Catalytic Double C-Cl Bond Activation in CH₂Cl₂ by Iron(III) Salts with Grignard Reagents

Abstract

Cross-coupling of Grignard reagents with dichloromethane is achieved using iron(III) catalysts. Aryl- and benzylmagnesium bromides show a range of activity toward double C-Cl bond activation resulting in the insertion of methylene fragments between two equivalents of the nucleophilic partner.

Key words

cross-coupling - iron - catalysis - arylation - Grignard reagent

References and Notes

• 1 de Meijere A. Diederich F. Metal-Catalyzed Cross-Coupling Reactions   2nd ed.:  Wiley-VCH; Weinheim: 2004.  p.938 
• 2a Frisch AC. Beller M. Angew. Chem. Int. Ed.  2005,  44:  674 
• 2b Netherton MR. Fu GC. Adv. Synth. Catal.  2004,  346:  1525 
• 3 Martin R. Fürstner A. Angew. Chem. Int. Ed.  2004,  43:  3955 
• 4 Zhou JR. Fu GC. J. Am. Chem. Soc.  2003,  125:  12527 
• 5a Frisch AC. Shaikh N. Zapf A. Beller M. Angew. Chem. Int. Ed.  2002,  41:  4056 
• 5b Kirchhoff JH. Dai CY. Fu GC. Angew. Chem. Int. Ed.  2002,  41:  1945 
• 5c Terao J. Watanabe H. Ikumi A. Kuniyasu H. Kambe N. J. Am. Chem. Soc.  2002,  124:  4222 
• 6a Csok Z. Vechorkin O. Harkins SB. Scopelliti R. Hu XL. J. Am. Chem. Soc.  2008,  130:  8156 
• 6b Vechorkin O. Csok Z. Scopelliti R. Hu XL. Chem. Eur. J.  2009,  15:  3889 
• 7 Liang LC. Chien PS. Lin JM. Huang MH. Huang YL. Liao JH. Organometallics  2006,  25:  1399 
• 8 Dias HVR. Browning RG. Polach SA. Diyabalanage HVK. Lovely CJ. J. Am. Chem. Soc.  2003,  125:  9270 
• 9 Blank B. Glatz G. Kempe R. Chem. Asian J.  2009,  4:  321 
• 10a Czaplik WM. Mayer M. Cvengros J. Jacobi von Wangelin A. ChemSusChem  2009,  2:  396 
• 10b Czaplik WM. Mayer M. Jacobi von Wangelin A. Angew. Chem. Int. Ed.  2009,  48:  607 
• 10c Sherry BD. Fürstner A. Acc. Chem. Res.  2008,  41:  1500 
• 10d Fürstner A. Angew. Chem. Int. Ed.  2009,  48:  1364 
• 10e Fürstner A. Krause H. Lehmann CW. Angew. Chem. Int. Ed.  2006,  45:  440 
• 10f Scheiper B. Bonnekessel M. Krause H. Fürstner A. J. Org. Chem.  2004,  69:  3943 
• 10g Seidel G. Laurich D. Fürstner A. J. Org. Chem.  2004,  69:  3950 
• 10h Neumann SM. Kochi JK. J. Org. Chem.  1975,  40:  599 
• 10i Tamura M. Kochi J. Synthesis  1971,  303 
• 10j Tamura M. Kochi J. J. Am. Chem. Soc.  1971,  93:  1487 
• 10k Bedford RB. Bruce DW. Frost RM. Goodby JW. Hird M. Chem. Commun.  2004,  2822 
• 10l Bica K. Gaertner P. Org. Lett.  2006,  8:  733 
• 10m Cahiez G. Chaboche C. Mahuteau-Betzer F. Ahr M. Org. Lett.  2005,  7:  1943 
• 10n Chowdhury RR. Crane AK. Fowler C. Kwong P. Kozak CM. Chem. Commun.  2008,  94 
• 10o Reckling AM. Martin D. Dawe LN. Decken A. Kozak CM. J. Organomet. Chem.  2011,  696:  787 
• 11 Fürstner A. Martin R. Krause H. Seidel G. Goddard R. Lehmann CW. J. Am. Chem. Soc.  2008,  130:  8773 
• 12a Nakamura M. Matsuo K. Ito S. Nakamura B. J. Am. Chem. Soc.  2004,  126:  3686 
• 12b Bedford RB. Betham M. Bruce DW. Danopoulos AA. Frost RM. Hird M. J. Org. Chem.  2006,  71:  1104 
• 12c Bedford RB. Bruce DW. Frost RM. Hird M. Chem. Commun.  2005,  4161 
• 12d Nagano T. Hayashi T. Org. Lett.  2004,  6:  1297 
• 12e Cahiez G. Habiak V. Duplais C. Moyeux A. Angew. Chem. Int. Ed.  2007,  46:  4364 
• 13 Nishii Y. Wakasugi K. Tanabe Y. Synlett  1998,  67 
• 14 Qian X. Dawe LN. Kozak CM. Dalton Trans.  2011,  40:  933 
• 16 Noda D. Sunada Y. Hatakeyama T. Nakamura M. Nagashima H. J. Am. Chem. Soc.  2009,  131:  6078 
• 17 Bedford RB. Nakamura M. Gower NJ. Haddow MF. Hall MA. Huwe M. Hashimoto T. Okopie RA. Tetrahedron Lett.  2009,  50:  6110 
• 18 Nagano T. Hayashi T. Org. Lett.  2005,  7:  491 

