Catalytic Enantioselective Halolactonization of Enynes and Alkenes

Abstract

New organocatalysts have been developed for the enantioselective halolactonization of (Z)-1,3-enynes and 1,1-disubstituted alkenes. In the case of 1,3-enynes, the carboxylate nucleophile and halogen electrophile were added to the conjugated π-system from the same face. Up to 99% ee was achieved for the 1,4-syn-bromolactonization of conjugated (Z)-1,3-enynes. Based on the results from the enyne halolactonization, a second generation of catalysts was designed for simple olefins. Up to 91% ee was observed for chlorolactonization of 1,1-disubstituted alkenes. The catalysts developed for the enantioselective halolactonization of both enynes and alkenes are composed of a cinchona alkaloid skeleton tethered to a urea group.

Toward Catalytic, Enantioselective Chlorolactonization of 1,2-Disubstituted Styrenyl Carboxylic Acids

“…21 Substrate 1 undergoes highly selective chlorolactonization at room temperature with only 5 mol % catalyst loading using 1,3-dichlorodimethylhydantoin (DCDMH) as a chlorenium source (Scheme 3, eq 1). The authors propose an activation of halogenating reagent by hydrogen bonding with the catalyst.…”

Highly Enantioselective Bromocyclization of Allylic Amides with a P/P=O Double‐Site Lewis Base Catalyst

“…In contrast, the counterpart with an electron‐rich para ‐methyl substituent gave the product 2 m in high yield and enantioselectivity (Scheme c). When cyclohexene‐substituted enyne 1 n was used, regioselective bromination occurred on the proximal olefin to the amide functionality, furnishing the corresponding oxazoline 2 n in 78 % ee (Scheme d) …”

Alkynes in Organocatalysis

“…The reaction is catalyzed by the bifunctional catalyst VII, which promotes the 1,4-syncyclization and the subsequent formation of enantiomerically enriched bromoallenes 13. [16] This reaction can be successfully applied to (Z)-1,3-enynes bearing either an aliphatic carboxylic acid or a substituted benzoic acid.…”