Effects of solvents and water in Ti(III)-mediated radical cyclizations of epoxygermacrolides.: Straightforward synthesis and absolute stereochemistry of (+)-3α-hydroxyreynosin and related eudesmanolides

被引:97
作者
Barrero, AF [1 ]
Oltra, JE [1 ]
Cuerva, JM [1 ]
Rosales, A [1 ]
机构
[1] Univ Granada, Fac Sci, Dept Organ Chem, E-18071 Granada, Spain
关键词
D O I
10.1021/jo016277e
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
The Cp2TiCl-mediated rearrangement of 1,10-epoxy-11beta,13-dihydrocostunolide (4) was carried out using different solvents and additives to develop an expeditious procedure for the synthesis of natural eudesmanolides via free-radical chemistry. In the nonhalogenated solvents THF, berizene, and toluene the transannular cyclization, initiated by the homolytic opening of the oxirane ring, selectively led to the desired exocyclic alkene 5. When water was added to THF, however, the main product was reduced eudesmanolide S. Experiments with D2O confirmed that the H-4 of 8 comes from water. To rationalize these results, a mechanistic hypothesis based on a water-solvated Cp-2-TiCl complex is proposed. Finally, the usefulness Of Cp-2-TiCl for the Synthesis of natural eudesmanolides has been proved using this reagent in the key step for the chemical preparation of (+)-3alpha-hydroxyreynosin (1) and (+)-reynosin (17). These syntheses confirmed the chemical structure of 1 and established the absolute stereochemistry of the natural products I and 17. The results obtained suggest that the combination of the biomimetic strategy employed, with Ti(III)-mediated free-radical chemistry, may come to represent a general method for the enantiospecific synthesis of more than 170 natural eudesmanolides containing an exocyclic double bond between C-4 and C-15.
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页码:2566 / 2571
页数:6
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