First Regioselective C-2 Lithiation of 3- and 4-Chloropyridines

Abstract

We have shown that the BuLi/LiDMAE reagent promotes the clean and regioselective C2 lithiation of 3‐ and 4‐chloropyridines, while other reagents such as LDA or BuLi/TMEDA lead to classical ortho lithiation products or mixtures of regioisomers. The method was successfully applied to the preparation of various reactive 2,3‐ and 2,4‐disubstituted pyridines.

A study on the BF3 directed lithiation of 3-chloro- and 3-bromopyridine

“…7e9 The later methods suffer from certain disadvantages, which include isolation of a product corresponding to addition to the azomethine bond 7 and use of excessive amount of the base. 8,9 The methodologies involving BF 3 prompted pyridine ring lithiation are an efficient route for the functionalization of various pyridine moieties. 10À15 The BF 3 -controlled metalation of 1a and 1b has been studied with highly expensive bimetallic tetramethylpiperidine (TMP) bases like, TMPMgCl$LiCl, (TMP) 4 Zr$4MgCl 2 $6LiCl and [ t Bu 2 Zn(TMP)Li] in THF.…”

Synthesis, Characterization, and Computational Studies of Selenium Derivatives of 3,5‐Dichloropyridine

“…The reaction of 1 with LDA (2.2 equiv) at À78°C afforded a dark reddish solution which on quenching with elemental selenium followed by treatment with iodomethane (1.2 equiv) furnished 3,5dichloro-4-(methylselenenyl)pyridine (6) and 3,5- May 2017 Synthesis, Characterization, and Computational Studies of Selenium Derivatives of 3,5-Dichloropyridine dichloro-2,4-bis(methylselenenyl)pyridine (7) in 39% and 17% yields, respectively (Scheme 2). The isolation of these 2 products clearly shows that the first attack of LDA on 1 takes place at the C-4 position, and the second attack takes place at the C-2 position.…”

“…Therefore, we thought of developing a methodology that could be tailored to incorporate selenium atom(s) at different positions in 3,5‐dichloropyridine. The lithiation of mono‐, di‐, and tri‐halopyridines is well developed and documented in literature ; however, these methodologies fail to incorporate selenium into the C─Li bond . We have explored the lithiation of 3,5‐dichloropyridine ( 1 ) both in the presence and absence of boron trifluoride etherate (BF 3 .Et 2 O) and have successfully inserted a selenium atom into the C─Li bond of lithiated 3,5‐dichloropyridine.…”

Synthesis of P,N-2,2′-biphenyl derivatives with central chirality

“…We assumed that an aminoethanol or ether moiety could direct a remote lithiation of the biphenyl backbone [13,14]. In order to test this hypothesis and to know the potential sites of deprotonation, we treated the alcohol 4a and the ether 4b easily prepared from aminobiphenyl with an alkyllithium.…”