Alpha-Oxygenation by Acylation-Rearrangement of Nitrones
Cummins, Clark Hughes
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https://hdl.handle.net/2142/70232
Description
Title
Alpha-Oxygenation by Acylation-Rearrangement of Nitrones
Author(s)
Cummins, Clark Hughes
Issue Date
1984
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Organic
Abstract
The acylation-rearrangement of N-alkylnitrones with acid chlorides and triethylamine affords a new method for the (alpha)-oxygenation of aldehydes and cyclic ketones via (alpha)-acyloxy imines. The reaction apparently proceeds by initial acylation of the nitrone oxygen, proton removal, and {3,3}-sigmatropic rearrangement of the resulting N-vinyl-O-acylhydroxylamine. Oxygen-18 labeling studies in one case showed that no scrambling of the carbonyl oxygens occurs during the rearrangement. Hydrolysis of the product imines provides the (alpha)-acyloxy aldehydes and cyclic ketones. The overall yields for the two- or three step reaction sequence are good, the conditions are quite mild, and the use of electrophilic oxidizing agents is obviated.
The stereoselectivity of the acylation-rearrangement was probed by studying the composition of the products obtained from (alpha)-oxygenation of citronellal, 5-norbornene-2-carboxaldehyde and 2-methylcyclohexanecarboxaldehyde. It was found that the rearrangement is only moderately stereoselective, providing nearly equal mixtures of diastereomeric products except for the case of norbornenecarboxaldehyde, which exhibits a strong exo steric bias.
The feasibility of generating nitrone anions was demonstrated by metallation with lithium diisopropylamide followed by silylation. A series of N-vinyl-O-trimethylsilylhydroxylamines was obtained in 35 to 72% yield. Unfortunately, attempts to acylate the nitrone anions or their trimethylsilyl derivatives with acid chlorides provided (alpha)-acyloxy imines in only low yield.
Reduction of the (alpha)-acyloxy imines obtained from acylation-rearrangement of N-tert-butyl and N-cyclohexylnitrones with lithium aluminum hydride affords N-tert-butyl and N-cyclohexylamino alcohols. This approach was not applicable to the synthesis of N-methylamino alcohols, since acylation rearrangement of an N-methylnitrone afforded a mixture of the expected (alpha)-acyloxy imine and an N-methyl imide by-product. Reduction of this mixture with lithium aluminum hydride furnished an inseparable mixture of amino alcohols.
Selective reduction of the carbon-nitrogen double bond of (alpha)-acyloxy imines afforded amino esters, one of which underwent spontaneous oxygen to nitrogen acyl transfer to provide the isomeric amido ester. Sodium borohydride reduction of (alpha)-(methoxycarbonyl)oxy imines, prepared by acylation-rearrangement of nitrones with methyl chloroformate, furnished 2-oxazolidinones. Saponification of an N-methyl-2-oxazolidinone opened a route to N-methylamino alcohols via acylation-rearrangement of nitrones.
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