15

It is proposed that the Grignard serves to form reduced iron species that act as catalyst, therefore yields based on Grignard used do not take into consideration the quantity of Grignard consumed by reduction of Fe(III). The presence of biaryls resulting from homocoupling of the Grignard reagents are commonly observed in the GC-MS chromato-grams of the reactions, however, the quantity of homo-coupled product varies considerably with the nature of the nucleophile.

19

General Experimental Conditions: Unless otherwise stated, all manipulations were performed under an atmosphere of anhyd oxygen-free nitrogen by means of standard Schlenk or glove box techniques. Dichloromethane was purified using an MBraun Solvent Purification System. Reagents were purchased from Aldrich, Alfa Aesar or Strem and used without further purification. Grignard reagents were titrated prior to use and analyzed by GC-MS after being quenched with dilute HCl (aq) to quantify biaryl complexes or other impurities present prior to their use in catalyst runs. Complex 1 was prepared according to the previously published procedure.^¹4 Anhydrous FeCl₃ (97%) from Aldrich was used for the synthesis of 1 and for cross-coupling catalysis experiments.
General Conditions for Room-Temperature Reactions; For 2.5 mol% [Fe] Loading with a 12.5-Fold Excess of CH ₂ Cl ₂ to ArMgBr (Table 1, Entry 2): Complex 1 (50.1 mg; 0.1 mmol of Fe) was added to a flask and dissolved in CH₂Cl₂ (4.24 g, 3.2 mL, 50 mmol). To this stirred solution was added o-tolylmagnesium bromide (4.0 mL, 1.0 M in THF, 4.0 mmol). The reaction mixture was stirred for 30 min, after which time it was quenched by adding HCl (2.0 M, 5.0 mL) and filtered through a 10 cm silica column. The products were detected and quantified using GC-MS (relative to standard curves) with dodecane as the internal standard. Reported yields were confirmed by ^¹H NMR on isolated product mixtures. Complete separation of products A and B was not possible given their structural similarity, hence the NMR spectra consistently showed contamination with minor products. Yields are reported with respect to Grignard reagent. Since the Grignard reagents are obtained in THF or Et₂O solutions, the addition of Grignard is concomitant with the addition of solvent, e.g. 4.0 mmol of a 1.0 M o-tolylmagnesium bromide solution results in the addition of 4.0 mL THF to the reaction.
Catalytic Method for Microwave Heating: In a glove box, 1 (25.0 mg, 0.05 mmol) or FeCl₃ (8.1 mg, 0.05 mmol) and a magnetic stir bar were added to a Biotage^TM microwave vial, which was sealed with a septum cap. To this vial was injected CH₂Cl₂ (2.13 g, 25.0 mmol), followed by slow injection of the Grignard reagent (2.0 mmol). The mixture was heated in a Biotage Initiator^TM Microwave Synthesizer using the following parameters: time = 10 min; temperature = 100 ˚C; prestirring = off; absorption level = high; fixed hold time = on. Upon completion, dodecane (1.9 mmol) was added to the mixture followed by 1 M HCl (aq; 5 mL). The product yields were quantified by GC-MS and for high-yielding reactions by ^¹H NMR as described for the general method.