New pyrazole-tethered Schiffs bases as ligands for the Suzuki reaction Anuradha Mukherjee and Amitabha Sarkar * Department of Organic Chemistry, Indian Association for The Cultivation of Science, Jadavpur, Kolkata 700 032, India Received 8 October 2004; revised 2 November 2004; accepted 8 November 2004 Abstract—Pyrazole-tethered Schiffs base ligands 2 promote Suzuki coupling of aryl bromides and chlorides with phenylboronic acid efficiently under mild conditions. Ó 2004 Elsevier Ltd. All rights reserved. Transition metal catalyzed cross-coupling reactions are useful tools in organic synthesis for constructing C–C bonds. 1 Among these, the coupling of an aryl halide with an organoboron reagent, the Suzuki reaction has emerged a favourite because of its mild conditions. 1c Pd–phosphine complexes 2,3 have been the most com- monly employed catalysts for the Suzuki reaction. The high price associated with bulky tertiary phosphines and difficulties associated with separation of the ligands and their degradation products, phosphine oxides, etc., from coupling products have encouraged researchers to explore alternative ligands. Recently a few nonphos- phine ligands such as N-heterocyclic carbenes (NHCs), 4 imidazol-2-ylidenes 5 and diazabutadienes 6 have been used in Suzuki coupling reactions. Recent developments in this area suggest that an elec- tron rich metal center (possibly aided by a r-donor ligand) facilitates oxidative addition and steric congestion around the metal accelerates the reductive elimination step. Accordingly, we designed ligand sys- tems depicted in Figure 1. There are two types of nitro- gen donor atoms in these potentially bidentate ligands. The pyrazole is expected to act as a hemilabile ligand 7 while the Schiffs base nitrogen acts as the principal donor. For comparison, an ortho-NMe 2 group (as in 1) instead of CH@N was also examined. 8a Ligand 1 did not catalyze the Suzuki coupling reaction at all. Deposition of Pd black commences after 1 h at room temperature and within a few minutes at 65–70 °C. This result indicates that a low valent Pd(0) complex cannot be stabilized by a hard donor like NMe 2 . The use of li- gands 2a–d, on the other hand, effected efficient coupling. The preparation of ligands 2 is depicted in Scheme 2. 8b,c The relative efficiency of the ligands 2a–d was assessed by reference to results of the Suzuki coupling between 4- bromoanisole and phenylboronic acid (Table 1). 0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2004.11.051 Keywords: Pyrazole; Schiffs base; N,N-donor system; Suzuki coupling; Pd. * Corresponding author. Tel.: +91 33 24734971; fax: +91 33 24732805; e-mail: ocas@iacs.res.in 1 2 N N R 2 R 1 X R 1 =R 2 =CH 3 X = NMe 2, R 1 =R 2 =CH 3 R 1 = CH 3 ,R 2 =t-Bu CH=NAr X= 2a N N CH N 2b N N CH N 2c N N CH N 2d N N CH N Figure 1. Tetrahedron Letters 46 (2005) 15–18 Tetrahedron Letters