Acidity measurements in THF. III. Aldimines and ketimines

Abstract

. Can. J. Chem. 61, 2729 (1983).The relative acidities of fiteen aldimines and ketirnines have been measured in THF using either ' " nrnr spectroscopy or trapping experiments with methyl iodide. The pK,'s are found to vary over a range of more than four pK units. The effects of structure on acidity indicate the acid-weakening effect of alkyl substitution in ketirnines to be due to steric effects. This interpretation is supported by the results of ab ir~itio calculations. The data also permit a quantitative estimation of the preference for the syn configuration of lithiated irnines to be at least four kcal/rnol. The anti selectivity previously reported for the lithiation of endocyclic irnines can be accounted for by angular constraints, as indicated by both ab initio calculations and pK, data on this class of irnine.ROBERT R. FRASER, MONIQUE BRESSE, NOEMI CHUAQUI-OFFERMANNS, K. N. HOUK et N. G. RONDAN. Can. J. Chern. 61, (1983).On a rnesurC les aciditCs relatives de quinze aldirnines et cCtirnines dans le THF en faisant appel soit ii la spectroscopie rrnn du "C ou i des expkriences de trappage avec I'iodure de rnCthyle. On a trouvC que les pK, varient sur plus de quatre unites de pK. Les effets de structure sur I'aciditC indiquent que l'abaissernent de I'aciditC lors de la substitution alkyle dans les cCtCrnines serait dC i des effets stCriques. Cette interprktation est en accord avec les rCsultats de calculs ab initio. Les donnCes perrnettent aussi d'Cvaluer quantitativement, i au rnoins 4 kcal/rnol, la prCfCrence pour la configuration sytz des irnines IithiCs. On peut expliquer la sClectivitC anti rapportCe anterieurernent lors de la lithiation d'irnines endocycliques en faisant appel i des contraintes angulaires qui sont suggCrCes i la fois par les calculs ab initio et les donnCes de pK, sur cette classe de cornposCs.[Traduit par le journal]During the course of our investigations on the chemistry of lithiated aldimines (1) and ketimines (2) a number of unusual results were encountered for which satisfactory explanations required further experimental support. For example, with but two exceptions the lithiation of aldimines and ketimines gave exclusively anions having the syn configuration, the main exception being the endocyclic imines 9 to 12 which formed anti lithio derivatives only (3).2 A second striking feature of the lithiation of ketimines concerns the regioselectivity of the reaction. Just as had been observed earlier for ketone oximes (4), oxime ethers ( 3 , and hydrazones (6), lithiation is markedly favored at a primary vs. secondary carbon atom (7) or at a secondary vs. a tertiary one (2,8). This is anomalous too, in the sense that the stability differences at primary, secondary, and tertiary carbons are normally small and in the reverse order when a change of sp3 to sp2 hybridization is involved (9, 10).As a potential aid to our understanding these results, we set out to obtain quantitative information on the deprotonation reaction, that is, to measure the relative acidities of a variety of imines o...

1-Azaallylic Anions in Heterocyclic Chemistry

“…9 As mentioned before, metalated 1-azaallylic anions have a syn (Z)-C-N stereochemistry preference. This configuration has been described and confirmed by ab initio calculations, [10][11][12][13] NMR studies, [14][15][16][17][18][19][20] X-ray analysis, 21,22 and experimental evidence. [23][24][25][26] The experimental evidence was rationalized via ab initio computational studies.…”

“…A pK a value around 30 in DMSO for R-protons of N-benzylketimines derived from acetone was estimated. 11 It should be mentioned that proton abstraction of imines by lithium dialkylamides is extraordinarily slow, compared to that of the corresponding keto analogues. This is a clear advantage, considering that the deprotonation of imines still proceeds smoothly without competitive proton transfer.…”

Carbolithiation of Styrenes with N-tert-butyl aldimines

“…Apparently the reaction proceeds via the addition of the vinylimidazole anion to the aldimine in a manner described in the LDA-mediated reaction of methylimidazole with propionaldehyde. 15 The pKa of methylimidazole, 16 being approximately 10 times larger than that of aldimines and ketimines, 17 can be used to explain this preferred addition mode.…”

Product Class 7: Imines

“…Concerning the first point, the deprotonation of imines (except endocyclic imines [350] ) results exclusively in anions with the syn configuration. [351,352] This syn effect is probably due to the fact that metalated imines occur as aggregates in solution, which are more stable in the syn configuration. [353,354] Concerning the stereochemistry around the C=C bond, no general rules can be put forward.…”

“…[358,359] The final point, regiochemistry of deprotonation, has been carefully investigated in the case of deprotonation of imines derived from pentan-3one. [356] In most cases, the least substituted carbon atom is deprotonated; [352,360] however, upon alkylation of heptan-2-imine with benzyl chloride, significant amounts of the more substituted isomer are formed. [361] Several factors such as the nitrogen substituent, the solvent, the temperature, and the base can control the regioselectivity.…”