Highly regioselective palladium-catalyzed direct arylation of oxazole at C-2 or C-5 with aryl bromides, chlorides, and triflates.
Complementary palladium-catalyzed methods for direct arylation of oxazole with high regioselectivity (>100:1) at both C-5 and C-2 have been developed for a wide range of aryl and heteroaryl bromides, chlorides, iodides, and triflates. C-5 arylation is preferred in polar solvents with phosphines 5 or 6, whereas C-2 arylation is preferred by nonpolar solvents and phosphine 3. This represents the first general method for C-5 selective arylation of oxazole and should see broad applicability in the synthesis of biologically active molecules. Additionally, potential mechanisms for these two competing arylation processes are proposed on the basis of mechanistic observations.
Strotman
Neil A
NA
Department of Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065, USA. neil_strotman@merck.com
Chobanian
Harry R
HR
Guo
Yan
Y
He
Jiafang
J
Wilson
Jonathan E
JE
D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D006842:Hydrocarbons, Brominated / Q000737:chemistry*; D006843:Hydrocarbons, Chlorinated / Q000737:chemistry*; D008698:Mesylates / Q000737:chemistry*; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
D006842:Hydrocarbons, Brominated; D006843:Hydrocarbons, Chlorinated; D008698:Mesylates; D010080:Oxazoles; D010165:Palladium