Rhodium-Catalyzed Regioselective C3Ar Functionalization of Tyrosines with Maleimides and Its Late-Stage Peptide Exemplification.

Pyridyloxy-directed Rh(III)-catalyzed regioselective C3Ar-H alkenylation of protected tyrosines was achieved with N-aryl and N-alkyl maleimides, furnishing a series of maleimide-appended tyrosine-based unnatural amino acids in good yields. Further, the late-stage exemplification of the strategy was successfully accomplished on tyrosine-containing dipeptides, tripeptides, and tetrapeptides in moderate reactivity. Also, the chemical applications of the strategy were successfully executed toward nailing tyrosine with other amino acids via a maleimide linker and intramolecular hydroarylation to produce tyrosine-centered stapled products and succinimide-glued macrocyclized products, respectively.

Synthesis of modified bile acids via palladium-catalyzed C(sp3)-H (hetero)arylation.

A Pd(II)-catalyzed strategy for the diastereo- and regioselective (hetero)arylation of unactivated C(sp3)-H bonds in bile acids is accomplished with aryl and heteroaryl iodides under solvent-free conditions using the 8-aminoquinoline auxiliary as a directing group. This methodology demonstrated excellent functional group tolerance with respect to aryl/heteroaryl iodides on O-protected N-(quinolin-8-yl)cholyl/deoxycholyl amides to afford ß-C(sp3)-H (hetero)arylated products in good-to-excellent yields. Moreover, the 8-aminoquinoline (AQ) auxiliary can easily be removed to obtain modified bile acids.

Ruthenium-catalyzed (spiro)annulation of N-aryl-2,3-dihydrophthalazine-1,4-diones with quinones to access pentacyclic spiro-indazolones and fused-cinnolines.

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, as well as the use of a ruthenium catalyst for such (spiro)annulative strategies with quinones over reported Rh/Ir-catalyts, underline the rewards of the disclosed protocols.

Regiodivergent Synthesis of Cinnoline-Fused Indazolones through Pd-Catalyzed Annulation of 1-Arylindazolones with Allenoates.

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.