A useful ligand for synthetic and catalysis researchers from Strem Chemicals UK

The phospholane-phosphite ligand, known as BOBPHOS came about in a project between Chirotech/ Dr Reddys (UK) and the Clarke group (University of St Andrews) aimed at accessing various drug intermediates using hydroformylation. It was found to essentially eliminate the linear aldehyde impurity (generally 5 to 15 %) that can be formed in the hydroformylation of styrene derivatives, and delivered essentially pure regioisomers with enantiomer ratios of around 95:5 and substrate to catalyst ratios of up to 10’100.¹

Its name derived from the laboratory ‘nickname’ for this project, which was seeking to take the Best Of Both the properties found in two of the leading PHOShorus ligands for hydroformylation, (S,S)-Kelliphite (CAS 729572-33)² and (S,S)-Ph-BPE (Strem 15- 0474, CAS 824395-67-7). The not-so well-chosen name has just stuck as its use has expanded, so it is listed alongside its technical name as BOBPHOS in the Strem catalogue (15 0557, CAS1373349-83-7). This product is now available from Strem (see diagram 1 - above).

This phospholane-phosphite ligand uniquely gives a strong preference for branched aldehyde formation with high enantioselectivity in Rh catalysed hydroformylation of alkenes that are normally disposed to forming linear aldehyde products.³

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It has also been used in a carbonylative cyclisation process to form a cyclic enamine with high regioselectivity^4. We have more recently found that BOBPHOS can be used in syngas-free enantioselective hydroformylation using CO surrogates.⁵

The Clarke Group  have not studied the use of this ligand in other reactions to any great extent, However Rh catalysts derived from BOBPHOS also give good control of enantioselectivity in a simple alkene hydrogenation (dimethyl itaconate hydrogenation gives 91% e.e.), which suggest it may be of value in other processes quite outside of its original purpose. Hopefully, this ligand will prove useful to synthetic chemists needing to access a range of chiral aldehydes, or to catalysis researchers who need a distinctive ligand structure to examine in their research.

1. Angew. Chem. Int. Ed. 2012, 51, 2477.
2. Org. lett. 6, 2004, 3277
3. Chem. Commun. 2014, 50, 1475.
4. Bielstein J. Org. Chem. 2015, 11, 622.
5.  Manuscript in preparation.

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