1,3-Dipolar Cycloaddition of Nitrone

• Characteristics

The 1,3-dipolar cycloaddition of  nitrones, a kind of 1,3-dipole to unsaturated (C–C double or triple bond) compounds is one of the useful synthetic method for preparing isoxazole, dihydro- and tetrahedron-isoxazole derivatives.  Particularly, the nitrone–olefin 1,3-dipolar cycloaddition is a powerful reaction in that it can create as many as three new contiguous stereogenic centers in a single step.

 

• Literature reference

<review>
・Huisgen, R. Angew. Chem. Int. Ed. 1963, 2, 565. DOI:10.1002/anie.196305651
・Huisgen, R. Angew. Chem. Int. Ed. 1963, 2, 633. DOI:10.1002/anie.196306331
・Confalone, P. N.; Huie, E. M. Org. React. 1988, 36, 1. DOI:10.1002/0471264180.or036.01 
・Gothelf, K. V.; Jorgensen, K. A. Chem. Rev. 1998, 98, 863. DOI: 10.1021/cr970324e
・Pellissier, H. Tetrahedron 2007, 63, 3235. DOI:10.1016/j.tet.2007.01.009

 

• Reaction mechanism

See, 1,3-dipolar cycloaddition (Not prepared yet)

• Example of reactions

   

Kita and coworkers reported lipase-catalyzed domino kinetic resolution of alpha-hydroxynitrones/intramolecular 1,3-dipolar cycloaddition for the asymmetric total synthesis of (–)-rosmarinecine.^[1] A domino reaction of the cyclic nitrone with the acyl donors in the presence of Candida antarctica lipase, fraction B underwent the kinetic resolution of cyclic nitrone, and subsequent intramolecular 1,3-dipolar cycloaddition to gave the corresponding products as single enantio- and diasteromer (91% ee).

 

Nagasawa and coworkers reported an enantioselective total synthesis of batzelladine A  based upon a strategy involving successive 1,3-dipolar cycloadditions.[2]  The 1,3-diploar cycloaddition reaction between 10 and the ester proceeded stereoselectively to give the isoxazolidine 12 as a single diastereomer.

• Bibliography

[1] Akai, S.; Tanimoto, K.; Kanao, Y.; Omura, S.; Kita, Y. Chem. Commun. 2005, 2369. DOI:10.1039/B419426H 
[2] Shimokawa, J.; Shirai, K.; Tanatani, A.; Hashimoto, Y.; Nagasawa, K. Angew. Chem. Int. Ed. 2004,43. 1559. DOI: 10.1002/anie.200353200

 

• Related Books

[amazonjs asin=”3527314393″ locale=”US” title=”Pericyclic Reactions – A Textbook: Reactions, Applications and Theory”][amazonjs asin=”3527320881″ locale=”US” title=”Handbook of Cyclization Reactions”]

 

• Related Links

・1,3-Dipole (Wikipedia)
・1,3-Dipolar cycloaddition (Wikipedia)
・Nitrone - Wikipedia
・nitone-olefin 3+2 cycloaddition - Wikipedia
・Catalysis of 1,3-Dipolar Cycloaddition of Nitornes （Denmark Group, PDF）
・1,3-Dipolar Cycloaddition Reactions of Nitrones with Alkenes (Takeda Group, PDF)

1, 3-dipole, cycloaddition, nitrogen