A simple, modular method for the synthesis of 3,4,5-trisubstituted pyrazoles.
A modular approach for the regiocontrolled preparation of pyrazoles bearing substituents on all three carbon atoms is described. Central to this method is the use of a switchable metal-directing group (MDG) to enable sequential direct lithiation of the 3- and 5-positions of the pyrazole ring. Pyrazole boronic esters obtained from these lithiated intermediates can undergo efficient Suzuki cross-coupling under the developed nonaqueous conditions, which minimize undesirable protolytic deboronation. Halogenation of the 4-position provides the means for substitution at the remaining carbon atom.
McLaughlin
Mark
M
Process Research, Merck Research Laboratories, Rahway, NJ 07065, USA. mark_mclaughlin@merck.com
Marcantonio
Karen
K
Chen
Cheng-Yi
CY
Davies
Ian W
IW
D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization
D011720:Pyrazoles