Asymmetric synthesis of amines and amine derivatives: I. The cerium-mediated diastereoselective addition of organometallic reagents to chiral pyrrolidine hydrazones. II. The enantioselective addition of organolithium reagents to imines and hydrazones

Nicaise, Olivier Jean-Charles

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https://hdl.handle.net/2142/20623 Copy

Description

Title

Asymmetric synthesis of amines and amine derivatives: I. The cerium-mediated diastereoselective addition of organometallic reagents to chiral pyrrolidine hydrazones. II. The enantioselective addition of organolithium reagents to imines and hydrazones

Author(s)

Nicaise, Olivier Jean-Charles

Issue Date

1993

Doctoral Committee Chair(s)

Denmark, Scott E.

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

Language

eng

Abstract

• Two conceptually different approaches to the asymmetric synthesis of amines and amine derivatives via the addition of organometallic reagents to the carbon-nitrogen double bond of azomethines has been investigated.
• The first approach consisted of the cerium-mediated diastereoselective addition of various organometallic compounds to chiral pyrrolidine hydrazones derived from several functionalized aldehydes. A stoichiometry study of the lanthanide-mediated addition of methyllithium to hydrocinnamaldehyde SAMEMP-hydrazone first established the superiority of the 1:1 CH$\sb3$Li/LnCl$\sb3$ (Ln = Ce, La) composition of the heterogeneous reagent, and the high level of diastereocontrol of the reaction was practically unchanged.
• The reactivity of chiral aliphatic, acetal, ether, glyoxylic, and masked-acid hydrazones with cerium-based reagents was examined, and the resulting aliphatic primary amines, $\alpha$-amino acetals, $\alpha$-amino aldehydes, and $\beta$-amino ethers were obtained in moderate to excellent yields and enantiomeric purities. The chiral $\alpha$,$\alpha$-dialkoxy hydrazones (acetal hydrazones) were found to be the most reactive chiral hydrazones. The isolation of the desired amine derivatives in enantiomerically enriched form and the recovery of the chiral auxiliary was realized via the use of lithium metal in liquid ammonia to effect the scission of the N-N bond in diastereomerically enriched protected hydrazines with complete preservation of the configurational integrity of the stereocenters.
• The second approach to the asymmetric synthesis of amines involved the use of an achiral hydrazone with an achiral organometallic compound in the presence of a certain amount of an external chiral controller. Following the unsuccessful development of an enantioselective lanthanide-based nucleophilic reagent, the addition of n-butyllithium to a N,N-dimethylhydrazone in the presence of a chiral ether afforded the primary amine in 26% ee. A significant level of enantioselectivity was then recorded for the same reaction with the use of a stoichiometric amount of chiral bis(oxazoline) ligand, i.e. 50% ee.
• This approach was mostly successful with the use of imines for the stoichiometric bis(oxazoline)-mediated addition of methyllithium and n-butyllithium. The N-aryl secondary amines were isolated almost quantitatively in enantiomerically enriched form, up to 92% ee. The reaction of methyllithium with imines in the presence of a catalytic amount of the chiral bis(oxazoline) ligand afforded the methyl adducts in 84% ee at best. The discovery of an efficient enantioselective addition of organolithium compounds to imines has given a new dimension to the project directed toward the asymmetric synthesis of amines. (Abstract shortened by UMI.)

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text

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http://hdl.handle.net/2142/20623

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Copyright 1993 Nicaise, Olivier Jean-Charles

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