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Article << Previous     |     Next >>   Contents Vol 66(2)

Generation and Reactions of Pyridyllithiums via Br/Li Exchange Reactions Using Continuous Flow Microreactor Systems

Aiichiro Nagaki A , Daisuke Yamada A , Shigeyuki Yamada A , Masatomo Doi A , Daisuke Ichinari A , Yutaka Tomida A , Naofumi Takabayashi A and Jun-ichi Yoshida A B

A Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
B Corresponding author. Email: yoshida@sbchem.kyoto-u.ac.jp

Australian Journal of Chemistry 66(2) 199-207 http://dx.doi.org/10.1071/CH12440
Submitted: 25 September 2012  Accepted: 28 November 2012   Published: 9 January 2013


 
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Abstract

A continuous flow microreactor method for generating and carrying out reactions on pyridyllithiums has been developed based on Br/Li exchange reactions of bromopyridines and dibromopyridines. The reactions can be carried out without using cryogenic conditions by virtue of short residence times and efficient heat transfer, while very low temperatures such as –78 or –110°C are required for conventional batch macro methods. Moreover, sequential introduction of two different electrophiles has been successfully achieved using dibromopyridines in an integrated flow microreactor system composed of four micromixers and four microtube reactors.





References

[1]  R. Chinchilla, C. Nájera, M. Yus, Chem. Rev. 2004, 104, 2667. and references cited therein
         | CrossRef | CAS |

[2]     (a) P. Knochel, Handbook of Functionalized Organometallics 2005 (Wiley-VCH: Weinheim).
      (b) A. Boudier, L. O. Bromm, M. Lotz, P. Knochel, Angew. Chem. Int. Ed. 2000, 39, 4414.
         | CrossRef |
      (c) P. Knochel, W. Dohle, N. Gommermann, F. F. Kneisel, F. Kopp, T. Korn, I. Sapountzis, V. A. Vu, Angew. Chem. Int. Ed. 2003, 42, 4302.
         | CrossRef |

[3]  J. Clayden, Organolithiums: Selectivity for Synthesis 2002 (Pergamon: Amsterdam).

[4]  (a) G. Quéguiner, F. Marsais, V. Snieckus, J. Epsztajn, Adv. Heterocycl. Chem. 1991, 52, 187.
         | CrossRef |
      (b) A. Godard, F. Marsais, N. Plé, F. Trécourt, A. Turck, G. Quéguiner, Heterocycles 1995, 40, 1055.
         | CrossRef |
      (c) F. Trécourt, B. Gervais, M. Mallet, G. Quéguiner, J. Org. Chem. 1996, 61, 1673.
         | CrossRef |
      (d) F. Trécourt, B. Gervais, O. Mongin, C. Le Gal, F. Mongin, G. Quéguiner, J. Org. Chem. 1998, 63, 2892.
         | CrossRef |
      (e) E. Pasquinet, P. Rocca, F. Marsais, A. Godard, G. Quéguiner, Tetrahedron 1998, 54, 8771.
         | CrossRef |
      (f) P. C. Gros, Y. Fort, Eur. J. Org. Chem. 2009, 4199.
         | CrossRef |

[5]  (a) H. Gilman, S. M. Spatz, J. Org. Chem. 1951, 16, 1485.
         | CrossRef | CAS |
      (b) H. Gilman, W. A. Gregory, S. M. Spatz, J. Org. Chem. 1951, 16, 1788.
         | CrossRef |
      (c) J. P. Wibaut, L. G. Heeringa, Recl. Trav. Chim. Pays Bas 1955, 74, 1003.
         | CrossRef |
      (d) W. E. Parham, R. M. Piccirilli, J. Org. Chem. 1977, 42, 257.
         | CrossRef |
      (e) G. R. Newkome, J. M. Roper, J. Organomet. Chem. 1980, 186, 147.
         | CrossRef |
      (f) M. Mallet, G. Quéguiner, Tetrahedron 1986, 42, 2253.
         | CrossRef |
      (g) M. Mallet, G. Branger, F. Marsais, G. Quéguiner, J. Organomet. Chem. 1990, 382, 319.
         | CrossRef |
      (h) D. Cai, D. L. Hughes, T. R. Verhoeven, Tetrahedron Lett. 1996, 37, 2537.
         | CrossRef |
      (i) R. H. Furneaux, G. Limberg, P. C. Tyler, V. L. Schramm, Tetrahedron 1997, 53, 2915.
         | CrossRef |
      (j) M. A. Peterson, J. R. Mitchell, J. Org. Chem. 1997, 62, 8237.
         | CrossRef |

