Additive-Free Pd-Catalysed C-2 Arylation of Tryptophan Derivatives with Diaryliodonium Salts

Abstract

An efficient, mild and Pd-catalysed C-2 arylation of Fmoc-L-tryptophan with diaryliodonium salts has been developed, giving easy access to C-2 arylated tryptophan derivatives. This protocol tolerates a variety of functional groups and proceeds smoothly in high yields without any additives. In addition, the chemoseletive C–H arylation with unsymmetrical salts is described.

Diaryliodoniums Salts as Coupling Partners for Transition-Metal Catalyzed C- and N-Arylation of Heteroarenes

“…Since the introduction of an aryl group drastically improves the intrinsic photophysical properties of the indole motif, some examples of palladium-mediated C-H bond arylation have been designed on tryptophan derivatives and more challenging tryptophan-containing peptides [68,69]. In 2015, Fairlamb developed the synthesis of 2-aryl-tryptophans using Pd(OAc) 2 in the presence of unsymmetrical diaryliodoniums composed of the sterically hindered mesityl group in ethylacetate as the solvent under mild conditions (Scheme 4a) [68].…”

“…The strategy was successfully extended to small tryptophan-containing dipeptides TfaGlyTrp-OMe and Tfa-LeuTrp-OMe (Scheme 4a) and to two peptides containing a C-terminal alanine residue (Ac-AlaTrpAla-OH and AcSerGlyTrpAla-OH) which had proved problematic with oxidative conditions such as Cu-mediated arylation (Scheme 4b). Li and co-workers described in 2018 a palladium-catalyzed C2 arylation of Fmoc-L-tryptophan using symmetrical and unsymmetrical diaryliodonium triflates with good chemoselectivities [69].…”

Palladium-Catalyzed Regioselective C-Arylation and C,N-Diarylation of N-Aryl-2,3-dihydrophthalazine-1,4-diones Using Diaryliodonium Salts

“…Particularly, the pioneering work by Sanford and co-workers towards direct C2-arylation of indoles, involving the generation of aryl-palladium(IV) species via oxidation of palladium(II) catalyst with diaryliodonium salts is worth appraising (Scheme 1a). 27 Following this work, several transition-metal-catalyzed C-H/N-H arylation strategies with diaryliodonium salts have been disclosed by leading scientists, including Fairlamb, 28 Li, 29 Kumar, 30 Vaccaro, 31 Glorius, 32 McGlacken, 33 Zhang, 34 Hong, 35 Gaunt, 36 Sharma, 37 Shi, 38 Wang, 39 and others to furnish highly valuable bi(hetero)aryl scaffolds (Scheme 1b-f). Interestingly, the functionalization of N-aryl-2,3-dihydrophthalazine-1,4-diones with iodonium salts remains unexplored.…”