A New Palladium(II)-Catalyzed Asymmetric Chlorohydrin Synthesis

Abstract

The Pd(II)-catalyzed oxidation of ethene in aqueous solution (Wacker reaction) gives exclusively acetaldehyde at low [Cl-] (1.0 M). At high [Cl-] (>2.5 M) and high [CuCl2] (>3 M), formation of ethylene chlorohydrin occurs to an appreciable extent (Scheme 1).1,2 Previous studies in these laboratories have shown that substitution of chloride by pyridine in the coordination sphere of PdCl4 to give PdCl3(pyridine) resulted in the formation of chlorohydrin at [Cl-] as low as 0.2 M.3,4 At this low [Cl-], PdCl4 gives only acetaldehyde at any [CuCl2]. This finding opens up the possibility of an asymmetric chlorohydrin synthesis with R-olefins. Pd(II) catalysts containing chiral auxiliaries should produce optically active products. The logical starting point is the replacement of pyridine with a chiral amine L*. Scheme 2 outlines the general reaction scheme with monodentate chiral amines such as (CH3)2C*NH(CH3)Ph. As shown, the two positional isomers, 2 and 3, arise from the two possible modes of hydroxypalladation. The ratio 2/3 of about 4 for propene and 1-pentene is typical for a number of catalysts. As expected, the optical purity of 2 was low, with ee’s of 10-15%. Catalysts with chiral chelating diphosphines should give much higher optical purities. However, the monometallic Pd(II) complex containing a diphosphine ligand is a neutral species and thus insoluble in the reaction media. The solution to this problem involved two different approaches. One approach used sulfonated chiral ligands while the other involved bimetallic complexes with a bridging diphosphine ligand.6 The structures of the two catalytic systems are shown below. Synthesis of the tetrasulfonated ligand involved treatment of Tol-BINAP with H2SO4 containing 20% SO3 at room temperature for 24 h followed by neutralization with NaOH.7 Recrystallization from methanol provided pure samples. Reaction with K2PdCl4 or PdCl2(PhCN)2 provided the chiral catalyst. 31P NMR measurements confirmed that all the tolyl rings were sulfonated. In these catalysts X ) Cl. Treatment of a solution of [Pd(CH3CN)4]BF4 in CH3CN with 1,3,5-pentanetriones gave the bimetallic triketone complexes. Addition of the chiral diphosphine ligand provided the chiral bimetallic complex. After purification, the products were characterized by elemental analysis and 1H13C and 31P NMR. As initially prepared, X is the CH3CN ligand. However, in the actual reaction mixtures, CH3CN is almost certainly replaced by Cl-. Gas uptake measurements using gas burets monitored the progress of the reactions.8,9 Propene oxidation was monitored by propene consumption. With the other nongaseous olefins the gas was dioxygen. This is possible because the CuCl formed in the first oxidation step to form chlorohydrin readily reacts with dioxygen to give CuCl2. Thus, as with the Wacker reaction, the chlorohydrin synthesis is a net air oxidation.