Angelw: Professor Dong guangbin, University of Chicago, U.S.A. realized guided group assisted palladium catalyzed γ - C (SP3) - H bond arylation of mercaptan

Controlling the site selectivity of C (SP 3) - H functionalization has always been a challenging task The transition metal catalysis involving nitrogen-containing guiding group (DGS) provides a feasible method for functionalization of C (SP 3) - H It is well known that the ligands with sulfur as coordination atom are strong ligands However, the sulfur directed functionalization of C (SP 3) - H is not much (scheme 1a) Because mercaptans are easy to dimer or couple with halogenated compounds, the site selective functionalization of mercaptan C (SP 3) - H bonds is difficult Recently, Professor Dong guangbin's research group at the University of Chicago designed an ingenious strategy of protecting the group, which realized the arylation of mercaptan γ - C (SP 3) - H bond Firstly, thiol is protected by reversible thiol Michael click reaction, then sulfur directed γ - C (SP 3) - H functionalization is realized under palladium catalysis, and finally scheme 1b is removed under alkaline condition This strategy provides an effective method for the synthesis of γ - arylated mercaptans The related research results were published in angelw Chem Int ed (DOI: 10.1002/anie.201807760) (source: angelw Chem Int ed.) it is clear that the appropriate protective group is conducive to the smooth progress of the reaction Through screening, the author determined that ethyl acrylate is the most suitable protective group for the reaction Then, the conditions of C (SP 3) - H aromatization of ethyl acrylate protected mercaptan at 1 a benzyl position were screened (Table 1) It was found that with 10 mol% PD (OAC) 2 as catalyst, AgTFA, natfa and m-nitrobenzoic acid as additives and MEOMS as mercaptan capturing agent, 1A could react with iodobenzene smoothly and the target product 3A / 3A '(8:1) was obtained in 76% yield (source: angelw Chem Int ed.) then, the author studied the substrate applicability of the reaction (Table 2) The target compound 3A - 3G can be obtained by the reaction of electron rich or electron deficient iodobenzene with 1a Methyl ketone, amide, TBS protected phenol, ester and other functional groups can also be tolerated in this reaction In addition, it is found that the reaction is advantageous when the adjacent position of the guiding group contains a large steric hindrance group (source: angelw Chem Int ed.) further, the author fine tuned the reaction conditions to realize the aromatization of the inactive C (SP 3) - H bond in the secondary mercaptan derivative (Table 3) The corresponding target products can be obtained by the reaction of different electric properties of iodobenzene with 4A Hydroxyl, halogen, cyano and other functional groups can also be compatible in the reaction However, primary and tertiary mercaptan derivatives are not suitable for this conversion (source: angelw Chem Int ed.) finally, the author realized the protection / C-H arylation / deprotection of mercaptan 6 (scheme 2a) by one pot method The corresponding compounds 9 and 10 (scheme 2b) were obtained by copper catalyzed cross coupling and S N ar reaction (source: angelw Chem Int ed.) conclusion: Professor Dong guangbin's research group at the University of Chicago has realized the γ - C (SP 3) - H arylation of mercaptan protected by ethyl acrylate by palladium catalysis The protecting group can be removed under alkaline conditions, which provides an effective method for the synthesis of γ - arylated mercaptan compounds.