[6]     (a) Books on microreactor synthesis: W. Ehrfeld, V. Hessel, H. Löwe, Microreactors 2000 (Wiley-VCH: Weinheim).
         (b) V. Hessel, S. Hardt, H. Löwe, Chemical Micro Process Engineering 2004 (Wiley-VCH Verlag: Weinheim).
         (c) J. Yoshida, Flash Chemistry: Fast Organic Synthesis in Microsystems 2008 (Wiley-Blackwell: Chichester).
         (d) V. Hessel, A. Renken, J. C. Schouten, J. Yoshida, Micro Process Engineering 2009 (Wiley-Blackwell: Weinheim).

[7]  (a) K. Jähnisch, V. Hessel, H. Löwe, M. Baerns, Angew. Chem. Int. Ed. 2004, 43, 406.
         | CrossRef |
      (b) G. N. Doku, W. Verboom, D. N. Reinhoudt, A. van den Berg, Tetrahedron 2005, 61, 2733.
         | CrossRef |
      (c) J. Yoshida, A. Nagaki, T. Iwasaki, S. Suga, Chem. Eng. Tech. 2005, 28, 259.
         | CrossRef |
      (d) P. Watts, S. J. Haswell, Chem. Soc. Rev. 2005, 34, 235.
         | CrossRef |
      (e) K. Geyer, J. D. C. Codee, P. H. Seeberger, Chem. – Eur. J. 2006, 12, 8434.
         | CrossRef |
      (f) A. J. deMello, Nature 2006, 442, 394.
         | CrossRef |
      (g) H. Song, D. L. Chen, R. F. Ismagilov, Angew. Chem. Int. Ed. 2006, 45, 7336.
         | CrossRef |
      (h) J. Kobayashi, Y. Mori, S. Kobayashi, Chem. – Asian. J. 2006, 1, 22.
         | CrossRef |
      (i) M. Brivio, W. Verboom, D. N. Reinhoudt, Lab Chip. 2006, 6, 329.
         | CrossRef |
      (j) B. P. Mason, K. E. Price, J. L. Steinbacher, A. R. Bogdan, D. T. McQuade, Chem. Rev. 2007, 107, 2300.
         | CrossRef |
      (k) B. Ahmed-Omer, J. C. Brandtand, T. Wirth, Org. Biomol. Chem. 2007, 5, 733.
         | CrossRef |
      (l) P. Watts, C. Wiles, Chem. Commun. 2007, 443.
         | CrossRef |
      (m) T. Fukuyama, M. T. Rahman, M. Sato, I. Ryu, Synlett 2008, 151.
      (n) J. Yoshida, A. Nagaki, T. Yamada, Chem. – Eur. J. 2008, 14, 7450.
         | CrossRef |
      (o) R. L. Hartman, K. F. Jensen, Lab Chip. 2009, 9, 2495.
         | CrossRef |
      (p) W. Lin, Y. Wang, S. Wang, H. Tseng, Nano Today 2009, 4, 470.
         | CrossRef |
      (q) K. Geyer, T. Gustafsson, P. H. Seeberger, Synlett 2009, 2382.
      (r) J. P. McMullen, K. F. Jensen, Annu. Rev. Anal. Chem. 2010, 3, 19.
         | CrossRef |
      (s) S. Marre, K. F. Jensen, Chem. Soc. Rev. 2010, 39, 1183.
         | CrossRef |
      (t) D. Webb, T. F. Jamison, Chem. Sci. 2010, 1, 675.
         | CrossRef |
      (u) J. P. McMullen, K. F. Jensen, Annu. Rev. Anal. Chem. 2010, 3, 19.
         | CrossRef |
      (v) J. Yoshida, H. Kim, A. Nagaki, ChemSusChem 2011, 4, 331.
         | CrossRef |

