Aluminoxy acetals from α-amino esters: Chirality transfer via sequential addition of hydride and C-nucleophiles. 2-Amino alcohols and sphingosines

Robin L Polt, Matt A. Peterson, Lynn Deyoung

Research output: Contribution to journalArticle

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Abstract

The reaction of α-imino esters (O'Donnell's Schiff bases) with aluminum hydrides to produce acetal-like intermediates and subsequent reaction with carbon nucleophiles has been studied. Treatment of optically pure imine-protected amino esters with iBu2AlH or iBu2AlH·Bu3Al, followed by RMgX or RLi provided threo-2-amino alcohols in high yield (73-85%) and excellent "syn" stereoselectivity (8:1 to >20:1, threo or like product preferred). Use of nonpolar solvents (CH2Cl2-hexane) provided the highest stereoselectivities. Use of the less-reactive iBu2AlH·iBu3Al complex lowered the amount of undesired primary alcohol products observed. Thermally labile aluminoxy acetal intermediates were observed by 1H NMR and were trapped with N-(trimethylsilyl)imidazole to produce relatively stable monosilyl acetals (mixed acetals). Alanine-derived Schiff bases 2a-e showed a correlation between the steric bulk of the ester and threo selectivity. The presence of THF reduced this correlation, suggesting the C-nucleophile addition involves a Lewis acid-assisted SN2-like displacement of the aluminoxy acetal or displacement of a tight-ion pair. In addition to the synthesis of optically pure arylethanolamines 6a-d from representative amino acids, threo-sphingosines 8a-d were synthesized from L-serine-derived Schiff base 4b, and 1-deoxy-threo-sphingosines 9a-d were synthesized from L-alanine in a similar fashion. Experimental details are provided.

Original languageEnglish (US)
Pages (from-to)5469-5480
Number of pages12
JournalJournal of Organic Chemistry
Volume57
Issue number20
StatePublished - 1992

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Amino Alcohols
Acetals
Nucleophiles
Sphingosine
Chirality
Hydrides
Esters
Schiff Bases
Stereoselectivity
Alanine
Lewis Acids
Imines
Hexanes
Aluminum
Serine
Carbon
Alcohols
Nuclear magnetic resonance
Ions
Amino Acids

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Aluminoxy acetals from α-amino esters : Chirality transfer via sequential addition of hydride and C-nucleophiles. 2-Amino alcohols and sphingosines. / Polt, Robin L; Peterson, Matt A.; Deyoung, Lynn.

In: Journal of Organic Chemistry, Vol. 57, No. 20, 1992, p. 5469-5480.

Research output: Contribution to journalArticle

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abstract = "The reaction of α-imino esters (O'Donnell's Schiff bases) with aluminum hydrides to produce acetal-like intermediates and subsequent reaction with carbon nucleophiles has been studied. Treatment of optically pure imine-protected amino esters with iBu2AlH or iBu2AlH·Bu3Al, followed by RMgX or RLi provided threo-2-amino alcohols in high yield (73-85{\%}) and excellent {"}syn{"} stereoselectivity (8:1 to >20:1, threo or like product preferred). Use of nonpolar solvents (CH2Cl2-hexane) provided the highest stereoselectivities. Use of the less-reactive iBu2AlH·iBu3Al complex lowered the amount of undesired primary alcohol products observed. Thermally labile aluminoxy acetal intermediates were observed by 1H NMR and were trapped with N-(trimethylsilyl)imidazole to produce relatively stable monosilyl acetals (mixed acetals). Alanine-derived Schiff bases 2a-e showed a correlation between the steric bulk of the ester and threo selectivity. The presence of THF reduced this correlation, suggesting the C-nucleophile addition involves a Lewis acid-assisted SN2-like displacement of the aluminoxy acetal or displacement of a tight-ion pair. In addition to the synthesis of optically pure arylethanolamines 6a-d from representative amino acids, threo-sphingosines 8a-d were synthesized from L-serine-derived Schiff base 4b, and 1-deoxy-threo-sphingosines 9a-d were synthesized from L-alanine in a similar fashion. Experimental details are provided.",
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