ABSTRACT
Efavirenz is an essential medicine for the treatment of HIV, which is still inaccessible to millions of people worldwide. A novel, semi-continuous process provides rac-Efavirenz with an overall yield of 45%. This streamlined proof-of-principle synthesis relies on the efficient copper-catalyzed formation of an aryl isocyanate and a subsequent intramolecular cyclization to install the carbamate core of Efavirenz in one step. The three-step method represents the shortest synthesis of this life-saving drug to date.
Subject(s)
Anti-HIV Agents/chemical synthesis , Benzoxazines/chemical synthesis , Alkynes , Anti-HIV Agents/chemistry , Benzoxazines/chemistry , Carbamates/chemistry , Catalysis , Copper/chemistry , Cyclization , Cyclopropanes , Isocyanates/chemistryABSTRACT
A palladium-catalyzed coupling of N-heterocycles with simple alcohols was achieved. The reaction is initiated by peroxide and does not require the use of stoichiometric acid for activation of the heterocycle.
Subject(s)
Alcohols/chemistry , Alcohols/chemical synthesis , Palladium/chemistry , Catalysis , Heterocyclic Compounds/chemistry , Molecular Structure , StereoisomerismABSTRACT
An efficient rhodium(III)-catalyzed C-H activation and subsequent conjugate addition was achieved under mild conditions. The reaction utilized inert arenes to replace stoichiometric organometallic reagents and can tolerate various functional groups as well as air and water.
