Lewis acid complexed heteroatom carbanions; synthesis of some α-pyridyl alcohols

Abstract

Metallation of BF3-pyridine complex with lithium tetramethylpiperidide (LTMP) in ether at -78 "C, followed by reaction with carbonyl compounds, affords a-pyridyl alcohols in good yields. a-Pyridyl alcohols, which are intermediates of some pharmacological interest ,132 are often synthesised from halogen derivatives or N-oxides of pyridine because direct metallation of this heterocycle is deemed impractical.3-5 It was, therefore, of interest to see if Lewis acid complexation can be used for this purpose (Scheme 1).6Our attempts to obtain the alcohol 3a through deprotonation of pyridine with the highly hindered base lithium tetramethylpiperidide (LTMP) furnished only 2,2'-bipyridy17 at -78"C, while no reaction was observed at -120°C. However, treatment of an ether solution? of the BF3-complex 1 with LTMP at -78 "C, followed by addition of benzaldehyde afforded 3a8 in 85% yields.$ The alcohol 3b9 (87%) was t Use of tetrahydrofuran (THF) as solvent gave inferior yields. Also reactions with methyl iodide and benzyl chloride proceeded poorly.

Synthesis and characterization of 3,5-lutidinyl chalcogen and -dichalcogen compounds: X-ray crystal structure of bis(3,5-dimethyl-2-pyridyl) diselenide and 2,6-bis(selenomethyl)-3,5-lutidine

“…Kessar et al reported the lithiation of pyridine aided by BF 3 complexation with lithium tetramethyl piperidine (LTMP). [15] However, it is for the first time that selective mono-and dilithiation of 3,5-lutidine ring has been achieved by using BF 3 -complexed 3,5-lutidine with lithium diisopropylamide (LDA) or lithium tetramethyl piperidine (LTMP). Single-crystal X-ray studies of bis(3,5-dimethyl-2-pyridyl) diselenide (5), having a rare CeSeeSeeC torsion angle of 180 (4), and 2,6-bis(selenomethyl)-3,5-lutidine (7) have also been reported.…”

A novel neutral organic electron donor with record half-wave potential

“…31 Initially, the synthesis of diketone 22 directly from Weinreb amide 19 and 4-DMAP 20 was attempted using Fort's direct 5 deprotonation protocol, 32 however this was unsuccessful. Kessar 33 used N-trifluoroboration of pyridine to acidify the 2-position of the ring, and the resulting pyridinium ylid was used for C-C bond-formation. The same BF 3 adduct has also been utilized by Sammakia 34 of the configurational isomers are very high relative to 26, (density functional calculations using the B3LYP 6-31G* functional in a DMF continuum show that changing one of the inter-ring alkenes from E to Z affords the next most favourable isomer, but that is 23 kcal/mole higher in energy than 26) and 5 accordingly, populations of minor isomers arising in this way are unlikely as the cause of the broad signals in the NMR spectrum.…”

Side‐Chain Retention During Lithiation of 4‐Picoline and 3,4‐Lutidine: Easy Access to Molecular Diversity in Pyridine Series

“…(4-Methylpyridin-2-yl)(phenyl)methanone (2e): [12] Column chromatography (hexanes/EtOAc, 90:10) yielded 2e (614 mg, 78%) as a yellow oil. (4-Methylpyridin-2-yl)-3-phenylmethanol (2f): [6] Column chromatography (hexanes/EtOAc, 70:30 ) yielded 2f (476 mg, 60%) as a beige solid. 1 Methylpyridin-2-yl)butan-2-ol (2g): Column chromatography (hexanes/EtOAc, 50:50) yielded 2g (449 mg, 68%) as an orange oil.…”

“…This Scheme 1 was accomplished by treatment of 1 with BF 3 ·OEt 2 and subsequent lithiation with an excess of LTMP, and is known as Kessar's reaction. [6] Although efficient, this process implies the regeneration of neutral substituted pyridine from the BF 3 Ϫpyridinium species. Our approach is to incorporate the pyridine nitrogen atom into nBuLi-containing lithium aggregates, [7] the enhancement of proton acidities and proximity effects being expected to promote selective C-2 lithiation ( Figure 1).…”