Decahydroquinolines, conformation

The Aae in piperidine of 0.48 ppm is increased to 0.66 ppm (for the 6-methylene protons) in 3,3-dimethylpiperidine (measurements in CH2C12 solution below coalescence temperature for ring inversion). This was taken as an indication of an increase in N-Heq conformer in the latter compound.42 Measurements on decahydroquinolines however, showed43 the insensitivity of this parameter to N-H orientation (e.g. 19 and 20 gave Aae values of 0.61 and 0.54 ppm, respectively). 

The use of 13C-NMR chemical shifts in estimating the position of conformational equilibria may be illustrated by reference to the conformational equilibria of the /V-methyl group in (V-methyl-rrans-decahydroquinoline (55 56).93 94... 

The conformational properties of a range of iV-nitrosodecahydroquino-lines have been based on 13C- and H-NMR spectral data. The Af-ni-troso-2/J-methyl-tran.s-decahydroquinoline (151), for example, in which the unfavorable interaction between substituents cannot be relieved by inversion as in yV-nitroso-2,6-cis-dimethylpiperidine (Section III,C,l,c) adopts conformations with the piperidine ring in a boat or twist form.204... 

At -61°C the H-NMR spectrum of /V-methyl-cis-octahydrocarbostyril shows signals for 8a-H in both conformers 167 and 168. On this basis Wi values were recorded from room-temperature spectra of a variety of derivatives existing as equilibria. The N-inside conformation was preferred for the JV-H compound, whereas the N-outside conformation was preferred for the N-Me compound. This is different from the situation in N-methyl-cis-decahydroquinoline and may be due to a closer approach of N-Me to the C-8 methylene in 167 than in 160 as a result of a flattened sp2-hybridized nitrogen atom.211... 

A series of studies have been reported on the basicities and nucleo-philicities of 4-substituted and 4,4 -disubstituted piperidines, together with related work on decahydroquinolines.211-215 Substituent effects on pKa values determined in methanol of 4,4 -disubstituted A-methyl-piperidines216,217 and 1,2,5-trimethylpiperidines (25)218 were found to be dependent on o i.e., as expected, resonance effects are absent, the hydroxyl substituent where present taking the axial conformation (24),216 owing to a bridging molecule of methanol. 

Fig. 13. Two different conformations for as- decahydroquinoline with the same absolute configuration (a) as in gephyrotoxin, Fig. 12, and (b) as in pumi 10 oxin C, Fig. iq -phe numbering coincides with the numbering in the respective molecules. 

Ehrenstein and Bunge (265) found that the derivatives of cis-decahydroquinoline and cis-decalin are more easily dehydrogenated than the corresponding trans forms according to these authors, the facts found by them are in conformity with the multiplet theory. 

Spande TE, Jain P, Garraffo HM, Pannell LK, Yeh HJC, Daly JW, Fukumoto S, Imamura K, Tokuyama T, Torres JA, Snelling RR, Jones TH (1999) Occurrence and Significance of Decahydroquinolines from Dendrobatid Poison Frogs and a Myrmicine Ant Use of H and C NMR in Their Conformational Analysis. J Nat Prod 62 5... 

Some n.m.r. studies on cis- and /ra s-decahydroquinolines and their acyl derivatives lead to the conclusions that (i) the troiw-isomer has a twin-chair conformation (ii) the cw-isomer (31) prefers the twin-chair... 

The preferential conformation of a substituent at the nitrogen atom of piperidine seems to depend on its size and the state of solvation of the p electrons . Thus it was found that the steric requirements of the unsolvated pair are less than those of a proton or a methyl group , for example in equation (80) equilibrium favours form 137 over 138 at room temperature in benzene solution ( 88% for R = H, and 94% for R = CH3), as was shown by dipole-moment measurements . On the other hand, the solvated electron pair has larger steric requirements than an A -hydrogen, as shown for example from the kinetics of equilibration of epimers of methyl A -methyl-decahydroquinoline-4-carboxylate (139) . Results from the n.m.r. spectroscopy of piperidine and iV-methylpiperidine in methanol (a... 

Nitrogen inversion in a series of bicyclic hydrazines has been characterized from low temperature lineshapes obtained at the natural abundance level (53). Two sets of resonances separated by 1-2 ppm coalesced into singlets in the range 90-100 ppm over the temperature range 250-280 K. Activation free energy inversion barriers of 12.7-14.8 kcal/mol were consistent with those obtained from proton and experiments. Similarly, conformational equilibria in jpis-decahydroquinolines have been elucidated by comparison of shifts in rigid compounds with those in conformationally mobile ones (54). 

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