Biphenyl-Based Phosphine Ligands

Introduction

A family of biphenyl ligands for transition-metal-catalyzed cross-coupling reactions is becoming well documented in the literature. [1-5] Buchwald and colleagues invented and developed ligands 1 and 2, which have found utility in C-C,² C-N [2a] [3a] [3c] and C-O [3b] bond formation.

Figure 1 Biphenyl-based phosphine ligands

Palladium complexes supported by ligands 1 and 2 are ­efficient catalysts for C-C, and C-heteroatom (C-N and C-O) bond formation of aryl halides, [2] [3] triflates [3a] and ­sulfonates. [4] Catalysts supported by the ligands shown in Figure 1 are reactive, efficient and operationally simple to generate. Ligand 1 is effective for hindered substrates at very low catalyst loadings (0.000001 mol%) [2] compared with ligand 2. The efficiency of catalysts derived from ligands 1 and 2 is most likely due to a combination of ­several factors such as steric and electronic properties, ­basicity of the phosphorus and their abilities to form ­palladacycles. [2]

Preparation of the ligands 1 and 2

Ligands 1 and 2 were prepared in high yields in a one-pot transformation (Scheme 1) and are also now commer­cially available. [2b] They are generally air-stable, white, crystalline solids that require no special handling. These ligands interact in unusual and interesting manners with the metal and thereby modulate the reactivity of the metal for various transformations. There is also a balance ­between steric and electronic properties among these compounds. [2b]

Scheme 1

References and Notes

• 1a Tomori H. Fox JM. Buchwald SL. J. Org. Chem.  2000,  65:  5334 
• 1b Huang X. Anderson KW. Zim D. Jiang L. Klapars A. Buchwald SL. J. Am. Chem. Soc.  2003,  125:  6653 
• 2a Wolfe JP. Buchwald SL. Angew. Chem. Int. Ed.  1999,  38:  2413 
• 2b Wolfe JP. Singer RA. Yang BH. Buchwald SL. J. Am. Chem. Soc.  1999,  121:  9550 
• 3a Wolfe JP. Tomori H. Sadighi JP. Yin J. Buchwald SL. J. Org. Chem.  2000,  65:  1158 
• 3b Aranyos A. Old DW. Kiyomori A. Wolfe JP. Sadighi JP. Buchwald SL. J. Am. Chem. Soc.  1999,  121:  4369 
• 3c Strieter ER. Blackmond DG. Buchwald SL. J. Am. Chem. Soc.  2003,  125:  13978 
• 4a Lakshman MK. Hilmer JH. Martin JQ. Keeler JC. Dinh YQV. Ngassa FN. Russon LM. J. Am. Chem. Soc.  2001,  123:  7779 
• 4b Lakshman MK. Thomson PF. Nuqui MA. Hilmer JH. Sevova N. Boggess B. Org. Lett.  2002,  4:  1479 
• 4c Gunda P. Russon LM. Lakshman MK. Angew. Chem. Int. Ed.  2004,  43:  6372 
• 4d Lakshman MK. Gunda P. Pradhan P. J. Org. Chem.  2005,  70:  10329 
• 5 Nieto-Oberhuber C. López S. Echavarren AM. J. Am. Chem. Soc.  2005,  127:  6178 
• 6 Dhondi PK. Chisholm JD. Org. Lett.  2006,  8:  67 
• 7 Wu TYH. Schultz PG. Org. Lett.  2002,  4:  4033