Ruthenium‐Catalyzed Sulfoalkenylation of Acetanilides and Dual‐Use of the Catalyst Directing Group

Abstract

In contrast to vinylsulfonates and vinylsulfones, vinylsulfonamides are unreactive in Pd‐catalyzed oxidative Heck‐coupling reactions with acetanilides. This limitation has been resolved by using a C−H‐activation protocol based on Ru−Cu−Ag‐catalysis. Overall, the Ru−Cu−Ag‐catalyzed conditions turned out to be more reliable and showed better reproducibility than the Pd‐catalyzed C−H‐activation. The coupling products thus obtained are functionalized styrenyl sulfones and –sulfonamides which can be used as starting materials for the synthesis of sulfonyl pyrroles and sulfonyl pyrrolo[2,3‐c]quinolines.

Orthogonal Arylation of a Diene‐Sulfonamide Using Cationic Transition Metal Catalysts

“…We have previously found that the Ru-catalyzed CÀ H-activation conditions developed by the groups of Ackermann [28] and Jeganmohan [29] can be used for alkenylation reactions of acetanilides with a tertiary ethenesulfonamide. [17] To investigate whether these conditions allow the efficient differentiation between the electron rich and electron deficient double bond in our test diene, we reacted sulfonamide 6 and acetanilide (11 a) in a 2 : 1 ratio in the presence of [Ru(p-cymene)Cl 2 ] 2 , Cu(OAc) 2 • H 2 O and AgSbF 6 in refluxing 1,2-dichloroethane. A single product was isolated that could be identified as sulfonamide 12 a from its 1 H NMR spectrum.…”

“…We applied a slightly modified protocol to the oxidative coupling of acetanilides with phenylvinylsulfone (H 2 C=CHSO 2 Ph) and ethyl ethenesulfonate (H 2 C=CHSO 2 OEt), [16] but found that secondary (H 2 C=CHSO 2 NHBn) and tertiary sulfonamides (H 2 C=CHSO 2 N(CH 3 )Bn) do not react under these conditions. Given the particular importance of the sulfonamide group for medicinal chemistry issues, we strove to close this gap and found that a catalyst system originally introduced by the groups of Ackermann [28] and Jeganmohan [29] that consists of [RuCl 2 (p‐cymene)] 2 , Cu(OAc) 2 ⋅ H 2 O and AgSbF 6 also enables the oxidative ortho ‐alkenylation of acetanilides with the tertiary ethene sulfonamide mentioned above [17] . A survey of reviews [30–39] and original literature [40–45] on Ru‐catalyzed C−H‐activating alkenylations reveals that mostly “activated”, i.e.…”

“…[15] In a parallel investigation we examined oxidative alkenylations of acetanilides using the same sulfonyl substituted ethenes. [16][17] Such reactions, often referred to as Fujiwara-Moritani-reaction, [18][19] proceed via CÀ H-activation of arenes [20][21][22][23][24] and are initiated by attack of an electrophilic transition metal catalyst at the electron-rich arene. In most cases catalyst directing groups are required to achieve satisfactory regioselectivity.…”

“…Given the particular importance of the sulfonamide group for medicinal chemistry issues, we strove to close this gap and found that a catalyst system originally introduced by the groups of Ackermann [28] and Jeganmohan [29] that consists of [RuCl 2 (p-cymene)] 2 , Cu(OAc) 2 • H 2 O and AgSbF 6 also enables the oxidative ortho-alkenylation of acetanilides with the tertiary ethene sulfonamide mentioned above. [17] A survey of reviews [30][31][32][33][34][35][36][37][38][39] and original literature [40][41][42][43][44][45] on Ru-catalyzed CÀ Hactivating alkenylations reveals that mostly "activated", i.e. electron deficient olefins, in particular acrylates are used in these alkenylations.…”