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Experiment 8, page 1

Department ofChemistry, Imperial College
Third YearAdvanced Practical Organic Chemistry

EXPERIMENT 8:
TRANSFER HYDROGENATION IN THE REDUCTION OF KETONES

Aims of the experiment
To prepare NiCl₂(PPh₃)₂and examine its use as a transfer hydrogenation catalyst for the reduction of ketones to alcohols, using iso-propanol as the hydride source.

Techniques used/learned:
Preparation of transition metal complexes; recrystallisation.

Introduction
Hydrogenation is a commonly used technique in organic chemistry.¹The combination of gaseous hydrogen in conjunction with a heterogeneous transition metal catalyst has been used to effect many useful reductions, egalkenes, alkynes and aromatics to alkanes; nitro, nitrile, imine and oxime groups to amines; and cleavage of benzylic ethers and amines (useful in protecting group chemistry). The use of modified catalysts (such as the partially poisoned Lindlar palladium catalyst) can allow selective reactions or partial reductions, egof alkynes to Z-alkenes. More recently, well defined transition metal complexes such as chloro(tristriphenylphosphine) rhodium(I) (Wilkinson's catalyst, discovered at Imperial College)²have found wide application as homogeneous catalysts. Often these are more efficient than their heterogeneous counterparts, since the active hydrogenation species and the substrate for reduction are in the same (liquid) phase. The use of such complexes has opened the way for the design of efficient asymmetric catalysts, using chiral ligands in the metal complex (often phosphines). In this fashion, one can enantioselectively reduce a range of functional groups (egalkenes, ketones, imines and enamides - the latter two are useful for the synthesis of amino acids). This is an important industrial process: for example, it is used in the asymmetric commercial synthesis of the important anti-Parkinson's agent L-DOPA.³ The area of transfer hydrogenation is of growing interest. Although hydrogen is a relatively cheap reducing agent, it does pose issues of handling and containment. For example, reactions need to be done with the rigorous exclusion of air (to prevent possible explosions), and often need to be carried out at elevated pressures to overcome phase transfer. The use of alternative, readily soluble reducing agents to transfer hydrogen to a metal catalyst is therefore of interest. Typical agents include cyclohexadiene (which loses hydrogen to generate benzene), formate salts (effectively generates H^-and CO₂), and alcohols (which are oxidised to ketones).

R²_i-PrOH

In this experiment, you will prepare an achiral homogeneous hydrogenation catalyst (NiCl₂(PPh₃)₂) and examine its use as a transfer hydrogenation catalyst for ketones.