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Synthesis of Alkynyl Ketones by Sonogashira Cross-Coupling Of

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Synthesis of Alkynyl Ketones by Sonogashira Cross-Coupling Of catalysts Article ArticleSynthesis of Alkynyl Ketones by Sonogashira SynthesisCross-Coupling of Alkynyl of Acyl Ketones Chlorides by Sonogashira with Terminal Cross- CouplingAlkynes Mediated of Acyl Chlorides by Palladium with CatalystsTerminal DepositedAlkynes Mediatedover Donor-Functionalized by Palladium Catalysts Silica GelDeposited over Donor-functionalized Silica Gel Miloslav Semler, Filip Horký and Petr Štˇepniˇcka* Miloslav Semler, Filip Horký and Petr Štěpnička * Department of Inorganic Chemistry, Faculty of Science, Charles University, Hlavova 2030, Department128 40 Prague, of CzechInorganic Republic; Chemistry, [email protected] Faculty of Scie (M.S.);nce, Charles fi[email protected] University, Hlavova (F.H.) 2030, 128 40 Prague, Czech* Correspondence: Republic; [email protected] [email protected] (M.S.); [email protected] (F.H.) * Correspondence: [email protected] Received:Received: 25 25 September September 2020; 2020; Accepted: Accepted: 12 12 Oc Octobertober 2020; 2020; Published: Published: 14 15 October October 2020 2020 Abstract: Palladium catalysts deposited over silica gel bearing simple amine≡ ( Si(CH2)3NH2) Abstract: Palladium catalysts deposited over silica gel bearing simple amine ( Si(CH≡ 2)3NH2) and compositeand composite functional functional amide amide pendants pendants equipped equipped with various with various donor groups donor in groups the terminal in the terminalposition position≡ ( Si(CH2)3NHC(O)CH2Y, Y = SMe, NMe2 and PPh2) were prepared and evaluated in ( Si(CH2)3≡NHC(O)CH2Y, Y = SMe, NMe2 and PPh2) were prepared and evaluated in Sonogashira- typeSonogashira-type cross-coupling cross-coupling of acyl chlorides of acyl with chlorides terminal with alkynes terminal to give alkynes 1,3-disubstituted to give 1,3-disubstituted prop-2-yn-1- ones.prop-2-yn-1-ones. Generally, the Generally, catalysts showed the catalysts good showedcatalytic goodactivity catalytic in the reactions activity in of the aroyl reactions chlorides of aroylwith arylchlorides alkynes with under aryl alkynesrelatively under mild relatively reaction mildconditions reaction even conditions without even adding without a copper adding co-catalyst. a copper However,co-catalyst. their However, repeated their use repeated was compromised use was compromised by a significant by loss a significant of activity loss after of the activity first catalytic after the run.first catalytic run. Keywords:Keywords: depositeddeposited catalysts; catalysts; palladium; palladium; functional functional amides; amides; Sonogashira Sonogashira reaction; reaction; alkynyl alkynylketone synthesisketone synthesis 1. Introduction 1. Introduction The first examples of Sonogashira-type cross-coupling of terminal alkynes with acyl chlorides to The first examples of Sonogashira-type cross-coupling of terminal alkynes with acyl chlorides to give alkynyl ketones (Scheme1) were reported by Crisp and O’Donoghue in 1989 [ 1], who reacted furoyl give alkynyl ketones (Scheme 1) were reported by Crisp and O’Donoghue in 1989 [1], who reacted chlorides with alkynes in the presence of [PdCl2(PhCN)2]/CuI and triethylamine to produce alkynyl furoyl chlorides with alkynes in the presence of [PdCl2(PhCN)2]/CuI and triethylamine to produce furanyl ketones. With [PdCl2(PPh3)2]/CuI and similar catalysts, this reaction subsequently made it alkynyl furanyl ketones. With [PdCl2(PPh3)2]/CuI and similar catalysts, this reaction subsequently possible to synthesize a number of alkynyl ketones in organic solvents [2,3], in water (when adding made it possible to synthesize a number of alkynyl ketones in organic solvents [2,3], in water (when sodium dodecyl sulfate as a phase transfer reagent) [4–7] and even in a flow reactor (when using adding sodium dodecyl sulfate as a phase transfer reagent) [4–7] and even in a flow reactor (when unsupported Pd(OAc)2 as the catalyst) [8]. using unsupported Pd(OAc)2 as the catalyst) [8]. R1 cat. 2 R1 H +R2COCl R base O Scheme 1. Sonogashira cross-coupling of alkynes and acyl chlorides resulting in alkynyl ketones. Scheme 1. Sonogashira cross-coupling of alkynes and acyl chlorides resulting in alkynyl ketones. Alongside the development of homogenous catalysts, various heterogeneous catalytic systems Alongside the development of homogenous catalysts, various heterogeneous catalytic systems were devised for this cross-coupling reaction. Wang et al. [9] studied the coupling of aromatic chlorides were devised for this cross-coupling reaction. Wang et al. [9] studied the coupling of aromatic and cinnamoyl chloride with ethynylbenzene mediated by [PdCl2(PPh3)2]/CuI deposited on KF-alumina chlorides and cinnamoyl chloride with ethynylbenzene