- Heterocyclic Allylsulfones as Latent Heteroaryl Nucleophiles in Palladium-Catalyzed Cross-Coupling Reactions
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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.
- Markovic, Tim,Murray, Philip R.D.,Rocke, Benjamin N.,Shavnya, Andre,Blakemore, David C.,Willis, Michael C.
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p. 15916 - 15923
(2018/11/23)
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- Catalyst Selection Facilitates the Use of Heterocyclic Sulfinates as General Nucleophilic Coupling Partners in Palladium-Catalyzed Coupling Reactions
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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.
- Markovic, Tim,Rocke, Benjamin N.,Blakemore, David C.,Mascitti, Vincent,Willis, Michael C.
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supporting information
p. 6033 - 6035
(2017/11/27)
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- One-Pot Palladium-Catalyzed Cross-Coupling Treble of Borylation, the Suzuki Reaction and Amination
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A methodology for a sequential palladium-catalyzed cross-coupling procedure consisting of borylation, the Suzuki reaction and amination has been developed for the assembly of molecules with multi-aryl backbones. The linchpin of this development is the meta-terarylphosphine ligand, Cy*Phine, which has been employed as an air- and moisture-stable precatalyst, Pd(Cy*Phine)2Cl2, to improve the efficiency of one-pot borylation–Suzuki reactions. Additionally, the reactivity of the Pd-Cy*Phine system could be tuned to furnish a one-pot, borylation–Suzuki reaction–amination (BSA) cross-coupling treble. The methodology successfully integrated complementary conditions for three distinctly different and modular reactions. Average yields of 74–94% could be achieved for each segment that cumulatively afforded 50–84% yield over the entire three-step sequence in a single pot. (Figure presented.).
- Jong, Howard,Eey, Stanley T.-C.,Lim, Yee Hwee,Pandey, Sangeeta,Iqbal, Nurul Azmah Bte,Yong, Fui Fong,Robins, Edward G.,Johannes, Charles W.
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supporting information
p. 616 - 622
(2017/02/23)
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- Functionalized heteroarylpyridazines and pyridazin-3(2H)-one derivatives via palladium-catalyzed cross-coupling methodology
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(Chemical Equation Presented) A general method for the synthesis of functionalized pyridazinylboronic acids/esters is described involving a directed ortho metalation (DoM)-boronation protocol (Schemes 1 and 2). A comprehensive study of the reactivity of t
- Clapham, Kate M.,Batsanov, Andrei S.,Greenwood, Ryan D. R.,Bryce, Martin R.,Smith, Amy E.,Tarbit, Brian
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p. 2176 - 2181
(2008/09/19)
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- Preparation of functionalized aryl- and heteroarylpyridazines by nickel-catalyzed electrochemical cross-coupling reactions
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(Chemical Equation Presented) A general efficient electrochemical method for the preparation of aryl- and heteroarylpyridazines in a nickel-catalyzed cross-coupling reaction of 3-chloro-6-methoxypyridazine and 3-chloro-6- methylpyridazine with a range of functionalized aryl or heteroaryl halides is reported.
- Sengmany, Stephane,Leonel, Eric,Polissaint, Frantz,Nedelec, Jean-Yves,Pipelier, Muriel,Thobie-Gautier, Christine,Dubreuil, Didier
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p. 5631 - 5636
(2008/02/09)
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- New catalysts for Suzuki-Miyaura coupling reactions of heteroatom- substituted heteroaryl chlorides
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(Chemical Equation Presented) The new air-stable PdCl2{PR 2(Ph-R′)}2 complexes, readily prepared from commercial reagents, exhibit unique efficiency as catalysts for the Suzuki-Miyaura coupling reactions of a variety of he
- Guram, Anil S.,Wang, Xiang,Bunel, Emilio E.,Faul, Margaret M.,Larsen, Robert D.,Martinelli, Michael J.
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p. 5104 - 5112
(2008/02/07)
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- New air-stable catalysts for general and efficient Suzuki-Miyaura cross-coupling reactions of heteroaryl chlorides
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New air-stable PdCl2{ PtBu2(p-R-Ph)} 2 (R = H, NMe2, CF3,) complexes represent simple, general, and efficient catalysts for the Suzuki-Miyaura cross-coupling reactions of aryl halides including five-membered heteroaryl halides and heteroatom-substituted six-membered heteroaryl chlorides with a diverse range of arylboronic acids. High product yields (89-99% isolated yields) and turn-over-numbers (10 000 TON) are observed.
- Guram, Anil S.,King, Anthony O.,Allen, John G.,Wang, Xianghong,Schenkel, Laurie B.,Chan, Johann,Bunel, Emilio E.,Faul, Margaret M.,Larsen, Robert D.,Martinelli, Michael J.,Reider, Paul J.
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p. 1787 - 1789
(2007/10/03)
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- Synthesis of substituted 3-amino-6-arylpyridazines via Suzuki reaction
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Starting from the commercially available 3,6-dichloropyridazine, N3- substituted 3-amino-6-arylpyridazines were prepared in good yields and under mild conditions by means of two simple steps: a nucleophilic substitution and a palladium-catalyzed Suzuki coupling.
- Parrot,Rival,Wermuth
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p. 1163 - 1168
(2007/10/03)
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