All You Need to Know About Asymmetric Phase Transfer Catalysis (PTC)

The subject of asymmetric PTC has moved on a lot since the early days in the 1980’s when the group of Dolling and Grabowski at Merck were pioneering the method on the scale up of manufacturing a drug substance. (Dolling U H et al, J Am Chem Soc, 1984, 106, 446; Hughes D L et al, J Org Chem, 1987, 52, 4745). Although the names of Corey in the US, and Lygo in the UK have been recently associated with asymmetric PTC, more recently it is the name Keiji Maruoka (Japan) who has published widely on the subject, and is becoming another key person in the field. Maruoka’s group has focussed on totally synthetic PTC’s rather than relying on alkaloid skeletons for their synthesis. The PTC’s catalyse a wide range of reactions.

He has recently written an excellent 45 page review in Angewandte with his colleague Takashi Ooi (Ooi T and Maruoka K, Angew Chem Int Ed, 2007, 45, 422-4266) which covers the entire field of asymmetric PTC catalysed chemistry.

One example is the use of the Neber rearrangement to synthesise α-aminoketones.
Since the original Merck study over 20 years ago there haven’t been too many detailed studies related to scale up issues, and this review, which focuses on key reactions, does not address issues important to process chemists, such as atom efficiency, catalyst quantity and purity, catalyst stability under basic conditions, reuse and recycle, and environmental issues related to PTC’s. These issues will all need to be addressed before the new reactions, described in the review, can be used in the manufacture of complex APIs. Trevor Laird.



Trevor Laird