Highly diastereofacial anti-aldol reaction

Practical synthesis of optically active anti-2-alkyl-3-hydroxycarboxylic acid ester units

Michio Kurosu, M. Lorca

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

A variety of esters derived from commercially available norephedrine were used in diastereoselective anti-aldol reactions. The aldol reaction of designed 2-(N-2-methylbenzyl-N-2,4,6-trimethylbenzyl)-amino-1-phenylpropanol esters 4a-d with aldehydes furnished anti-2-alkyl-3-hydroxycarboxylic acid esters in excellent diastereomeric ratios (>98:2) when LDA-Cp2ZrCl2 (0.3 equiv) was used for enolization, followed by transmetalation into the zirconium enolate for aldolization. The novel auxiliary 3 for the anti-aldol reaction does not exhibit the ordinary basicity of tertiary amines; 3 can be extracted from acidic media with organic solvents. Its use is, therefore, very advantageous not only for extraction of the aldol products from the acidic water solutions; but also for recovering the chiral auxiliary 3 after the reductive cleavage. Treatment of aldol or 3-protected aldol products with DIBAL-H or LiAIH4 affords the versatile synthons, 2-alkyl-propane-1,3-diols or those 3-protected diols in >98% ee's together with 3 in nearly quantitative recovery.

Original languageEnglish (US)
Pages (from-to)1205-1209
Number of pages5
JournalJournal of Organic Chemistry
Volume66
Issue number4
DOIs
StatePublished - Feb 23 2001

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Esters
Acids
Phenylpropanolamine
Propane
Alkalinity
Aldehydes
Organic solvents
Amines
3-hydroxybutanal
Recovery
Water

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

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title = "Highly diastereofacial anti-aldol reaction: Practical synthesis of optically active anti-2-alkyl-3-hydroxycarboxylic acid ester units",
abstract = "A variety of esters derived from commercially available norephedrine were used in diastereoselective anti-aldol reactions. The aldol reaction of designed 2-(N-2-methylbenzyl-N-2,4,6-trimethylbenzyl)-amino-1-phenylpropanol esters 4a-d with aldehydes furnished anti-2-alkyl-3-hydroxycarboxylic acid esters in excellent diastereomeric ratios (>98:2) when LDA-Cp2ZrCl2 (0.3 equiv) was used for enolization, followed by transmetalation into the zirconium enolate for aldolization. The novel auxiliary 3 for the anti-aldol reaction does not exhibit the ordinary basicity of tertiary amines; 3 can be extracted from acidic media with organic solvents. Its use is, therefore, very advantageous not only for extraction of the aldol products from the acidic water solutions; but also for recovering the chiral auxiliary 3 after the reductive cleavage. Treatment of aldol or 3-protected aldol products with DIBAL-H or LiAIH4 affords the versatile synthons, 2-alkyl-propane-1,3-diols or those 3-protected diols in >98{\%} ee's together with 3 in nearly quantitative recovery.",
author = "Michio Kurosu and M. Lorca",
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N2 - A variety of esters derived from commercially available norephedrine were used in diastereoselective anti-aldol reactions. The aldol reaction of designed 2-(N-2-methylbenzyl-N-2,4,6-trimethylbenzyl)-amino-1-phenylpropanol esters 4a-d with aldehydes furnished anti-2-alkyl-3-hydroxycarboxylic acid esters in excellent diastereomeric ratios (>98:2) when LDA-Cp2ZrCl2 (0.3 equiv) was used for enolization, followed by transmetalation into the zirconium enolate for aldolization. The novel auxiliary 3 for the anti-aldol reaction does not exhibit the ordinary basicity of tertiary amines; 3 can be extracted from acidic media with organic solvents. Its use is, therefore, very advantageous not only for extraction of the aldol products from the acidic water solutions; but also for recovering the chiral auxiliary 3 after the reductive cleavage. Treatment of aldol or 3-protected aldol products with DIBAL-H or LiAIH4 affords the versatile synthons, 2-alkyl-propane-1,3-diols or those 3-protected diols in >98% ee's together with 3 in nearly quantitative recovery.

AB - A variety of esters derived from commercially available norephedrine were used in diastereoselective anti-aldol reactions. The aldol reaction of designed 2-(N-2-methylbenzyl-N-2,4,6-trimethylbenzyl)-amino-1-phenylpropanol esters 4a-d with aldehydes furnished anti-2-alkyl-3-hydroxycarboxylic acid esters in excellent diastereomeric ratios (>98:2) when LDA-Cp2ZrCl2 (0.3 equiv) was used for enolization, followed by transmetalation into the zirconium enolate for aldolization. The novel auxiliary 3 for the anti-aldol reaction does not exhibit the ordinary basicity of tertiary amines; 3 can be extracted from acidic media with organic solvents. Its use is, therefore, very advantageous not only for extraction of the aldol products from the acidic water solutions; but also for recovering the chiral auxiliary 3 after the reductive cleavage. Treatment of aldol or 3-protected aldol products with DIBAL-H or LiAIH4 affords the versatile synthons, 2-alkyl-propane-1,3-diols or those 3-protected diols in >98% ee's together with 3 in nearly quantitative recovery.

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