Catalytic Enantioselective Halolactonization of Enynes and Alkenes

• Published in: Chemistry : a European journal 2012-06, Vol.18 (23), p.7296-7305
• Main Authors: Zhang, Wei, Liu, Na, Schienebeck, Casi M., Decloux, Kyle, Zheng, Suqing, Werness, Jenny B., Tang, Weiping
• Format: Article
• Language: English
• Subjects: Alkadienes - chemistry; Alkaloids; Alkenes; Alkynes - chemistry; allenes; Bromine - chemistry; Catalysis; Catalysts; Chemistry; Combinatorial Chemistry Techniques; Cyclization; enynes; Halogens; halolactonization; Lactones - chemistry; Models, Chemical; Molecular Structure; Nucleophiles; Olefins; organocatalysts; Stereoisomerism; Ureas
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201103809

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. Wearing a halo: New organocatalysts have been developed for the enantioselective 1,4‐syn‐bromolactonization of conjugated (Z)‐1,3‐enynes and the 1,2‐chlorolactonization of 1,1‐disubstituted alkenes (see scheme). Up to 99 and 91 % ee values, respectively, were achieved for these two halolactonizations.