Stereocontrolled synthesis of triazacyclopenta[cd]pentalenes by intramolecular 1,3-dipolar cycloaddition reactions of azomethine imines

Journal of Organic Chemistry

Volumn 67, Issue 22, 2002, Pages 7880-7883

  Bélanger, Guillaume ^a,b   Hong, Fang Tsao ^a,c   Overman, Larry E ^a   Rogers, Bruce N ^a,d   Tellew, John E ^a,e   Trenkle, William C ^a,f  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITÉ DE SHERBROOKE   (Canada)

^c AMGEN INC   (United States)

^d PFIZER INC   (United States)

^e NEUROCRINE BIOSCIENCES INC   (United States)

^f BROWN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOCONDENSATIONS;

ACYLATION; ADDITION REACTIONS; HYDRAZINE; STEREOCHEMISTRY; SYNTHESIS (CHEMICAL);

ESTERS;

ALKALOID; AZOMETHINE IMINE; CYCLOPENTANE DERIVATIVE; GUANIDINE DERIVATIVE; HETEROCYCLIC AMINE; HYDRAZINE DERIVATIVE; IMINE; PALAU'AMINE; PYRROLE DERIVATIVE; STYLOGUANIDINE; TRIAZACYCLOPENTA[CD]PENTALENE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; CHEMICAL STRUCTURE; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; STEREOCHEMISTRY; SYNTHESIS;

CYCLOPENTANES; IMINES; MOLECULAR STRUCTURE; STEREOISOMERISM;

EID: 0036827533     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo026282y     Document Type: Article

References (34)

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2. (b) Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320.
3. (c) Pharmacia, 301 Henrietta Street, Kalamazoo, MI 49007-4940.
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30. The inefficiency of the cycloaddition in xylenes could be due, in part, to the poor solubility of thiosemicarbazide in this solvent.
31. Product 27a forms slowly at room temperature over the course of 10-14 days when the solvent is acetic acid. Although, the cyclocondensation of 12a with acylhydrazines in refluxing xylenes undoubtedly proceeds as depicted in Scheme 1, an alternative mechanism is possible when the solvent is acetic acid. Dehydroamino esters are well-known to exhibit ambiphilic reactivity. Thus, the finding that the cyclocondensation of 12a with thiosemicarbazide occurs optimally in acetic acid, and even at room temperature, suggests that this cyclocondensation likely takes place by an asynchronous or stepwise mechanism. In the stepwise limit, the cycloadduct would be the result of an intramolecular Mannich cyclization followed by subsequent cyclization of the acylated hydrazine with an N-acyl- or N-sulfonyliminium ion intermediate.
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33. 6
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