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. 2017 Oct 19;73(42):6067-6079.
doi: 10.1016/j.tet.2017.08.052.

Exploring hydroamination-cycloaddition-fragmentation sequences to access polycyclicguanidines and vinyl-2-aminoimidazoles

Ki-Hyeok Kwon  1 , Anne V Edwards  1 , Miao Yang  1 , Ryan E Looper  1
Affiliations

Exploring hydroamination-cycloaddition-fragmentation sequences to access polycyclicguanidines and vinyl-2-aminoimidazoles

Ki-Hyeok Kwon et al. Tetrahedron. .

Abstract

The intramolecular hydroamination of a guanidine on an eneyne unit affords a guanidine-substituted diene capable of reacting with dienophiles. These substrates undergo [4+2]-cycloaddition reactions to generate a series of complex cyclic- and spirocyclic-guanidines. Select substrates can further undergo a ring opening-elimination cascade that ultimately reveals a vinyl-2-aminoimidazole. As such this cascade reaction may find application in the synthesis of oroidin-type natural products and their analogues.

Keywords: 2-aminoimidazoles; Alkaloids; Cycloaddition; Heterocycle; Hydroamination.

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Figures

Figure 1
Figure 1
Biogenesis of complex pyrrole-2-aminoimidazole alkaloids form simple precursors.
Scheme 1
Scheme 1
Applications of ene-ynes in the the guanidine hydroamination sequence.
Scheme 2
Scheme 2
6-endo-selective hydroamination / [4+2]-cycloaddition sequence to access polyclicguanidines.
Scheme 3
Scheme 3
Scope of the 6-endo-selective hydroamination / [4+2]-cycloaddition sequence.
Scheme 4
Scheme 4
5-exo-selective hydroamination / [4+2]-cycloaddition sequence.
Scheme 5
Scheme 5
5-exo-selective hydroamination / [4+2]-cycloaddition-fragmentation sequence.
Scheme 6
Scheme 6
Scope of the [4+2]-Cycloaddition-fragmentation sequence to access vinyl-2-aminoimidazoles.
Scheme 7
Scheme 7
[4+2]-Cycloaddition sequence with an acylnitroso-dienophile.
Scheme 8
Scheme 8
Hydroamination-Michael addition-[4+2]-cycloaddition sequence.
See this image and copyright information in PMC

References

    1. Forte B, Malgesini B, Piutti C, Quartieri F, Scolaro A, Papeo G. A Submarine Journey: The Pyrrole-Imidazole Alkaloids. Marine Drugs. 2009;7(4):705–753. - PMC - PubMed
    1. Wang X, Ma Z, Wang X, De S, Ma Y, Chen C. Dimeric pyrrole-imidazole alkaloids: Synthetic approaches and biosynthetic hypotheses. Chemical communications (Cambridge, England) 2014;50(63):8628–8639. - PMC - PubMed
    1. Harris TL, Worthington RJ, Melander C. Potent Small-Molecule Suppression of Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus. Angew Chem Int Ed. 2012;51(45):11254–11257. - PMC - PubMed
    2. Yeagley AA, Su Z, McCullough KD, Worthington RJ, Melander C. N-Substituted 2-aminoimidazole inhibitors of MRSA biofilm formation accessed through direct 1,3-bis(tert-butoxycarbonyl)guanidine cyclization. Org Biomol Chem. 2013;11(1):130–137. - PubMed
    3. Worthington RJ, Richards JJ, Melander C. Non-Microbicidal Control of Bacterial Biofilms with Small Molecules. Anti-Infect Agents. 2014;12(1):120–138.
    1. Al Mourabit A, Potier P. Sponge’s Molecular Diversity Through the Ambivalent Reactivity of 2-Aminoimidazole: A Universal Chemical Pathway to the Oroidin-Based Pyrrole-Imidazole Alkaloids and Their Palau’amine Congeners. European Journal of Organic Chemistry. 2001;2001(2):237–243.
    1. Gainer MJ, Bennett NR, Takahashi Y, Looper RE. Regioselective Rhodium (II)‐Catalyzed Hydroaminations of Propargylguanidines. Angew Chem. 2011;123(3):710–713. - PMC - PubMed