Construction Of Quaternary Carbon Centers Research Articles

Facile Construction of Quaternary Carbon Centers via Dinuclear Titanium(III)‐Catalyzed Reductive Coupling of Tertiary Chlorides and Activated Olefins

AbstractThe establishment of all‐carbon quaternary carbon centers represents a pivotal aspect in the synthesis of numerous natural products and pharmaceutical compounds, underscoring its paramount significance in synthetic organic chemistry. Herein, we present a novel synthetic strategy for the generation of quaternary carbon centers through the reductive coupling of tertiary halides, catalyzed by dinuclear (salen)titanium catalysts. This catalytic framework demonstrates notable reactivity towards tertiary chlorides while maintaining inertness towards secondary and primary chlorides, thereby facilitating exceptional chemoselectivity for C−C bond formation. The reaction proceeds with remarkable efficiency across a diverse range of substrates under mild reaction conditions.

DFT Insight into a Strain-Release Mechanism in Bicyclo[1.1.0]butanes via Concerted Activation of Central and Lateral C-C Bonds with Rh(III) Catalysis.

Transition-metal-catalyzed, strain-release-driven transformations of "spring-loaded" bicyclo[1.1.0]butanes (BCBs) are considered potent tools in synthetic organic chemistry. Previously proposed strain-release mechanisms involve either the insertion of the central C-C bond of BCBs into a metal-carbon bond, followed by β-C elimination, or the oxidative addition of the central or lateral C-C bond on the transition metal center, followed by reductive elimination. This study, employing DFT calculations on a Rh(III)-catalyzed model system in a three-component protocol involving oxime ether, BCB ester, and ethyl glyoxylate for constructing diastereoselective quaternary carbon centers, introduces an unusual strain-release mechanism for BCBs. In this mechanism, the catalytic reaction is initiated by the simultaneous cleavage of two C-C bonds (the central and lateral C-C bonds), resulting in the formation of a Rh-carbene intermediate. The new mechanism exhibits a barrier of 21.0 kcal/mol, making it energetically more favorable by 11.1 kcal/mol compared to the previously suggested most favorable pathway. This unusual reaction mode rationalizes experimental observation of the construction of quaternary carbon centers, including the excellent E-selectivity and diastereoselectivity. The newly proposed strain-release mechanism holds promise in advancing our understanding of transition-metal-catalyzed C-C bond activation mechanisms and facilitating the synthesis of transition metal carbene complexes.

Iron-Catalyzed C(sp3)-C(sp3) Coupling to Construct Quaternary Carbon Centers.

The construction of quaternary carbon centers via C-C coupling protocols remains challenging. The coupling of tertiary C(sp3) with secondary or tertiary C(sp3) counterparts has been hindered by pronounced steric clashes and many side reactions. Herein, we have successfully developed a type of bisphosphine ligand iron complex-catalyzed coupling reactions of tertiary alkyl halides with secondary alkyl zinc reagents and efficiently realized the coupling reaction between tertiary C(sp3) and secondary C(sp3) with high selectivity for the initial instance, which provided an efficient method for the construction of quaternary carbon centers with high steric hindrance. The combination of an iron catalyst and directing group of the substrate makes the great challenging transformation possible.

Regio- and Chemoselective Formal (4+1) Carbocyclization of Chalcones with Internal Alkynes via Rhodium(III) Catalysis.

A rhodium(III)-catalyzed oxidative cyclization of chalcones with internal alkynes is reported, generating biologically important 3,3-disubstituted 1-indanones along with reusable aromatic aldehydes. This transformation features unique (4+1) reaction mode, excellent regioselectivity in alkyne insertion, broad substrate scope, allows for the construction of quaternary carbon centers, and is scalable. Steric hindrance from substrate and ligand probably controls the chemoselectivity of this carbocyclization. Importantly, this discovery enables a practical two-step protocol switching the overall reaction of acetophenones with internal alkynes from a (3+2) to a (4+1) annulation.

