Water as a Hydride Source in Palladium‐Catalyzed Enantioselective Reductive Heck Reactions

Abstract

Pd-catalyzed intramolecular asymmetric carbopalladation of N-aryl acrylamides followed by reduction of C(sp 3 )-Pd intermediate using diboron-water as ah ydride source afforded enantioenriched 3,3-disubstituted oxindoles in high yields and enantioselectivities.W hen heavy water was used as ad euterium donor in combination with bis(catecholato)diboron (Cat 2 B 2 ), deuterium was incorporated into the products with high synthetic efficiency.The ligand determined both the enantioselectivity of the reaction and the reaction pathways, therebya ffording either hydroarylation (reductive Heck)o rcarboborylation products. Scheme 1. Pd-catalyzed reductive Heck reaction.[*] Dr.

Enantioselective Dearomative Difunctionalization of Indoles by Palladium‐Catalyzed Heck/Sonogashira Sequence

“…Besides,a ne nantioselective vinylborylation of alkenes was recently developed by Tong and coworkers. [4d] In spite of this progress, [5] one-step construction of vicinal stereocenters,b yc apturing the secondary s-alkylpalladium species,r emains underdeveloped. [6] Moreover,t he development of other types of trapping agents to terminate an asymmetric Heck reaction is highly desirable.…”

“…Slightly lower enantioselectivities were observed when [Pd(dba) 2 ]w as replaced by either Pd(CH 3 CN) 2 Cl 2 or Pd(OAc) 2 (entries 3a nd 4). Subsequent ligand examination revealed that the amino substituent of BINOL-based phosphoramidite ligands significantly influenced the enantioselectivity (entries [5][6][7][8][9][10][11][12][13][14]. Increasing the size of the amino substituent could improve the enantioselectivity.T he diisopropyl amino ligand L3 led to 84 %y ield and 62 % ee,w hile relatively lower ee values were achieved for L2 and L4, bearing benzyl and n-butyl substituents,r espectively (entries 5-7).…”

“…Excellent enantioselectivities for the products 3a30 and 3a35 were achieved with 3,3-dimethylbut-1-yne and ethynyltrimethylsilane as substrates.Gratifyingly,indolines bearing acetal (3a29), chloride (3a32), alcohol (3a33, 3a34), and propene (3a36)were isolated in moderate yields and good to excellent enantioselectivities for the reactions with the corresponding aliphatic alkynes.The reaction of apropargylic imide with 1a led to the product 3a31 in 50 %y ield and 91 % ee,a nd the absolute configuration was determined to be 10R/11S based on its single-crystal X-ray analysis. [11] Finally,n onterminal alkynes [3-phenylpropiolic acid (4)a nd 2-methyl-4-phenylbut-3-yn-2-ol (5)] were also tested in the reaction (Scheme 3). Thep roduct 3a1 was obtained in either lower yield or lower ee,probably because of the poor solubility of the acid 4 in the solvent, and the background reactions without chiral ligand in both cases.…”

Enantioselective Dearomative Difunctionalization of Indoles by Palladium‐Catalyzed Heck/Sonogashira Sequence

“…[2] In sharp contrast, the corresponding asymmetric reactions are rather limited. [4d] In spite of this progress, [5] one-step construction of vicinal stereocenters,b yc apturing the secondary s-alkylpalladium species,r emains underdeveloped. Besides,a ne nantioselective vinylborylation of alkenes was recently developed by Tong and coworkers.…”

“…Subsequent ligand examination revealed that the amino substituent of BINOL-based phosphoramidite ligands significantly influenced the enantioselectivity (entries [5][6][7][8][9][10][11][12][13][14]. Surprisingly,t he addition of CuI (5 mol %) as ac o-catalyst fully suppressed the reaction (entry 2).…”