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. 2018 Sep 10;57(37):12081-12085.
doi: 10.1002/anie.201806295. Epub 2018 Aug 19.

Synthesis of N-H Bearing Imidazolidinones and Dihydroimidazolones Using Aza-Heck Cyclizations

Feiyang Xu  1 , Scott A Shuler  1 , Donald A Watson  1
Affiliations

Synthesis of N-H Bearing Imidazolidinones and Dihydroimidazolones Using Aza-Heck Cyclizations

Feiyang Xu et al. Angew Chem Int Ed Engl. .

Abstract

The synthesis of unsaturated, unprotected imidazolidinones via an aza-Heck reaction is described. This palladium-catalyzed process allows for the cyclization of N-phenoxy ureas onto pendant alkenes. The reaction has broad functional group tolerance, can be applied to complex ring topologies, and can be used to directly prepare mono- and bis-unprotected imidazolidinones. By addition of Bu4 NI, dihydroimidazolones can be accessed from the same starting materials. Improved conditions for preparing unsaturated, unprotected lactams are also reported.

Keywords: aza-Heck reaction; catalysis; dihydroimidazolones; imidazolidinones; palladium.

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Figures

Figure 1.
Figure 1.
Representative Bioactive Imidazolidinones.
Figure 2.
Figure 2.
State-of-the-Art in Imidazolidinone Synthesis.
Scheme 1.
Scheme 1.
Access to N-Phenoxy Ureas.
Scheme 2.
Scheme 2.
Substrate Scope.
Scheme 3.
Scheme 3.
Access to Tricyclic Imidazolidinone Using Aza-Heck Strategies
Scheme 4.
Scheme 4.
Preparation of Dihydroimidazolones.
Scheme 5.
Scheme 5.
Preparation of Factor Xa Inhibitor 49.
Scheme 6.
Scheme 6.
Examples of Lactam Substrates
See this image and copyright information in PMC

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