A New and Practical Procedure for Asymmetric 1,4-Addition of Boronic Acids to α,β-Unsaturated Ketones Catalyzed by Rh-(R)-Digm-BINAP System

Abstract

Rh-catalyzed C-C bond asymmetric formation under basic conditions in organoaqueous or alcoholic solvents has been described using the atropoisomeric water-soluble ligand (R)-Digm-BINAP. The addition of phenylboronic acid to cyclohexenone has been efficiently optimized leading to quantitative yield and enantio­meric excesses up to 98% using 1-3 mol% catalyst. Easy product-catalyst separation has been found using ethylene glycol as the reaction solvent. Other α,β-unsaturated ketones and boronic acids could be engaged in the 1,4-addition. The mole fraction of the catalyst could be decreased to 0.005% with still acceptable ee. A TON of 13200 was obtained.

Key words

chiral cationic water-soluble ligand - boronic acids - α,β-unsaturated ketones - asymmetric C-C bond formation - rhodium

References

• 1 Cornils B. Herrmann WA. In Applied Homogeneous Catalysis with Organometallic Compound   VCH; New York: 1996. 
• 2 McCarthy M. Guiry PJ. Tetrahedron  2001,  57:  3809 
• 3 Cornils B. Herrmann WA. In Aqueous-Phase Organometallic Catalysis   Wiley-VCH; New York: 1998. 
• 4a Sinou D. Adv. Synth. Catal.  2002,  344:  221 
• 4b Lindström UM. Chem. Rev.  2002,  102:  2751 
• 4c Li CJ. Chan TK. Organic Reactions in Aqueous Media   JohnWiley & Son; New York: 1997. 
• 4d Organic Synthesis in Water   Grieco PA. Blacky Academic and Professional; London: 1998. 
• 5a Genêt J.-P. Reductions in Organic Synthesis, A.C.S. Symposium Series 641   ACS; New York: 1996.  p.31-51  
• 5b Ratovelomanana-Vidal V. Genêt J.-P. J. Organomet. Chem.  1998,  567:  163 
• 5c Ratovelomanana-Vidal V. Genêt J.-P. Can. J. Chem.  2000,  78:  846 
• For recent reviews on Pd-catalyzed reactions, see:
• 6a Genêt J.-P. Savignac M. J. Organomet. Chem.  1999,  576:  305 
• 6b Genêt J.-P. Savignac M. Lemaire-Audoire S. In IUPAC Monographs: Chemistry for the 21^st Century, Transition Metal Catalysed Reactions   Murahashi S.-I. Davies SG. Blackwell; London: 1999.  p.55 
• 7a Michelet V. Galland J.-C. Charruault L. Savignac M. Genêt J.-P. Org. Lett.  2001,  3:  2065 
• 7b Dupuis C. Adiey K. Charruault L. Michelet V. Savignac M. Genêt J.-P. Tetrahedron Lett.  2001,  42:  6523 
• 8 Amengual R. Genin E. Michelet V. Savignac M. Genêt J.-P. Adv. Synth. Catal.  2002,  344:  393 
• 9a Guerreiro P. Ratovelomanana-Vidal V. Genêt J.-P. Dellis P. Tetrahedron Lett.  2001,  42:  3423 
• 9b Guerreiro P, Genêt J.-P, and Dellis P. inventors; French patent,  99 15217. 
• 9c Lemaire M, ter Halle R, Samson E, Colasson B, and Spagnol M. inventors; French Patent  99 02510. For the synthesis of (R)-Diam-BINAP, see:
• 9d See also: ter Halle R. Colasson B. Schulz E. Spagnol M. Lemaire M. Tetrahedron Lett.  2000,  41:  643 
• 10 Amengual R. Michelet V. Genêt J.-P. Tetrahedron Lett.  2002,  43:  5905 
• 11 Takaya Y. Ogasawara M. Hayashi T. Sakai M. Miyaura N. J. Am. Chem. Soc.  1998,  120:  5579 
• 12a Sakuma S. Sakai M. Itooka R. Miyaura N. J. Org. Chem.  2000,  65:  5951 
• 12b Hayashi T. Senda T. Takaya Y. Ogasawara M. J. Am. Chem. Soc.  1999,  121:  11591 
• 12c Sakuma S. Miyaura N. J. Org. Chem.  2001,  66:  8944 
• 12d Hayashi T. Senda T. Ogasawara M. J. Am. Chem. Soc.  2000,  122:  10716 
• 13a Pucheault M. Darses S. Genêt J.-P. Tetrahedron Lett.  2002,  43:  6155 
• 13b Pucheault M. Darses S. Genêt J.-P. Eur. J. Org. Chem.  2002, in press
• 14a Takaya Y. Ogasawara M. Hayashi T. Tetrahedron Lett.  1998,  39:  8479 
• 14b Takaya Y. Senda T. Kurushima H. Ogasawara M. Hayashi T. Tetrahedron: Asymmetry  1999,  10:  4047 
• 14c Takaya Y. Ogasawara M. Hayashi T. Tetrahedron Lett.  1999,  40:  6957 
• 14d Takaya Y. Ogasawara M. Hayashi T. Chirality  2000,  12:  469 
• 14e Sakuma S. Miyaura N. J. Org. Chem.  2001,  66:  6852 
• For recent reviews on asymmetric 1,4-addition, see:
• 15a Hayashi T. Synlett  2001,  879 
• 15b Krause N. Hoffmann-Röder A. Synthesis  2001,  171 
• 15c Sibi MP. Manyem S. Tetrahedron  2000,  56:  8033 
• 16 Reetz M. Moulin D. Gosberg A. Org. Lett.  2001,  3:  4083 
• 17 Kuriyama M. Tomioka K. Tetrahedron Lett.  2001,  42:  921 
• 18 Hayashi T. Takahashi M. Takaya Y. Ogasawara M. J. Am. Chem. Soc.  2002,  124:  5052 

19

Unpublished results (E. Genin, D.E.A. Multinational de Chimie Moléculaire de l’Ecole Polytechnique).

20

Ethylene glycol, purchased from Acros, contains 0.05% water and was used without further treatment.

21

Typical procedure : A solution of Rh(acac)(C₂H₄)₂ (1.3 mg, 0.006 mmol) and (R)-Digm-BINAP (5.0 mg, 0.006 mmol) in degassed ethyleneglycol (1.0 mL) was stirred under argon for 15 minutes at room temperature, then phenylboronic acid (122 mg, 1 mmol), sodium carbonate (43 mg, 0.4 mmol) and cyclohexenone (20 µL, 0.2 mmol) were successively added. The heterogeneous mixture was stirred at 100 °C until completion of the reaction (gas chromatography). After cooling at room temperature the solution was extracted two times with ethyl acetate. The combined organic layers were filtered on a short pad of silica gel and evaporated under reduced pressure. A slight yellow oil (34 mg, 100%) was obtained. The purity of the compound was checked by gas chromatography and ¹H NMR. The enantiomeric excess was determined by HPLC (Daicel Chiralcel OD-H, hexane/i-PrOH = 98:2, 1 mL/min).