573676-03-6Relevant articles and documents
Heterocyclic Allylsulfones as Latent Heteroaryl Nucleophiles in Palladium-Catalyzed Cross-Coupling Reactions
Markovic, Tim,Murray, Philip R.D.,Rocke, Benjamin N.,Shavnya, Andre,Blakemore, David C.,Willis, Michael C.
supporting information, p. 15916 - 15923 (2018/11/23)
Heterocyclic sulfinates are effective reagents in palladium-catalyzed coupling reactions with aryl and heteroaryl halides, often providing high yields of the targeted biaryl. However, the preparation and purification of complex heterocylic sulfinates can be problematic. In addition, sulfinate functionality is not tolerant of the majority of synthetic transformations, making these reagents unsuitable for multistep elaboration. Herein, we show that heterocyclic allylsulfones can function as latent sulfinate reagents and, when treated with a Pd(0) catalyst and an aryl halide, undergo deallylation, followed by efficient desulfinylative cross-coupling. A broad range of allyl heteroarylsulfones are conveniently prepared, using several complementary routes, and are shown to be effective coupling partners with a variety of aryl and heteroaryl halides. We demonstrate that the allylsulfone functional group can tolerate a range of standard synthetic transformations, including orthogonal C- and N-coupling reactions, allowing multistep elaboration. The allylsulfones are successfully coupled with a variety of medicinally relevant substrates, demonstrating their applicability in demanding cross-coupling transformations. In addition, pharmaceutical agents crizotinib and etoricoxib were prepared using allyl heteroaryl sulfone coupling partners, further demonstrating the utility of these new reagents.
Catalyst Selection Facilitates the Use of Heterocyclic Sulfinates as General Nucleophilic Coupling Partners in Palladium-Catalyzed Coupling Reactions
Markovic, Tim,Rocke, Benjamin N.,Blakemore, David C.,Mascitti, Vincent,Willis, Michael C.
supporting information, p. 6033 - 6035 (2017/11/27)
A range of 5- and 6-membered heterocycle-derived sulfinates are shown to be effective nucleophilic coupling partners with aryl chlorides and bromides using Pd(0) catalysis. The use of optimal reaction conditions, specifically incorporating a P(t-Bu)2Me-derived Pd catalyst, allowed reactions to be performed at moderate temperatures and enabled the inclusion of a variety of sensitive functional groups. Challenging heterocyclic sulfinates, including pyrazine, pyridazine, pyrimidine, pyrazole, and imidazole, were all shown to perform well.
Discovery of novel 6,6-heterocycles as transient receptor potential vanilloid (TRPV1) antagonists
Blum, Charles A.,Caldwell, Timothy,Zheng, Xiaozhang,Bakthavatchalam, Rajagopal,Capitosti, Scott,Brielmann, Harry,De Lombaert, Stéphane,Kershaw, Mark T.,Matson, David,Krause, James E.,Cortright, Daniel,Crandall, Marci,Martin, William J.,Murphy, Beth Ann,Boyce, Susan,Jones, A. Brian,Mason, Glenn,Rycroft, Wayne,Perrett, Helen,Conley, Rachael,Burnaby-Davies, Nicola,Chenard, Bertrand L.,Hodgetts, Kevin J.
experimental part, p. 3330 - 3348 (2010/09/07)
The transient receptor potential cation channel, subfamily V, member 1 (TRPV1) is a nonselective cation channel that can be activated by a wide range of noxious stimuli, including capsaicin, acid, and heat. Blockade of TRPV1 activation by selective antago
