A tender-hearted Pd­(II)-catalyzed C–H activation of 1-arylindazolones followed by an oxidative [4 + 2] annulation reaction has been accomplished, engaging allenoates as annulating partners. Using this strategy, two different regioisomeric forms of cinnoline-fused indazolones possessing internal and exocyclic double bonds were synthesized in acetic acid and dioxane, respectively. Mild and aerobic conditions, avoiding the use of any metal–oxidant, highlights the rewards of this oxidative annulation protocol.

A Rh(III)-catalyzed [5+2] annulation of vinyl tyrosines with symmetrical and unsymmetrical internal alkynes was achieved, furnishing a series of oxepine-mounted tyrosine-based unnatural amino acids. In addition, the chemical applicability of the developed strategy was exemplified by stapling amino acid/peptide-appended alkynes with vinyl tyrosines and late stage functionalization of tyrosine-containing dipeptides and tripeptide with internal alkynes. P roteins perform differentiated functions such as metabolic reaction catalysis, DNA replication, stimulus response, and transportation of molecules in living organisms. 1 Though genetic code expansion of natural amino acids results in the synthesis of most proteins, yet co-translational amalgamation of a few unnatural amino acids (UAAs) into proteins offers unprecedented site-specific protein manipulation ability in living systems. 2 The incorporation of UAAs into a protein of interest (POI) thus provides access to modified natural biologics that could be used in applied areas such as proteomics, diagnostics, asymmetric syntheses, and drug delivery. 3 In addition, unnatural amino acids and their resulting peptides are found to be stable toward proteolytic enzymes, populating exclusive conformational space with distinct bioactivities. 4 Accordingly, focused efforts have been devoted in the recent past to synthesize designer UAAs via α-C(sp 3 )−H, β-C(sp 3 )− H, γ-C(sp 3 )−H, δ-C(sp 3 )−H, and C(sp 2 )−H bond functionalization under metal-catalyzed conditions to furnish UAAs. 5 Interestingly, the crucial importance of tyrosine in protein sequences and the presence of a phenolic functionality have provided an appealing tunable site for selective functionalization and assembling heterocyclic architectures with the aid of appropriate coupling partners. 6 Under this domain, a few C(sp 2 )−H bond functionalization strategies at the C-2 and/or C-3 position(s) on the aryl moiety in tyrosine and tyrosinecontaining peptides, including alkenylation, 7 acylation, 8 iodination, 9 arylation, 10 and recently disclosed acyloxylation, 11 have been successfully achieved via C−H activation (Scheme 1a). However, efficient strategies involving mounting a

Regioselective C-arylation and C,N-diarylation in 2-aryl-2,3-dihydrophthalazine-1,4-diones have been successfully accomplished with diaryliodonium salts under base-mediated slightly modified Pd-catalyzed conditions. These ligand-driven transformations provided a variety of diversely decorated bi(hetero)aryls in good-to-excellent yields, while N-arylated product could be obtained under similar Pd-catalyzed conditions in absence of a ligand.