[8]  (a) A. Nagaki, K. Kawamura, S. Suga, T. Ando, M. Sawamoto, J. Yoshida, J. Am. Chem. Soc. 2004, 126, 14702.
         | CrossRef | CAS |
      (b) A. Nagaki, M. Togai, S. Suga, N. Aoki, K. Mae, J. Yoshida, J. Am. Chem. Soc. 2005, 127, 11666.
         | CrossRef |
      (c) P. He, P. Watts, F. Marken, S. J. Haswell, Angew. Chem. Int. Ed. 2006, 45, 4146.
         | CrossRef |
      (d) K. Tanaka, S. Motomatsu, K. Koyama, S. Tanaka, K. Fukase, Org. Lett. 2007, 9, 299.
         | CrossRef |
      (e) H. R. Sahoo, J. G. Kralj, K. F. Jensen, Angew. Chem. Int. Ed. 2007, 46, 5704.
         | CrossRef |
      (f) C. H. Hornung, M. R. Mackley, I. R. Baxendale, S. V. Ley, Org. Process Res. Dev. 2007, 11, 399.
         | CrossRef |
      (g) T. Fukuyama, M. Kobayashi, M. T. Rahman, N. Kamata, I. Ryu, Org. Lett. 2008, 10, 533.
         | CrossRef |
      (h) C. Wiles, P. Watts, Org. Process Res. Dev. 2008, 12, 1001.
         | CrossRef |
      (i) A. Nagaki, E. Takizawa, J. Yoshida, J. Am. Chem. Soc. 2009, 131, 1654.
         | CrossRef |
      (j) A. Nagaki, E. Takizawa, J. Yoshida, Chem. Lett. 2009, 38, 486.
         | CrossRef |
      (k) I. C. Wienhofer, A. Studer, M. T. Rahman, T. Fukuyama, I. Ryu, Org. Lett. 2009, 11, 2457.
         | CrossRef |
      (l) A. R. Bogdan, S. L. Poe, D. C. Kubis, S. J. Broadwater, D. T. McQuade, Angew. Chem. Int. Ed. 2009, 48, 8547.
         | CrossRef |
      (m) T. Tricotet, D. F. O’Shea, Chem. – Eur. J. 2010, 16, 6678.
      (n) D. L. Browne, M. Baumann, B. H. Harji, I. R. Baxendale, S. V. Ley, Org. Lett. 2011, 13, 3312.
         | CrossRef |
      (o) C. F. Carter, H. Lange, D. Sakai, I. R. Baxendale, S. V. Ley, Chem. – Eur. J. 2011, 17, 3398.
         | CrossRef |
      (p) N. Zaborenko, M. W. Bedore, T. F. Jamison, K. F. Jensen, Org. Process Res. Dev. 2011, 15, 131.
         | CrossRef |
      (q) T. Noél, S. Kuhn, A. J. Musachio, K. F. Jensen, S. L. Buchwald, Angew. Chem. Int. Ed. 2011, 50, 5943.
         | CrossRef |
      (r) A. C. Gutierrez, T. F. Jamison, Org. Lett. 2011, 13, 6414.
         | CrossRef |
      (s) W. Shu, L. Pellegatti, M. A. Oberli, S. L. Buchwald, Angew. Chem. Int. Ed. 2011, 50, 10665.
         | CrossRef |
      (t) W. Shu, S. L. Buchwald, Angew. Chem. Int. Ed. 2012, 51, 5355.
         | CrossRef |
      (u) A. Nagaki, Y. Moriwaki, J. Yoshida, Chem. Commun. 2012, 48, 11211.
         | CrossRef |

