Convenient Palladium-Catalyzed Preparation of Primary Anilines Using a Fluorous Benzophenone Imine Reagent

Abstract

A novel fluoroalkyl benzophenone imine reagent (f-BPI) serves as a convenient ammonia surrogate for the palladium-catal­yzed Buchwald-Hartwig amination of aryl halides. The highly ­fluorinated imine moiety acts as a handle for rapid purification of intermediates using fluorous chromatographic techniques, and is ­removed in a subsequent stage by acid hydrolysis to provide the ­corresponding primary anilines.

Key words

amination - arylation - cross-coupling - palladium-catal­yzed - fluorous

References

• For recent reviews on palladium-catalyzed aryl amination methods, see:
• 2a Hartwig JF. Angew. Chem., Int. Ed. Engl.  1998,  37:  2046 
• 2b Wolfe JP. Wagaw S. Marcoux J.-F. Buchwald SL. Acc. Chem. Res.  1998,  31:  805 
• 2c Yang BH. Buchwald SL. J. Organomet. Chem.  1999,  576:  125 
• 2d Hartwig JF. Modern Amination Methods   Ricci A. Wiley-VCH; Weinheim: 2000. 
• Palladium-catalyzed aryl aminations utilizing ammonia surrogates to prepare primary anilines:
• 3a Wolfe JP. Åhman J. Sadighi JP. Singer RA. Buchwald SL. Tetrahedron Lett.  1997,  38:  6367 
• 3b Jaime-Figueroa S. Liu Y. Muchowski JM. Putman DG. Tetrahedron Lett.  1998,  39:  1313 
• 3c Hori K. Mori M. J. Am. Chem. Soc.  1998,  120:  7651 
• 3d Lim CW. Lee S. Tetrahedron  2000,  56:  5131 
• 3e Lee S. Jørgensen M. Hartwig JF. Org. Lett.  2001,  3:  2729 
• 3f Huang X. Buchwald SL. Org. Lett.  2001,  3:  3417 
• 3g Harris MC. Huang X. Buchwald SL. Org. Lett.  2002,  4:  2885 
• 3h Weigand K. Pelka S. Org. Lett.  2002,  4:  4689 
• For recent reviews on fluorous chemistry, see:
• 4a Zhang W. Tetrahedron  2003,  59:  4475 
• 4b Curran DP. Hadida S. Studer A. He M. Kim S.-Y. Luo Z. Larhed M. Hallberg M. Linclau B. In Combinatorial Chemistry: A Practical Approach   Vol. 2:  Fenniri H. Oxford Univ Press; Oxford: 2000.  p.327-352  
• 5 Curran DP. Synlett  2001,  1488 
• 7a Parlow JJ. Naing W. South MS. Flynn DL. Tetrahedron Lett.  1997,  38:  7959 
• 7b Aberler NS. Ganesan A. Lambert JN. Saubern S. Smith R. Tetrahedron Lett.  2001,  42:  1975 
• 7c Ley SV. Schucht O. Thomas A. Murray PJ. J. Chem. Soc., Perkin Trans. 1  1999,  1251 
• 7d

  Available from Argonaut Technologies, Inc. (www.argotech.com).

• 9a Abramovitch RA. Challand SR. Scriven EFV. J. Org. Chem.  1972,  37:  2705 
• 9b Chami Z. Gareil M. Pinson J. Saveant JM. Thiebault A. J. Org. Chem.  1991,  56:  586 
• 9c Bromilow J. Brownlee RTC. Craik DJ. Sadek M. Taft RW. J. Org. Chem.  1980,  45:  2429 
• 10a Brown EV. Kipp WH. J. Org. Chem.  1971,  36:  170 
• 10b Krein DM. Sullivan PJ. Turnbull K. Tetrahedron Lett.  1996,  37:  7213 
• 10c

  See also: Ref. [9c]

• 11a Landesberg JM. Katz L. Olsen C. J. Org. Chem.  1972,  37:  930 
• 11b Landesberg JM. Katz L. Olsen C. J. Org. Chem.  1972,  37:  930 
• 11c

  See also: Ref. [9c]

• 12 Stock LM. Wasielewski MR. J. Am. Chem. Soc.  1977,  99:  50 
• 13 Sprecher M. Kost D. J. Am. Chem. Soc.  1994,  116:  1016 
• 14a Strand JW. Kovacic P. J. Am. Chem. Soc.  1973,  95:  2977 
• 14b Hirayama M. J. Chem. Soc., Perkin Trans. 2  1982,  443 
• 15a Bunnett JF. Gloor BF. Heterocycles  1976,  5:  377 
• 16a Casarini A. Dembech P. Lazzari D. Marini E. Reginato G. Ricci A. Seconi G. J. Org. Chem.  1993,  58:  5620 
• 16b Wachi K. Terada A. Chem. Pharm. Bull.  1980,  28:  45 
• 16c Singha NC. Sathyanarayana DN. J. Chem. Soc., Perkin Trans. 2  1997,  157 
• Reported methods to regenerate benzophenone imines from benzophenones:
• 18a Dzieduszycka M. Martelli S. Tarasiuk J. Paradziej-Lukowicz J. Borowski E. J. Med. Chem.  1991,  34:  541 
• 18b Verardo G. Giumanini AG. Strazzolini P. Poiana M. Synth. Commun.  1988,  18:  1501 
• 18c Rahman O. Kihlberg T. Langstroem B. J. Chem. Soc., Perkin Trans. 1  2002,  23:  2699 
• 18d Mizufune H. Irie H. Katsube S. Okada T. Mizuno Y. Arito M. Tetrahedron  2001,  57:  7501 
• 18e Brenner DG. Cavolowsky KM. Shepard KL. J. Heterocycl. Chem.  1985,  22:  805 

1

Undergraduate Research Intern, May-August 2003.

6

We used either a slurry-packed plug of commercially available FluoroFlash fluorous silica gel or pre-packed FluoroFlash cartridges available from both Fluorous Technologies, Inc. (www.fluorous.com) and Biotage, Inc. (www.biotage.com). Pre-packaged cartridges are compatible with many MPLC systems.

8

The obtained physical data was identical to material obtained from a commercial vendor.

17

We tried to regenerate f-BPI 2 from the recovered ketone 5 by a number of known amination conditions (ref. 18) but were ultimately unsuccessful. The original preparation of 2 was achieved at FTI by other methods.