Abstract
Electron-rich bulky phosphine forms the most effective Pd catalyst systems for cross coupling reactions as they enhance the rate determining step of the catalytic cycle. The quest for an affordable and efficient ligand, prompted the implementation of tertiary bicylic phosphine ligands (Phoban family) in Pd-catalysed cross coupling reactions. Phoban (isomers mixture phosphabicyclo[3.3.1]nonane and phosphabicyclo[4.2.1]nonane) ligand is derived from cis, cis-1,5-cyclooctadiene and considered to be good electron donors, sterically bulk and have an unsymmetrical geometry to assist with an active catalytic system. Catalytic efficiency of phoban was investigated in Suzuki-Miyaura and Heck- Mizoroki cross coupling reactions, and the outcome of the study after an extensive optimisation study of various reaction parameters showed that palladium catalysts derived from 9-eicosyl-9-phosphabicyclononane (L2) gave superior results. This ligand L2 has also been demonstrated by SASOL R & D to be an excellent ligand in Co-catalysed hydroformylation reactions. The results obtained in this study have illustrated that this ligand L2 can facilitate couplings of a wide range of electronically diverse aryl bromides and chlorides with various coupling partners in Suzuki and Heck reactions. The implementation of 9-eicosyl-9-phosphabicyclononane in Heck and Suzuki reactions, provided the desired coupled products in 30-90% yields. In addition, this novel palladium catalyst derived from phoban was applied in the synthesis of industrial important products. The efficacy of this novel catalyst in Suzuki reaction was demonstrated in the synthesis of Felbinac (an anti-inflammatory drug under the trade name Traxam) and OTBN (an anti-hypertensive drug intermediate). Similarly, the success of the new protocol in Heck reaction was exemplified in the synthesis of octinoxate (trade names: Eusolex 2292 and Uvinul MC80; UV absorbers or filters), raspberry ketone derivatives (4-phenyl-2-butanone and 4-(4-methoxyphenyl)-2-butanone) used as flavourants. These products were successfully synthesised in yields ranging from 51 to 94% (GC).
M.Sc. (Chemistry)