Diverse meta‐C−H Functionalization of Arenes across Different Linker Lengths

Abstract

Arenes containing conformationally flexible long alkylchains have been successfully functionalizedatthe metaposition. Good to excellent meta selectivity is achieved for systems with up to 20 atoms between the target CÀHbond and the coordinating heteroatom of the directing group.T he palladium-catalyzed functionalization reactions include alkylation, cyanation, olefination, and acetoxylation. The meta selectivity is exclusively governed by the design of flexible pyrimidine-based scaffolds.

Di-Palladium Complexes are Active Catalysts for Mono-N-Protected Amino Acid Accelerated Enantioselective C-H Functionalization

“…Di-palladium-MPAA complexes of both dmaf and bhp were previously characterized by high resolution mass spectrometry ( Figure 3C-E). 35 The mass spectra of these complexes indicate the presence of ions consistent with higher nuclearity aggregates and, as others have noted, 27,32,33,57 mono-palladium MPAA species (SI Figure 24&78). While observation of a complex in a reaction mixture (particularly in the gas phase) does not indicate its relevance to catalysis, 58 the studies outlined below suggest that di-palladium complexes containing a Pd2(MPAA)1 fragment (shown in red in Figure 3C/D) similar to those observed by MS ( Fig.…”

“…Given the general structural ambiguity surrounding Pd-MPAA catalysis, mechanistic models generally defer to the widely-held notion that MPAA ligands coordinate mono-palladium species by di-or mono-anionic chelation (Figure 2A and B, respectively). 1,[29][30][31][32][33] Figure 1: (A) MPAA induced, enantioselective cyclopalladation. 12 (B) Pd-MPAA catalyzed enantioselective C-H functionalization.…”

Para‐Selective Cyanation of Arenes by H‐Bonded Template

“…Hydrolysis of 2a in presence of TsOH gave para-cyanated silanol 6,w hich is av aluable substrate for directed ortho-functionalizationa nd late-stage modifications. The silanol 6 was used as ad irecting group for ortho-olefination 7 [18] and meta-alkylation 9 [19] by installing a pyrimidine-based directing group. To demonstrate practical efficacy of this protocol the large-scale synthesis of 2w was successfully performed under otherwise identical reaction conditions (Figure 6b).…”

“…After successful para-cyanation of phenol, the template was removed in situ using TBAF( Figure 7) and DG m was installed to obtain further CÀHf unctionalized phenols 10.T he strong electron withdrawing influence of the cyano group in 10 led to preferential formation of ortho-alkylated phenol 11. [19] Subsequently,t his tri-substituted sterically hindered compound 11 was furthera lkylated and olefinated to obtain tetra-substituted arenes 12 and 13.S uch iterativeC ÀHf unctionalization reactions can demonstrate the utility of this direct protocol without involving functional group interconversion strategies and by avoiding requirement of pre-installation of functional moieties.…”

para-Selective Cyanation of Arenes by H-Bonded Template

“…Hydrolysis of 2a in presence of TsOH gave para cyanated silanol 6, which is a valuable substrate for directed ortho functionalization and late stage modifications. The silanol was used as directing group for ortho olefination 18 and meta alkylation 19 by installing a pyrimidine based directing group. To demonstrate practical efficacy of this protocol the large scale synthesis of 2w was successfully performed under otherwise identical reaction conditions (Scheme 5b).…”