Synthesis Of Unsymmetrical Ketones Research Articles

Unsymmetrical Ketone Synthesis via Selective Nickel-Catalyzed Reductive Carbonylation

Unsymmetrical Ketone Synthesis via Selective Nickel-Catalyzed Reductive Carbonylation

Synthesis of unsymmetrical ketones via dual catalysed cross-coupling of α,β-unsaturated carboxylic acids with aryldiazonium salts.

A visible light-enabled synthesis of unsymmetrical ketones has been accomplished by the cross-coupling of α,β-unsaturated carboxylic acids and aryldiazonium salts embracing a synergistic eosin Y and Co(OAc)2·4H2O catalysis. The reaction involves decarboxylative aerobic CC bond cleavage, and is endowed with the creation of new C-C and C-O bonds with good substrate scope.

Synthesis of α‐Aryl Ketones by Harnessing the Non‐Innocence of Toluene and its Derivatives: Enhancing the Acidity of Methyl Arenes by a Brønsted Base and their Mechanistic Aspects

AbstractKetones are the key functional group that recurs in chemistry and biology, and accessing them through simple and economic ways is highly desirable. Herein, we report the synthesis of unsymmetrical ketones from abundant toluene and alkyl esters, where volatile alcohols are the sole byproduct. This protocol applies to a repertoire of substrates bearing electron‐donating, electron‐withdrawing, and neutral substituents. Most importantly, the organometallic ferrocenyl ester underwent aroylation with ease. This method is the first example to furnish diketones from methyl arenes and diesters. Furthermore, cyclic imide was synthesized by this protocol utilizing KN(SiMe3)2 as a ′nitrogen′ source. Density functional theory studies provide insight into deprotonation of toluene by K+‐π interaction by increasing its acidity, and this being the rate‐determining step.

Vinyl Azides as Radical Acceptors in the Vitamin B12-Catalyzed Synthesis of Unsymmetrical Ketones.

Vinyl azides are very reactive species and as such are useful building blocks, in particular, in the synthesis of N-heterocycles. They can also serve as precursors of ketones. These form in reactions of vinyl azides with nucleophiles or radicals. We have found, however, that under light irradiation vitamin B12 catalyzes the reaction of vinyl azides with electrophiles to afford unsymmetrical carbonyl compounds in decent yields. Mechanistic studies revealed that alkyl radicals are key intermediates in this transformation.

Nickel/Benzophenone Dual-Catalyzed Synthesis of Unsymmetrical Ketones

Nickel/Benzophenone Dual-Catalyzed Synthesis of Unsymmetrical Ketones

Structurally Diverse Acyl Bicyclobutanes: Valuable Strained Electrophiles.

Bicyclo[1.1.0]butanes (BCBs) are highly strained carbocycles that have emerged as versatile synthetic tools, particularly for the construction of functionalized small molecules. This work reports two efficient pathways for the rapid preparation of over 20 structurally diverse BCB ketones, encompassing simple alkyl and aryl derivatives, as well as unprecedented amino acid, dipeptide, bioisostere, and bifunctional linchpin reagents currently inaccessible using literature methods. Analogues are readily forged in two steps and in high yields from simple carboxylic acids or through unsymmetrical ketone synthesis beginning with a convenient carbonyl dication equivalent. The utility of this novel toolbox of strained electrophiles for the selective modification of proteinogenic nucleophiles is highlighted.

Synthesis of unsymmetrical ketones by applying visible-light benzophenone/nickel dual catalysis for direct benzylic acylation.

Herein, we report a dual catalytic system for the direct benzylic C-H acylation reaction furnishing a variety of unsymmetrical ketones. A benzophenone-derived photosensitizer combined with a nickel catalyst has been established as the catalytic system. Both acid chlorides and anhydrides are able to acylate the benzylic position of toluene and other methylbenzenes. The method offers a valuable alternative to late transition metal catalyzed C-H acylation reactions.

Acyl Radicals from Acylsilanes: Photoredox-Catalyzed Synthesis of Unsymmetrical Ketones

Acyl radicals were smoothly generated from acylsilanes under photoredox-catalyzed conditions. These radicals were formed upon ultraviolet B (UV-B), solar, or visible light irradiation by using decatungstate and acridinium salts as photocatalysts. Acylation of Michael acceptors and a few styrenes resulted in a smooth preparation of unsymmetrical ketones in yields up to 89%.

