α-Hydroxy Cyclopentenones from α-Diketones

Author:

Batson William A.1,Sethumadhavan Divakaramenon1,Tius Marcus A.1

Affiliation:

1. Department of Chemistry, 2545 The Mall, University of Hawaii, Honolulu, Hawaii 96822, and The Cancer Research Center of Hawaii, 1236 Lauhala Street, Honolulu, Hawaii 96813

Publisher

American Chemical Society (ACS)

Subject

Organic Chemistry,Physical and Theoretical Chemistry,Biochemistry

Reference20 articles.

1. General Procedure for the LiTMP-Mediated Cyclization.A solution of LiTMP (0.5 M, 1.1 equiv) was prepared by the addition ofn-BuLi to TMP in THF at 0 °C. The solution was kept at 0 °C for 0.5 h and then was cooled to −78 °C. During this time, the α-diketone was dissolved in THF (0.1 M) and allowed to stand over activated 4 Å molecular sieves for 0.5 h under nitrogen. The dry α-diketone was quickly added to the cold stirring solution of LiTMP via cannula at −78 °C. The reaction mixture was allowed to warm to room temperature over 15 min and was allowed to stir until the reaction was complete, as judged by TLC (ca. 2−24 h). The reaction mixture was cooled to 0 °C, 1 M HCl was added, and the aqueous phase was extracted with Et2O. The organic phase was dried (MgSO4), concentrated and purified by flash column chromatography over silica gel (5% EtOAc/hexanes) to afford the α-hydroxycyclopentenone.

2. General Procedure of the Yb(OTf)3-Mediated Cyclization.The α-diketone and Yb(OTf)3were dissolved in DMSO (0.04−0.1 M) at room temperature under nitrogen. To this solution was added pyrrolidine (1 equiv), and the reaction mixture was allowed to stir at room temperature until the reaction was judged to be complete by TLC (ca. 6−24 h). The solution was diluted with water and the aqueous phase was extracted with Et2O. The organic phase was dried (MgSO4), concentrated, and purified by flash column chromatography over silica gel (5% EtOAc/hexanes) to afford the α-hydroxycyclopentenone.

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