Rh(III)-Catalyzed C7-Thiolation and Selenation of Indolines

Abstract

The rhodium(III)-catalyzed intermolecular C7-thiolation and selenation of indolines with disulfides and diselenides were developed. This protocol relies on the use of a removable pyrimidyl directing group to access valuable C-7 functionalized indoline scaffolds with ample substrate scope and broad functional group tolerance.

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“… 856 , 857 The thiolation of indolines was instead reported by Wang using Rh catalysis and stoichiometric amounts of Ag oxidant; even in this case, high temperatures had to be used. 858 More recently, two interesting reports were released by Ackermann and Glorius for the thiolation of indoles and indolines respectively. Glorius's approach focused on the use of aromatic thiols and Co( iii ) as catalyst, requiring the combined action of superstoichiometric Cu and BQ as oxidants ( Scheme 145A ).…”

Concise Total Syntheses of (+)-Haplocidine and (+)-Haplocine via Late-Stage Oxidation of (+)-Fendleridine Derivatives

“…Existing methods for introduction of the desired ortho -C–O bond in simple indolines require the use of toxic lead or thallium reagents and often give product mixtures. 35 Prompted by successful indoline ortho -C–H functionalizations to give C–C, 36 C–N, 37 C–Se, and C–S bonds, 38 we focused on development of the first transition metal catalyzed indoline ortho -C–H acetoxylation. Our most promising results involving palladium–catalyzed ortho -acetoxylation 39 of N -acetylindoline (±)- 22a as a model substrate are summarized in Table 2.…”

“…We posited that an unproductive N9-amine coordination to palladium may outcompete the N1- amide, consistent with the absence of basic nitrogens in substrates that efficiently undergo metal-catalyzed C–H functionalization. 33–38,42 Thus, we envisioned a strategy to deactivate the N9-amine by exploiting the reversible opening of the C19-hemiaminal ether of (+)-acetylaspidoalbidine ( 4 ). Heating hexacyclic alkaloid (+)- 4 in a mixture of acetic acid and acetic anhydride (10:1, v/v) at 100 °C for 6 h led to quantitative conversion to the corresponding C19-iminium acetate ester 26 (X=H, Scheme 6).…”

Cu‐Catalyzed Directed C7−H Imidation of Indolines via Cross‐Dehydrogenative Coupling

“…Formation of deuterium incorporated starting material (Scheme 4b, 4c) under deuterium scrambling experiment with CD 3 OD implies that there might be the involvement of a reversible CÀ H bond cleavage. [9] The result of the primary kinetic isotope effect studies (intermolecular and parallel, Scheme 4d, 4e) indicated that the CÀ H bond cleavage step was not the rate determining. We also found (Scheme 4f) that the electronically rich indolines are more reactive than the electronically poor substrates.…”

“…[6] In particular, the C7-substituted amino variants exhibiting diverse bioactivity profiles have received much attention (Scheme 1a). While a number of reports have demonstrated direct C7 functionalization of indolines largely for the construction of CÀ C bond via transition metal catalyzed chelation-assisted CÀ H activation, [7] only a handful number of reports on CÀ O [8] /S [9] /Se [9] and CÀ N [10] bond formation are known (Scheme 1b). Zhu et al for the first time disclosed a ruthenium-catalyzed method for the formation of CÀ N bond at the C7 of indolines using organic sulfonyl azides that have previously been used by Chang and other groups as CÀ H amidating reagent to various other scaffolds.…”