosphorus derivatives of aziridines in asymmetric synthesis and expanding the scope of their applicability, chiral aziridine-phosphines obtained earlier in our laboratory were used as chiral catalysts in the asymmetric Morita–Baylis–Hillman reaction of methyl vinyl ketone and methyl acrylate with various aromatic aldehydes. The desired chiral products were formed in moderate to high chemical yields and with enantiomeric excess reaching value of 98% ee in some cases. The use of catalysts being pairs of enantiomers led to the desired products with opposite absolute configurations.

The Application of Biocatalysis in the Preparation and Resolution of Morita-Baylis-Hillman Adducts and Their Derivatives.

The Morita-Baylis-Hillman (MBH) reaction affords highly functionalised allylic alcohols containing a new stereogenic centre. These MBH adducts are very versatile and have been transformed into a large range of products, some of which have medicinal potential. Several examples of asymmetric syntheses of MBH adducts have been reported, although a generally applicable method remains to be developed. Biocatalytic approaches for the synthesis and enzymatic kinetic resolution of MBH adducts have been reported, and are discussed in detail in this review. Enzymes able to catalyse the asymmetric MBH reaction have been identified, but selectivity and efficiency have generally been low. Lipases, esterases and nitrile-converting enzymes have all been successfully applied in the resolution of MBH adducts, with excellent selectivity being realised in most cases.

Design and enantioselective synthesis of 3-(α-acrylic acid) benzoxaboroles to combat carbapenemase resistance.

Chiral 3-substituted benzoxaboroles were designed as carbapenemase inhibitors and efficiently synthesised via asymmetric Morita–Baylis–Hillman reaction. Some of the benzoxaboroles were potent inhibitors of clinically relevant carbapenemases and restored the activity of meropenem in bacteria harbouring these enzymes. Crystallographic analyses validate the proposed mechanism of binding to carbapenemases, i.e. in a manner relating to their antibiotic substrates. The results illustrate how combining a structure-based design approach with asymmetric catalysis can efficiently lead to potent β-lactamase inhibitors and provide a starting point to develop drugs combatting carbapenemases.

Stereoselective Construction of Entire Diastereomeric Stereotetrads Based on an Asymmetric Morita–Baylis–Hillman Reaction

A method for the enantio‐ and diastereoselective construction of all possible stereoisomers of a polypropionate stereotetrad having four contiguous stereogenic centers has been developed. The approach features an iterative sequence of cinchona‐alkaloid‐catalyzed Morita–Baylis–Hillman reaction and subsequent diastereoselective hydrogenation. By this method, benzaldehyde was successfully converted into eight diastereoisomeric 3,5‐dihydroxy‐2,4‐dimethyl‐5‐phenylpentanoic acid ester derivatives with high enantiomeric purities (99 % ee) in 25–67 % overall yield (eight steps) in a reagent‐controlled manner.

Asymmetric Morita-Baylis-Hillman Reaction: Catalyst Development and Mechanistic Insights Based on Mass Spectrometric Back-Reaction Screening.

An efficient protocol for the evaluation of catalysts for the asymmetric Morita-Baylis-Hillman (MBH) reaction was developed. By mass spectrometric back-reaction screening of quasi-enantiomeric MBH products, an efficient bifunctional phosphine catalyst was identified that outperforms literature-known catalysts in the MBH reaction of methyl acrylate with aldehydes. The close match between the selectivities measured for the forward and back reaction and kinetic measurements provided strong evidence that the aldol step and not the subsequent proton transfer is rate- and enantioselectivity-determining.

Asymmetric Morita–Baylis–Hillman reaction catalyzed by pepsin

Pepsin from porcine gastric mucous shown catalytic promiscuity was first discovered to catalyze the Morita–Baylis–Hillman (MBH) reaction between aromatic aldehydes with 2-cyclohexen-1-one or 2-cyclopenten-1-one in a two-phase medium of phosphate buffer/cyclohexane in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO). The best results of the corresponding MBH products up to 77% yield and 38% ee were achieved.

Unified synthesis of tirandamycins and streptolydigins.

The asymmetric total syntheses of tirandamycins A-D and tirandalydigin as well as the synthesis of the left-hand fragment of streptolydiginone and streptolydigin from a common intermediate are described. The comprehensive approach features the highly enantio- and diastereoselective assembly of the anti,anti,syn-stereotetrad unit which relies on a cinchona alkaloid-catalyzed asymmetric Morita-Baylis-Hillman reaction.

Asymmetric Morita–Baylis–Hillman reaction of isatins with α,β-unsaturated γ-butyrolactam as the nucleophile

Download options Please wait... Supplementary files Supplementary information PDF (76646K) Article information DOI https://doi.org/10.1039/C3RA41115J Article type Communication Submitted 07 Mar 2013 Accepted 07 May 2013 First published 07 May 2013 Download Citation RSC Adv., 2013,3, 10127-10130 BibTex EndNote MEDLINE ProCite ReferenceManager RefWorks RIS Permissions Request permissions Asymmetric Morita–Baylis–Hillman reaction of isatins with α,β-unsaturated γ-butyrolactam as the nucleophile Z. Duan, Z. Zhang, P. Qian, J. Han and Y. Pan, RSC Adv., 2013, 3, 10127 DOI: 10.1039/C3RA41115J To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page. If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given. If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page. Read more about how to correctly acknowledge RSC content. Social activity Tweet Share Search articles by author Zhiqiang Duan Zirui Zhang Ping Qian Jianlin Han Yi Pan

ChemInform Abstract: Chiral Phosphine‐Squaramide‐Catalyzed Morita—Baylis—Hillman Reaction: Enantioselective Synthesis of 3‐Hydroxy‐2‐oxindoles.

