Metal-free [2 + 2]-photocycloaddition of (Z)-4-aryliden-5(4H)-oxazolones as straightforward synthesis of 1,3-diaminotruxillic acid precursors: Synthetic scope and mechanistic studies

The direct [2 + 2]-photocycloaddition of (Z)-2-phenyl-4-aryliden-5(4H)-oxazolones 1 to give 1,3-diaminotruxillic cyclobutane derivatives 2 in very good yields (75-100%) is reported. The reaction takes place by irradiation of CHCl solutions of 1 with blue light (465 nm) provided by light-emitting dio...

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Detalles Bibliográficos
Autores: García-Montero, Ángel, Rodríguez-García, Antonio M., Juan, Alberto, Velders, Aldrik H., Denisi, Antonio, Jiménez-Osés, Gonzalo, Gómez-Bengoa, Enrique, Cativiela, Carlos, Gómez, M. Victoria, Urriolabeitia, Esteban P.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2017
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/164903
Acceso en línea:http://hdl.handle.net/10261/164903
Access Level:acceso abierto
Palabra clave:Photochemistry
[2 + 2]-Photocycloaddition
Truxillic acids
Oxazolones
In-line NMR
Flow chemistry
Diradical species
DFT calculations
Descripción
Sumario:The direct [2 + 2]-photocycloaddition of (Z)-2-phenyl-4-aryliden-5(4H)-oxazolones 1 to give 1,3-diaminotruxillic cyclobutane derivatives 2 in very good yields (75-100%) is reported. The reaction takes place by irradiation of CHCl solutions of 1 with blue light (465 nm) provided by light-emitting diode (LED) lamps of low power (around 1 W) for 72 h. Four isomers of the 1,3-diaminotruxillic cyclobutanes 2 were obtained; all of them fully characterized by a combination of nuclear magnetic resonance (NMR) spectroscopy and X-ray diffraction analysis. The reaction shows a certain selectivity, since one of the isomers (the epsilon) is obtained preferentially, and works for electron-releasing and electron-withdrawing substituents at the arylidene ring. A novel setup is presented for the in-line monitoring of the continuous flow photoassisted synthesis of the cyclobutane derivatives 2 by NMR spectroscopy, with the microreactor dramatically reducing reaction times to only 30 min with clear product distribution of up to four isomers. The mechanism of this [2 + 2]-photocycloaddition has been calculated by density functional theory (DFT) methods, explaining all experimental findings. The reaction takes place through a stepwise formation of two new C-C bonds through a transient diradical singlet intermediate. The isomeric distribution of the final products is not due to equilibration processes but instead reflects the kinetic preference during the rate limiting C-C bond formation step.