Cp₂ZrCl₂-Mediated Three-Component Coupling Reactions of CO₂, Ethylene (or Alkynes), and Electrophiles Leading to Carboxylic Acid Derivatives

Abstract

Zirconacycles 1 and 2 can be simply generated from Cp₂ZrCl₂, EtMgBr, and an atmospheric pressure of CO₂. The treatment of Cp₂ZrCl₂ with EtMgBr followed by exposure to CO₂ generates zirconacycle 1, which can react with various electrophiles to give a variety of carboxylic acid derivatives. Unsaturated zirconacycles 2 can also generated from Cp₂ZrCl₂, EtMgBr, alkynes, and CO₂. Complexes 2 react with electrophiles to give α,β-unsaturated acids stereoselectively.

Key words

carbon dioxide - carboxylic acids - Grignard reactions - metallacycles - nucleophilic additions - alkynes

References

• 1a Yin X. Moss JR. Coord. Chem. Rev.  1999,  181:  27 
• 1b Walther D. Ruben M. Rau S. Coord. Chem. Rev.  1999,  182:  67 
• 2a Inoue Y. Izumida H. Sasaki Y. Hashimoto H. Chem. Lett.  1976,  863 
• 2b Jessop PG. Ikariya T. Noyori R. Chem. Rev.  1995,  95:  259 
• 2c Munshi P. Main AD. Linehan JC. Tai C.-C. Jessop PG. J. Am. Chem. Soc.  2002,  124:  7963 
• 3 For recent reviews, see: Darensbourg DJ. Holtcamp MW. Coord. Chem. Rev.  1996,  153:  155 
• Recent papers, see:
• 4a Paddock RL. Nguyen ST. J. Am. Chem. Soc.  2001,  123:  11498 
• 4b Shen Y.-M. Duan W.-L. Shi M. J. Org. Chem.  2003,  68:  1559 
• 4c Shen Y.-M. Duan W.-L. Shi M. Adv. Synth. Catal.  2003,  345:  337 
• 4d Lu X.-B. Liang B. Zhang Y.-J. Tian Y.-Z. Wang Y.-M. Bai C.-X. Wang H. Zhang R. J. Am. Chem. Soc.  2004,  126:  3732 
• 5a Nakano K. Nozaki K. Hiyama T. J. Am. Chem. Soc.  2003,  125:  5501 
• 5b Lu X.-B. Wang Y. Angew. Chem. Int. Ed.  2004,  43:  3574 
• 5c Byrne CM. Allen SD. Lobkovsky EB. Coates GW. J. Am. Chem. Soc.  2004,  126:  11404 
• 6a Rahim MA. Matsui Y. Matsuyama T. Kosugi Y. Bull. Chem. Soc. Jpn.  2003,  76:  2191 
• 6b Qin Z. Thomas CM. Lee S. Coates GW. Angew. Chem. Int. Ed.  2003,  42:  5484 
• 6c Olah GA. Torok B. Joschek JP. Bucsi I. Esteves PM. Rasul G. Prakash GKS. J. Am. Chem. Soc.  2002,  124:  11379 
• 7 Takimoto M. Shimizu K. Mori M. Org. Lett.  2001,  3:  3345 
• 8 Takimoto M. Kawamura M. Mori M. Org. Lett.  2003,  5:  2599 
• 9a Takimoto M. Mori M. J. Am. Chem. Soc.  2001,  123:  2895 
• 9b Takimoto M. Mori M. J. Am. Chem. Soc.  2002,  124:  10008 
• 10a Tsuda T. Kiyoi T. Miyane T. Saegusa T. J. Am. Chem. Soc.  1988,  110:  8570 
• 10b Louie J. Gibby JE. Farnworth MV. Tekavec TN. J. Am. Chem. Soc.  2002,  124:  15188 
• 10c Tekavec TN. Arif AM. Louie J. Tetrahedron  2004,  60:  7431 
• 11 For a review on CO, see: Colquhoun HM. Thompson DJ. Twigg MV. Carbonylation: Direct Synthesis of Carbonyl Compounds   Plenum Press; New York: 1991. 
• A related nickel complex has been reported. See:
• 12a Hoberg H. Peres Y. Krüger C. Tsay Y.-H. Angew. Chem., Int. Ed. Engl.  1987,  26:  771 
• 12b Hoberg H. Ballesteros A. Sigan A. Jegat A. Milchereit A. Synthesis  1991,  395 
• 13 Takahashi T. Li Y. In Titanium and Zirconium in Organic Synthesis   Marek I. Wiley-VCH; Weinheim: 2002.  p.50-85  
• 14 Alt HG. Denner CE. J. Organomet. Chem.  1990,  390:  53 
• 15 Nakamura E. Aoki S. Sekiya K. Oshino H. Kuwajima I. J. Am. Chem. Soc.  1987,  109:  8056 
• 16a Takahashi T. Kotora M. Kasai K. Suzuki N. Nakajima K. Organometallics  1994,  13:  4183 
• 16b Lipshutz BH. Segi M. Tetrahedron  1995,  51:  4407 
• 18 Negishi E. Takahashi T. Baba S. Van Horn DE. Okukado N. J. Am. Chem. Soc.  1987,  109:  2393 
• 19a Takahashi T. Kageyama M. Denisov V. Hara R. Negishi E. Tetrahedron Lett.  1993,  34:  687 
• 19b Li Y. Matsumura H. Yamanaka M. Takahashi T. Tetrahedron  2004,  60:  1393 
• 20 For related complexes, see: Takahashi T. Xi C. Ura Y. Nakajima K. J. Am. Chem. Soc.  2000,  122:  3228 
• 22 Takahashi T. Xi C. Ura Y. Nakajima K. J. Am. Chem. Soc.  2000,  122:  3228 
• Six reported on the Ti-mediated reaction of alkynes with CO₂ and several electrophiles, such as Br₂, I₂, NBS, and aldehydes. See:
• 23a Six Y. J. Chem. Soc, Perkin Trans. 1  2002,  1159 
• 23b Six Y. Eur. J. Org. Chem.  2003,  1157 

