Development and Challenges in Copper-Catalyzed Asymmetric Ullmann-Type Coupling Reactions

Abstract

Ullmann-type coupling is one of the most powerful methods for the formation of aryl C–C, C–N, and C–O bonds. Yet asymmetric Ullmann coupling has received little attention because of the great challenges in both ligand and reaction designs. The success of the first catalytic enantioselective intramolecular Ullmann C–N coupling reaction through an asymmetric desymmetrization strategy offers a new way to develop enantioselective variants of such reactions. This paper addresses the importance of the desymmetrization strategy in Ullmann-type couplings and outlines some future directions in this field.

Key words

copper catalysis - asymmetric desymmetrization - ­Ullmann coupling - enantioselectivity - indolines

• References and Notes


For important reviews on copper-catalyzed coupling reactions, see:
• 1a Ley SV, Thomas AW. Angew. Chem. Int. Ed. 2003; 42: 5400
• 1b Beletskaya IP, Cheprakov AV. Coord. Chem. Rev. 2004; 248: 2337
• 1c Evano G, Blanchard N, Toumi M. Chem. Rev. 2008; 108: 3054
• 1d Monnier F, Taillefer M. Angew. Chem. Int. Ed. 2009; 48: 6954
• 1e Ma D, Cai Q. Acc. Chem. Soc. 2008; 41: 1450
• 1f Surry DS, Buchwald SL. Chem. Sci. 2010; 1: 13
• 1g Beletskaya IP, Cheprakov AV. Organometallics 2012; 31: 7753

For examples of biaryl compound synthesis via chiral substrate-induced asymmetric Ullmann coupling, see:
• 2a Stavrakov G, Keller M, Breit B. Eur. J. Org. Chem. 2007; 5726
• 2b Gorobets E, McDonald R, Keay BA. Org. Lett. 2006; 8: 1483
• 2c Meyers AI, Nelson TD, Moorlag H, Rawon DJ, Meier A. Tetrahedron 2004; 60: 4459
• 2d Spring DR, Krishnan S, Schreiber SL. J. Am. Chem. Soc. 2000; 122: 5656
• 2e Lipshutz BH, Kayser F, Liu Z.-P. Angew. Chem. Int. Ed. Engl. 1994; 33: 1842
• 2f Nelson TD, Meyers AI. J. Org. Chem. 1994; 59: 2655
• 2g Rawal VH, Florjancic AS, Singh SP. Tetrahedron Lett. 1994; 35: 8985
• 2h Miyano S, Tobita M, Hashimoto H. Bull. Chem. Soc. Jpn. 1981; 54: 3522
• 2i Miyano S, Tobita M, Nawa M, Sato S, Hashimoto H. J. Chem. Soc., Chem. Commun. 1980; 1233
• 3 Xie X, Chen Y, Ma D. J. Am. Chem. Soc. 2006; 128: 16050

For some important reviews on kinetic resolution, see:
• 4a Pellissier H. Tetrahedron 2008; 64: 1563
• 4b Vedejs E, Jure M. Angew. Chem. Int. Ed. 2005; 44: 3974
• 4c Huerta FF, Minidis AB. E, Bäckvall J.-E. Chem. Soc. Rev. 2001; 30: 321
• 4d Noyori R, Tokunaga M, Kitamura M. Bull. Chem. Soc. Jpn. 1995; 68: 36

For some important reviews on asymmetric desymmetrization, see:
• 5a García-Urdiales E, Alfonso I, Gotor V. Chem. Rev. 2005; 105: 313
• 5b Willis MC. J. Chem. Soc., Perkin Trans. 1 1999; 1765
• 5c Studer A, Schleth F. Synlett 2005; 3033
• 5d Rovis T In New Frontiers in Asymmetric Catalysis . Mikami K, Lautens M. John Wiley & Sons, Inc; New York: 2007: 275-309
• 5e Atodiresei I, Schiffers I, Bolm C. Chem. Rev. 2007; 107: 5683
• 6 Zhou F, Guo J, Liu J, Ding K, Yu S, Cai Q. J. Am. Chem. Soc. 2012; 134: 14326
• 7 Typical Procedure: A mixture of 1 or 3 (0.25 mmol), ligand (0.05 mmol), CuI (0.025 mmol) and Cs₂CO₃ (0.375 mmol) in 1,4-dioxane (1.0 mL) was stirred at r.t. for 10 h. H₂O (5.0 mL) and EtOAc (5.0 mL) were added and the organic phase was separated. The aqueous phase was extracted with EtOAc and the combined organic phase was washed with H₂O and brine, and dried over Na₂SO₄. The solvent was removed under reduced pressure and the residue was loaded on a silica column and purified by flash chromatography to afford the desired products.

For some recent important papers on the mechanism of copper-catalyzed reactions, see:
• 8a Huang Z, Hartwig JF. Angew. Chem. Int. Ed. 2012; 51: 1028
• 8b Chen B, Hou X.-L, Li Y.-X, Wu Y.-D. J. Am. Chem. Soc. 2011; 133: 7668
• 8c Huffmann LM, Stahl SS. Dalton Trans. 2011; 8959
• 8d Casitas A, King AE, Parella T, Costas M, Stahl SS, Ribas X. Chem. Sci. 2010; 1: 326
• 8e Strieer ER, Bhayana B, Buchwald SL. J. Am. Chem. Soc. 2009; 131: 78
• 8f Zhang S.-L, Liu L, Fu Y, Guo Q.-X. Organometallics 2007; 26: 4546