Solid Phase Approaches to N-Heterocycles Using a Sulfur Linker Cleaved by SmI₂

Abstract

A sulfur HASC (alpha-hetero-atom substituted carbonyl) linker has been utilized in solid-phase approaches to oxindoles and tetrahydroquinolones. The route to oxindoles employs the first Pummerer cyclizations on solid phase, whereas the route to tetrahydroquinolones involves a microwave-assisted Heck reaction followed by a Michael cyclization. In both cases, the linker is cleaved in a traceless fashion by electron transfer from samarium(II) iodide. The routes illustrate the compatibility of the linker system with a number of reaction types and its utility for library synthesis.

Discovery of Novel Acetamide-Based Heme Oxygenase-1 Inhibitors with Potent In Vitro Antiproliferative Activity

“…Compounds 5l – m , 6a – d , 6f – h , 7a , 7f , 8o , 9l , and 10 have been reported in the literature, and characterization data matched those reported. 41 − 50 …”

Mizoroki–Heck Reactions: Modern Solvent Systems and Reaction Techniques

“…For easy catalyst recovery, solid-supported systems were often used. An α-heteroatom-substituted carbonyl linker has been utilized in solid-phase approaches to oxinolines by Pummerer cyclization [206]. The reaction performed with s/c = 20 in the presence of phosphine ligands (ratio ligand/palladium-precursor = 1 : 1) in 88-99% yield at 7 h reaction time.…”

Asymmetric Synthesis of Crispine A: Constructing Tetrahydroisoquinoline Scaffolds Using Pummerer Cyclizations

“…Finally, reductive radical elimination of the thiophenyl group using Bu 3 SnH and cat. AIBN in toluene at refluxing conditions yielded target compound R (+)‐crispine A in excellent yield (Scheme ) 21. The analytical and spectroscopic data of the obtained product was identical to those of the natural product2 with optical rotation [ α ] D 25 = +93 ( c = 1, CHCl 3 ) [Reported2 [ α ] D 25 = +91 (MeOH)].…”