Manganese‐Catalyzed C−H Alkynylation: Expedient Peptide Synthesis and Modification

Abstract

Manganese(I)-catalyzed C-H alkynylations with organic halides occurred with unparalleled substrate scope, and thus enabled step-economical C-H functionalizations with silyl, aryl, alkenyl, and alkyl haloalkynes. The versatility of the manganese(I) catalysis manifold enabled C-H couplings with haloalkynes featuring, among others, fluorescent labels, steroids, and amino acids, thereby setting the stage for peptide ligation as well as the efficient molecular assembly of acyclic and cyclic peptides. A plausible catalytic cycle was proposed.

Backbone‐Enabled Directional Peptide Macrocyclization through Late‐Stage Palladium‐Catalyzed δ‐C(sp2)−H Olefination

“…[16] To achieve peptide macrocyclization, Albericio/Lavilla utilized Pd-catalyzed C-2 arylation of the indole side chain of tryptophans (Trp) by iodo-aryl amino acids to synthesize stapled peptides with aryl-aryl crosslinks. [19] More recently,C hen and co-workers reported ah ighly efficient and general strategy to prepare constrained cyclic peptides using 8aminoquinoline-directed intramolecular arylation of C(sp 3 ) À Hb onds in the presence of Pd catalyst. [18] Furthermore,aMn-catalyzed C À Halkynylation method is developed for late-stage peptide modification and macrocyclization.…”

C−H Functionalization of Indoles by 3d Transition‐Metal Catalysis

“…Many base metal‐catalyzed alkynylation reactions are mostly limited to the use of activated alkynes containing a silyl protecting group, which increases two additional steps of protection and deprotection. To avoid these limitations, Ackermann and co‐workers reported the first Mn(I)‐catalyzed C−H alkynylation of indoles with aryl and alkyl‐substituted alkynyl halides (Scheme ) . In this report, authors accomplished the alkynylation reaction by using MnBr(CO) 5 metal precursor along with BPh 3 as a Lewis‐acidic additive.…”

Late‐Stage Diversification through Manganese‐Catalyzed C−H Activation: Access to Acyclic, Hybrid, and Stapled Peptides

“…[7] Thus,n oble-metal palladium and ruthenium catalysts have set the stage for versatile peptide diversification, as reported by the groups of Lavilla/Albericio, [8] Corey, [9] Chen, [10] Daugulis, [11] Shi, [12] Yu, [13] and Ackermann, [14] among others. [20] As part of our program on sustainable CÀHactivation, [21] we now report on the first manganese-catalyzed CÀHa llylation of structurally complex peptides with easily accessible Morita-Baylis-Hillman adducts.N otable features of our strategy include 1) an unprecedented manganese(I)-catalyzed peptide C À Ha lkylation, 2) the first metal-catalyzed peptide modifications that install synthetically useful a,b-unsaturated esters, 3) orthogonal late-stage diversification, and 4) au niquely versatile manganese catalyst that proved applicable to CÀH fusion with peptides,n atural products,s teroids,d rug molecules,a nd nucleobases,among others ( Figure 1). [20] As part of our program on sustainable CÀHactivation, [21] we now report on the first manganese-catalyzed CÀHa llylation of structurally complex peptides with easily accessible Morita-Baylis-Hillman adducts.N otable features of our strategy include 1) an unprecedented manganese(I)-catalyzed peptide C À Ha lkylation, 2) the first metal-catalyzed peptide modifications that install synthetically useful a,b-unsaturated esters, 3) orthogonal late-stage diversification, and 4) au niquely versatile manganese catalyst that proved applicable to CÀH fusion with peptides,n atural products,s teroids,d rug molecules,a nd nucleobases,among others ( Figure 1).…”