Rhodium(III)‐Catalyzed Amidation of Unactivated C(sp³)H Bonds

Abstract

Nitrogenation by direct functionalization of CÀH bonds represents an important strategy for constructing C À N bonds.R hodium(III)-catalyzed direct amidation of unactivated C(sp 3 ) À Hb onds is rare,e specially under mild reaction conditions.H erein, ab road scope of C(sp 3 )ÀHb onds are amidated under rhodium catalysis in high efficiency using 3-substituted 1,4,2-dioxazol-5-ones as the amide source.T he protocol broadens the scope of rhodium(III)-catalyzed C(sp 3 ) À Ha ctivation chemistry,a nd is applicable to the latestage functionalization of natural products. Scheme 4. CÀHa midation of other aliphaticO -methylk etoximes. Reaction conditions: 1( 0.2 mmol), 2m (0.21 mmol), AgOPiv (32 mol %), [{RhCp*Cl 2 } 2 ](4mol %), AgSbF 6 (16 mol %), DCE (3.0 mL), 80 8 8C, 12 h, sealed tube under nitrogen. Yield is that of product isolateda fter column chromatography.[a] Reaction was performed with AgOAc (8 mol %) in CH 2 Cl 2 at 25 8 8C. [b] Reaction was performed with AgOAc (8 mol %) in CH 2 Cl 2 at 80 8 8C.Scheme 5. Late-stage C(sp 3 )ÀHa midation. Reaction conditions: 1o (0.2 mmol), 2( 0.21 mmol), AgOPiv (32 mol %), [{RhCp*Cl 2 } 2 ] (4 mol %), AgSbF 6 (16 mol %), DCE (3.0 mL), 80 8 8C, 12 h, sealed tube under nitrogen. Yield is that of product isolated after column chromatography.[a] Reaction was performed with 2 (0.24 mmol), AgOPiv (8 mol %), CH 2 Cl 2 at 60 8 8C.Scheme 6. Deprotection of C(sp3)ÀHamination products.Scheme 7. Mechanistic studies.

Facile Synthesis of Chiral Arylamines, Alkylamines and Amides by Enantioselective NiH‐Catalyzed Hydroamination

“…Subsequent stereospecific NÀO bond insertion with one of the N-coupling partners followed by reductive elimination would produce an enantioenriched a-chiral amine product. [13][14][15] Herein, we report the first example of an NiH-catalyzed asymmetric reductive hydroamination reaction. Instead of the complex, expensive, multistep-synthesized chiral phosphine ligands associated with CuHcatalyzed hydroamination, only a simple and easily synthesized chiral N,N-bioxazoline ligand is employed as the source of chirality in this mild and robust protocol.…”

Facile Synthesis of Chiral Arylamines, Alkylamines and Amides by Enantioselective NiH‐Catalyzed Hydroamination

“…Subsequent stereospecific NÀO bond insertion with one of the N-coupling partners followed by reductive elimination would produce an enantioenriched a-chiral amine product. [13][14][15] Herein, we report the first example of an NiH-catalyzed asymmetric reductive hydroamination reaction. Instead of the complex, expensive, multistep-synthesized chiral phosphine ligands associated with CuHcatalyzed hydroamination, only a simple and easily synthesized chiral N,N-bioxazoline ligand is employed as the source of chirality in this mild and robust protocol.…”

Dithiane-directed Rh(iii)-catalyzed amidation of unactivated C(sp3)–H bonds

“…Only a handful of examples exist for the activation of reactive C(sp 3 )–H bonds such as at acidic, allylic or benzylic positions 10. Regarding unactivated C(sp 3 )–H bonds, the high C–H bond strength, steric hinderance and low reactivity of the resulting Rh–C(alkyl) species are significant challenges which have only recently been reduced to practice by the seminal reports of You and Li 11. Both these reports have made a significant advancement to the field,12 but their use of strongly coordinating pyridyl and ketoxime functionality also highlights the need for identification of alternative directing groups which can be easily installed, cleaved, and enable synthetically useful downstream functionalization.…”