Research by Dr Hassan Harb (Lead Chemist) at Concept Life Sciences (Alderley Park) and Luke Whitaker (RSC Enterprise Plus funded industrial placement student) in collaboration with Dr Alexander Pulis (Lecturer in Organic Chemistry) at the University of Manchester has recently been published in Chemical Communications.
The paper entitled “One-pot borylation/Suzuki-Miyaura sp2–sp3 cross-coupling” discusses the first one-pot, two-step cross-coupling between readily available aryl (pseudo)halides and activated alkyl chlorides. This method streamlines the synthesis of diaryl methanes, α-aryl carbonyls and allyl aryl compounds. These are substructures that are commonly found in life changing drug molecules, such as elvitegravir (HIV antiviral), mycophenolic acid (immunosuppressive), repaglinide (antidiabetic) and indomethacin (pain relief).
The Suzuki-Miyaura cross-coupling2 is an invaluable C-C bond forming reaction available to synthetic organic chemists, but it can often be limited by the availability, isolation and stability of the boronate starting materials. This has led to the development of one-pot borylation/Suzuki couplings to form sp2–sp2 C-C bonds, where the intermediate boronates are not isolated.3,4 Suzuki/Miyaura couplings are not limited to sp2–sp2 couplings and the one-pot strategy has not previously been applied to sp2–sp3 bond formations.
The most economical diborane reagent, tetrakis(dimethylamino)diboron [B2(NMe2)4], and propylene glycol are used in a palladium catalysed borylation of aryl (pseudo)halides. The in situ generated aryl borons are then coupled with activated alkyl chlorides, such as benzyl chlorides, α-chloro carbonyls, and allyl chlorides, in a one-pot procedure. This efficient method is operationally simple and is broadly applicable to a range of substrates with differing electronics and functional groups.
Commenting on this research undertaken our group head of chemistry Dave Leese had the following to say “As a leading CRO, Concept Life Sciences are continually looking to add value to our clients projects and this work by Hassan in conjunction with the University of Manchester is typical of our innovative approach towards that. This modified methodology will allow us to access a broader range of compounds more easily and so more effectively explore different chemical space”
To find out more or download this paper please click here.
- L.Whitaker, H. Y. Harb, and A. P. Pulis, Chem. Commun. 2017, 53, 9364-9367
- N.Miyaura and Akira Suzuki, Chem. Rev., 1995, 95, 2457
- T.Ishiyama, M. Murata and N. Miyaura, J. Org. Chem., 1995, 60, 7508
- G.A. Molander, S. L. J. Trice and S. M. Kennedy, J. Org. Chem., 2012, 77, 8678