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Monday, September 24, 2012
Douglass F. Taber
University of Delaware

Development of Flow Reactions

For a review of a monograph by C. Wiles and P. Watts on applications of flow reactors in organic synthesis, see Org. Process. Res. Dev. 2011, 15, 947 (DOI: 10.1021/op200137w). For a review by Klavs S. Jensen of MIT of flow approaches, see Angew. Chem. Int. Ed. 2011, 50, 7502 (DOI: 10.1002/anie.201004637). Hans-René Bjřrsvik of the University of Bergen described (Org. Process. Res. Dev. 2011, 15, 997. DOI: 10.1021/op2000699) a multijet oscillating disc microreactor, and Andreas Schmid of the Technische Universität Dortmund (Adv. Synth. Catal. 2011, 353, 2511. DOI: 10.1002/adsc.201100394) and László Poppe of the Budapest University of Technology and Economics discussed (Adv. Synth. Catal. 2011, 353, 2481. DOI: 10.1002/adsc.201100329) continuous flow reactors for biotransformations.

Gases are readily handled in a flow apparatus. S. Chandrasekhar of the Indian Institute of Chemical Technology, Hyderabad demonstrated (Tetrahedron Lett. 2011, 52, 3865. DOI: 10.1016/j.tetlet.2011.05.042) partial deuteration of 1 to 2, using D2O as the deuterium source. Peter H. Seeberger of the Max Planck Institute of Colloids and Interfaces, Potsdam oxidized (Org. Lett. 2011, 13, 5008. DOI: 10.1021/ol2017643) 3 to 4 with singlet oxygen. Dong-Pyo Kim of Chungnam National University and Robert H. Grubbs of Caltech effected (Org. Lett. 2011, 13, 2398. DOI: 10.1021/ol200634y) ethenolysis of 5 to give 6 and 7. Takashi Takahashi of the Tokyo Institute of Technology showed (Chem. Commun. 2011, 47, 12661. DOI: 10.1039/C1CC15662D) that even phosgene could be handled in a flow system, using it to activate 8 for condensation with benzylamine to give 9.

In the liquid phase, Stephen L. Buchwald of MIT prepared (Angew. Chem. Int. Ed. 2011, 50, 8900. DOI: 10.1002/anie.201104652) 11 by the fluorination of 10. Jesús Alcázar of Janssen Pharmaceutical, Toledo, showed (Tetrahedron Lett. 2011, 52, 6058. DOI: 10.1016/j.tetlet.2011.08.144) that a nitrile 12 could be reduced in a flow system to the aldehyde 13.

Mark York of CSIRO prepared (Tetrahedron Lett. 2011, 52, 6267. DOI: 10.1016/j.tetlet.2011.09.083) the furan 16 by condensation of 14 with 15. Floris P. J. T. Rutjes of Radboud University Nijmegen used (Org. Process Res. Dev. 2011, 15, 783. DOI: 10.1021/op100338z) the careful controls of a flow reactor to optimize the exothermic combination of 17 with 18 to give 19.

Professor Buchwald demonstrated (Angew. Chem. Int. Ed. 2011, 50, 10665. DOI: 10.1002/anie.201105223) a flow protocol for the lithiation of 20 with in situ borylation and Pd-catalyzed coupling with 21 to give 22. Juan A. Rincón of Lilly S. A. effected (Org. Process Res. Dev. 2011, 15, 1428. DOI: 10.1021/op200162c) thermal rearrangement of 23 to 24. Matjaž Krajnc of the University of Ljubljana devised (Org. Process Res. Dev. 2011, 15, 817. DOI: 10.1021/op200061j) an aqueous phase transfer procedure for the Wittig condensation of 25 with 26 to give 27.

Although many interesting and potentially useful electrolytic synthetic protocols have been developed, these are only rarely used preparatively because of the expense of the to-scale electrolysis apparatus. Kazuhiro Chiba of the Tokyo University of Agriculture and Technology constructed (Tetrahedron Lett. 2011, 52, 4690. DOI: 10.1016/j.tetlet.2011.07.007) an electrochemical flow apparatus with which he oxidized 28 to the corresponding quinone, that then participated in a Diels-Alder cycloaddition with the diene 29 to give 30.

D. F. Taber, Org. Chem. Highlights 2012, September 24.