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

Angel García-Montero, Antonio M. Rodriguez, Alberto Juan, Aldrik H. Velders, Antonio Denisi, Gonzalo Jiménez-Osés, Enrique Gómez-Bengoa*, Carlos Cativiela, Maria Victoria Gómez, Esteban P. Urriolabeitia

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

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 CH2Cl2 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.
Original languageEnglish
Pages (from-to)8370-8381
JournalACS sustainable chemistry & engineering
Volume5
Issue number9
DOIs
Publication statusPublished - 2017

Keywords

  • DFT calculations
  • Diradical species
  • Flow chemistry
  • In-line NMR
  • Oxazolones
  • Photochemistry
  • Truxillic acids
  • [2 + 2]-Photocycloaddition

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