View source for Chemistry:Aza-Diels–Alder reaction

{{Reactionbox
| Name = Aza-Diels–Alder reaction
| Type = Cycloaddition
| NamedAfter = [[Biography:Otto Diels|Otto Diels]]<br />[[Biography:Kurt Alder|Kurt Alder]]
| Section3 = {{Reactionbox Identifiers
   | RSC_ontology_id = 0000092
 }}
}}
The '''aza-Diels–Alder reaction''' converts [[Chemistry:Imine|imine]]s and dienes to [[Chemistry:Tetrahydropyridine|tetrahydropyridine]]s. This [[Chemistry:Organic reaction|organic reaction]] is a modification of the [[Chemistry:Diels–Alder reaction|Diels–Alder reaction]]. The nitrogen atom can be part of the diene or the dienophile.

[[Image:Aza Diels Alder.gif|center|The Aza Diels–Alder reaction, general scope]]

The imine is often generated [[Biology:In situ|in situ]] from an [[Chemistry:Amine|amine]] and [[Physics:Formaldehyde|formaldehyde]]. An example is the reaction of [[Chemistry:Cyclopentadiene|cyclopentadiene]] with [[Chemistry:Benzylamine|benzylamine]] to an aza [[Chemistry:Norbornene|norbornene]].<ref>''N-benzyl-2-azanorbornene'' Paul A. Grieco and Scott D. Larsen [[Chemistry:Organic Syntheses|Organic Syntheses]], Coll. Vol. 8, p.31; Vol. 68, p.206 [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv8p0031 Article]</ref>

[[Image:Aza-Diels-Alder phenylmethylamine.gif|center]]

In the enantioselective Diels–Alder (DA) reaction of an [[Chemistry:Aniline|aniline]], [[Physics:Formaldehyde|formaldehyde]] and a [[Chemistry:Cyclohexenone|cyclohexenone]] [[Chemistry:Catalysis|catalyzed]] by (S)-[[Chemistry:Proline|proline]] even the diene is masked.<ref>''Direct Catalytic Enantioselective Aza-Diels-Alder Reactions'' Henrik Sundén, Ismail Ibrahem, Lars Eriksson, Armando Córdova Angewandte Chemie International Edition 4877 '''2005'''  [https://archive.today/20121216150136/http://www3.interscience.wiley.com/cgi-bin/abstract/110546882/ABSTRACT Abstract]</ref> 

[[Image:Aza Diels Alder proline.gif|center|S-proline enantioselective Aza Diels–Alder reaction]]

The [[Chemistry:Catalytic cycle|catalytic cycle]] starts with the reactions of the aromatic amine with [[Physics:Formaldehyde|formaldehyde]] to the [[Chemistry:Imine|imine]] and the reaction of the [[Chemistry:Ketone|ketone]] with [[Chemistry:Proline|proline]] to the diene. The second step, an endo trig cyclisation, is driven to one of the two possible [[Chemistry:Enantiomer|enantiomer]]s (99% [[Chemistry:Enantiomeric excess|ee]]) because the imine nitrogen atom forms a [[Chemistry:Hydrogen bond|hydrogen bond]] with the [[Chemistry:Carboxylic acid|carboxylic acid]] group of proline on the Si face. Hydrolysis of the final complex releases the product and regenerates the catalyst.

[[Image:Aza DA mechanism.png|center|catalytic cycle for S-proline enantioselective Aza Diels–Alder reaction]]

In 2014, Doyle and coworkers reported a Zn(OTf)<sub>2</sub>-catalyzed [4+2] cycloaddition reaction between two imines to form tetrahydropyrimidine products.<ref>Mandler, M. D.; Truong, P. M.; Zavalij, P. Y.; Doyle, M. P. Org. Lett. 2014, 16, 740-743.</ref>

==See also==
* Oxo Diels–Alder reaction
* [[Chemistry:Imine Diels–Alder reaction|Imine Diels–Alder reaction]]

== References ==
<references/>

{{DEFAULTSORT:Aza-Diels-Alder reaction}}
[[Category:Cycloadditions]]
[[Category:Nitrogen heterocycle forming reactions]]
[[Category:Name reactions]]

{{Sourceattribution|Aza-Diels–Alder reaction}}