Pyridine elaboration through organometallic intermediates: regiochemical control and completeness

Abstract

Pyridines carrying heterosubstituents (such as carboxy, amido, amino, alkoxy or trifluoromethyl groups or solely individual halogen atoms) can be readily and site selectively metalated. Subsequent reaction with a suitable electrophile opens rational access to a wealth of new building blocks for the synthesis of biologically active compounds. This approach relies on organometallic methods, which are both efficacious and extremely flexible as far as the substitution site and the product structure are concerned (86 references).

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

“…1,2 Treatment of 3-chloro-and 3-bromopyridine (1a and 1b, respectively) with lithium diisopropylamide (LDA) 3,4 or t BuLi 5 in THF at À78 C affords the C-4 substituted product. 6 A small amount of the C-2 substituted product has also been detected in the reactions involving LDA as the lithiating reagent. In case a complexing lithiating reagent ( n BuLieTMEDA, n BuLieLDMAE or TMSCH 2 LieLDMAE) is used, a shift in the site of lithiation from C-4 to C-2 is noticed.…”

Distant C-H Activation/Functionalization: A New Horizon of Selectivity Beyond Proximity

“…Functionalized pyridines are most important heteroarene frequently found in natural products, considered as biologically active compounds, clinically used as drugs and ligand (39)(40)(41)(42). Due to their immense importance there is continues efforts to develop catalytic method for the synthesis and functionalization of pyridine at different positions (43)(44)(45)(46)(47).…”

Recent Advances in Cycloaddition Reactions of Heterocyclic N-Oxides

“…General and useful synthetic methods exploiting N-oxides as starting materials have been developed, such as cine [6][7][8][9][10][11][12] and other types [13][14][15] of nucleophilic substitution, metalation with organometallic reagents [16], or, more recently, transition metal-catalyzed C-H activation of N-oxides of azines [17][18][19][20][21][22][23][24][25][26][27][28][29] and azoles [30][31][32][33]. The main focus of this review are useful and general synthetic approaches to the preparation of C-2 functionalized azines and azoles based on 1,3-dipolar cycloaddition that has been developed in recent years.…”