Regio‐ and Chemoselective Formal (4+1) Carbocyclization of Chalcones with Internal Alkynes via Rhodium(III) Catalysis

AbstractA rhodium(III)‐catalyzed oxidative cyclization of chalcones with internal alkynes is reported, generating biologically important 3,3‐disubstituted 1‐indanones along with reusable aromatic aldehydes. This transformation features unique (4+1) reaction mode, excellent regioselectivity in alkyne insertion, broad substrate scope, allows for the construction of quaternary carbon centers, and is scalable. Steric hindrance from substrate and ligand probably controls the chemoselectivity of this carbocyclization. Importantly, this discovery enables a practical two‐step protocol switching the overall reaction of acetophenones with internal alkynes from a (3+2) to a (4+1) annulation.

Construction of CF<sub>3</sub>-containing Tetrasubstituted Carbon Frameworks by Way of <i>p</i>-Quinone Methides

Development of a new synthetic method for the construction of quaternary carbon centers with a trifluoromethyl group was realized by way of smooth 1,6-addition of various active methylene compounds to highly reactive δ-trifluoromethylated p-quinone methides generated in situ only with a catalytic amount of a base. A variety of aldehydes also behaved as nice nucleophiles with the aid of a NHC catalyst and the resultant products were further converted to such congested structures as the consecutive quaternary-tetrasubstituted carbons in a highly stereoselective manner. This method was also extended for the incorporation of heteroatoms like nitrogen, oxygen, and sulfur atoms.

Lewis Acid Mediated Conjugate Addition of Isocyanides to β-Hydroxy-α-diazo Carbonyls: Synthesis of β-Carboxamido-α-diazo Carbonyl Compounds

A Lewis acid mediated conjugate addition of isocyanides to β-hydroxy-α-diazo carbonyls has been developed for the first time. The reaction realizes the efficient construction of quaternary carbon centers and provides a novel and efficient strategy for the synthesis of β-carboxamido-α-diazo carbonyls that would be otherwise difficult to form in a single step. Further applications, including synthesis of methylenecyclohexane, spiro-β-lactam, and nitrogen-bridged tricyclic β-lactam, demonstrated the tremendous potential of the coupling reaction.

Lithium Enolate with a Lithium-Alkyne Interaction in the Enantioselective Construction of Quaternary Carbon Centers: Concise Synthesis of (+)-Goniomitine.

We report a method for direct enantioselective alkylation of 3-alkynoic and 2,3-alkendioic acids that form quaternary stereogenic centers, and application of this method to the total enantioselective synthesis of a complex alkaloid (+)-goniomitine. The methods were effective in the alkylation of both 3-alkynoic acids, 2,3-alkendioic acids substrates with a broad range of heterocyclic and functionalized alkyl group substituents. Accompanying crystallographic studies provide mechanistic insight into the structure of well-defined chiral aggregates, highlighting cation-π interactions between lithium and alkyne groups.

Lithium Enolate with a Lithium‐Alkyne Interaction in the Enantioselective Construction of Quaternary Carbon Centers: Concise Synthesis of (+)‐Goniomitine

AbstractWe report a method for direct enantioselective alkylation of 3‐alkynoic and 2,3‐alkendioic acids that form quaternary stereogenic centers, and application of this method to the total enantioselective synthesis of a complex alkaloid (+)‐goniomitine. The methods were effective in the alkylation of both 3‐alkynoic acids, 2,3‐alkendioic acids substrates with a broad range of heterocyclic and functionalized alkyl group substituents. Accompanying crystallographic studies provide mechanistic insight into the structure of well‐defined chiral aggregates, highlighting cation‐π interactions between lithium and alkyne groups.

Cooperative Rh(II)/Pd(0) Dual‐Catalyzed gem‐Difunctionalization of α‐Diazo Carbonyl Compounds: Construction of Quaternary Carbon Centers

AbstractThe efficient construction of quaternary carbon centers is a challenging task due to their enhanced structural complexity. Although the catalytic gem‐difunctionalization of α‐diazo carbonyl compounds via metal‐carbenoids is well‐documented, developing new methods to access quaternary carbon centers which are difficult or unattainable in monocatalysis is highly desirable. Dual catalysis where two different catalysts work concurrently has emerged as a powerful strategy to achieve new reactivity and selectivity. In this review, we highlight the recent advances in cooperative Rh(II)/Pd(0) dual catalysis for the construction of quaternary carbon centers, focusing on the synthetic utility of stable α‐diazo‐β‐keto‐esters and allylic carboxylates. Additionally, several challenging asymmetric Rh(II)/Pd(0) dual‐catalyzed transformations generating chiral quaternary carbon centers are also discussed.

