Pd(II)/Norbornene-Catalyzed Meta-C–H Alkylation of Nosyl-Protected Phenylalanines

Abstract

A Pd/norbornene-catalyzed direct meta-alkylation of nosyl-protected phenylalanine derivatives with alkyl iodides is reported in moderate to good yields. The use of diisopropyl bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate is identified as a more suitable transient mediator. A simple pyridine ligand is also essential for this reaction to proceed. No racemization was observed in this meta-methylation reaction.

Jenseits von Friedel und Crafts: dirigierte Alkylierung von C‐H‐Bindungen in Arenen

“…Yu et al übertrugen die Alkylierung von Aryloxazolinen mit den entsprechenden Te traalkylzinnreagentien außerdem auf die Methylierung und Ethylierung von Benzylderivaten, die Anwen-dungsbreite wurde aber nur anhand von in der Benzylposition dialkylierten Substraten untersucht. [212] 1)]. [211a] Ein verbessertes Verfahren wurde anschließend mit 2-Carbomethoxynorbornen entwickelt, das in Kombination mit Palladium(II)-acetat und einem maßgeschneiderten Ligand die meta-Alkylierung von Benzylcarboxamiden mit einer Auswahl an primären Alkyliodiden fçrderte (Schema 46).…”

Palladium(II)‐Initiated Catellani‐Type Reactions

“…[16] Whereas ortho-selective C À Hf unctionalization reactions of arenes have been well developed, meta-selective CÀHf unctionalization remains ac hallenge. [19] As eparate approach using Pd II /NBE cooperative catalysis was developed by the groups of Yu,Dong, Zhao,Shi, Ferreira, and others, [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] who drew inspiration from the Catellani reaction. [19] As eparate approach using Pd II /NBE cooperative catalysis was developed by the groups of Yu,Dong, Zhao,Shi, Ferreira, and others, [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] who drew inspiration from the Catellani reaction.…”

“…[21] Later on, they realized the meta C À Ha lkylation of benzylsulfonamide (sulfonamide as an ortho-directing group) by using Yu mediator 52 and simple isoquinoline as the ligand, generating the desired meta-alkylated products 54 in 45-72 % yield (Scheme 11 c). [23] In this process,a nother NBE derivative, diisopropyl bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate (56), was introduced together with simple pyridine as the optimal combination of mediator and ligand. [23] In this process,a nother NBE derivative, diisopropyl bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate (56), was introduced together with simple pyridine as the optimal combination of mediator and ligand.…”

“…Recently,s everal elegant strategies have been developed to address this issue, [16g,i, 17-19] for example,s teric-hindrancesensitive borylation, [17] ruthenium-catalyzed meta-selective C À Hf unctionalization, [18] and the use of aU -shaped template. [19] As eparate approach using Pd II /NBE cooperative catalysis was developed by the groups of Yu,Dong, Zhao,Shi, Ferreira, and others, [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] who drew inspiration from the Catellani reaction. As shown in Scheme 10, by taking advantage of the directed ortho palladation and Catellanis It should be pointed out that in these meta-selective C À H functionalization processes,s toichiometric silver salts are usually needed, which may act as ab ase for the C À H activation steps,asanoxidant to prevent the formation of Pd 0 species,a sw ell as ahalogen anion scavenger to promote the formation of Pd IV species.F urther studies illustrated the use of this strategy in generating derivatives of phenylacetic acid, b-arylethylamines,b enzyl amines,a nilines,and phenols.…”

“…[22] Very recently,D ing and co-workers reported the direct meta alkylation of nosyl-protected methyl esters of phenylalanine derivatives in moderate to high yields (Scheme 11 d). [23] In this process,a nother NBE derivative, diisopropyl bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate (56), was introduced together with simple pyridine as the optimal combination of mediator and ligand. Significantly,n or acemization occurred in this transformation.…”