mediated by [PdCl2(PPh3)2]/CuI deposited on under microwave irradiation. Subsequent reports described the use of conventional Pd/C[10], KF-alumina under microwave irradiation. Subsequent reports described the use of conventional Pd nanoparticles supported by poly(1,4-phenylene sulfide) [11] or by functionalized polystyrene, Pd/C [10], Pd nanoparticles supported by poly(1,4-phenylene sulfide) [11] or by functionalized PS-CH2NHC(S)NHN=C(Ph)C(Me)=N-OH (PS = polystyrene) (without a Cu co-catalyst) [12], polystyrene, PS-CH2NHC(S)NHN=C(Ph)C(Me)=N-OH (PS = polystyrene) (without a Cu co-catalyst) and applications of Pd/BaSO4 with a ZnCl2 co-catalyst [13,14] in similar reactions. [12], and applications of Pd/BaSO4 with a ZnCl2 co-catalyst [13,14] in similar reactions. Catalysts 2020, 10, 1186; doi:10.3390/catal10101186 www.mdpi.com/journal/catalysts Catalysts 2019, 9, x; doi: FOR PEER REVIEW www.mdpi.com/journal/catalysts CatalystsCatalysts 20202019,, 109, ,x 1186 FOR PEER REVIEW 22 ofof 1414 In 2009, Tsai et al. [15] reported the application of a Pd-bipyridyl complex grafted onto the In 2009, Tsai et al. [15] reported the application of a Pd-bipyridyl complex grafted onto the mesoporous molecular sieve MCM-41.Coupling reactions of various substrates mediated by this mesoporous molecular sieve MCM-41.Coupling reactions of various substrates mediated by this catalyst in neat triethylamine, in the presence of CuI and triphenylphosphine, proceeded catalyst in neat triethylamine, in the presence of CuI and triphenylphosphine, proceeded satisfactorily satisfactorily at low Pd loading (0.002–0.1 mol.%). More recently, Cai et al. [16] used a related Pd at low Pd loading (0.002–0.1 mol.%). More recently, Cai et al. [16] used a related Pd catalyst prepared catalyst prepared by depositing Pd(OAc)2 over an MCM-41 surface, modified by by depositing Pd(OAc)2 over an MCM-41 surface, modified by Si(CH2)3NHCH2CH2NH2 groups. ≡Si(CH2)3NHCH2CH2NH2 groups. At 0.2 mol.% Pd loading, and≡ with 0.2 mol.% CuI as a co-catalyst, At 0.2 mol.% Pd loading, and with 0.2 mol.% CuI as a co-catalyst, this material could be reused ten times this material could be reused ten times with only a marginal loss of activity (reaction in triethylamine with only a marginal loss of activity (reaction in triethylamine at 50 C). Other authors evaluated the at 50 °C). Other authors evaluated the related catalysts obtained from◦ supports bearing phosphine- related catalysts obtained from supports bearing phosphine-donor≡ groups, e.g., periodic mesoporous donor groups, e.g., periodic mesoporous silica with CH2CH2PPh2 substituents [17]+ and polystyrene silica with CH2CH2PPh2 substituents [17] and polystyrene modified by the –CH2P Ph2CH2CH2PPh2 modified by≡ the –CH2P+Ph2CH2CH2PPh2 Cl− moieties at the surface [18]. Cl moieties at the surface [18]. − Alkynyl ketones are valuable synthetic building blocks, opening an access to a range of useful Alkynyl ketones are valuable synthetic building blocks, opening an access to a range of useful compounds, such as intermediates for the synthesis of various heterocycles [19–23], biologically compounds, such as intermediates for the synthesis of various heterocycles [19–23], biologically active active compounds [24], naturally occurring compounds [25], liquid-crystalline materials [26], and compounds [24], naturally occurring compounds [25], liquid-crystalline materials [26], and ligands ligands for transition metal ions [27]. In particular, the promising results achieved with deposited for transition metal ions [27]. In particular, the promising results achieved with deposited catalysts catalysts in the cross-coupling of acyl chlorides and alkynes and the wide range of applications of in the cross-coupling of acyl chlorides and alkynes and the wide range of applications of coupling coupling products led us to consider using palladium catalysts deposited over the conventional silica products led us to consider using palladium catalysts deposited over the conventional silica gel bearing gel bearing donor-substituted amide pendants [28] at the surface (Scheme 2) [29], which were already donor-substituted amide pendants [28] at the surface (Scheme2)[ 29], which were already evaluated in evaluated in Suzuki-Miyaura biaryl coupling [30]. The results from our study of these catalysts are Suzuki-Miyaura biaryl coupling [30]. The results from our study of these catalysts are presented in presented in this contribution, with a particular focus on the reaction scope and a possible influence this contribution, with a particular focus on the reaction scope and a possible influence of the donor of the donor moieties within the functional supports that were varied. moieties within the functional supports that were varied. Scheme 2. Deposited catalysts used in this study. Scheme 2. Deposited catalysts used in this study. 2.
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