AbstractPhosphine‐squaramide compounds catalyze the asymmetric Morita—Baylis—Hillman reaction.

A Bifunctional β‐Isocupreidine Derivative as Catalyst for the Enantioselective Morita–Baylis–Hillman Reaction and a Mechanistic Rationale for Enantioselectivity

AbstractStarting from β‐isocupreidine (β‐ICD), a series of difunctional catalysts were synthesized to ascertain their usefulness in the asymmetric Morita–Baylis–Hillman (MBH) reaction. The trichloroacetylcarbamate derivative was found to give the (R)‐MBH adducts in excellent optical purities (90–99 % ee) and moderate to good yields (43–83 %), in some cases, better than β‐ICD. A number of acrylates were also tested and 2,6‐dimethyl‐4‐nitrophenyl acrylate was identified as a suitable alternative to the popular hexafluoroisopropyl acrylate, with both the β‐ICD and trichloroacetylcarbamate derivatives. The mechanism of the rate‐ and selectivity‐determining step was ascertained by means of experimental observations and a computational investigation aimed at clarifying the transition state structures is reported. These studies have clarified the reasons for the effectiveness of these structurally related catalysts in the asymmetric MBH reaction between acrylates and aldehydes.

ChemInform Abstract: Asymmetric Morita—Baylis—Hillman Reaction of 2‐Cyclohexen‐1‐one Catalyzed by Chiral Biaryl‐Based Bis(thiourea) Organocatalysts.

AbstractAmong the new organocatalysts, derivative (Ia) is found to be the most efficient one which can be used for aliphatic and aromatic aldehydes.

Organocatalytic Asymmetric Synthesis of Substituted 3-Hydroxy-2-oxindoles via Morita−Baylis−Hillman Reaction

We report a highly enantioselective Morita-Baylis-Hillman (MBH) reaction of isatins and acrolein to provide enantiomerically enriched 3-substituted 3-hydroxyoxindoles, which could serve as valuable synthetic building blocks. This is also the first time that a ketone has been used as the electrophile and acrolein as the nucleophile in a highly enantioselective catalytic asymmetric MBH reaction. Hatakeyama's catalyst, β-isocupreidine (1), turned out to be a powerful catalyst for this transformation.

ChemInform Abstract: MgI2‐Accelerated Enantioselective Morita—Baylis—Hillman Reactions of Cyclopentenone Utilizing a Chiral DMAP Catalyst.

AbstractFu′s planar‐chiral DMAP derivative (I) and MgI2 represent an efficient catalytic system for the asymmetric Morita—Baylis—Hillman reaction of aldehydes (II) with cyclopentenone (III).

Chiral 3-aminopyrrolidines as a rigid diamino scaffold for organocatalysis and organometallic chemistry

Over 20 new and easily prepared diamines were screened for the asymmetric Morita–Baylis–Hillman reaction. Chiral non-racemic 3-( N, N-dimethylamino)-1-methylpyrrolidine was found to promote efficiently the reaction of methyl vinyl ketone and substituted benzaldehydes. Enantiomeric excesses up to 73% were reached with electron-deficient benzaldehyde derivatives. After a simple deprotonation, one of these diamines was transformed into a chiral mixed aggregate for the enantioselective synthesis of ( R)-1- o-tolylethanol with 76% ee.

ChemInform Abstract: Bifunctional Chiral Phosphine‐Containing Lewis Base Catalyzed Asymmetric Morita—Baylis—Hillman Reaction of Aldehydes with Activated Alkenes.

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.

Bifunctional chiral phosphine-containing Lewis base catalyzed asymmetric Morita–Baylis–Hillman reaction of aldehydes with activated alkenes

A series of novel bifunctional chiral phosphine-containing Lewis bases were synthesized and successfully applied to the asymmetric Morita–Baylis–Hillman reaction of aldehydes with methyl vinyl ketone (MVK) and ethyl vinyl ketone (EVK) to give the corresponding adducts in moderate yields and enantioselectivities under mild reaction conditions.

ChemInform Abstract: Asymmetric Morita—Baylis—Hillman Reaction of Arylaldehydes with 2‐Cyclohexen‐1‐one Catalyzed by Chiral Bis(thio)urea and DABCO.

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.

Asymmetric Morita—Baylis—Hillman Reaction Catalyzed by Simple Amino Alcohol Derived Thioureas.

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, please click on HTML or PDF.

Asymmetric Morita—Baylis—Hillman Reaction Catalyzed by Isophoronediamine‐Derived Bis(thio)urea Organocatalysts.

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, please click on HTML or PDF.