- Palladium-catalyzed enolate arylation as a key C-C bond-forming reaction for the synthesis of isoquinolines
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The palladium-catalyzed coupling of an enolate with an ortho-functionalized aryl halide (an α-arylation) furnishes a protected 1,5-dicarbonyl moiety that can be cyclized to an isoquinoline with a source of ammonia. This fully regioselective synthetic route tolerates a wide range of substituents, including those that give rise to the traditionally difficult to access electron-deficient isoquinoline skeletons. These two synthetic operations can be combined to give a three-component, one-pot isoquinoline synthesis. Alternatively, cyclization of the intermediates with hydroxylamine hydrochloride engenders direct access to isoquinoline N-oxides; and cyclization with methylamine, gives isoquinolinium salts. Significant diversity is available in the substituents at the C4 position in four-component, one-pot couplings, by either trapping the in situ intermediate after α-arylation with carbon or heteroatom-based electrophiles, or by performing an α,α-heterodiarylation to install aryl groups at this position. The α-arylation of nitrile and ester enolates gives access to 3-amino and 3-hydroxyisoquinolines and the α-arylation of tert-butyl cyanoacetate followed by electrophile trapping, decarboxylation and cyclization, C4-functionalized 3-aminoisoquinolines. An oxime directing group can be used to direct a C-H functionalization/bromination, which allows monofunctionalized rather than difunctionalized aryl precursors to be brought through this synthetic route.
- Pilgrim, Ben S.,Gatland, Alice E.,Esteves, Carlos H. A.,McTernan, Charlie T.,Jones, Geraint R.,Tatton, Matthew R.,Procopiou, Panayiotis A.,Donohoe, Timothy J.
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p. 1065 - 1090
(2016/01/15)
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- Modular isoquinoline synthesis using catalytic enolate arylation and in situ functionalization
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A methyl ketone, an aryl bromide, an electrophile, and ammonium chloride were combined in a four-component, three-step, and one-pot coupling procedure to furnish substituted isoquinolines in overall yields of up to 80%. This protocol utilizes the palladiu
- Pilgrim, Ben S.,Gatland, Alice E.,McTernan, Charlie T.,Procopiou, Panayiotis A.,Donohoe, Timothy J.
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p. 6190 - 6193
(2014/01/17)
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- New fluorescent isoquinoline derivatives
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Various structural modifications of 3-amino and 3-hydroxyisoquinolines have been carried out to provide new fluorescent derivatives. The transformations involved nucleophilic substitution of a bromine atom or a triflate moiety at positions 1 and 3, respectively, as well as the condensation reaction of a 3-amino group with triethyl orthoformate and subsequent transformation with amines to give amidines. The new compounds have been studied by fluorescence spectroscopy.
- Balog, József,Riedl, Zsuzsanna,Hajós, Gy?rgy,Miskolczy, Zsombor,Biczók, László
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p. 5264 - 5266
(2011/10/19)
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