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Title:Direction and Stabilization of Alpha' and Beta Metalations by Tertiary Carboxamides
Author(s):Wallin, Anne Parson
Doctoral Committee Chair(s):Beak, Peter
Department / Program:Chemistry
Discipline:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(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.
Issue Date:1988
Type:Text
Description:194 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1988.
URI:http://hdl.handle.net/2142/72266
Other Identifier(s):(UMI)AAI8908884
Date Available in IDEALS:2014-12-17
Date Deposited:1988


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