Pd‐Catalyzed C(sp²)−H Alkoxycarbonylation of Phenethyl‐ and Benzylamines with Chloroformates as CO Surrogates

Abstract

The site-selective functionalization of CÀHb onds within ac omplex molecule remains ac hallengingt ask of capital synthetic importance.H erein, an unprecedented Pdcatalyzed C(sp 2)ÀHa lkoxycarbonylation of phenylalanine derivatives and other amines featuring picolinamide as the directing group (DG) is reported.T his oxidative coupling is distinguished by its scalability,o perational simplicity,a nd avoidst he use of toxic carbon monoxide as the C 1 source. Remarkably,t he easy cleavage of the DG enables the efficient assembly of isoindolinonec ompounds. Density Func-tionalT heory calculations support aP d II /Pd IV catalytic cycle.

Metal‐Catalyzed C(sp2)−H Functionalization Processes of Phenylalanine‐ and Tyrosine‐Containing Peptides

“…Inspired by the work of Shi on the alkoxycarbonylation reactions with alkyl chloroformates as an alternative and safer C1 source, [49] Correa and co‐workers have recently disclosed a scalable Pd‐catalyzed C(sp 2 )−H alkoxycarbonylation method of picolinamide‐protected amines, including a variety of Phe derivatives [50] . Although the process often resulted in separable mixtures of mono‐ and difunctionalized compounds with a preferential formation of the dialkoxycarbonylated product when using natural Phe derivatives, the introduction of ortho ‐ or meta ‐substituents within the aryl ring resulted in the exclusive mono‐alkoxycarbonylated compounds (Scheme 19).…”

Pd-catalyzed site-selective C(sp2)–H chalcogenation of amino acids and peptides using a picolinamide auxiliary

“…[54][55][56][57][58][59] However, the C-H functionalizations of phenylalanine and phenylglycine have shown significant progress. [60][61][62][63][64][65][66][67][68][69] Native chalcogenated amino acids have been shown to play significant roles in the structural and functional organization of peptides/proteins owing to the additional noncovalent interactions made by chalcogen atoms. Thus, it has been attractive to investigate aryl-chalcogenated amino acids and peptides.…”

Pd‐Catalyzed Arylation and Benzylation of Tyrosine at the δ−C(sp2)−H and C(2) Positions: Expanding the Library of Unnatural Tyrosines

“…With regard to the functionalization of the ortho /C(2)−H position of tyrosines; examples involving olefination, [12a–c] iodination, [12d] alkoxycarbonylation, [13a] acylation, [13b] bromination [13b] amination [14a–d] and carbonylation [14e,f] have been reported. Additionally, examples involving trifluoromethylation [15a] and olefination [15b] and an example of Pd‐catalyzed intramolecular C(2)−H arylation of tyrosine in peptides have been reported [15c] .…”

“…[6a,10] Owing to their importance, there has been a vested interest in developing methods for the synthesis of modified tyrosines via different routes [6][7][8][9] including the CÀ H functionalization method. [11][12][13][14][15][16] The expansion of libraries of tyrosine congeners such as phenylalanine and phenylglycine has been explored via the Pd-catalyzed C(2)À H functionalization (viz. ortho C-H arylation, benzylation, etc).…”