Gold Catalysis: Domino Reaction of En-Diynes to Highly Substituted Phenols

• Published in: Chemistry : a European journal 2011-07, Vol.17 (29), p.8195-8201
• Main Authors: Hashmi, A. Stephen K., Häffner, Tobias, Rudolph, Matthias, Rominger, Frank
• Format: Article
• Language: English
• Subjects: Alcohol; alkynes; Chemistry; domino reactions; furans; gold; Phenols
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201100305

By Sonogashira coupling of 1,7‐heptadiynes and 1,8‐octadiynes with 2‐iodoallyl alcohols, various substrates that bear a 2‐alkynylallyl alcohol moiety tethered to an additional alkyne were prepared in one step. Subjection to nitrogen acyclic carbene (NAC)/gold(I) catalysts delivered highly substituted phenols in an efficient domino reaction. Furan derivatives were formed as intermediates; this was proven by in situ NMR spectroscopy. The uncommon substitution pattern of these furans opens the way for a selective formation of phenols that contain the hydroxyl group in the meta position to the ring junction, which previously was not possible by gold‐catalyzed furan‐yne cyclization. Furthermore, interesting mechanistic insights were obtained by products derived from secondary allyl alcohols. In this case, in addition to the phenolic compounds, a ketone is formed by 1,2‐alkyl shift. Domino effect: An untypical but synthetically very useful selectivity of the gold‐catalyzed phenol synthesis is observed in the conversion of easily accessible en‐diynols. Mechanistic studies by in situ NMR spectroscopy confirm the normal reaction pathway that involves furan‐ynes. Carbene ligands on the gold(I) catalysts are pivotal for a successful conversion.