Conjugate Addition Of Boronic Acids Research Articles

Highly Enantioselective Chiral Diol-Catalyzed Conjugate Addition of Boronic Acids to α,β-Unsaturated Trifluoromethyl Ketones.

The (R)-3,3'-(3,5-(CF3)2-C6H3)2-BINOL-catalyzed enantioselective conjugate addition of organic boronic acids to α,β-unsaturated 1,1,1-trifluoromethyl ketones affords corresponding addition products bearing a stereogenic center at the β-position in moderate to high yields and excellent enantioselectivities (up to 99% ee), without any 1,2-addition product formation. Moreover, this catalytic protocol features mild reaction conditions, a broad substrate scope, suitability for alkenylboronic acids and (hetero)arylboronic acids, and easy scale-up.

Enantioselective Synthesis of Chiral Organosilicon Compounds by Organocatalytic Asymmetric Conjugate Addition of Boronic Acids to β-Silyl-α,β-Unsaturated Ketones.

Herein, we report (R)-3,3'-(3,5-(CF3)2-C6H3)2-BINOL-catalyzed enantioselective conjugate addition of organic boronic acids to β-silyl-α,β-unsaturated ketones, furnishing moderate to excellent yields of the corresponding β-silyl carbonyl compounds with stereogenic centers in excellent enantioselectivities (up to 98% ee). Moreover, the catalytic system features mild reaction conditions, high efficiency, broad substrate scope, and easy scale-up.

Enantioselective Conjugate Addition of Boronic Acids to α,β-Unsaturated 2-Acyl Imidazoles Catalyzed by Chiral Diols.

Herein, we report the enantioselective conjugate addition of organic boronic acids to α,β-unsaturated 2-acyl imidazoles using (R)-3,3'-I2-BINOL as the catalyst. The catalytic system shows high efficiency and tolerance to alkenylboronic acids and heteroarylboronic acids. The corresponding Michael addition products were obtained in moderate to excellent yields and with moderate to excellent enantioselectivities (up to 97% ee). A gram-scale reaction was also conducted, and the desired product was obtained in high yield with no erosion in enantioselectivity. Finally, the synthetic utility of the methodology was demonstrated by transforming the 2-acyl imidazole moiety to the corresponding aldehyde, carboxylic acid, ester, and amide derivatives.

Chiral dihydroxytetraphenylene-catalyzed enantioselective conjugate addition of boronic acids to β-enaminones

An efficient (S)-2,15-Cl2-DHTP-catalyzed enantioselective conjugate addition of organic boronic acids to β-enaminones has been developed.

Organocatalyzed Enantioselective Conjugate Addition of Boronic Acids to β,γ-Unsaturated α-Ketoesters.

We report herein the (R)-3,3'-Br2-BINOL-catalyzed enantioselective conjugate addition of organic boronic acids to β,γ-unsaturated α-ketoesters to generate the corresponding Michael addition products in moderate to high yields and with moderate to excellent enantioselectivities (up to 99% ee). This catalytic system features characteristics of mild reaction conditions, high efficiency, and tolerance to alkenylboronic acids and heteroarylboronic acids.

Correction to "Chiral Hydroxytetraphenylene-Catalyzed Asymmetric Conjugate Addition of Boronic Acids to Enones".

RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to “Chiral Hydroxytetraphenylene-Catalyzed Asymmetric Conjugate Addition of Boronic Acids to Enones”Guo-Li Chai*Guo-Li ChaiMore by Guo-Li Chaihttp://orcid.org/0000-0002-1342-6217, A-Qiang SunA-Qiang SunMore by A-Qiang Sun, Dong ZhaiDong ZhaiMore by Dong Zhaihttp://orcid.org/0000-0003-3155-4607, Juan WangJuan WangMore by Juan Wang, Wei-Qiao DengWei-Qiao DengMore by Wei-Qiao Deng, Henry N. C. WongHenry N. C. WongMore by Henry N. C. Wonghttp://orcid.org/0000-0002-3763-3085, and Junbiao ChangJunbiao ChangMore by Junbiao ChangCite this: Org. Lett. 2019, 21, 16, 6584Publication Date (Web):August 8, 2019Publication History Received29 July 2019Published online8 August 2019Published inissue 16 August 2019https://doi.org/10.1021/acs.orglett.9b02663Copyright © 2019 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views687Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (411 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Chiral Hydroxytetraphenylene-Catalyzed Asymmetric Conjugate Addition of Boronic Acids to Enones.

( S)-2,15-Br2-DHTP-catalyzed asymmetric conjugate addition of boronic acids to β-trifluoromethyl α,β-unsaturated ketones and enones was studied. The reaction afforded the corresponding Michael addition products in moderate to high yields with excellent enantioselectivities (up to 99:1 er). This catalytic system features mild reaction conditions, high efficiency, and tolerance to heteroarylboronic acids.

