Base-Mediated Regio- and Stereoselective Intermolecular Addition of Alkynes to N-Heterocycles

Abstract

The regio- and stereoselective addition of N-heterocycles to alkynes using KOH is reported. Formation of (Z)-isomers and their conversion to (E)-products were found to be dependent upon time as well as the choice of base. Selective attack of N-heterocycles on a more electrophilic alkynyl carbon was supported by DFT calculations, and the stereochemistry of the products was established by X-ray crystallographic studies and intramolecular cyclization of ortho-haloalkynes in indolo-[2,1-a]isoquinolines.

Chemoselective Synthesis of Unsymmetrical Internal Alkynes or Vinyl Sulfones via Palladium‐Catalyzed Cross‐Coupling Reaction of Sodium Sulfinates with Alkynes

“…1,2‐Di‐ para ‐tolylethyne (3aa): 17 White solid; mp 126–127 °C; 1 H NMR (400 MHz, CDCl 3 ): δ =7.42 (d, J =8.0 Hz, 2 H), 7.15 (d, J =8.0 Hz, 2 H), 2.37 (s, 3 H); 13 C NMR (100 MHz, CDCl 3 ): δ =138.2, 131.4, 129.1, 120.4, 88.9, 21.5; IR (KBr): ν =3064, 2924, 1647, 1513, 1454, 815, 747 cm −1 ; MS (EI): m / z =206, 191, 165, 115, 102, 89.…”

“…1‐Methoxy‐4‐(phenylethynyl)benzene (3bb): 17 Yellow solid; mp 58–60 °C; 1 H NMR (400 MHz, CDCl 3 ): δ =7.52–7.50 (m, 2 H), 7.48 (d, J =8.5 Hz, 2 H), 7.39–7.28 (m, 3 H), 6.89 (d, J =8.5 Hz, 2 H), 3.83 (s, 3 H); 13 C NMR (100 MHz, CDCl 3 ); δ =159.6, 133.0, 131.4, 128.3, 127.9, 123.6, 115.4, 114.0, 89.4, 88.1, 55.3; IR (KBr): ν =3064, 2928, 1601, 1510, 1441, 1250, 1179, 1029, 834, 754 cm −1 ; MS (EI): m / z =208, 193, 165, 139, 104, 77.…”

2‐(1‐Benzotriazolyl)pyridine: A Robust Bidentate Ligand for the Palladium‐Catalyzed CC (Suzuki, Heck, Fujiwara–Moritani, Sonogashira), CN and CS Coupling Reactions

“…Thiophene halide 1e , on coupling with 8c , afforded the tetra‐alkynylated coupling product 9g in 60% yields (entry 7). Compounds 9e , 9f and 9 g are useful synthetic intermediate and can be further used for metal‐catalyzed tandem reactions23a,b and Bergman cyclizations 33…”

Nucleophilic Addition versus SNAr Study: Chemo‐, Regio‐ and Stereoselective Hydrothiolation of Haloaryl Alkynes over S‐Arylation of Aryl Halides

“…Base‐promoted nucleophilic addition of N‐ and S‐nucleophiles onto alkynes has attracted considerable interest in recent years because such type of reactions lead to the formation of C(sp 2 )‐N, and C(sp 2 )‐S bonds from economical and commercially available chemicals without using expensive metal catalysts, and with excellent regio‐ and stereoselectivity . The groups of Knochel,– Ackermann,– Zhang, Stradiotto, and our group– have investigated the application of hydroamination chemistry in the synthesis of various N‐heterocycles using transition metals. Recently Trofimov and co‐workers and we– have explored the superbasic system (KOH/DMSO) with an unusual basicity ( p K a =30–32) for nucleophilic additions of N‐heterocycles onto alkynes.…”