Nickel-Catalyzed Enantioselective C(sp 3 )–H Arylation of Ketones with Aryl Ethers via Selective C Ar –O Cleavage to Construct All-Carbon Quaternary Stereocenters

Nickel-Catalyzed Enantioselective C(sp ³ )–H Arylation of Ketones with Aryl Ethers via Selective C _Ar –O Cleavage to Construct All-Carbon Quaternary Stereocenters

Construction of quaternary carbon centers by KOtBu-catalyzed α-homoallylic alkylation of lactams with 1,3-dienes

We report a KOtBu-catalyzed α-homoallylic alkylation of lactams with 1,3-dienes.

Enantioselective Synthesis of Nitriles Containing a Quaternary Carbon Center by Michael Reactions of Silyl Ketene Imines with 1-Acrylpyrazoles

The enantioselective construction of quaternary carbon centers is a marked challenge in asymmetric catalysis research. It is extremely difficult when a chiral catalyst can not distinguish the facial selectivity of the substrate through bond interactions. Here we realized an enantioselective Michael reaction of silyl ketene imines to 1-acrylpyrazoles using a chiral N,N'-dioxide-Co(II) complex. The protocol is highly efficient for the construction of nitrile-, aryl-, and dialkyl-bearing carbon centers and has been successful applied in the divergent synthesis of pharmaceuticals and natural products. The through-space dispersion interactions between unbound silyl ketene imines and the 1-acrylpyrazole-bonded catalyst play a key role in facilitating the reactivity and the enantioselectivity of this process.

Catalytic Asymmetric Allylic Substitution with Copper(I) Homoenolates Generated from Cyclopropanols.

By using copper(I) homoenolates as nucleophiles, which are generated through the ring-opening of 1-substituted cyclopropane-1-ols, a catalytic asymmetric allylic substitution with allyl phosphates is achieved in high to excellent yields with high enantioselectivity. Both 1-substituted cyclopropane-1-ols and allylic phosphates enjoy broad substrate scopes. Remarkably, various functional groups, such as ether, ester, tosylate, imide, alcohol, nitro, and carbamate are well tolerated. Moreover, the present method is nicely extended to the asymmetric construction of quaternary carbon centers. Some control experiments argue against a radical-based reaction mechanism and a catalytic cycle based on a two-electron process is proposed. Finally, the synthetic utilities of the product are showcased by means of the transformations of the terminal olefin group and the ketone group.

Catalytic Asymmetric Allylic Substitution with Copper(I) Homoenolates Generated from Cyclopropanols

AbstractBy using copper(I) homoenolates as nucleophiles, which are generated through the ring‐opening of 1‐substituted cyclopropane‐1‐ols, a catalytic asymmetric allylic substitution with allyl phosphates is achieved in high to excellent yields with high enantioselectivity. Both 1‐substituted cyclopropane‐1‐ols and allylic phosphates enjoy broad substrate scopes. Remarkably, various functional groups, such as ether, ester, tosylate, imide, alcohol, nitro, and carbamate are well tolerated. Moreover, the present method is nicely extended to the asymmetric construction of quaternary carbon centers. Some control experiments argue against a radical‐based reaction mechanism and a catalytic cycle based on a two‐electron process is proposed. Finally, the synthetic utilities of the product are showcased by means of the transformations of the terminal olefin group and the ketone group.

