Catalytic-Enantioselective Methoxycarbonylation of 1,3-Dichloroarenetricarbonyl-chromium(0) Complexes: A Desymmetrization Approach to Planar Chirality

Abstract

The Pd-catalyzed mono-methoxycarbonylation of pro­chiral 1,3-dichloroarene-Cr(CO)₃ complexes was investigated. In the presence of the chiral ferrocene ligand (R,S _P )-PPF-pyrrolidine the planar-chiral products were obtained with up to 90% ee (53% yield). A strong dependence of the enantioselectivity on the reaction time was observed. A kinetic study using η⁶-(2,6-dichlorotoluene)-Cr(CO)₃ revealed that the initial enantiomeric purity of the mono-methoxycarbonylated product is further enhanced due to a kinetic resolution (S = 4.3) connected to the formation of the bis-methoxycarbonylated side-product.

arene complexes - asymmetric catalysis - chromium - kinetic resolution - palladium.

References

For recent reviews see:

1a Schmalz H.-G. Siegel S. In Transition Metals for Organic Synthesis   Vol. 1:  Beller M. Bolm C. Wiley-VCH; Weinheim: 1998.  p.550 

1b Hegedus LS. Transition Metals in the Synthesis of Complex Organic Molecules   University Science Books; Sausalito CA: 1999.  Chap. 10.

1c Kündig EP. Pache SH. In Science of Synthesis   Cat. 1, Vol. 2:  Imamoto T. Houben-Weyl; Thieme Verlag: 2003.  p.155 

For recent reviews see:

2a Gibson SE. Ibrahim H. Chem. Commun.  2002,  2465 

2b Bolm C. Muniz K. Chem. Soc. Rev.  1999,  28:  51 

For some recent examples, see:

3a Ratni H. Kündig EP. Org Lett.  1999,  1:  1997 

3b Monovich LG. Le Huerou Y. Ronn M. Molander GA. J. Am. Chem. Soc.  2000,  122 

3c Dehmel F. Lex J. Schmalz H.-G. Org Lett.  2002,  4:  3915 

See, for instance:

4a Davies SG. Goodfellow CL. J. Chem. Soc., Perkin Trans. 1  1990,  393 

4b Gibson SE. Reddington EG. Chem. Commun.  2000,  989 

5 Malézieux B. Jaouen G. Salaün J. Howell JAS. Palin MG. McArdle P. O’Gara M. Cunningham D. Tetrahedron: Asymmetry  1992,  3:  375 

6a Uemura M. Nishimura H. Hayashi T. Tetrahedron Lett.  1993,  34:  107 

6b Uemura M. Nishimura H. Hayashi T. J. Organomet. Chem.  1994,  473:  129 

7 Gotov B. Schmalz H.-G. Org. Lett.  2001,  3:  1753 

8 Merlic CA. Zechman AL. Miller MM. J. Am. Chem. Soc.  2001,  123:  11101 

9

1a: Mp: 123 °C. ¹H NMR (CDCl₃, 250 MHz): δ = 5.17 (d,
2 H, J = 6.3 Hz), 5.48 (t, 1 H, J = 6.3 Hz), 5.59 (br s, 1 H). ¹³C NMR (CDCl₃, 63 MHz): δ = 87.2, 90.1, 91.9 (d), 113.3, 230.3 (s). 1b: Mp: 95 °C. ¹H NMR (CDCl₃, 250 MHz): δ = 2.48 (s, 3 H); 5.29-5.37 (m, 3 H). ¹³C NMR (CDCl₃, 63 MHz): δ = 17.3 (q), 89.5, 90.4 (d), 103.2, 113.4, 230.9 (s). 1c: Mp: 82 °C. ¹H NMR (CDCl₃, 250 MHz): δ = 3.95 (s, 3 H), 5.21-5.30 (m, 3 H). ¹³C NMR (CDCl₃, 63 MHz): δ = 65.8 (q), 87.7, 89.7 (d), 109.6, 131.9, 230.5 (s).

10 Mahaffy CAL. Pauson P. Inorg. Synth.  1979,  XIX:  154 

11 Hayashi T. Mise T. Fukushima M. Kagotani M. Nagashima N. Hamada Y. Matsumoto A. Kawakami S. Konishi M. Yamamoto K. Kumada M. Bull. Chem. Soc. Jpn.  1980,  53:  1138 

12

Typical procedure: Complex 1b (148.5 mg, 0.5 mmol) and 5-PdCl₂ (16.2 mg, 0.025 mmol) were placed under argon in a flame-dried Schlenk flask equipped with a reflux condenser. Deoxygenated anhydrous methanol (3.3 mL) and triethylamine (1.7 mL) were added via a syringe and the reaction mixture was degassed and flushed with argon four times and finally flushed with CO. After stirring at 40 °C for 1 h the reaction mixture was cooled in an ice-bath, diluted with MTBE and filtered through a pad of silica. Upon concentration of the filtrate the received orange oil was sub-jected to column chromatography (silica, CyHex/MTBE =
8/1): 1b (10.3 mg, 7%), 2b (101.9 mg, 64%, orange oil) and 3b (39.2 mg, 23%, orange crystals).

