Organic Process Research & Development
Article
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(17) It is worth noting that milled bases, particularly K3PO4, often
exhibit a pronounced increase in hygroscopicity compared with the
unmilled bases.
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for the Coupling of 2-Aminopyridine Derivatives. Chem. - Eur. J. 2017,
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(29) For examples of the use of DBU in intramolecular direct
arylation at 145−180 °C, see: (a) Hostyn, S.; Van Baelen, G.;
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Lemiere, G. L. F.; Maes, B. U. W. Synthesis of α-Carbolines Starting
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(30) (a) Dennis, J. M.; White, N. A.; Liu, R. Y.; Buchwald, S. L.
Breaking the Base Barrier: An Electron-Deficient Palladium Catalyst
Enables the Use of a Common Soluble Base in C−N Coupling. J. Am.
Chem. Soc. 2018, 140, 4721−4725. (b) Dennis, J. M.; White, N. A.;
Liu, R. Y.; Buchwald, S. L. Pd-Catalyzed C−N Coupling Reactions
Facilitated by Organic Bases: Mechanistic Investigation Leads to
Enhanced Reactivity in the Arylation of Weakly Binding Amines. ACS
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(31) (a) Ikawa, T.; Barder, T. E.; Biscoe, M. R.; Buchwald, S. L. Pd-
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(b) Hicks, J. D.; Hyde, A. M.; Cuezva, A. M.; Buchwald, S. L. Pd-
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(32) (a) Wolfe, J. P.; Buchwald, S. L. Palladium-Catalyzed
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(23) Inankur, B.; Simmons, E.; Dong, L.; Treitler, D.; Rogers, A.;
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(34) Lovinger, G. J.; Aparece, M. D.; Morken, J. P. Pd-Catalyzed
Conjunctive Cross-Coupling between Grignard-Derived Boron “Ate”
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(35) Edelstein, E. K.; Namirembe, S.; Morken, J. P. Enantioselective
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(24) DBU is available in bulk quantities from Chem-Impex (up to
186 L) and Oakwood (up to 200 kg) at a cost of ca. $40/kg ($6/
mol).
́
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(36) For the related use of NaOTf to sequester chloride from
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(26) For pKa measurements on strong organic bases in organic
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(37) An in situ-generated iPr2EtNH+p-NO2PhCO2 salt has been
reported to promote halide ionization in asymmetric Heck reactions.
See: Wu, C.; Zhou, J. Asymmetric Intermolecular Heck Reaction of
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(27) A single example of the Et3N-mediated, Pd-catalyzed
intramolecular amination of an aryl iodide has been reported. See:
(a) Wolfe, J. P.; Rennels, R. A.; Buchwald, S. L. Intramolecular
palladium-catalyzed aryl amination and aryl amidation. Tetrahedron
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activated heteroaryl chlorides with secondary amines was reported.
See: (b) Murthy Bandaru, S. S.; Bhilare, S.; Chrysochos, N.; Gayakhe,
V.; Trentin, I.; Schulzke, C.; Kapdi, A. R. Pd/PTABS: Catalyst for
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(28) Tundel, R. E.; Anderson, K. W.; Buchwald, S. L. Expedited
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(40) (a) DeAngelis, A. J.; Gildner, P. G.; Chow, R.; Colacot, T. J.
Generating Active “L-Pd(0)” via Neutral or Cationic π-Allylpalladium
H
Org. Process Res. Dev. XXXX, XXX, XXX−XXX