One pot synthesis of unsymmetrical ketones from carboxylic and boronic acids via PyClU-mediated acylative Suzuki coupling

A synthetic procedure for the preparation of ketones from easily accessible carboxylic acids has been developed. This methodology proceeds via in situ activation of the carboxylic acid with PyClU, followed by the palladium-catalyzed acylative cross-coupling with boronic acids. The reaction is performed in one pot, without the need of phosphine ligands, at room temperature and in reaction times of 2h or less. The scope of the reaction is robust with aryl boronic and carboxylic acids.

A phosphine-free, heterogeneous palladium-catalyzed atom-efficient carbonylative cross-coupling of triorganoindiums with aryl halides leading to unsymmetrical ketones

A phosphine-free heterogeneous palladium-catalyzed carbonylative cross-coupling of triorganoindiums with aryl halides for the synthesis of unsymmetrical ketones has been described.

Direct conversion of cinnamate esters into β,β-disubstituted ketones mediated by cyano-magnesio cuprates

The clean synthesis of unsymmetrical ketones from carboxylic acid derivatives has been a challenge in the organic community dating back over 80 years. Herein we report the conversion of simple alkyl cinnamates to β,β-disubstituted ketones with cyano-magnesio cuprates in high yields with no observation of tertiary alcohol byproduct. The lack of tertiary alcohol is attributed to a putative enolate intermediate that serves as a ketone protecting group. A distinctive steric inhibition trend was observed related to both the size of the R group on the parent ester and the nucleophilic cuprate. Lastly, we demonstrate that this reaction can be coupled with known copper mediated allylic substitution reactions yielding β,γ-disubstituted ketone (8) from parent α-chloro-β,γ-ethylenic ester (7).

One‐pot Unsymmetrical Ketone Synthesis Employing a Pyrrole‐Bearing Formal Carbonyl Dication Linchpin Reagent

AbstractA one‐pot procedure for the synthesis of unsymmetrical ketones utilizing a pyrrole‐bearing carbonyl linchpin reagent (carbonyl linchpin N,O‐dimethylhydroxylamine pyrrole; CLAmP) is reported. In contrast to other carbonyl dielectrophile equivalents, CLAmP enables the synthesis of ketones from a variety of organolithium and Grignard reagents. The electrophilic nature of CLAmP enables the addition of less reactive as well as thermally unstable nucleophiles. CLAmP was designed to form kinetically stable tetrahedral intermediates upon the addition of organometallic nucleophiles. Evidence for the existence of persistent tetrahedral intermediates was obtained through in situ IR studies.

One-pot Unsymmetrical Ketone Synthesis Employing a Pyrrole-Bearing Formal Carbonyl Dication Linchpin Reagent.

A one-pot procedure for the synthesis of unsymmetrical ketones utilizing a pyrrole-bearing carbonyl linchpin reagent (carbonyl linchpin N,O-dimethylhydroxylamine pyrrole; CLAmP) is reported. In contrast to other carbonyl dielectrophile equivalents, CLAmP enables the synthesis of ketones from a variety of organolithium and Grignard reagents. The electrophilic nature of CLAmP enables the addition of less reactive as well as thermally unstable nucleophiles. CLAmP was designed to form kinetically stable tetrahedral intermediates upon the addition of organometallic nucleophiles. Evidence for the existence of persistent tetrahedral intermediates was obtained through in situ IR studies.

ChemInform Abstract: Preparation of Unsymmetrical Ketones from Tosylhydrazones and Aromatic Aldehydes via Formyl C—H Bond Insertion.

AbstractA convenient procedure for the synthesis of unsymmetrical ketones from bench‐stable tosylhydrazones and aryl aldehydes is reported.

Preparation of Unsymmetrical Ketones from Tosylhydrazones and Aromatic Aldehydes via Formyl C–H Bond Insertion

Preparation of ketones by insertion of diazo compounds into the formyl C-H bond of an aldehyde is an attractive procedure, but use of structurally diverse diazo compounds is hampered by preparation and safety issues. A convenient procedure for the synthesis of unsymmetrical ketones from bench-stable tosylhydrazones and aryl aldehydes is reported. The procedure can be performed in one pot from the parent carbonyl compound and needs only a base, with no additional promoters being required.

Pd-catalyzed Fukuyama cross-coupling of secondary organozinc reagents for the direct synthesis of unsymmetrical ketones

The coupling of acyl electrophiles with organometallic reagents represents a convergent route toward complex and versatile ketone products. Despite the mild conditions and high functional group tolerance, the cross-coupling of carboxylic acid derivatives, such as thioesters, and secondary organometallic reagents is an underdeveloped transformation. Herein, we disclose a convenient and efficient protocol for the Pd-catalyzed Fukuyama cross-coupling of secondary organozinc reagents with thioester electrophiles. Under these mild conditions, a range of thioesters possessing sensitive functional groups can be coupled with either activated or unactivated secondary organozinc halides in good yields. This method was expanded to include an acid chloride substrate, generating an aryl alkyl ketone in high yield. In addition, a modest dynamic kinetic resolution of the organozinc reagent can be achieved using chiral phosphoramidite ligands to furnish enantioenriched ketone products.

