129822-52-2Relevant articles and documents
Formation of Aza-ortho-quinone Methides under Room Temperature Conditions: Cs2CO3 Effect
Walden, Daniel M.,Jaworski, Ashley A.,Johnston, Ryne C.,Hovey, M. Todd,Baker, Hannah V.,Meyer, Matthew P.,Scheidt, Karl A,Cheong, Paul Ha-Yeon
, p. 7183 - 7189 (2017)
Since the first report of a facile, room temperature process to access aza-ortho-quinone methides (aoQMs) by Corey in 1999, this chemistry has remained dormant until our report of an enantioselective catalytic example in 2014. We report a theoretical and experimental study of the key to success behind these successful examples to enable broader exploitation of this useful intermediate. We have discovered that transformations involving the aoQM are remarkably facile with barriers 30 kcal/mol), precluding their formation under mild conditions. The use of Cs2CO3 as base is critical. It provides a thermodynamically and kinetically favorable means to form aoQMs, independent of the salt solubility and base strength. The exothermic formation of salt byproducts provides a driving force (average ΔG = -30.8 kcal/mol) compensating for the majority of the inherent unfavorable thermodynamics of aoQM formation.
N-heterocyclic-carbene-catalyzed synthesis of 2-aryl indoles
Hovey, M. Todd,Check, Christopher T.,Sipher, Alexandra F.,Scheidt, Karl A.
supporting information, p. 9603 - 9607 (2014/10/15)
A convergent and efficient transition-metal-free catalytic synthesis of 2-aryl-indoles has been developed. The interception of a highly reactive and transient aza-ortho-quinone methide by an acyl anion equivalent generated through N-hetereocyclic carbene catalysis is central to this successful strategy. High yields and a wide scope as well as the streamlined synthesis of a kinase inhibitor are reported. Umpolung: N-heterocyclic carbene catalysis is used for the convergent and efficient transition-metal-free synthesis of 2-aryl-indoles. The interception of a highly reactive and transient aza-ortho-quinone methide by an acyl anion equivalent is central to this successful strategy. The reaction exhibits high yields and a wide scope, and it has been applied to a streamlined synthesis of a kinase inhibitor.
