- N-Pyridylmethylephedrine derivatives in the catalytic asymmetric addition of diethylzinc to aldehydes and diphenylphosphinoylimines
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N-Pyridylmethyl-substituted Ephedra derivatives were synthesized by either direct alkylation or reductive alkylation of (1R,2S)-norephedrine, (1S,2S)-pseudo norephedrine, and (1R,2S)-ephedrine. These derivatives were then employed in asymmetric addition reactions with diethylzinc and aldehydes and diphenylphosphinoylimines. The use of the diastereomers from the Ephedra family allowed for a systematic evaluation of the contribution of the N-pyridylmethyl.
- Banerjee, Sucharita,Groeper, Jonathan A.,Standard, Jean M.,Hitchcock, Shawn R.
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experimental part
p. 2154 - 2161
(2010/03/03)
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- Stereocontrolled alkylative construction of quaternary carbon centers
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Protocols for the stereodefined formation of α,α-disubstituted enolates of pseudoephedrine amides are presented followed by the implementation of these in diastereoselective alkylation reactions. Direct alkylation of α,α-disubstituted pseudoephedrine amide substrates is demonstrated to be both efficient and diastereoselective across a range of substrates, as exemplified by alkylation of the diastereomeric pseudoephedrine α-methylbutyramides, where both substrates are found to undergo stereospecific replacement of the α-C-H bond with α-C-alkyl, with retention of stereochemistry. This is shown to arise by sequential stereospecific enolization and alkylation reactions, with the alkyl halide attacking a common π-face of the E- and Z-enolates, proposed to be opposite the pseudoephedrine alkoxide side chain. Pseudoephedrine α-phenylbutyramides are found to undergo highly stereoselective but not stereospecific α-alkylation reactions, which evidence suggests is due to facile enolate isomerization. Also, we show that α,α-disubstituted pseudoephedrine amide enolates can be generated in a highly stereocontrolled fashion by conjugate addition of an alkyllithium reagent to the s-cis-conformer of an α-alkyl-α,β-unsaturated pseudoephedrine amide, providing α,α-disubstituted enolate substrates that undergo alkylation in the same sense as those formed by direct deprotonation. Methods are presented to transform the α-quaternary pseudoephedrine amide products into optically active carboxylic acids, ketones, primary alcohols, and aldehydes. Copyright
- Kummer, David A.,Chain, William J.,Morales, Marvin R.,Quiroga, Olga,Myers, Andrew G.
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supporting information; experimental part
p. 13231 - 13233
(2009/02/06)
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- 1,2-Aminothioethers Derived from Ephedrine and Pseudoephedrine: Heterobidentate Ligands for the Palladium-Catalysed Asymmetric Allylic Substitution Reaction
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Heterobidentate sulfide-tertiary amine ligands incorporating 1,2-aminothioethers derived from ephedrine and pseudoephedrine have been prepared and used successfully in the palladium-catalysed asymmetric allylic substitution reaction, giving ees of up to 89 percent. The stereoelectronic effects operating in the reactions are discussed.
- Page, Philip C. Bulman,Heaney, Harry,Reignier, Serge,Rassias, Gerasimos A.
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- The Reductive Cleavage of Cyclic Aminol Ethers to N,N-Dialkylamino-derivatives: Modifications to the Eschweiler-Clarke Procedure
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The reductive cleavage of cyclic aminol ethers to give N-alkylamino-derivatives in very high yields can be achieved using chlorotrimethylsilane in the presence of sodium cyanoborohydride: in the case of cyclic aminol ethers derived from formaldehyde the Eschweiler-Clarke reaction can be carried out in formic acid heated under reflux in the absence of formaldehyde.
- Page, Philip C. Bulman,Heaney, Harry,Rassias, Gerasimos A.,Reignier, Serge,Sampler, Edward P.,Talib, Salem
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p. 104 - 106
(2007/10/03)
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- (1S,2S)-2-Amino-1-phenyl-1,3-propanediol, a spin off from chloramphenicol manufacture, as chiral synthon for (1S, 2S)-pseudoephedrine and (R)-phenylalaninol
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(1S,2S)-2-Amino-1-phenyl-1,3-propanediol (3a), a discarded optically active material in one of the processes for the manufacture of chloramphenicol, has been transformed into (S,S)-pseudoephedrine (4) and (R)-phenylalaninol (5). The opposite selectivity of highly regioselective oxidative ring opening of the benzaldehyde acetal of (1S,2S)-2-phthalimido-1-phenyl-1,3-propanediol by NBS and highly regioselective ring opening of the cyclic sulphite of the same substrate by LiBr are the key steps in the transformations respectively.
- Akamanchi,Ranbhan,Shah
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p. 293 - 302
(2007/10/03)
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- Application of the Mitsunobu reaction to ephedrines and some related amino alcohols. Aspects of intramolecular participation of the amino group
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Inversion of configuration at the benzylic hydroxyl group of (1S,2S)-pseudoephedrine (2) to afford (1R,2S)-ephedrine is known to be a difficult process.The Mitsunobu reactions of 1 and 2 might offer a route to achieve such inversions.In fact Mitsunobu reactions on 1 and 2 are known to proceed via aziridines formed on intramolecular SN2 substitution by the amine functionality.The Mitsunobu reactions of N-methylated and N-benzylated ephedrines have been found to proceed via the corresponding aziridinium ions.These aziridinium ions can be opened (SN2 substitution) by nucleophiles like phthalimide and thiols.Intramolecular participation in 2 can be avoided by use of the tert-butyloxycarbonyl-(BOC) or benzyloxycarbonyl- (CBZ) protected derivatives.Mitsunobu reactions on these derivatives lead to inversion of configuration at the benzylic hydroxyl center.In contrast the BOC and CBZ derivatives of 1 are deprotected under Mitsunobu conditions.The Mitsunobu reactions of threo (1S,2S)-2-amino-1,3-propanediol have also been examined.An attempt to achieve protection by reaction with dimethylformamide dimethyl acetal led to the more substituted 2-oxazoline as established by X-ray crystallography.The desired inversion of configuration of the benzylic hydroxylic group was eventually achieved by protection of the amino substituent as the phthalimide and protection of the primary hydroxyl group as the tosylate.
- Poelert, Martin A.,Hulshof, L. A.,Kellogg, Richard M.
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p. 355 - 364
(2007/10/02)
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