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Synlett 2002(2): 0290-0294
DOI: 10.1055/s-2002-19748
LETTER
© Georg Thieme Verlag Stuttgart · New York

Lithiation and Stereoselective Transformations of 3-Aroyl-2,2,4,4-tetramethyloxazolidines (TMO Amides), a New Class of Acid-labile Atropisomeric Amides

Mark Anstiss, Jonathan Clayden*, Alexander Grube, Latifa H. Youssef
Department of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK
Fax: +44(161)2754939; e-Mail: j.p.clayden@man.ac.uk.;
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Publication History

Received 4 October 2001
Publication Date:
02 February 2007 (online)

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Abstract

Aromatic amides 4 (3-aroyl-2,2,4,4-tetramethyloxazolidines or TMO amides) derived by acylation of 2,2,4,4-tetramethyloxazolidine 6 undergo ortho- and lateral lithiation reactions. Given sufficient steric hindrance to bond rotation, they exhibit atropisomerism about the Ar-CO bond and the Ar-CO axis is able to control the atroposelective formation of new stereogenic centres. Unlike amides derived from hindered secondary amines such as diisopropylamine, the 3-aroyl-2,2,4,4-tetramethyloxazolidines are acid-sensitive, and treatment with methanesulfonic acid gives lactones or lactams by cyclisation onto the amide group.

Key words

atropisomerism - lithiation - amides - stereoselectivity - lactones

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12

Although it is standard practice to perform ortholithiations in the presence of TMEDA (see ref. [1] ), we have found that TMEDA is generally unnecessary in lithiations of N,N-diisopropylamides, though it is required to avoid formation of ketones by ”dimerisation" of N,N-diethylamides.

18

High selectivity under thermodynamic control is a feature of amides with adjacent stereogenic centres bearing well-contrasted small, medium and large groups. For further discussion, see ref. [3] and ref. [19]

23

Presumably, stereoelectronics favour antiperiplanarity of C-O σ* and the more electron-rich C4-N bond.