Palladium‐Catalysed C(sp³)−H Glycosylation for the Synthesis of C‐Alkyl Glycoamino Acids

Abstract

We have developed a highly efficient and practical approach for palladium‐catalyzed trifluoroacetate‐promoted N‐quinolylcarboxamide‐directed glycosylation of inert β‐C(sp3)−H bonds of N‐phthaloyl α‐amino acids with glycals under mild conditions. For the first time, C(sp3)−H activation for glycosylation was achieved to build C‐alkyl glycosides. This method facilitates the synthesis of various β‐substituted C‐alkyl glycoamino acids and offers a tool for glycopeptide synthesis.

Transition-Metal-Catalyzed, Coordination-Assisted Functionalization of Nonactivated C(sp3)–H Bonds

“…In 2020, both the Liu and the Ackermann groups took advantage of C­(sp 3 )–H alkenylation transformations to develop methods for palladium­(II)-catalyzed β-C­(sp 3 )–H glycosylation of amino acids and peptides. 8-Aminoquinoline was employed by Liu and co-workers as a DG to enable the glycosylation of various N -phthaloyl α-amino acids (Scheme a) . The Ackermann group used triazolyldimethylmethyl (TAM) as their main DG and were also able to employ 8-aminoquinoline as a DG under slightly altered conditions to achieve the glycosylation of various N -phthaloyl α-amino acids (Scheme b) .…”

“…8-Aminoquinoline was employed by Liu and co-workers as a DG to enable the glycosylation of various N-phthaloyl α-amino acids (Scheme 110a). 312 The Ackermann group used triazolyldimethylmethyl (TAM) as their main DG and were also able to employ 8-aminoquinoline as a DG under slightly altered conditions to achieve the glycosylation of various N-phthaloyl α-amino acids (Scheme 110b). 313 In addition, an unprecedented late-stage glycosylation of internal peptides directed by TAM was also achieved.…”

Emerging Organometallic Methods for the Synthesis of C‐Branched (Hetero)aryl, Alkenyl, and Alkyl Glycosides: C−H Functionalization and Dual Photoredox Approaches

“…published a similar protocol (Scheme 15) to synthesize similar compounds 24 , by replacing AdCO 2 H with TFA, in good yields (63–83 %) and moderate to excellent diastereoselectivities (3:1 to >20:1 diastereomeric ratio (d.r.)) [53] . Both teams showed through deuterium kinetic studies that C(sp 3 )−H bond cleavage was not the rate‐limiting step of the catalytic cycle and the mechanism depicted in Scheme 4 seems to be reasonable in that case too.…”

Synthesis of C‐Aryl Glycosides via Ru‐Catalyzed Remote C−H Glycosylation of 8‐Aminoquinoline Amides

“…Compared to above coupling approaches, CÀ H activation, an effective strategy to construct CÀ C bonds without pre-functioned coupling partners, has been widely used in synthesis of C-Aryl glycosides. [11] The groups of Ye, Chen, Liu and our group have explored various N-quinolyl-group-directed ortho-CÀ H glycosylation reaction, [12] respectively (Scheme 1b). In addition, glycosyl radical addition reaction was other strategy to synthesize C-Aryl glycosides with excellent stereoselectivity.…”