[9]  (a) T. Schwalbe, V. Autze, M. Hohmann, W. Stirner, Org. Process Res. Dev. 2004, 8, 440.
         | CrossRef | CAS |
      (b) X. Zhang, S. Stefanick, F. J. Villani, Org. Process Res. Dev. 2004, 8, 455.
         | CrossRef |
      (c) H. Pennemann, V. Hessel, H. Löwe, Chem. Eng. Sci. 2004, 59, 4789.
         | CrossRef |
      (d) D. M. Ratner, E. R. Murphy, M. Jhunjhunwala, D. A. Snyder, K. F. Jensen, P. H. Seeberger, Chem. Commun. 2005, 578.
      (e) T. Kawaguchi, H. Miyata, K. Ataka, K. Mae, J. Yoshida, Angew. Chem. Int. Ed. 2005, 44, 2413.
         | CrossRef |
      (f) O. Flogel, J. D. C. Codee, D. Seebach, P. H. Seeberger, Angew. Chem., Int. Ed. 2006, 45, 7000.
         | CrossRef |
      (g) F. R. Carrel, K. Geyer, D. C. Jeroen, J. D. C. Codee, P. H. Seeberger, Org. Lett. 2007, 9, 2285.
         | CrossRef |
      (h) Y. Ushiogi, T. Hase, Y. Iinuma, A. Takata, J. Yoshida, Chem. Commun. 2007, 2947.
         | CrossRef |
      (i) A. Nagaki, Y. Tomida, J. Yoshida, Macromolecules 2008, 41, 6322.
      (j) A. Nagaki, Y. Tomida, A. Miyazaki, J. Yoshida, Macromolecules 2009, 42, 4384.
         | CrossRef |

[10]  (a) J. Yoshida, Chem. Commun. 2005, 4509.
         | CrossRef | CAS |
      (b) J. Yoshida, A. Nagaki, T. Yamada, Chem. – Eur. J. 2008, 14, 7450.
         | CrossRef |
      (c) J. Yoshida, Chem. Rec. 2010, 10, 332.
         | CrossRef |
      (d) A. Nagaki, N. Takabayashi, Y. Moriwaki, J. Yoshida, Chem. – Eur. J. 2012, 18, 11871.
         | CrossRef |

[11]  (a) H. Usutani, Y. Tomida, A. Nagaki, H. Okamoto, T. Nokami, J. Yoshida, J. Am. Chem. Soc. 2007, 129, 3046.
         | CrossRef | CAS |
      (b) A. Nagaki, Y. Tomida, H. Usutani, H. Kim, N. Takabayashi, T. Nokami, H. Okamoto, J. Yoshida, Chem. – Asian J. 2007, 2, 1513.
         | CrossRef |
      (c) A. Nagaki, N. Takabayashi, Y. Tomida, J. Yoshida, Org. Lett. 2008, 10, 3937.
         | CrossRef |
      (d) A. Nagaki, N. Takabayashi, Y. Tomida, J. Yoshida, Beilstein J. Org. Chem. 2009, 5, 1.
         | CrossRef |
      (e) Y. Tomida, A. Nagaki, J. Yoshida, Org. Lett. 2009, 11, 3614.
         | CrossRef |
      (f) A. Nagaki, C. Matsuo, S. Kim, K. Saito, A. Miyazaki, J. Yoshida, Angew. Chem. Int. Ed. 2012, 51, 3245.
         | CrossRef |

[12]  (a) A. Nagaki, H. Kim, J. Yoshida, Angew. Chem. Int. Ed. 2008, 47, 7833.
         | CrossRef | CAS |
      (b) A. Nagaki, H. Kim, J. Yoshida, Angew. Chem. Int. Ed. 2009, 48, 8063.
         | CrossRef |
      (c) A. Nagaki, H. Kim, Y. Moriwaki, C. Matsuo, J. Yoshida, Chem. – Eur. J. 2010, 16, 11167.
         | CrossRef |
      (d) A. Nagaki, H. Kim, C. Matuo, J. Yoshida, Org. Biomol. Chem. 2010, 8, 1212.
         | CrossRef |
      (e) H. Kim, A. Nagaki, J. Yoshida, Nature Commun. 2011, 2, 264.
         | CrossRef |

