Steric effects pyridines

The low yields of 6,6 -disubstituted-2,2 -bipyridincs recorded in Table I are probably the result of steric retardation of the adsorption of 2-substituted pyridines. This view is supported by the observation that 2-methylpyridine is a much weaker poison for catalytic hydrogenations than pyridine. On the other hand, the quinolines so far examined (Table II) are more reactive but with these compounds the steric effect of the fused benzene ring could be partly compensated by the additional stabilization of the adsorbed species, since the loss of resonance energy accompanying the localization of one 71-electron would be smaller in a quinoline than in a pyridine derivative. 

Cobalt trifluoride fluorination corresponds to the electron-transfer mechanism via a radical cation. RF groups attached to the ring enhance the stability of intermediate dienes and monoenes. Perfluoroalkyl pyridines, pyrazines, and pyrimidines were successfully fluorinated but pyridazines eliminated nitrogen. The lack of certain dienes was attributed to the difference in stability of FC=C and RFC=C and steric effects [81JCS(P1)2059]. 

Another type of steric effect is the result of an entropy effect. The compound 2,6-di-fert-butylpyridine is a weaker base than either pyridine or 2,6-dimethylpyridine. The reason is that the conjugate acid (8) is less stable than the conjugate acids of nonsterically hindered pyridines. In all cases, the conjugate acids are hydrogen bonded to a water molecule, but in the case of 8 the bulky tert-butyl groups restrict rotations in the water molecule, lowering the entropy. 

An unusually slow relaxation has been observed for the 2,6-pyridine-dicarboxaldimine cobalt(II) complex [Co(2,6-(CH3NH=CH)2py)2](PFg)2 in solution. Thus a relaxation time -c = 83 ns has been reported [99], the rate constants being among the lowest found. It has been suggested that nonelectronic factors such as partial ligand dissociation, steric effects or solvent interaction may be rate determining in this equilibrium. 

Scheme 52 explains the [(Cp )Rh(MeCN)3]2+-assisted regioselective hydrogenation of pyridines, benzoquinolines, acridines as well as indoles and benzothiophene.258 The relative hydrogenation rates were attributed to both electronic and steric effects, the rate generally decreasing with increasing basicity and steric hindrance at the nitrogen atom. 

The hydrogenations become analogous to those involving HMn(CO)5 (see Section II,D), and to some catalyzed by HCo(CN)53 (see below). Use of bis(dimethylglyoximato)cobalt(II)-base complexes or cobaloximes(II) as catalysts (7, p. 193) has been more thoroughly studied (189, 190). Alkyl intermediates have been isolated with some activated olefinic substrates using the pyridine system, and electronic and steric effects on the catalytic hydrogenation rates have been reported (189). Mechanistic studies have appeared on the use of (pyridine)cobaloxime(II) with H2, and of (pyridine)chlorocobaloxime(III) and vitamin B12 with borohydride, for reduction of a,/3-unsaturated esters (190). Protonation of a carbanion... 

When the diazirine was decomposed thermally, avoiding its electronically excited state, the yield of fragmentation products dropped to 1-2%. Further analysis revealed that, under photolytic conditions, cyclobutenes 27 and 28 were formed from both the carbene (63%) and directly from the excited diazirine (17%) fragmentation accounted for the remainder of the material balance. LFP studies by the pyridine ylide method gave rate constants for 19 —> 27 (1.3 x 106 s-1) and 19 — 28 (2.5 x 105 s-1), with the 5-fold preference for CH2 migration to 27 over CMe2 migration to 28 attributed to differential steric effects.45... 

The acyclic version of Larock s heteroannulation was successfully applied to the synthesis of highly substituted pyridines [166]. The annulation of rert-butylimine 210 with phenyl propargyl alcohol produced pyridine 211 regioselectively in excellent yield. The regiochemistry obtained was governed by steric effects. Furthermore, the choice of imines was crucial to the success of the heteroannulations. terr-Butylimine was the substrate of choice, since all other imines including methyl, isopropyl, allyl and benzyl imines failed completely to produce the desired heterocyclic products. 

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