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.

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 

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.

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 

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.