5004-46-6Relevant articles and documents
Light-Enabled Radical 1,4-Aryl Migration Via a Phospho-Smiles Rearrangement
De Abreu, Maxime,Belmont, Philippe,Brachet, Etienne
, p. 3758 - 3767 (2021/02/01)
Rearrangement reactions in organic chemistry are attractive strategies to build efficiently complex scaffolds, in just one step, from simple starting materials. Among them, aryl migrations are certainly one of the most useful and straightforward rearrangement for building attractive carbon-carbon bonds. Of note, anionic aryl migration reactions have been largely described compared to their radical counterparts. Recently, visible-light catalysis has proven its efficiency to generate such radical rearrangements due to the concomitant loss of a particle (often CO2 or SO2), which is the driving-force of the reaction. Here, we disclose a Smiles-type rearrangement, triggered by a phosphorus-containing unit (arylphosphoramidate), therefore called "phospho-Smiles"rearrangement, allowing a Csp2-Csp2 bond formation thanks to a 1,4-aryl migration reaction. In addition, combining this approach with a radical hydroamination/amination reaction produces an amination/phospho-Smiles cascade particularly attractive, for instance, to investigate the synthesis of the phthalazine core, a scarcely described scaffold of interest for medicinal chemistry projects.
Phosphoramidates as Transient Precursors of Nitrogen-Centered Radical Under Visible-Light Irradiation: Application to the Synthesis of Phthalazine Derivatives
De Abreu, Maxime,Selkti, Mohamed,Belmont, Philippe,Brachet, Etienne
, p. 2216 - 2222 (2020/03/19)
Phosphoramidates are for the first time presented as efficient N-Centered Radical (NCR) precursors under visible-light irradiation. More precisely among this class of phosphorus-derived compounds, we studied the radical reactivity of phosphonohydrazones, under mild reaction conditions, which allowed the synthesis of a wide and diversified library of the scarcely reported phthalazine scaffold. Mechanistic investigations confirmed the formation of a NCR from these brand-new phosphonohydrazones (derivatived from phosphoramidates), which were further engaged in an intramolecular 6-exo-dig cyclization to provide phthalazines. Compared to other pre-activated moieties, the phosphoramidate group is self-immolative, thus enhancing its attractiveness for the C?N bond formation. (Figure presented.).
Alcohols as alkylating agents in heteroarene C-H functionalization
Jin, Jian,MacMillan, David W. C.
, p. 87 - 90 (2015/09/15)
Redox processes and radical intermediates are found in many biochemical processes, including deoxyribonucleotide synthesis and oxidative DNA damage. One of the core principles underlying DNA biosynthesis is the radical-mediated elimination of H2O to deoxygenate ribonucleotides, an example of 'spin-centre shift', during which an alcohol C-O bond is cleaved, resulting in a carbon-centred radical intermediate. Although spin-centre shift is a well-understood biochemical process, it is underused by the synthetic organic chemistry community. We wondered whether it would be possible to take advantage of this naturally occurring process to accomplish mild, non-traditional alkylation reactions using alcohols as radical precursors. Because conventional radical-based alkylation methods require the use of stoichiometric oxidants, increased temperatures or peroxides, a mild protocol using simple and abundant alkylating agents would have considerable use in the synthesis of diversely functionalized pharmacophores. Here we describe the development of a dual catalytic alkylation of heteroarenes, using alcohols as mild alkylating reagents. This method represents the first, to our knowledge, broadly applicable use of unactivated alcohols as latent alkylating reagents, achieved via the successful merger of photoredox and hydrogen atom transfer catalysis. The value of this multi-catalytic protocol has been demonstrated through the late-stage functionalization of the medicinal agents, fasudil and milrinone.
Nature of Reissert Analogs Derived from N,N-Dialkyl and N,N-Diaryl Carbamoyl Chlorides
Kant, Joydeep,Popp, Frank D.,Uff, Barrie C.
, p. 1065 - 1070 (2007/10/02)
Reissert analogs were prepared from the reaction of isoquinoline and phthalazine with carbamoyl chlorides and cyanide using the methylene chloride-water method.Alkylation, condensation, Michael addition, and hydrolysis reactions of these Reissert analogs have been studied and found in many cases, to be similar to those of the isoquinoline Reissert compound.
A Search for Lone-Pair Interactions in Forward and Reverse Menschutkin Reactions of Some Diaza Heterocycles
Deady, Leslie W.
, p. 163 - 170 (2007/10/02)
The rates of methylation (forward reaction) of phthalazine (1), 1,8-naphthyridine (2), 1,10-phenanthroline (3), and of some ring methyl derivatives are compared with the rates of demethylation of the corresponding N-methyl quaternary iodides.It was observed for (2), and especially for (3), that a nitrogen lone pair in place of a CH group (quinoline and 8-methylquinoline, respectively) aids the forward reaction but does not have a commensurate retarding effect on the reverse process.In contrast to (3), 2,2'-bipyridine showed behaviour typical of α-substituted pyridines.The introduction of a 2-methyl group into (3) had an appreciable rate-enhancing effect on methylation (at N 10) and this is interpreted as evidence for lone-pair cooperativity in the forward reaction
