“On Water” Direct and Site‐Selective Pd‐Catalysed CH Arylation of (NH)‐Indoles

Abstract

This communication describes the development of a versatile catalytic system based on palladium(II) acetate/bis(diphenylphosphino)methane [PdA C H T U N G T R E N N U N G (OAc) 2 /dppm] that works "on water" giving site-selective C À H arylation of (NH)-indoles without protecting or directing groups. Remarkably, the control of regioselectivity was achieved by small changes in the "extra-catalytic" base/halide partners. These innovative methodologies allow a highyielding access to both C2 and C3-arylindoles, as well as 2,3-diarylindoles, and display high chemo/regioselectivities and structural versatility with regard to either indole or aryl moieties.

Structure–Activity Study of Bioisosteric Trifluoromethyl and Pentafluorosulfanyl Indole Inhibitors of the AAA ATPase p97

“…The C,H-bond activation 42 strategy was selected for the preparation of methoxy-indole intermediate 33 (Scheme 3). C-2 arylation of 31 with 3-bromoiodobenzene 32 led to the coupling product 33 in high selectivity but moderate yield (44%).…”

“…41 Subsequently, a more direct synthesis of 16 was accomplished by a C,H-arylation of commercially available 5-trifluoromethylindole with 3-bromoiodobenzene, which provided indole 16 in 49% yield. 42 A different indole synthesis 43 was used for the preparation of the pentafluorosulfanyl analogue 13. Pd(0)-catalyzed coupling of bromide acetal 18 with amine 17 41 followed by selective acetal hydrolysis provided aldehyde building block 19.…”

Cross‐Coupling of Heteroarenes by CH Functionalization: Recent Progress towards Direct Arylation and Heteroarylation Reactions Involving Heteroarenes Containing One Heteroatom

“…of LiOH·H 2 O, 5 mol% PdA C H T U N G T R E N N U N G (OAc) 2 and 5 mol% dppm provided 3-aryl-1H-indoles with site selectivity values ranging from 4:1 to 14:1 (Scheme 126). [163] Djakovitch and co-workers also proposed a mechanistic rationalization for the C-3 and C-2 selective arylations according to which 3-arylindoles were obtained by an electrophilic C-3 palladation of indoles by the electrophilic cationic species A (Figure 33). …”

“…asc.wiley-vch.de dppm (Scheme 125). [163] The protocol was tolerant for both electron-poor and electron-rich aryl bromides and gave C-2 arylated indoles in 42-77% yield with C-2:C-3 ratios from 4:1 to > 99:1. In Scheme 125, the site selectivity values, expressed as C-2:C-3 ratios, are reported in brackets.…”

“…[162] In 2010, a versatile catalyst system based on PdA C H T U N G T R E N N U N G (OAc) 2 /bis(diphenylphosphino)methane (dppm) that works "on water" giving site selective arylation of free NH-indoles with aryl halides was developed by Djakovitch and co-workers. [163] The control of the site-selectivity was achieved by small changes in the base/halide partners so that both C-2 and C-3 arylylated 1H-indoles could be obtained. asc.wiley-vch.de dppm (Scheme 125).…”