Correction to “Chiral Brønsted Acid-Catalyzed Formal α-Vinylation of Cyclopentanones for the Enantioselective Construction of Quaternary Carbon Centers”

ADVERTISEMENT RETURN TO ISSUEPREVCorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to “Chiral Brønsted Acid-Catalyzed Formal α-Vinylation of Cyclopentanones for the Enantioselective Construction of Quaternary Carbon Centers”Satavisha KayalSatavisha KayalDepartment of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, JapanMore by Satavisha Kayal, Jun KikuchiJun KikuchiDepartment of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, JapanMore by Jun Kikuchihttps://orcid.org/0000-0001-9892-8832, Masahiro ShimizuMasahiro ShimizuDepartment of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, JapanMore by Masahiro Shimizu, Naoya ShinagawaNaoya ShinagawaDepartment of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, JapanMore by Naoya Shinagawa, Shigenobu UmemiyaShigenobu UmemiyaDepartment of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, JapanMore by Shigenobu Umemiyahttps://orcid.org/0000-0002-1793-856X, and Masahiro Terada*Masahiro TeradaDepartment of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan* E-mail: [email protected]More by Masahiro Teradahttps://orcid.org/0000-0002-0554-8652Cite this: ACS Catal. 2021, 11, 14, 8956–8957Publication Date (Web):July 7, 2021Publication History Published online7 July 2021Published inissue 16 July 2021https://doi.org/10.1021/acscatal.1c02714Copyright © 2021 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views732Altmetric-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 (888 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Chemical structure,Organic compounds,Reaction mechanisms,Redox reactions,Stereochemistry Get e-Alerts

Construction of Quaternary Carbon Center via NHC Catalysis Initiated by an Intermolecular Heck-Type Alkyl Radical Addition.

A quaternary carbon center containing an oxindole motif is constructed via NHC-catalyzed transition-metal and aldehyde-free intermolecular Heck-type alkyl radical addition initiated annulation. This redox-neutral protocol also features a simple procedure, broad substrate scope, good functional group tolerance and could be smoothly amplified to a gram scale. The mechanism study shows that the reaction possibly undergoes two folds of SET processes with an NHC radical cation intermediate involved.

Use of Strain-Release for the Diastereoselective Construction of Quaternary Carbon Centers.

Herein, we describe the formation of quaternary carbon centers with excellent diastereoselectivity via a strain-release protocol. An organometallic species is generated by Cp*Rh(III)-catalyzed C-H activation, which is then coupled with strained bicyclobutanes (BCBs) and a prochiral carbon electrophile in a three-component reaction. This work illustrates a rare example of BCBs in transition metal catalysis and demonstrates their broad potential to access novel reaction pathways. The method developed exhibits ample functional group tolerance, and the products can be further transformed into valuable α-quaternary β-lactones. Preliminary mechanistic investigations suggest a twofold C-C bond cleavage sequence involving σ-bond insertion and an ensuing β-carbon elimination event.

Nickel-catalyzed formation of quaternary carbon centers using tertiary alkyl electrophiles.

Transformation of sterically hindered tertiary alkyl electrophiles under nickel-catalyzed conditions to forge C(sp3)-C bonds and simultaneously create challenging all-carbon quaternary centers has received growing attention in the recent years. The unique nature of nickel featuring flexible oxidation states ranging from Ni0 to NiIV, allows the effective activation of tertiary alkyl electrophiles through ionic (2e) or radical pathways. In nickel-catalyzed coupling of tertiary alkyl electrophiles, the competitive β-H elimination upon the resulting alkyl-Ni intermediate is relatively slow, thus benefiting the C-C bond forming process. Meanwhile, nickel-catalyzed radical addition of tertiary alkyl electrophiles to unsaturated C-C bonds has also advanced rapidly due to the successful incorporation of carboxylic acid and alcohol derivatives as radical precursors, and more importantly due to further interception of the intermediate radical adducts with nucleophiles and electrophiles to accomplish three-component cascade reactions. This review highlights these state-of-the-art nickel-catalyzed transformations of tertiary electrophiles, organized by reaction types with emphasis on the reaction mechanisms.

Transition-Metal-Free Cross-Coupling by Using Tertiary Benzylic Organoboronates.

The transition-metal-free cross-coupling of alkyl or aryl electrophiles by using tertiary benzylic organoboronates is reported. This reaction involves the generation of tertiary alkyl anions from organoboronates in the presence of an alkoxide base and then their substitution reactions. This protocol allows the simple and efficient construction of quaternary carbon centers.