Regiospecific Nucleophilic Attack at the γ‐Position of 1‐(2,6‐Dimethyl‐4‐oxo‐1,4‐dihydro‐1‐pyridyl)pyridinium Compounds; Novel Synthesis of 4‐Substituted Pyridines

Abstract

reported herein gave spectral data in full accord with the assigned structures. New compounds which were sufficiently stable to allow for full characterization gave satisfactory elemental analyses and/or molecular weight measurements (high resolution mass spectrometry). 17) G. H. Posner, D. J. Brunelle, L. Sinoway, Synthesis 1974, 662. (81 In the case of [(6a)-(6d)], silyl enol ether formation was highly regioselective [exclusive or nearly exclusive formation of (70)-(7d)].-When lithium 2.2.6.6-tetramethylpiperidide was used as a base in the place of lithium diisopropylamide, (10) was formed as the major product.191 For studies related to the thermal rearrangement of methylene(viny1)cyclopropane systems, see also W E.

Synthesis of Pyridine and Dihydropyridine Derivatives by Regio- and Stereoselective Addition toN-Activated Pyridines

“…Katritzky, Sammes, and co-workers also applied the strategy of using 2,6-dimethyl blocking groups in the addition of Grignard reagents to N -(2,6-dimethyl-4-oxopyridin-1-yl)pyridinium salts (Scheme , 142 ). − The resulting 4-substituted pyridine could previously only be prepared in multistep syntheses, and the method proved to be complementary to that previously reported with pyridine N -oxides. The resulting crude reaction mixtures consisted of both the dihydropyridine intermediate and the 4-substituted pyridine.…”

“…The addition of enolates to N – N -pyridinium salts is well documented. Lithium enolates of ketones add selectively at the 4-position of N -(2,6-dimethyl-4-oxopyridin-1-yl)pyridinium salts due to the blocking effect of the methyl groups (Table ). , Unlike what is observed with the addition of Grignard reagents, the target pyridine was not obtained and the 4-substituted dihydropyridine intermediate could be readily isolated and purified on Al 2 O 3 . The addition of LDA to the mixture of the pyridinum and ketone gave selective addition of the kinetic enolate.…”

“…The addition of LDA to the mixture of the pyridinum and ketone gave selective addition of the kinetic enolate. Importantly, even α,α-disubstituted enolates were reactive enough to add, forming an all-carbon quaternary center in 52% yield . Picoline derivatives of the N -(2,6-dimethyl-4-oxopyridin-1-yl)pyridinium salts were also operative.…”

C–H Functionalization of Azines

“…The generation of the alkoxide is critical for the C6-alkylation with high regioselectivity. The products can be good precursors for asymmetric hydrogenation reactions. , Although it is beyond the scope of this review, N -activated azines − and two-step nucleophilic addition/oxidations − are widely utilized for the synthesis of substituted pyridines.…”

Addition of Grignard Reagents to Quinolinium Salts: Evidence for a Unique Redox Reaction between a 1,4- and a 1,2-Dihydroquinoline

“…CuI; RCu·BF 3 ) 7 and titanium reagents 8 were employed. In a conceptually different approach, Katritzky, and subsequently Akiba, have shown that by using pyridinium salts containing bulky substituents that can shield the 2- and 6-positions the attack of Grignard reagents can be forced to occur preferentially at the 4-position. To the best of our knowledge, studies on the prospects of such an approach in the case of quinolinium salts have not been previously reported …”