Regioselective preparation of 2-substituted 3,4-diaryl pyrroles: a concise total synthesis of ningalin B.
Methylisocyanoacetate undergoes a 2 + 3 cycloaddition with alpha,beta-unsaturated nitriles to provide a regioselective synthesis of 2-substituted 3,4-diaryl pyrroles. The ease of preparation of alpha,beta-unsaturated nitriles allows the rapid synthesis of pyrroles with varied substituents. Using this method, a key intermediate (1) for the synthesis of the marine natural products lukianol A, lamellarin O, and lamellarin Q was prepared in two steps. A total synthesis of ningalin B (11) was also accomplished utilizing this methodology.
Bullington
James L
JL
Discovery Research, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 1000 Route 202, Raritan, New Jersey 08869, USA. jbulling@prdus.jnj.com
Wolff
Russell R
RR
Jackson
Paul F
PF
D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D006575:Heterocyclic Compounds, 3-Ring / Q000032:analysis / Q000138:chemical synthesis*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011720:Pyrazoles / Q000138:chemical synthesis; D011758:Pyrroles / Q000032:analysis / Q000138:chemical synthesis*; D013237:Stereoisomerism
D006575:Heterocyclic Compounds, 3-Ring; D011720:Pyrazoles; D011758:Pyrroles; C116875:lukianol A; C409782:ningalin B