Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Aug 26;52(35):9247-50.
doi: 10.1002/anie.201302720. Epub 2013 Jul 3.

Desymmetrization of meso-2,5-diallylpyrrolidinyl ureas through asymmetric palladium-catalyzed carboamination: stereocontrolled synthesis of bicyclic ureas

Nicholas R Babij  1 , John P Wolfe
Affiliations

Desymmetrization of meso-2,5-diallylpyrrolidinyl ureas through asymmetric palladium-catalyzed carboamination: stereocontrolled synthesis of bicyclic ureas

Nicholas R Babij et al. Angew Chem Int Ed Engl. .

Abstract

The stereoselective synthesis of fused bicyclic ureas 8 is accomplished via enantioselective Pd-catalyzed desymmetrizing carboamination reactions of meso-2,5-diallylpyrroldinyl urea 7c. The reactions generate a C–N bond, a C–C bond, and afford products bearing three stereocenters with good diastereoselectivity (6–12:1 dr) and enantioselectivity (up to 95:5 er). The N-(p-chlorophenyl) group can be cleaved in good yield using a two step sequence. In addition, 8c was transformed to a tricyclic guanidine product using a four-step (two pot) procedure and was converted to 9-epi-batzelladine k in seven steps.

Keywords: alkaloids; asymmetric catalysis; desymmetrization; heterocycles; palladium.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Bioactive guanidine alkaloids prepared from bicyclic urea precursors
Scheme 1
Scheme 1
Synthesis of bicyclic ureas via Pd-catalyzed asymmetric desymmetrization
Scheme 2
Scheme 2
Conversion of 8c to a tricyclic guanidine derivative
Scheme 3
Scheme 3
Conversion of 8c to 9-epi-batzelladine K.
See this image and copyright information in PMC

References

    1. For reviews, see: Enriquez-Garcia A, Kündig EP. Chem. Soc. Rev. 2012;41:7803–7831. Diaz de Villegas MD, Galvez JA, Etayo P, Badorrey R, Lopez Ram de Viu P. Chem. Soc. Rev. 2011;40:5564–5587. Rovis T. In: New Frontiers in Asymmetric Catalysis. Mikami K, Lautens M, editors. Hoboken, NJ: Wiley; 2007. pp. 275–309. Mikami K, Yoshida A. J. Synth. Org. Chem., Jpn. 2002;60:732–739. Trost BM. Isr. J. Chem. 1997;37:109–118.

    1. Berlinck RGS, Trindade-Silva AE, Santos MFC. Nat. Prod. Rep. 2012;29:1382–1406. - PubMed
    2. Berlinck RGS, Burtoloso ACB, Trindade-Silva AE, Romminger S, Morais RP, Bandeira K, Mizuno CM. Nat. Prod. Rep. 2010;27:1871–1907. - PubMed
    3. Berlinck RGS, Burtoloso ACB, Kossuga MH. Nat. Prod. Rep. 2008;25:919–954. - PubMed
    4. Berlinck RGS, Kossuga MH. Nat. Prod. Rep. 2005;22:516–550. - PubMed
    5. Bewley CA, Ray S, Cohen F, Collins SK, Overman LE. J. Nat. Prod. 2004;67:1319–1324. - PubMed
    1. Laville R, Thomas OP, Berrue F, Marquez D, Vacelet J, Amade P. J. Nat. Prod. 2009;72:1589–1594. - PubMed
    2. Gallimore WA, Kelly M, Scheuer PJ. J. Nat. Prod. 2005;68:1420–1423. - PubMed
    3. Hua H–M, Peng J, Dunbar DC, Schinazi RF, de Castro Andrews AG, Cuevas C, Garcia-Fernandez LF, Kelly M, Hamann MT. Tetrahedron. 2007;63:11179–11188.
    4. Patil AD, Kumar NV, Kokke WC, Bean MF, Freyer AJ, De Brosse C, Mai S, Truneh A, Faulkner DJ, Carte B, Breen AL, Hertzberg RP, Johnson RK, Westley JW, Potts BCM. J. Org. Chem. 1995;60:1182–1188.
    1. Takishima S, Ishiyama A, Iwatsuki M, Otoguro K, Yamada H, Omura S, Kobayashi H, van Soest RWM, Matsunaga S. Org. Lett. 2009;11:2655–2658. - PubMed
    2. Takishima S, Ishiyama A, Iwatsuki M, Otoguro K, Yamada H, Omura S, Kobayashi H, van Soest RWM, Matsunaga S. Org. Lett. 2010;12:896. - PubMed
    1. Martin V, Vale C, Bondu S, Thomas OP, Vieytes MR, Botana LM. Chem. Res. Toxicol. 2013;26:169–178. - PubMed
    2. Braekman JC, Daloze D, Tavares R, Hajdu E, Van Soest RWM. J. Nat. Prod. 2000;63:193–196. - PubMed
    3. Jares-Erijman EA, Sakai R, Rinehart KL. J. Org. Chem. 1991;56:5712–5715.

Publication types

MeSH terms