Intramolecular 1,6-addition to 2-pyridones. Mechanism and synthetic scope

Journal of Organic Chemistry

Volumn 75, Issue 11, 2010, Pages 3766-3774

  Gallagher, Timothy ^a   Derrick, Ian ^b   Durkin, Patrick M ^a   Haseler, Claire A ^a   Hirschhäuser, Christoph ^a   Magrone, Pietro ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2-PYRIDONES; ENOLATES; IN-SITU IR; NUCLEOPHILIC ADDITIONS; SIDE REACTIONS; TRICYCLIC PRODUCTS;

ADDITION REACTIONS; AMIDES; ESTERS; KETONES;

SYNTHESIS (CHEMICAL);

2 PYRIDONE DERIVATIVE; ALKALOID DERIVATIVE; AMIDE; ESTER; ISOQUIONOLINONE DERIVATIVE; KETONE; LACTAM; OCTANOIN; PYRIMIDINONE DERIVATIVE; QUINOLINE DERIVATIVE; THIOLACTAM; UNCLASSIFIED DRUG;

1,6 ENOLATE ADDITION; ADDITION REACTION; ARTICLE; CHEMICAL STRUCTURE; CYCLIZATION; INFRARED RADIATION; LUPIN; OXIDATION;

ALKALOIDS; ESTERS; PYRIDONES;

EID: 77952998618     PISSN: 00223263     EISSN: 15206904     Source Type: Journal    
DOI: 10.1021/jo100514a     Document Type: Article

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23. 2 to trap the putative extended enolate (and cyclized) product (compare 7 → 8 → 5a/b, Scheme 2). No evidence for an oxidized product analogous to 5a (or a regioisomer) or 5b was obtained, and only 25a was recovered. It is difficult to understand why enolization should be particularly inhibited in the case of lactam 25a, and these experiments cannot exclude the possibility that cyclization of 25a does, nevertheless, occur (1,2- or 1,6-addition) but that the product is unstable with respect to ring opening on work up.
24. -1 resolution. The MCT detector operates at liquid nitrogen temperature.
25. These IR signals were consistent with the neat IR spectrum of lactam 1.
26. -1. See
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28. An IR spectrum of HMDS is available at http://www.Acros.com.
29. These IR signals were consistent with the neat IR spectrum of lactam 2α.
30. In addition to the substrates shown, a series of 4-substituted pyridones variants of 1, leading to the corresponding 4-substituted cytisine analogues, have also been successfully employed in this chemistry.