SN2′ Addition of Cuprates to Acyclic Vinyloxiranes. Synthesis of Tylactone and Tylonolide Subunits

James A. Marshall, Thomas D Crute, Jeffrey D. Hsi

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Abstract

The chiral acyclic vinyloxiranes 8 and 18 undergo highly anti selective SN2′ additions upon treatment with Et2CuLi and (S)-PMBOMOCH2CH(CH3)CH2Cu(CN)Li, respectively. The product of the former addition, diol 9, affords the α-epoxide 12 upon epoxidation with m-CPBA. Conversion to acetonide 15, a possible C-1-C-7 segment of tylactone, was effected by hydrogenation of the methylene acetonide 14 obtained from epoxide 12 through LiNEt2 elimination and ketalization with 2,2-dimethoxypropane (2,2-DMP). Allylic alcohol 24b, a close analogue of diol 9, gave only the β-epoxide 25b upon treatment with m-CPBA. Epoxidation with magnesium monoperoxyphthalic acid (MMPP), however, yielded a separable 53:47 mixture of β-and α-epoxides 25b and 26b. The former was carried on to acetonide 29 by a sequence involving basic elimination (LiNEt2), treatment with 2,2-DMP, and hydrogenation. Acetonide 30, a diastereomer of 29, was prepared from epoxide 26b by a parallel sequence. Acetonide 30 was converted to the lactol methyl ether 48, an intermediate in Nicolaou's synthesis of O-micinosyl tylonolide, through displacement of tosylate 43 with KCN and then reduction (DIBAH), methanolysis (HCl, MeOH), silylation (TBSOTf, 2,6-lutidine), and finally PMBOM cleavage (DDQ). An identical sequence was applied to acetonide 29 resulting in the isomeric lactol methyl ether 37.

Original languageEnglish (US)
Pages (from-to)115-123
Number of pages9
JournalJournal of Organic Chemistry
Volume57
Issue number1
DOIs
StatePublished - Jan 1 1992
Externally publishedYes

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Epoxy Compounds
Methyl Ethers
Epoxidation
Hydrogenation
Magnesium
protylonolide
Acids
2,2-dimethoxypropane
3-chloroperbenzoic acid

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

SN2′ Addition of Cuprates to Acyclic Vinyloxiranes. Synthesis of Tylactone and Tylonolide Subunits. / Marshall, James A.; Crute, Thomas D; Hsi, Jeffrey D.

In: Journal of Organic Chemistry, Vol. 57, No. 1, 01.01.1992, p. 115-123.

Research output: Contribution to journalArticle

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abstract = "The chiral acyclic vinyloxiranes 8 and 18 undergo highly anti selective SN2′ additions upon treatment with Et2CuLi and (S)-PMBOMOCH2CH(CH3)CH2Cu(CN)Li, respectively. The product of the former addition, diol 9, affords the α-epoxide 12 upon epoxidation with m-CPBA. Conversion to acetonide 15, a possible C-1-C-7 segment of tylactone, was effected by hydrogenation of the methylene acetonide 14 obtained from epoxide 12 through LiNEt2 elimination and ketalization with 2,2-dimethoxypropane (2,2-DMP). Allylic alcohol 24b, a close analogue of diol 9, gave only the β-epoxide 25b upon treatment with m-CPBA. Epoxidation with magnesium monoperoxyphthalic acid (MMPP), however, yielded a separable 53:47 mixture of β-and α-epoxides 25b and 26b. The former was carried on to acetonide 29 by a sequence involving basic elimination (LiNEt2), treatment with 2,2-DMP, and hydrogenation. Acetonide 30, a diastereomer of 29, was prepared from epoxide 26b by a parallel sequence. Acetonide 30 was converted to the lactol methyl ether 48, an intermediate in Nicolaou's synthesis of O-micinosyl tylonolide, through displacement of tosylate 43 with KCN and then reduction (DIBAH), methanolysis (HCl, MeOH), silylation (TBSOTf, 2,6-lutidine), and finally PMBOM cleavage (DDQ). An identical sequence was applied to acetonide 29 resulting in the isomeric lactol methyl ether 37.",
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AB - The chiral acyclic vinyloxiranes 8 and 18 undergo highly anti selective SN2′ additions upon treatment with Et2CuLi and (S)-PMBOMOCH2CH(CH3)CH2Cu(CN)Li, respectively. The product of the former addition, diol 9, affords the α-epoxide 12 upon epoxidation with m-CPBA. Conversion to acetonide 15, a possible C-1-C-7 segment of tylactone, was effected by hydrogenation of the methylene acetonide 14 obtained from epoxide 12 through LiNEt2 elimination and ketalization with 2,2-dimethoxypropane (2,2-DMP). Allylic alcohol 24b, a close analogue of diol 9, gave only the β-epoxide 25b upon treatment with m-CPBA. Epoxidation with magnesium monoperoxyphthalic acid (MMPP), however, yielded a separable 53:47 mixture of β-and α-epoxides 25b and 26b. The former was carried on to acetonide 29 by a sequence involving basic elimination (LiNEt2), treatment with 2,2-DMP, and hydrogenation. Acetonide 30, a diastereomer of 29, was prepared from epoxide 26b by a parallel sequence. Acetonide 30 was converted to the lactol methyl ether 48, an intermediate in Nicolaou's synthesis of O-micinosyl tylonolide, through displacement of tosylate 43 with KCN and then reduction (DIBAH), methanolysis (HCl, MeOH), silylation (TBSOTf, 2,6-lutidine), and finally PMBOM cleavage (DDQ). An identical sequence was applied to acetonide 29 resulting in the isomeric lactol methyl ether 37.

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