17

The reaction was carried out in a 20 mL two-necked flask equipped with a condenser and an inlet tube. To a solution of Cp₂ZrCl₂ (1 mmol, 292 mg) in THF (10 mL) under an atmosphere of dry nitrogen was added EtMgBr (3.0 M solution in Et₂O, 2.2 mmol, 740 µL) at -78 °C. After the mixture was stirred for 1 h at the same temperature, carbon dioxide was bubbled from CO₂ balloon and the reaction mixture was allowed to warm to 0 °C. After the mixture was stirred for 30 min, CuI (1.2 mmol, 228.6 mg) and allyl bromide (1.2 mmol) was added to the reaction mixture, which was stirred at 60 °C for 12 h. Then, the reaction mixture was quenched with 1 N HCl and extracted with Et₂O. The organic layer was extracted with 4 N NaOH aq and the aqueous layer was neutralized with 6 N HCl, washed with Et₂O and brine, dried over MgSO₄. A crude product was obtained after evaporation of the residue in vacuo.
5-Bromohex-5-enoic Acid (4): colorless oil. ¹H NMR (CDCl₃): δ = 1.91 (tt, J = 7.3, 7.3 Hz, 2 H, CH₂), 2.39 (t, J = 7.3 Hz, 2 H, CH₂CO), 2.49 (t, J = 7.3 Hz, 2 H, CH₂C=), 5.44 (d, J = 1.9 Hz, 1 H, CH=), 5.60-5.61 (m, 1 H, CH=). ¹³C NMR (CDCl₃): δ = 22.6 (CH₂), 32.3 (CH₂CO), 40.3 (CH₂C=), 117.6 (CH₂=), 133.1 (C=), 179.6 (CO). IR (neat): 2944 (s), 2913 (s), 2753 (m), 2670 (m), 1720 (s), 1704 (s), 1629 (s), 1452 (s), 1430 (s), 1411 (s), 1245 (s), 1201 (s), 1180 (s), 1118 (s), 1060 (w), 1035 (w), 1002 (w), 925 (s), 890 (s), 779 (m), 644 (w), 605 (w), 555 (w), 532 (m). MS: m/z calcd for C₆H₁₀81BrO₂: 194.9844; found: 194.9859.

21

The reaction was carried out in a 20 mL two-necked flask equipped with a condenser and a three-way cock. To a solution of Cp₂ZrCl₂ (1 mmol, 292.3 mg) in THF (10 mL) under an atmosphere of dry nitrogen was added EtMgBr (3.0 M solution in Et₂O, 2.2 mmol, 740 µL) at -78 °C. After the mixture was stirred for 1 h at the same temperature reaction mixture was allowed to warm to 0 °C, and alkyne (1.0 mmol) was added. After the mixture was stirred, the flask was changed with CO₂ and warmed to 50 °C. After the mixture was stirred for 1 h, the reaction mixture was quenched with 1 N HCl and extracted with Et₂O. The organic layer was extracted with 4 N NaOH aq and aqueous layer was neutralized with 6 N HCl, washed with Et₂O and brine, dried over MgSO₄. The solvent was evaporated in vacuo and afforded products.
2,3-Diethylhexa-2,5-dienoic Acid (13): colorless oil. ¹H NMR (CDCl₃): δ = 1.05 (t, J = 7.6 Hz, 3 H, CH₃), 1.06 (t, J = 7.6 Hz, 3 H, CH₃), 2.16 (q, J = 7.6 Hz, 2 H, CH₂), 2.35 (q, J = 7.6 Hz, 2 H, CH₂), 3.17 (d, J = 6.6 Hz, 1 H, =CCH₂C=), 5.01 (dd, J = 8.5, 1.9 Hz, 1 H, CH₂=), 5.06 (dd, J = 15.4, 1.9 Hz, 1 H, CH₂=), 5.75-5.90 (m, 1 H, CH=). ¹³C NMR (CDCl₃): δ = 12.8 (CH₃), 14.1 (CH₃), 22.8 (CH₂), 26.3 (CH₂), 38.4 (=CCH₂C=), 115.8 (CH₂=), 129.2 (COC=), 136.1 (CH=), 151.6 (C=), 174.5 (CO). IR (neat): 3077 (s), 2971 (s), 2935 (s), 2877 (s), 1681 (s), 1637 (s), 1617 (s), 1455 (m), 1403 (s), 1376 (m), 1301 (s), 1251 (s), 1191 (s), 1122 (w), 1049 (w), 997 (m), 948 (m), 912 (s), 788 (m), 746 (w) cm^-1. MS: m/z calcd for C₁₀H₁₆O₂: 168.1150; found: 168.1157.