[13]  (a) A. Nagaki, E. Takizawa, J. Yoshida, J. Am. Chem. Soc. 2009, 131, 1654.
         | CrossRef | CAS |
      (b) A. Nagaki, E. Takizawa, J. Yoshida, Chem. – Eur. J. 2010, 16, 14149.
         | CrossRef |

[14]  A. Nagaki, E. Takizawa, J. Yoshida, Chem. Lett. 2009, 38, 1060.
         | CrossRef | CAS |

[15]  A. Nagaki, S. Tokuoka, S. Yamada, Y. Tomida, K. Oshiro, H. Amii, J. Yoshida, Org. Biomol. Chem. 2011, 9, 7559.
         | CrossRef | CAS |

[16]  Y. Tomida, A. Nagaki, J. Yoshida, J. Am. Chem. Soc. 2011, 133, 3744.
         | CrossRef | CAS |

[17]  (a) S. Goto, J. Velder, S. E. Sheikh, Y. Sakamoto, M. Mitani, S. Elmas, A. Adler, A. Becker, J.-M. Neudörfl, J. Lex, H.-G. Schmalz, Synlett 2008, 9, 1361.
      (b) T. Brodmann, P. Koos, A. Metzger, P. Knochel, S. V. Ley, Org. Process Res. Dev. 2012, 16, 1102.
         | CrossRef |

[18]  A. Nagaki, S. Yamada, M. Doi, Y. Tomida, N. Takabayashi, J. Yoshida, Green Chem. 2011, 13, 1110.
         | CrossRef | CAS |

[19]  (a) S. Suga, D. Yamada, J. Yoshida, Chem. Lett. 2010, 39, 404.
         | CrossRef | CAS |
      (b) A. Nagaki, A. Kenmoku, Y. Moriwaki, A. Hayashi, J. Yoshida, Angew. Chem. Int. Ed. 2010, 49, 7543.
         | CrossRef |
      (c) J. Yoshida, K. Saito, T. Nokami, A. Nagaki, Synlett 2011, 2011, 1189.
         | CrossRef |

[20]  (a) M. Mallet, G. Quéguiner, Tetrahedron 1979, 35,
         | CrossRef | CAS |
      (b) M. Mallet, G. Quéguiner, Tetrahedron 1985, 41, 3433.
         | CrossRef |
      (c) G. J. Quallich, D. E. Fox, R. C. Friedmann, C. W. Murtiashaw, J. Org. Chem. 1992, 57, 761.
         | CrossRef |

[21]  (a) W. E. Parham, R. M. Piccirilli, J. Org. Chem. 1977, 42, 257.
         | CrossRef | CAS |
      (b) X. Wang, P. Rabbat, P. O’Shea, R. Tillyer, E. J. J. Grabowski, P. J. Reider, Tetrahedron Lett. 2000, 41, 4335.
         | CrossRef |
      (c) P. C. Gros, A. Doudouh, C. Woltermann, Chem. Commun. 2006, 2673.
         | CrossRef |
      (d) A. Doudouh, C. Woltermann, P. C. Gros, J. Org. Chem. 2007, 72, 4978.
         | CrossRef |

[22]  (a) E. De Vos, E. L. Esmans, F. C. Alderweireldt, J. Heterocycl. Chem. 1993, 30, 1245.
         | CrossRef | CAS |
      (b) Y. Uchida, N. Echikawa, S. Oae, Heteroat. Chem. 1994, 5, 409.
         | CrossRef |
      (c) D. Cai, D. L. Hughes, T. R. Verhoeven, Tetrahedron Lett. 1996, 37, 2537.
         | CrossRef |


   
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