Recent Advances in Direct Pyridine C-H Activation Strategies

Background: Pyridine is one of the most ubiquitous hetero-aromatic moieties in pharmaceutical chemistry and it has enormous importance in a plethora of fields. From a synthetic chemistry standpoint, pyridine moiety has been used as a directing group in C-H activation strategies to functionalize various rings. However, this unique feature to participate as a directing group hinders developing methodologies to carry out C-H activation on the pyridine ring itself. One of the simplest solutions is to block the activity of ring nitrogen at the cost of two extra steps. Here, in this review, along with the blocking, we will briefly mention some interesting ways to get around this problem and the remaining challenges ahead. Objective: The coordinating ability of pyridine N poses a big challenge toward C-H functionalization on the pyridine ring. This review summarizes some of the recent methods towards this challenge. Method: Some key ideas towards that goal have been described. Here, the C-H activation strategies are categorised as follows: (1) Pyridine N-oxide mediated C-H activation, (2) Dimerization of C-H activation of pyridine, (3) Direct Pyridine C2-H activation, (4) Direct Pyridine C3-H activation and (5) Direct Pyridine C4-H activation. Results: Several methods have been highlighted that can be utilised to prepare C-H functionalized products with regiospecificity that subsequently may be manipulated into interesting products which are difficult to attain easily. Conclusion: This review explores various new direct C-H activation methods on pyridine which attempts to fill the void of traditional synthetic protocols in regard to regioselective pyridine functionalization. This review also explores the limitations of current methodologies which must be wiped off to attain a mature state in need of the pharmaceutical industry.