Solid-Phase Approach to Tetrahydroquinolones Using a Sulfur Linker Cleaved by SmI₂

Abstract

[reaction: see text] A sulfur alpha-heteroatom-substituted carbonyl (HASC) linker has been utilized in a solid-phase approach to tetrahydroquinolones. The route illustrates the compatibility of the linker system with palladium-catalyzed transformations and its utility for library synthesis. The linker is cleaved by electron transfer from samarium(II) iodide.

Enantioselective palladium(0)-catalyzed intramolecular cyclopropane functionalization: access to dihydroquinolones, dihydroisoquinolones and the BMS-791325 ring system

“…Dihydroquinolones are common structures among natural products and bioactive compounds. 11 Cyclopropyl substituted congeners are not oxidizable to the corresponding aromatic quinolones. A rapid C–H functionalization access to this compound class would represent a significant advantage compared to the N -triflyl tetrahydroquinoline product range.…”

Lanthanide reagents in solid phase synthesis

“…In this case LiCl is used to increase the reducing ability of the lanthanide reagent (Scheme 29). 34 In the same study, we have illustrated the feasibility of a cyclative-cleavage strategy using the linker family. 34 Treatment of immobilised sulfone 56 with SmI 2 results in cleavage and cyclisation to give tetrahydroquinoline 57.…”

“…34 In the same study, we have illustrated the feasibility of a cyclative-cleavage strategy using the linker family. 34 Treatment of immobilised sulfone 56 with SmI 2 results in cleavage and cyclisation to give tetrahydroquinoline 57. This cyclisation may proceed by either a radical or anionic mechanism (Scheme 30).…”

“…We have also used the sulfur linker in a route to tetrahydroquinolones that involves a microwave-assisted Heck reaction followed by a Michael cyclisation. 34 At the end of the sequence, tetrahydroquinolines such as 55 are released from the polymer support by reduction of intermediate sulfones 54 with SmI 2 . In this case LiCl is used to increase the reducing ability of the lanthanide reagent (Scheme 29).…”

From Polymer to Small Organic Molecules: A Tight Relationship between Radical Chemistry and Solid-Phase Organic Synthesis

“…Heterocycle synthesis was performed following this strategy using a sulfur-linkage [ 21 , 22 , 23 ]. Benzylthiol resin 27 was prepared from Merrifield resin, treated with the appropriate α-bromoacetamide and oxidized ( Scheme 9 ).…”