亚洲免费av电影一区二区三区,日韩爱爱视频,51精品视频一区二区三区,91视频爱爱,日韩欧美在线播放视频,中文字幕少妇AV,亚洲电影中文字幕,久久久久亚洲av成人网址,久久综合视频网站,国产在线不卡免费播放

        ?

        Free amino group-directed C(sp2)-H arylation of α-amino-β-aryl esters by palladium catalysis

        2024-04-05 02:28:26YueGaoYuDuWeipingSu
        Chinese Chemical Letters 2024年2期

        Yue Gao ,Yu Du,* ,Weiping Su,*

        a State Key Laboratory of Structural Chemistry,Fujian Institute of Research on the Structure of Matter,Chinese Academy of Sciences,Fuzhou 350002,China

        b Fujian Science & Technology Innovation Laboratory for Optoelectronic Information of China,Fuzhou 350108,China

        c University of Chinese Academy of Sciences,Beijing 100049,China

        Keywords: Native amino-directed Palladium catalyst C(sp2)-H arylation α-Amino-β-aryl ester Chiral α-amino acid

        ABSTRACT Native amino-directed palladium-catalyzed C(sp3)-H activation/functionalization has been developed for modification of α-amino acids and peptides.Herein a palladium(II)-catalyzed C(sp2)-H arylation of αamino-β-aryl esters has been disclosed,using the native amino as the directing group.A variety of chiral α-amino-β-aryl esters can be functionalized to give the corresponding ortho-substituted mono-and diarylated products.

        α-Amino acids (α-AAs) are an important class of natural chiral compounds which are essential building blocks of proteins and peptides.The modification of easily availableα-AAs that provides new molecules bears great practical potential in chemistry,chemical biology,drug discovery and other disciplines [1-4].In recent years,C-H activation catalysis has gradually emerged as a powerful tool forα-AAs [5-9] and peptides [10-12] modification in an atom-and step-economical manner.However,the existing methodsviaC-H activation often require installation of either directing auxiliaries or introducing protecting groups to manipulate the reactivity,the development of novel methods using native carboxyl or amino groups as directing groups has attracted substantial attention.In contrast to the steady progress of carboxylate-directed inert C-H activation [13-16] and its application in modifyingα-AAs [17-21],free NH2-directed transformation is less studied [22-23].

        In order to suppress the high propensity to form strong binding and less active bis-amine complexes of primary amines with metal catalysts [24],a protonation strategy of using acetic acid as the solvent [25] was employed by Shi to realize the NH2-directedγ-C(sp3)-H acetoxylation of aliphatic primary amines (Scheme 1a)[26].Applying the same strategy toα-AAs modification,an effi-cient NH2-directedγ-C(sp3)-H arylation ofα-amino esters was developed by Yao (Scheme 1b) [27,28],and substrates were further expanded toN-terminus unprotected oligopeptides [29,30].Meanwhile,native amino-directed palladium-catalyzed C(sp2)-H arylation of primary amines had also been developed (Scheme 1c)[31,32].Aryl substitutedα-AAs are an important class of naturalα-AAs (e.g.,Phe,Trp,Tyr) and derivatives.However,at present,native NH2-directed C(sp2)-H functionalization of suchα-AAs has rarely been discussed [32].In this context,herein we report a native amino-directed palladium(II)-catalyzed C(sp2)-H arylation ofα-amino-β-aryl esters with various aryl iodides (Scheme 1d).A variety of chiralα-amino esters could be arylated by this method directly.

        Scheme 1.NH2-directed C-H functionalization of primary amines.

        As shown in Table 1,the research was commenced with exploring the coupling reaction of model substrates (S)-phenylalanine methyl ester1aand 4-methyliodobenzene2ain the presence of palladium acetate (Pd(OAc)2,5 mol%) andN-acetyl-glycine (NAc-Gly,40 mol%) as a ligand,along with 1.2 equiv.of trifluoromethanesulfonic acid (TfOH) as the proton source and 1.25 equiv.of silver carbonate (Ag2CO3),warmed at 120°C for 24 h in hexafluoroisopropanol (HFIP) under air.The desiredortho-arylated products3a(mono-arylated) and4a(di-arylated) were obtained in yields of 48% and 25% separately (entry 1).Then lots of control experiments were performed to find the optimal conditions (see Supporting information for more reaction conditions evaluation).Various mono-N-protected amino acids (MPAAs) [1,33] were examined(entries 1-5),N-acetyl-valine (N-Ac-Val) is the superior one that affords the highest yields of3aand4a(entry 3).The screening of acid additives showed that TfOH is the best choice (entries 6-8).It should be noteworthy that no target molecules were obtained without the addition of acid,suggesting the critical role of acid in inhibiting the strong binding of the amino group with palladium.A survey of inorganic bases revealed that Ag2CO3significantly outperform others in promoting the reaction (entries 9-11),and silver salts play an irreplaceable role as iodide scavenger [34].Other polar or nonpolar solvents were also tested,however,no positive effect was observed (entries 12 and 13).Extending reaction time to 36 h led to a little increase of the combined yields of3aand4a(entry 14),further extending reaction time to 48 h failed to take effect (entry 15).Besides,the use of other palladium-catalysts instead of Pd(OAc)2led to an erosion in the yield (entries 16-18).The di-arylation increased significantly (>60% yield) with the catalyst loading of Pd(OAc)2increased to more than 20 mol%,while the mono-arylation was almost disappeared.The results indicate that the poor selectivity is caused by the lack of activity of the catalytic system.