13

rac- 2a: Orange crystals. Mp: 76 °C. ¹H NMR (C₆D₆, 250 MHz): δ = 3.31 (s, 3 H), 4.19 (t, 1 H, J = 6.5 Hz), 4.62 (d, 1 H, J = 6.5 Hz), 5.18 (d, 1 H, J = 6.5 Hz), 5.83 (br s, 1 H).
¹³C NMR (C₆D₆, 63 MHz): δ = 52.5 (q), 90.1, 90.3 (d), 91.0 (s), 92.3, 92.6 (d), 109.8, 165.4, 230.5 (s). 3a: Orange crystals. Mp: 90 °C. ¹H NMR (CDCl₃, 250 MHz): δ = 3.88 (s, 6 H), 5.25 (t, 1 H, J = 6.6 Hz), 6.27 (dd, 2 H, J = 6.6 Hz, 1.1 Hz), 6.82 (br s, 1 H). ¹³C NMR (CDCl₃, 63 MHz): δ = 53.0 (q), 87.2 (d), 87.7 (s), 95.5 (d), 165.1, 228.3 (s). rac-2b: Orange-reddish oil. ¹H NMR (CDCl₃, 250 MHz): δ = 2.63 (s, 3 H), 3.88 (s, 3 H), 5.21 (t, 1 H, J = 6.5 Hz), 5.78 (dd, 1 H, J = 6.5 Hz, 0.8 Hz), 5.87 (dd, 1 H, J = 6.5 Hz, 0.8 Hz). ¹³C NMR (CDCl₃, 63 MHz): δ = 17.2, 53.0 (q), 87.5 (d), 91.8 (s), 93.8, 94.9 (d), 108.0, 109.7, 166.3, 230.2 (s). 3b: Orange crystals. Mp: 93 °C. ¹H NMR (CDCl₃, 250 MHz): δ = 2.69 (s, 3 H), 3.86 (s, 6 H), 5.12 (t, 1 H, J = 6.6 Hz), 6.18 (d, 2 H, J = 6.6 Hz). ¹³C NMR (CDCl₃, 63 MHz): δ = 17.8, 52.9 (q), 85.1 (d), 91.7 (s), 97.2 (d), 111.3, 166.2, 229.3 (s). rac- 2c: Orange-reddish oil. ¹H NMR (C₆D₆, 300 MHz): δ = 3.34 (s, 3 H), 3.58 (s, 3 H), 3.97 (t, 1 H), 4.87 (d, 1 H), 5.19 (d, 1 H). ¹³C NMR (C₆D₆, 75 MHz): δ 52.8, 64.7 (q), 86.5 (d), 89.0 (s), 92.5, 94.0 (d), 105.3, 137.9, 164.8, 230.8 (s). 3c: Orange crystals. Mp: 109 °C. ¹H NMR (CDCl₃, 250 MHz): δ = 3.89 (s, 9 H), 4.94 (t, 1 H, J = 6.3 Hz), 6.19 (d, 2 H, 6.3 Hz). ¹³C NMR (CDCl3, 63 MHz): δ = 53.0, 65.1 (q), 83.8 (d), 86.2 (s), 96.2 (d), 142.1, 164.6, 228.6 (s).

14

Samples were taken from the reaction mixture in intervals of 15 min. After dilution with the HPLC eluent (i-propanol/n-hexane = 10:90) and filtration through Celite®, the mixtures were analyzed by HPLC (DAICEL Chiralcel OJ, external calibration).

15a Kagan HB. Fiaud JC. In Topics in Stereochemistry   Vol. 18:  Eliel E. L., Wilen S. H., Wiley; New York: 1988.  p.249 

15b Keith JM. Larrow JF. Jacobsen EN. Adv. Synth. Catal.  2001,  343:  5 

15c For an example in arene-Cr(CO)₃ chemistry, see: Carpentier J.-F. Pamart L. Maciewjeski l. Castanet Y. Brocard J. Mortreux A. Tetrahedron Lett.  1996,  37:  167 

16a Koide H. Uemura M. Chem. Commun.  1998,  2483 

16b

[α]₅₈₉ ²⁶ = -100.0 in CHCl₃ for pure ent- 6.