A stereospecific geminal alkylation scheme en route to CP-225, 917 and CP-263,114

Angewandte Chemie - International Edition

Volumn 37, Issue 13-14, 1998, Pages 1880-1882

  Kwon, Ohyun ^a   Su, Dai Shi ^b   Meng, Dongfang ^a,b   Deng, Wei ^b   D'Amico, Derin C ^a   Danishefsky, Samuel J ^a,b  

^a Havemeyer Hall ^*  (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

Alkylations; Natural products; Photooxidations; Synthetic methods; Ylides

Indexed keywords

EID: 0032479767     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1521-3773(19980803)37:13/14<1880::AID-ANIE1880>3.0.CO;2-5     Document Type: Article

References (15)

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8. 3. CuI (cat.), PhH, 50°C). Addition of lithium ethoxy-acetylide provided only a 21 % yield of a tertiary alcohol (with 43% starting material recovered). The formation of the corresponding α,β-unsaturated ester from this product was not successful. A Peterson-type reaction with ethyl lithiotrimethylsilylacetate afforded only a 28% yield of the α,β-unsaturated ester (with 34% starting material recovered). By contrast, Reformatsky reaction provided almost complete transformation to a β-hydroxy ester. However, dehydration of this compound has thus far not been achieved. A modified Reformatsky reaction (with methyl dichloroacetate and Zn in the presence of diethylaluminum chloride: K. Takai, Y. Hotta, K. Oshima, H. Nozaki, Bull. Chem. Soc. Jpn. 1980, 53, 1698) produced the α,β-unsaturated ester in 73% yield. Early attempts to deliver a one-carbon fragment to the enoate have not been productive. Given our success in spirobutanone formation, these studies have not yet been pursued in detail.
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12. At the present time we cannot be certain whether lactone formation occurs upon acidification of the product obtained upon opening of the four-membered ring (seco-cleavage product) or by the more interesting possibility wherein the C1 hydroxyl participates as the nucleophile in the cleavage step following bis-sulfenylation.
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15. The construction of the C5-C6 bridgehead double bond has been accomplished recently: D. Meng, Columbia University, unpublished results.