Regioselective Multicomponent Synthesis of 2,4,6-Trisubstituted Phenols from Fischer Alkynyl Carbene Complexes

• Published in: European journal of organic chemistry 2016-03, Vol.2016 (7), p.1314-1323
• Main Authors: López, Julio, de la Cruz, Fabiola N., Flores-Conde, María Inés, Flores-Álamo, Marcos, Delgado, Francisco, Tamariz, Joaquín, Vázquez, Miguel A.
• Format: Article
• Language: English
• Subjects: Alcohol; Alkynes; Carbene ligands; Cycloaddition; Fischer carbenes; Phenols
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201501211

A series of 2,4,6‐trisubstituted phenols 7a–7p has been prepared in moderate to good yields (23–77 %) by a retro‐Diels–Alder reaction from hindered tricyclic alcohols 6a–6q, using mild acidic conditions. The tricyclic alcohols were obtained by reduction of highly functionalized cyclohexadienones 5a–5q, which in turn were regioselectively prepared under mild conditions in high yields by treatment of a series of stable chromium(0) and tungsten(0) Fischer dienyl carbenes 4a–4g with different terminal alkynes 3a–3l. Carbenes 4a–4g were prepared by a [4+2] cycloaddition of alkynylethoxy carbene complexes 1a–1g with 1,2,3,4,5‐pentamethylcyclopentadiene (2). In a complementary route, compounds 5a–5q were also obtained by a multicomponent reaction in yields similar to those obtained in the multistep process (25–84 %), starting from 1a–1g, 2, and 3a–3l. The phenol products have a wide range of potential applications, and may be useful intermediates for further transformations. 2,4,6‐Trisubstituted phenols were prepared by a retro‐Diels–Alder reaction from hindered tricyclic alcohols under acidic conditions. The tricyclic alcohols were obtained by the reduction of cyclohexadienones, which in turn were prepared by the reaction of Fischer dienyl carbenes with terminal alkynes. The dienyl carbenes were prepared from alkynyl Fischer carbenes and pentamethylcyclopentadiene.