Rh-catalysed asymmetric conjugate addition of boronic acids to nitroalkenes employing a P-chiral P,π-hybrid ligand

A P-chiral P,π-hybrid ligand was applied to the asymmetric conjugate addition of aryl boronic acids to β-substituted nitroalkenes.

ChemInform Abstract: 1,2‐Stereochemical Induction in the PdII‐Catalyzed Conjugate Addition of Boronic Acids.

Palladium(II) catalysis has been used in the substrate-controlled 1,2-chiral induction of the conjugate addition of boronic acids to enantiopure α,β-unsaturated ketones and esters without competition from the Mirozoki–Heck reaction. Bedford's palladacycle was found to control the stereoselectivity without the need for additional chiral ligands. We report that the PdII-catalyzed conjugate addition reaction between boronic acids and acyclic ketones or esters that bear a hydroxyl substituent at their γ-position (glyceraldehyde derivatives) can afford high levels of anti stereoselection, comparable to those reported previously using more expensive RhI catalysts. On the other hand, high levels of syn stereoselectivity were observed with acyclic esters that bear an amino substituent at their γ-position (serine derivatives). In this case, the levels of stereoselection could be enhanced by using cyclic derivatives derived from Garner's aldehyde.

Catalytic enantioselective construction of quaternary stereocenters: assembly of key building blocks for the synthesis of biologically active molecules.

The ever-present demand for drugs with better efficacy and fewer side effects continually motivates scientists to explore the vast chemical space. Traditionally, medicinal chemists have focused much attention on achiral or so-called "flat" molecules. More recently, attention has shifted toward molecules with stereogenic centers since their three-dimensional structures represent a much larger fraction of the chemical space and have a number of superior properties compared with flat aromatic compounds. Quaternary stereocenters, in particular, add greatly to the three-dimensionality and novelty of the molecule. Nevertheless, synthetic challenges in building quaternary stereocenters have largely prevented their implementation in drug discovery. The lack of effective and broadly general methods for enantioselective formation of quaternary stereocenters in simple molecular scaffolds has prompted us to investigate new chemistry and develop innovative tools and solutions. In this Account, we describe three approaches to constructing quaternary stereocenters: nucleophilic substitution of 3-halooxindoles, conjugate addition of boronic acids to cyclic enones, and allylic alkylation of enolates. In the first approach, malonic ester nucleophiles attack electrophilic 3-halooxindoles, mediated by a copper(II)-bisoxazoline catalyst. A variety of oxindoles containing a benzylic quaternary stereocenter can be accessed through this method. However, it is only applicable to the specialized 3,3-disubstituted oxindole system. To access benzylic quaternary stereocenters in a more general context, we turned our attention to the enantioselective conjugate addition of carbon nucleophiles to α,β-unsaturated carbonyl acceptors. We discovered that in the presence of catalytic palladium-pyridinooxazoline complex, arylboronic acids add smoothly to β-substituted cyclic enones to furnish ketones with a β-benzylic quaternary stereocenter in high yields and enantioselectivities. The reaction is compatible with a wide range of arylboronic acids, β-substituents, and ring sizes. Aside from benzylic quaternary stereocenters, a more challenging motif is a quaternary stereocenter not adjacent to an aromatic group. Such centers represent more general structures in chemical space but are more difficult to form by asymmetric catalysis. To address this greater challenge, and motivated by the greater reward, we entered the field of palladium-catalyzed asymmetric allylic alkylation of prochiral enolate nucleophiles about a decade ago. On the basis of Tsuji's work, which solved the issue of positional selectivity for unsymmetrical ketones, we discovered that the phosphinooxazoline ligand effectively rendered this reaction enantioselective. Extensive investigations since then have revealed that the reaction exhibits broad scope and accepts a range of substrate classes, each with its unique advantage in synthetic applications. A diverse array of carbonyl compounds bearing α-quaternary stereocenters are obtained in excellent yields and enantioselectivities, and more possibilities have yet to be explored. As an alternative to palladium catalysis, we also studied iridium-catalyzed asymmetric allylic alkylations that generate vicinal quaternary and tertiary stereocenters in a single transformation. Overall, these methods provide access to small molecule building blocks with a single quaternary stereocenter, can be applied to various molecular scaffolds, and tolerate a wide range of functional groups. We envision that the chemistry reported in this Account will be increasingly useful in drug discovery and design.

