Conformational Preference of 2‐(Halomethyl)‐ and 2‐(Oxymethyl)Pyridines: Microwave Spectrum, Ab Initio, and MM3 Studies of 2‐(Fluoromethyl)Pyridine

Abstract

One single conformer was assigned from the microwave spectrum of 2-(fluoromethyl)pyridine, investigated in the gas phase in the 26.0-39.0 GHz spectral region at about -10°C. Its Cα-F bond was found to be coplanar with the ring and anti to the N-C2 bond (syn to the C2-C3 bond). There was no indication in the microwave spectrum of the presence of other rotameric forms of the molecule. The results of the spectroscopic study were backed up by ab initio calculations at the MP2/6-31 G** (frozen core) level. These calculations predict that the assigned conformer is the only stable form of the molecule. The transition state was calculated to have the CH F group 180° from the stable anti conformation. The energy of the transition state was computed to be 20.2 kJ mol higher than the energy of the anti rotamer. The results are interpreted in terms of a stereoelectronic effect, and the orbital overlaps responsible for the observed effect are discussed. It is shown that 2-(fluoromethyl)pyridine serves as a good model for 2-(alkoxymethyl)pyridines, previously found to show the same conformational preference.

Synthesis of Versatile Chiral N,P Ligands Derived from Pyridine and Quinoline

“…The success of these ligands in the Ir-catalyzed hydrogenation of olefins [2][3][4] and imines, [5] and the intention to mimic the coordination sphere of Crabtree's catalyst ([(Cy 3 P)(pyridine)Ir(cod)]PF 6 ) [6] (Cy = cyclohexyl, cod = 1,5-cyclooctadiene) with a chiral bidentate ligand, motivated us to prepare chiral pyridyl phosphanes having the general structure 4.[7] On the basis of simple force-field calculations carried out with a fixed standard geometry for the P-Ir-N core and the known propensity of 2-(oxymethyl)pyridines to adopt an antiperiplanar conformation of the N-C-C-O fragment, [8] we anticipated that these ligands would form a rigid chelate ring in a[*] Dr. …”

Synthesis of Fluorinated 3,6-Dihydropyridines and 2-(Fluoromethyl)pyridines by Electrophilic Fluorination of 1,2-Dihydropyridines with Selectfluor®

“…N -Fluorobis(trifluoromethanesulfonyl)imide, (CF 3 SO 2 ) 2 NF, is a very attractive fluorinating agent because of its favourable physical properties and high reactivity, but it is not commercially available. In the reaction of 2-(chloromethyl)pyridine with potassium fluoride, 2-(fluoromethyl)pyridines can be also obtained (Finkelstein reaction, S N 2 reaction that involves the exchange of one halogen atom for another) [ 28 ] or in the reaction of 2-pyridinylmethanol derivatives with (diethylamino)sulfur trifluoride [ 29 ].…”

“…It should also be noted that, despite the fact that fluorine- and trifluoromethyl-substituted pyridines have been very extensively studied, there are very limited data on 2- and 4-(fluoromethyl)pyridines in the literature [ 24 , 25 , 26 , 27 , 28 , 29 ], which makes these compounds attractive for investigations.…”

“…In this paper, we studied the electrophilic fluorination reaction of 1,2-dihydropyridines 1a-k with Selectfluor ® (Table 1). (fluoromethyl)pyridines in the literature [24][25][26][27][28][29], which makes these compounds attractive for investigations.…”

Synthesis of Versatile Chiral N,P Ligands Derived from Pyridine and Quinoline

“… The success of these ligands in the Ir‐catalyzed hydrogenation of olefins2–4 and imines,5 and the intention to mimic the coordination sphere of Crabtree's catalyst ([(Cy 3 P)(pyridine)Ir(cod)]PF 6 )6 (Cy=cyclohexyl, cod=1,5‐cyclooctadiene) with a chiral bidentate ligand, motivated us to prepare chiral pyridyl phosphanes having the general structure 4 7. On the basis of simple force‐field calculations carried out with a fixed standard geometry for the P‐Ir‐N core and the known propensity of 2‐(oxymethyl)pyridines to adopt an antiperiplanar conformation of the N‐C‐C‐O fragment,8 we anticipated that these ligands would form a rigid chelate ring in a boat conformation ( 6 ), thus generating a similar steric environment around the Ir atom as the PHOX ligands. However, as oxazoline and pyridine ligands are expected to have different electronic effects on a coordinated metal, we thought that pyridine‐derived ligands, such as 4 , could induce new patterns of reactivity and selectivity.…”