Iodocarbocyclization Reaction of β-Ketoesters and Alkynes

Abstract

Iodocyclopentenes are formed at room temperature upon straight reaction of delta-alkynyl-beta-ketoesters with I2 for several hours. Cyclizations involving terminal and substituted (alkyl, aryl, Br, I) alkynes were accessed. Twelve examples with yields ranging from 20% up to 80% are reported (out of them eight cases are above 60%). These results present the first examples of the iodonium-promoted 5-endo-dig carbocyclization of active methyne substrates onto alkynes.

When gold can do what iodine cannot do: A critical comparison

“…Notably, Toste and co-workers also reported a valuable gold-catalyzed enantioselective variant of the Conia-ene reaction between ß-dicarbonyl compounds and alkynes [107]. Barluenga and co-workers successively developed a 5-endo approach to the iodocarbocyclization between ß-keto esters and non-terminal alkynes (Scheme 13) [108]. Initially, 1,2-addition of iodine to alkynes such as 45 proved problematic, which was resolved by decreasing the molarity of the iodine in CH 2 Cl 2 from 0.3 M to 0.05 M. This favored the cyclization process and eliminated competing reaction pathways.…”

Molecular Iodine-Mediated Cyclization of Tethered Heteroatom-Containing Alkenyl or Alkynyl Systems

“…In another development involving iodine–mediated cyclization, a series of δ-alkynyl-β-ketoesters 85 were reacted with iodine in dichloromethane at room temperature for several hours ( Scheme 31 ) [ 57 ]. This 5- endo-dig mode of carbocyclization of active methylene compounds 85 onto terminal and internal alkynes led to novel iodocyclopentenes 86 in 20–80% yield.…”

Halogens and noble gases

“…In the first examples of iodonium promoted 5endo-dig carbocyclization of active methylene groups onto alkynes, d-alkynyl-bketoesters affords iodocyclopentenes upon treatment with iodine in CH 2 Cl 2 . 20 Iodine has also been demonstrated to effect the high-yield oxidation of primary alcohols and primary, secondary and tertiary amines to the corresponding nitriles in liquid ammonia. 21…”