Niobium-Catalyzed Reduction of Monofluoroarenes with LiAlH₄

Abstract

It was found that monofluoroarenes were reduced to the corresponding hydrodefluorinated arenes by the treatment of 5 mol% of NbCl₅ and LiAlH₄. Based on the substituent effect observed, an aromatic nucleophilic substitution mechanism is proposed.

Key words

fluorine - reductions - nucleophilic aromatic substitutions - niobium - hydrodefluorination catalyst

References

• For review, see:
• 1a Kiplinger JL. Richmond TG. Osterberg CE. Chem. Rev.  1994,  94:  373 
• 1b Alonso F. Beletskaya IP. Yus M. Chem. Rev.  2002,  102:  4009 
• For examples, see:
• 2a Aizenberg M. Milstein D. Science  1994,  265:  359 
• 2b Aizenberg M. Milstein D. J. Am. Chem. Soc.  1995,  117:  8674 
• 2c Edelbach BL. Jones WD. J. Am. Chem. Soc.  1997,  119:  7734 
• 2d Braun T. Cronin L. Higgitt CL. McGrady JE. Perutz RN. Reinhold M. New J. Chem.  2001,  25:  19 
• 2e Kraft BM. Jones WD. J. Organomet. Chem.  2002,  658:  132 
• 2f Laev SS. Evtefeev VU. Shteingarts VD. J. Fluorine Chem.  2001,  110:  43 
• For examples of stoichiometric reductions, see:
• 3a Imamoto T. Takeyama T. Kusumoto T. Chem. Lett.  1985,  1491 
• 3b Kraft BM. Lachicotte RJ. Jones WD. J. Am. Chem. Soc.  2001,  123:  10973 
• 3c For catalytic reductions, see: Li H. Liao S. Xu Y. Chem. Lett.  1996,  1059 
• 3d See further: Yang H. Gao H. Angelici RJ. Organometallics  1999,  18:  2285 
• 3e Young RJ. Grushin VV. Organometallics  1999,  18:  294 
• 3f Kuhl S. Schneider R. Fort Y. Adv. Synth. Catal.  2003,  345:  341 
• 3g Cellier PP. Spindler J.-F. Taillefer M. Cristau H.-J. Tetrahedron Lett.  2003,  44:  7191 
• 3h See also: Yus M. Synlett  2001,  1197 
• 4 Oshima and Sato reported reduction of organic compounds employing stoichiometric amounts of low valent niobium species generated from NbCl₅ and NaAlH₄. See: Sato M. Oshima K. Chem. Lett.  1982,  157 
• It was reported that treatment of NbCl₅ with 2 molar amounts of n-Bu₃SnH gave NbCl₃ (DME) complex with gas evolution:
• 8a Roskamp EJ. Pedersen SF. J. Am. Chem. Soc.  1987,  109:  6551 
• 8b Hartung JB. Pedersen SF. Organometallics  1990,  9:  1414 
• 8c See also: Tebbe FN. Parshall GW. J. Am. Chem. Soc.  1971,  93:  3793 
• 8d Klabunde U. Parshall GW. J. Am. Chem. Soc.  1972,  94:  9081 
• 9 A variety of h⁶-arene complexes of niobium and tantalum have been reported: Morris MJ. In Comprehensive Organometallic Chemistry II   Vol. 5:  Abel AW. Stone FGA. Wilkinson G. Pergamon; New York: 1995.  p.471 
• 11a Djukic and coworkers reported hydride attack to h⁶-fluoro(triisopropyl)benzene chromium tricarbonyl complex. See: Djukic JP. Geysermans P. Rose-Munch F. Rose E. Tetrahedron Lett.  1991,  32:  6703 
• 11b

  Jones and coworkers proposed an aromatic nucleophilic addition mechanism for their reduction of fluorobenzene with zirconium hydride, see ref. 3b. We rejected a mechanism in which the niobium hydride species undergoes aromatic nucleophilic substitution and adopted a direct hydride attack mechanism because use of n-Bu₃SnH instead of LiAlH₄ resulted in 88% recovery of the p-fluorobiphenyl (5 mol% of NbCl₅, 2.4 molar amounts of n-Bu₃SnH, reflux in DME, 4 h).

• It is already known that some η⁶-arene complexes of transition metals such as chromium, iron, and manganese undergo aromatic nucleophilic substitution, but liberation of arene ligand does not take place readily and stoichiometric amounts of the metal are required. For reviews, see:
• 12a Semmelhack MF. In Comprehensive Organometallic Chemistry II   Vol. 12:  Abel AW. Stone FGA. Wilkinson G. Pergamon; New York: 1995.  p.929 
• 12b For reactions of fluorobenzene complexes: Mahaffy CAL. Pauson PL. J. Chem. Res.  1979,  128 
• 12c Baldoli C. DelButtero P. Licandro E. Maiorana S. Gazz. Chim. Ital.  1988,  118:  409 

5

p-Fluorobiphenyl reacted with LiAlH₄ alone to give 13% yield of biphenyl and 81% recovery of the starting material after 4 h reflux in DME.

6

Typical Procedure: To a DME solution (3 mL) of p-fluorobiphenyl (217 mg, 1.26 mmol) and NbCl₅ (17 mg, 0.06 mmol) was added LiAlH₄ (96 mg, 2.52 mmol) in one portion. The clear yellow solution turned to dark gray immediately and gas evolved exothermically. After being refluxed for 4 h, the reaction mixture was quenched with H₂O at 0 °C. Sodium tartrate (0.2 g) was added and extraction with EtOAc gave the crude mixture. Purification by silica gel column chromatography (hexane) afforded biphenyl (176 mg, 1.14 mmol, 91%).

7

When LiAlH₄ was added to a DME solution of fluoroarene and NbCl₅, gas evolved exothermically.

10

Use of LiAlD₄ instead of LiAlH₄ resulted in quantitative formation of p-deuteriobiphenyl of 79% D (5 mol% of NbCl₅, 2.0 equiv of LiAlD₄, reflux in DME, 4 h; deuterium incorporation was determined based on integrals of ¹H NMR spectrum).