University of Illinois Urbana-Champaign

Direction and Stabilization of Alpha' and Beta Metalations by Tertiary Carboxamides

Wallin, Anne Parson

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Description

Title
Direction and Stabilization of Alpha' and Beta Metalations by Tertiary Carboxamides
Author(s)
Wallin, Anne Parson
Issue Date
1988
Doctoral Committee Chair(s)
Beak, Peter
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
  • Metalations $\alpha\sp\prime$ and $\beta$ to a tertiary amide have been investigated. Control and understanding of the regiochemistry of these novel metalations is discussed.
  • In the $\alpha\sp\prime$ lithiation of a tertiary amide, the use of allyl or benzyl anion stabilizing groups allows for $\alpha\sp\prime$ deprotonation anti to the amide carbonyl as shown for the reactions of syn-N-n-pro-pyl, anti-N-(2-propenyl)-2,4,6-triisopropylbenzamide and syn-N-isopropyl,anti-N-benzyl-2,4,6-triisopropylbenzamide with $s$-butyl-lithium/tetramethylethylenediamine. The rates of isomerization about the amide bond for several N,N-dialkyl-2,4,6-triisopropylbenzamides have been determined, and the investigation of both rotational isomers in these metalation/substitution sequences provides the first unambiguous evidence of a lithiation anti to a directing group for a dipole stabilization carbanion.
  • It has been shown that the amide provides at least a three-fold enhancement in the acidity of an $\alpha\sp\prime$ amido anion over that of an $\alpha$ amino anion. The effect of amide structure, base and solvent on a number of related $\alpha\sp\prime$ lithiations has been studied.
  • In the $\beta$ lithiations of selected tertiary amides we have found the preferential deprotonation of a $\beta$ hydrogen over a more acidic $\alpha$ proton can be observed. Specifically both the $R\sp\*,R\sp\*$ and $R\sp\*,S\sp\*$ diastereomers of N,N-diisopropyl-2,3-dimethyl-4-pentene-carboxamides and of N,N-diisopropyl-2-methyl-3-phenylthiobutanecarboxamides upon treatment with $s$-butyllithium/tetramethylethylenediamine and trapping with methanol-d1 give deuteriation at the $\beta$ position. The $(R\sp\*,R\sp\*)N,N$-diisopropyl-2-methyl-3-phenylbutanecarboxamide also undergoes $\beta$ deprotonation, but $\alpha$ deprotonation is observed for $(R\sp\*,S\sp\*)N,N$-diisopropyl-2-methyl-3-phenylbutanecarboxamide. The $\beta$ lithiation is under kinetic control but gives an equilibrated $\beta$ lithio amide which then reacts with an electrophile under kinetic control. A model which rationalizes the kinetic competition between $\beta$ and $\alpha$ lithiation is presented.
Graduation Semester
1988
Type of Resource
text
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http://hdl.handle.net/2142/72266

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