1,2‐Stereochemical Induction in the PdII‐Catalyzed Conjugate Addition of Boronic Acids

AbstractPalladium(II) catalysis has been used in the substrate‐controlled 1,2‐chiral induction of the conjugate addition of boronic acids to enantiopure α,β‐unsaturated ketones and esters without competition from the Mirozoki–Heck reaction. Bedford's palladacycle was found to control the stereoselectivity without the need for additional chiral ligands. We report that the PdII‐catalyzed conjugate addition reaction between boronic acids and acyclic ketones or esters that bear a hydroxyl substituent at their γ‐position (glyceraldehyde derivatives) can afford high levels of anti stereoselection, comparable to those reported previously using more expensive RhI catalysts. On the other hand, high levels of syn stereoselectivity were observed with acyclic esters that bear an amino substituent at their γ‐position (serine derivatives). In this case, the levels of stereoselection could be enhanced by using cyclic derivatives derived from Garner's aldehyde.

Experimental mechanistic insight into the BINOL-catalyzed enantioselective conjugate addition of boronates to enones

The diol-catalyzed enantioselective conjugate addition of boronic acids and boronate esters has seen significant development in the last decade. However, no experimental mechanistic studies related to this transformation have been reported to date. Hammett plot-based analysis of reaction rates has been performed with aryl substitution both at the carbonyl and at the olefin of an enone electrophile. The resulting trends indicate that C–C bond formation is the likely rate limiting step.

ChemInform Abstract: Alkene‐Assisted Nickel‐Catalyzed Regioselective 1,4‐Addition of Organoboronic Acid to Dienones: A Direct Route to All‐Carbon Quaternary Centers.

AbstractA nickel‐catalyzed, highly regioselective conjugate addition of boronic acids to dienones to form 1,4‐addition products with an all‐carbon quaternary center is described.

Transition-Metal-Free Reactions of Boronic Acids: 1,3-Stereochemical Induction in the Substrate-Controlled Conjugate Addition

The substrate-controlled 1,3-stereoselective conjugate addition of boronic acids and potassium trifluoroborates under metal-free conditions has been developed. This reaction affords bicyclic acetals, which have been used as key intermediates in the stereodivergent synthesis of polysubstituted tetrahydropyrans.

ChemInform Abstract: PdII‐Catalyzed Conjugate Addition of Boronic Acids to Ketoglutaconic Esters Toward the Synthesis of Functionalized Pyridazin‐3(2H)‐ones with Neuroprotective Activity.

AbstractThe dicationic palladium catalyst is found to be efficient for the regioselective conjugate addition of boronic acids to ketoglutaconic esters.

ChemInform Abstract: Trifluoroacetic Anhydride‐Catalyzed Conjugate Addition of Boronic Acids to α,β‐Unsaturated Ketones.

AbstractThe conjugate addition of boronic acids (II) to α,β‐unsaturated ketones (I) catalyzed by acylating reagents is explored.

PdII‐Catalyzed Conjugate Addition of Boronic Acids to Ketoglutaconic Esters toward the Synthesis of Functionalized Pyridazin‐3(2H)‐ones with Neuroprotective Activity

AbstractThe development of the regioselective conjugate addition of boronic acids to ketoglutaconic esters under transition metal catalysis is reported. Among the different catalysts tested for this transformation, the dicationic PdII catalysts generated with Pd(OCOCF3)2, dppben, and HBF4 performed best in terms of yields, regioselectivities and avoidance of Heck‐type by‐products. The resulting 4‐aryl‐2‐oxopentadienoates were transformed into pyridazin‐3(2H)‐ones, potentially useful for the therapy of neurodegenerative diseases. These compounds simultaneously exhibited β‐secretase activity, inhibition of β‐amyloid (βA) aggregation, and disaggregation of pre‐formed βA fibrils, and also had a good scavenging profile for intracellular reactive oxygen species (ROS).

Trifluoroacetic anhydride—catalyzed conjugate addition of boronic acids to α,β-unsaturated ketones

The conjugate addition of boronic acids to α,β-unsaturated ketones catalyzed by acylating reagents has been explored. The results show that trifluoroacetic anhydride catalyzes the addition of vinylboronic acids under experimentally simple and metal-free conditions for a variety of substrates with good yields.

Trifluoroacetic Anhydride Promoted Tandem Conjugate Addition of Boronic Acids/Acetal Ring Opening

A new stereoselective tandem reaction consisting of the metal-free conjugate addition of boronic acids followed by an intramolecular ring opening of a cyclic acetal has been disclosed. Optically pure polysubstituted tetrahydropyrans have been synthesized diastereoselectively by this new reaction. Two new C-C bonds and up to three stereocenters are formed in a single step, allowing the generation of quaternary stereocenters.

Novel Ligand for Rh-Catalyzed Asymmetric Conjugate Addition

This paper describes the development of a new class of chiral olefin-sulfur ligands for enantioselective rhodium-catalyzed conjugate addition of boronic acids to various enones. The corresponding products can be obtained in good to excellent yield and enantioselectivity.