        Table 1Optimization of reaction conditions.a

        With the optimal conditions (Table 1,entry 14),the generality of this C(sp2)-H arylated method was first evaluated with variousα-amino-β-aryl esters (Scheme 2).In order to ensure the reliability of the yields,all data represent the average of (more than)two independent experiments.A variety ofα-amino esters with electron-rich or -deficient aryl groups (1b-1n),naphthyl (1o),could react under the optimal conditions to generate the corresponding arylated products3and4.Generally,the presence of an electron donating group (1b,1c,1h,1l) led to a higher yield than that derived from an electron withdrawing group (1e-1g,1i-1k,1m-1n),which probably because the former can promote the reductive elimination.α-Amino-β-aryl ester bearing apara-substituent(1b-1g) would give a mixture of mono-and di-arylated products(3b-3g&4b-4g),whileortho-andmeta-substituted substrates (1h-1o) led to only mono-arylation (3h-3o).By now the method appears not applicable for site-selective C-H functionalization of peptides containing Phe as the N-terminus,both C(sp2)-H and C(sp3)-H arylation were observed after reactions (details see Supporting information).

        Scheme 2.Scope of α-amino-β-aryl esters.Reactions were performed on a 0.4 mmol scale.Yields are isolated yields.

        Further investigation of coupling reagents,aryl iodides,was carried out under the optimal conditions with (S)-phenylalanine methyl ester1a(Scheme 3).Various functional groups such as methoxy,alkyl,phenyl,trifluoromethyl,ester and halogen groups at thepara-ormeta-position were tolerated,generating mixtures of mono-and di-arylated products (3b’-3n’&4b’-4n’).In contrast,ortho-substituted iodobenzene doesn’t work in this reaction.Fluorenyl derivative (2o) also worked well to give the corresponding mono-and di-arylated products (3o’&4o’) in a moderate combined yield.Regrettably,the method is not applicable to heteroaryl iodides orα-amino-β-heteroaryl esters (e.g.,Trp-OMe).

        Scheme 3.Scope of aryl iodides.Reactions were performed on a 0.4 mmol scale.Yields are isolated yields.

        Chiral HPLC analysis of arylated products derived from (R)-and(S)-phenylalanine methyl esters showed that there is a little erosion in enantiomeric excess (di-arylated product4a,88%ee,see Supporting information),revealing that partial racemization occurred during the reaction due to the basicity and high temperature.In order to verify the directing effect of the native NH2,as shown in Scheme 4,methyl 3-phenylpropanoate1pandN,Ndimethyl-Phe-OMe1qwere subjected to the reaction,and no observation of the desired C(sp2)-H arylation.The results exclude the possible ester-directed C-H activation.

        Scheme 4.Additional control experiments.

        In summary,an efficient and practical Pd(II)-catalyzed C(sp2)-H arylation ofα-amino-β-aryl esters with various aryl iodides has been developed,using the native NH2as the directing group.A variety of chiralα-amino esters could be functionalized by this method to give the corresponding mono-and di-arylated products with a little erosion in enantiomeric excess.The method features broad substrate scope,excellent functional group tolerance and mild conditions.Further exploration of this protocol for C(sp2)-H arylation of oligopeptides and structure modification of polypeptide drugs is currently underway in our laboratory.

        Declaration of competing interest

        The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

        Acknowledgments

        This work was supported by the National Key Research and Development Program of China (No.2018YFA0704502),the National Natural Science Foundation of China (Nos.21871261,21931011),and Fujian Science & Technology Innovation Laboratory for Optoelectronic Information of China (No.2021ZZ105).

        Supplementary materials

        Supplementary material associated with this article can be found,in the online version,at doi:10.1016/j.cclet.2023.108505.

        色五月丁香五月综合五月| av在线手机中文字幕| 亚洲成人av一区免费看| 乱老年女人伦免费视频| 国产内射999视频一区| 中文字幕一区二区三区人妻精品 | 国产精品国产三级国产三不| 亚洲国产一区二区网站| 午夜亚洲av日韩av无码大全| 午夜福利电影| 爆乳无码AV国内| 亚洲天堂av在线免费观看| 色爱av综合网站| 精品性影院一区二区三区内射| 美女视频永久黄网站免费观看国产| 一级老熟女免费黄色片| 国产肉体xxxx裸体137大胆| 欧美日韩在线免费看| 日韩精品极品视频在线观看蜜桃| 一区二区三区日韩亚洲中文视频| 曰欧一片内射vα在线影院| 亚洲综合自拍| 日本在线观看一区二区三区视频| 亚洲国产婷婷香蕉久久久久久| 午夜精品久久久久久久久久久久| 国产精品美女黄色av| 青青草视频在线观看精品在线| 无码国产精品久久一区免费| 精品久久无码中文字幕| 黑丝美女喷水在线观看| 久久国内精品自在自线| 夜夜躁狠狠躁2021| 狠狠亚洲婷婷综合色香五月| 亚洲一区二区在线观看av| 六月丁香综合在线视频| 亚洲日韩专区在线视频| 亚洲国产线茬精品成av| 久久久亚洲av波多野结衣| 少妇spa推油被扣高潮| 国产不卡在线免费视频| 男女18视频免费网站|