C–H Bond Alkylation of Cyclic Amides with Maleimides via a Site-Selective-Determining Six-Membered Ruthenacycle

Abstract

The first example of a ruthenium-catalyzed C-H bond alkylation via six-membered ruthenacycles is presented. This is disclosed for the C-H bond alkylation of biologically relevant cyclic amides with maleimide derivatives. The cyclic tertiary amide core acted as a directing group (DG) enabling formation of six-membered cycloruthenated species responsible for the control of the regio-and site-selectivity of the reaction as well as the excellent functional group tolerance. Unexpectedly, cyclic amides were found to be better DGs than pyridine-containing ones or cyclic imides for this type of C-H bond functionalization.

Ruthenium(II)‐Catalyzed C−H Alkenylation of 1,8‐Naphthalimide with Cyclic Imide as a Weakly Coordinating Directing Group

“…Remarkably, cyclohexyl ring at N ‐position of naphthalimide also participated well in the reaction to give good yields for monosubstituted and disubstituted products ( 3 m – 3 p ; 66–77%). Surprisingly, the alkenylation was proceeded regioselectively at the 1,8‐naphthalimide ring instead of N ‐phenyl, thus favored five membered Ru‐complex with 1,8‐naphthalimide ( 3 q – 3 t ; 61–74%) [15a,22] . However the introduction of heteroaryl group such as pyrazine and pyrimidine rings at N ‐position of 1,8‐naphthalimide ring leads to only 5 to 10% conversion.…”

“…MS (ESI): m/z calculated for C 32 H 31 NO 6 [M + 1] + 526. 22,found 526.22. Anal Calcd: C,73.13;H,5.95;N,2.66.…”

Iridium(I)-Catalyzed Isoindolinone-Directed Branched-Selective Aromatic C–H Alkylation with Simple Alkenes

“…All the ligands were purchased from Strem Chemicals and were used as received. All starting materials 1a–p were prepared according to literature methods [ 22 , 23 , 24 ].…”

“…Recently, Gramage-Doria and coworkers successfully realized the site-selective C–H functionalization of N -arylisoindolinones by employing ruthenium catalysis. With aryl boronic acids, maleimides or activated alkenes such as α,β-unsaturated alkenes or styrenes as the functionalizing agents ( Scheme 1 A), the ortho C–H functionalization of the N -aryl ring was achieved with high efficiency [ 21 , 22 , 23 ]. Inspired by these advances, we decided to develop new types of C–H functionalization strategies by focusing on the biologically relevant N -arylisoindolinone motif.…”

Steering Site‐Selectivity in Transition Metal‐Catalyzed C−H Bond Functionalization: the Challenge of Benzanilides

“…Ruthenium catalysts enabling C−H bond alkylations in the anilide ring of benzanilides are also scarce. For instance, N ‐substituted maleimides were found to react with N ‐arylisoindolinones giving rise to the product resulting from C−H bond ortho ‐alkylation in the anilide ring (Scheme ) . In a complementary strategy, it was shown that products resulting from C−H bond ortho ‐alkylation in the anilide ring can be prepared upon a sequence involving ruthenium‐catalyzed C−H bond alkenylation and palladium‐catalyzed hydrogenation (Scheme ) …”