Asymmetric PTCs can be made by alkylation of commercially available alkaloids such as quinine and cinchonidine. However, commercially available cinchonidine often contains up to 10% of dihydrocinchonidine, which will also alkylate to give a mixture of cinchonidinium and dihydrocinchonidinium salts which are hard to separate. When carrying out asymmetric phase transfer alkylations, the presence of up to 10% dihydro salt could influence the enantiomeric excess of the product.

When using powdered NaOH as base in these types of alkylation, the particle size of the NaOH can also be important. It has been found by some companies that commercially available powdered NaOH is not as good as pre-milled material in-house. A further complication in these types of process is the presence of small amounts of water, which can often be beneficial, but not always- it depends on the process. So all these factors may need to be studied in scaling up PTC processes.

For more information see the forthcoming special issue on PTC in Organic Process R&D, 2010, Issue 3.

The enantioselectivity of a reaction can sometimes be reversed simply by changing the structure of the chiral PTC, in what seems a minor way but which affects the conformational flexibility of the catalyst, This approach has recently been explored by the group of Ma in China to the addition of ntiroalkanes to unsaturated ketones, to give high ee of either enantiomer (Angew Chem Int Ed, 2010, 49, 2772-2776).