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. 2007 Aug 31;72(18):6816-23.
doi: 10.1021/jo070978f. Epub 2007 Aug 4.

Type 2 intramolecular N-acylazo Diels-Alder reaction: regio- and stereoselective synthesis of bridgehead bicyclic 1,2-diazines

Claudia L Molina  1 , Chun P Chow, Kenneth J Shea
Affiliations

Type 2 intramolecular N-acylazo Diels-Alder reaction: regio- and stereoselective synthesis of bridgehead bicyclic 1,2-diazines

Claudia L Molina et al. J Org Chem. .

Abstract

The type 2 intramolecular N-acylazo Diels-Alder reaction provides a regio- and stereoselective synthesis of bicyclic 1,2-diazine systems. A new method for the generation of N-acylazo dienophiles with tetra-n-butylammonium periodate is reported. X-ray crystallographic analysis allowed the quantification of structural distortions of the nonplanar bridgehead olefin and lactam functionalities in 1,2-diazine cycloadducts 11 and 15. Caprolactams and enantholactams were formed by stereoselective bridgehead alkene reduction, a process that transfers stereochemistry from the bridgehead lactam nitrogen to the bridgehead carbon. The sequence of transformations offers a convenient route for the diastereoselective synthesis of medium-ring nitrogen heterocycles and 1,4-diamines.

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Figures

Figure 1
Figure 1
ORTEP plots of cycloadducts 11 and 15 at the 50% probability level.
Scheme 1
Scheme 1
Examples of the hetero type 2 intramolecualr Diels-Alder reaction.
Scheme 2
Scheme 2
Synthesis of Hydrazides 8 and 9.
Scheme 3
Scheme 3
Type 2 intramolecular Diels-Alder reaction with N-acylazo dienophiles 10.
Scheme 4
Scheme 4
Oxidation reaction of hydrazides with n-Bu4NIO4.
Scheme 5
Scheme 5
Type 2 intramolecular Diels-Alder reaction of N-acylazo dienophile 14.
Scheme 6
Scheme 6
Oxidation reaction of hydrazide 9.
Scheme 7
Scheme 7
Lewis acid catalyzed T2IMDA reaction of N-acylazo dienophile 14.
Scheme 8
Scheme 8
Synthesis of lactams 17 and 19.
Scheme 9
Scheme 9
Synthesis of hydrazide 21 and 23.
Scheme 10
Scheme 10
Diastereoselective T2IMDA reaction of hydrazide 21.
Scheme 11
Scheme 11
Catalytic hydrogenation of cycloadduct 24.
Scheme 12
Scheme 12
Catalytic Hydrogenation and N-N bond cleavage of cycloadduct 24.
Scheme 13
Scheme 13
Diastereoselective T2IMDA reaction of hydrazide 23.
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