A Rh(III)-catalyzed strategy involving the [4+1] annulation of 2-arylphthalazine-1,4-diones with α-diazo carbonyl compounds was developed, accessing a series of unprecedented hydroxy-dihydroindazolo-fused phthalazines in good to excellent yields. By varying the additive, phthalazino-fused cinnolines were synthesized under Rh-catalyzed conditions via [4+2] annulation between the same starting materials. Notably, such two strategies showed a good functional group tolerance and high atom efficiency.

An Ir-catalyzed tandem strategy for the synthesis of indazolone-fused cinnolines by [4 + 2] annulation of 1-arylindazolones with α-diazo carbonyl compounds.

A mild Rh-catalyzed method was developed for the synthesis of hydroxyimino functionalized indazolo[1,2-a]cinnolines and phthalazino[2,3-a]cinnolines by reductive [4 + 2] annulation between 1-arylindazolones and 2-aryl-2,3-dihydrophthalazine-1,4diones with varied nitroolefins. The targeted oxime decorated tetracyclic fused cinnolines were synthesized via sequential C−H activation/olefin insertion/reduction under reducing-agent-free conditions.

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 phenyliodine(III) diacetate mediated umpolung reactivity of the tertiary amines with suitably substituted o-hydroxybenzyl and phenyl groups is exploited to facilitate o-C(sp)-H functionalization to afford diaryl ethers. The presence of an o-CHO and secondary amine functionalities in the resulting diaryl ether, generated in situ, were utilized for synthesis of dibenzoxazepines and dibenzoxazepinones. Mild conditions and relative broad substrate scope, and potential for further diversification of the diaryl ethers are highlights of this methodology.

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

Ru(II)-catalyzed strategies were developed for the [4+1] and [4+2] oxidative coupling between N-aryl-2,3-dihydrophthalazine-1,4-diones and 1,4-benzoquinones, achieving spiro-indazolones and fused-cinnolines, respectively. Mild, aerobic and external oxidant-free conditions, and the use of...

Serendipitous and expedite transformation of 1-aryl- and 2-aryl-1,2-dihydro-3H-indazol-3-ones to 1,2-di(hetero)aryl- and 2,3-di(hetero)aryl-2,3-dihydroquinazolin-4(1H)-ones, respectively, was achieved in high efficiency by reacting them with aldehydic N-tosylhydrazones. The protocol proceeded through a cascade process involving base-mediated Pd-carbenoid generation by the decomposition of N-tosylhydrazones, nucleophilic attack of indazolone on the Pd-carbenoid complex, and intramolecular ring expansion via N–N bond cleavage. The utility of the strategy is demonstrated toward the synthesis of bioactive NPS 53574, a calcium receptor antagonist.