ChemInform Abstract: Rhodium‐Catalyzed Acyl‐Transfer Reaction Between Benzyl Ketones and Thioesters: Synthesis of Unsymmetric Ketones by Ketones CO—C Bond Cleavage and Intermolecular Rearrangement.

AbstractThe desired products are obtained together with the esters which result from the acyl transfer (for example Ph‐CO‐S‐Me or Oct‐CO‐O‐Pcp).

Rhodium-Catalyzed Acyl-Transfer Reaction between Benzyl Ketones and Thioesters: Synthesis of Unsymmetric Ketones by Ketone CO–C Bond Cleavage and Intermolecular Rearrangement

In the presence of catalytic amounts of RhH(CO)(PPh3)3 and 1,2-bis(diphenylphosphino)benzene (dppBz), acyl groups were transferred between benzyl ketones and thioesters/aryl esters. The rhodium complex catalyzed the cleavage of ketone CO-C bonds and intermolecular rearrangement giving unsymmetric ketones. The acyl-transfer reaction also occurred with 1-(p-chlorophenyl)-3-(p-cyanophenyl)propane-2-one giving unsymmetric ketones.

ChemInform Abstract: Atom‐Economical Synthesis of Unsymmetrical Ketones Through Photocatalyzed C—H Activation of Alkanes and Coupling with CO and Electrophilic Alkenes.

ChemInformVolume 42, Issue 21 Isocyclic Compounds ChemInform Abstract: Atom-Economical Synthesis of Unsymmetrical Ketones Through Photocatalyzed C—H Activation of Alkanes and Coupling with CO and Electrophilic Alkenes. Ilhyong Ryu, Ilhyong Ryu Dep. Chem., Grad. Sch. Sci., Osaka Prefect. Univ., Osaka 599, JapanSearch for more papers by this authorAkihiro Tani, Akihiro Tani Dep. Chem., Grad. Sch. Sci., Osaka Prefect. Univ., Osaka 599, JapanSearch for more papers by this authorTakahide Fukuyama, Takahide Fukuyama Dep. Chem., Grad. Sch. Sci., Osaka Prefect. Univ., Osaka 599, JapanSearch for more papers by this authorDavide Ravelli, Davide Ravelli Dep. Chem., Grad. Sch. Sci., Osaka Prefect. Univ., Osaka 599, JapanSearch for more papers by this authorMaurizio Fagnoni, Maurizio Fagnoni Dep. Chem., Grad. Sch. Sci., Osaka Prefect. Univ., Osaka 599, JapanSearch for more papers by this authorAngelo Albini, Angelo Albini Dep. Chem., Grad. Sch. Sci., Osaka Prefect. Univ., Osaka 599, JapanSearch for more papers by this author Ilhyong Ryu, Ilhyong Ryu Dep. Chem., Grad. Sch. Sci., Osaka Prefect. Univ., Osaka 599, JapanSearch for more papers by this authorAkihiro Tani, Akihiro Tani Dep. Chem., Grad. Sch. Sci., Osaka Prefect. Univ., Osaka 599, JapanSearch for more papers by this authorTakahide Fukuyama, Takahide Fukuyama Dep. Chem., Grad. Sch. Sci., Osaka Prefect. Univ., Osaka 599, JapanSearch for more papers by this authorDavide Ravelli, Davide Ravelli Dep. Chem., Grad. Sch. Sci., Osaka Prefect. Univ., Osaka 599, JapanSearch for more papers by this authorMaurizio Fagnoni, Maurizio Fagnoni Dep. Chem., Grad. Sch. Sci., Osaka Prefect. Univ., Osaka 599, JapanSearch for more papers by this authorAngelo Albini, Angelo Albini Dep. Chem., Grad. Sch. Sci., Osaka Prefect. Univ., Osaka 599, JapanSearch for more papers by this author First published: 28 April 2011 https://doi.org/10.1002/chin.201121061Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume42, Issue21May 24, 2011 RelatedInformation

Atom‐Economical Synthesis of Unsymmetrical Ketones through Photocatalyzed CH Activation of Alkanes and Coupling with CO and Electrophilic Alkenes

Atom‐Economical Synthesis of Unsymmetrical Ketones through Photocatalyzed CH Activation of Alkanes and Coupling with CO and Electrophilic Alkenes