9- Azabicyclo undecanes

Azabicyclo[2.1.0]pentane-3-carboxylic acid antimicrobial activity, 7, 346 l-Azabicyclo[3.3.3]undecane — see Manxine 1 - Aza-2-boracyclohexane, 1 -methyl-synthesis, 1, 647... 

Bohlmann et al. (118-121) observed that an infrared absorption band between 2700-2800 cm is characteristic of a piperidine derivative possessing at least two axial carbon-hydrogen bonds in antiperiplanar position to the free-electron pair on the nitrogen atom. The possibility of forming an enamine by dehydrogenation can be determined by this test. Compounds which do not fulfill this condition cannot usually be dehydrogenated (50, 122,123). Thus, for example, yohimbine can be dehydrogenated by mercuric acetate,whereas reserpine or pseudoyohimbine do not react (124). The quinolizidine (125) enamines (Scheme 4), l-azabicyclo(4,3,0)-nonane, l-azabicyclo(5,3,0)decane, l-azabicyclo(5,4,0)undecane, and l-azabicyclo(5,5,0)dodecane have been prepared in this manner (112,126). 

The tricarbonylchromium complex 6 of methyl 1/f-azepine-l-carboxylate undergoes photoin-duced [6 + 4] 7t-cycloadditions with dienes, e.g. 7, to give, after decomplexation with oxygen, azabicyclo[4.4.1]undecanes, e.g. 8, in high yields.276... 

However, in more complicated amines, this straight correlation is violated. The bicyclic tertiary amine l-azabicyclo[4.4.4]tetradecane (22) and the acyclic tertiary amine n-Bu3N have nearly the same first IP (7.84 and 7.90 eV, respectively), but the proton affinity of the bicyclic amine is 20 kcal mol 1 lower than that of the acyclic52. On the other hand, for other bridge-head tertiary amines like l-azabicyclo[2.2.2]octane (quinuclidine, 20) and l-azabicyclo[3.3.3]undecane (manxine, 21) the expected relation between proton affinities and IP values is observed. The extraordinary properties of l-azabicyclo[4.4.4]tetradecane (22) are caused by its unusual conformation the nitrogen lone-pair is directed inward into the bicycle where protonation is not possible. In the protonated form, the strained out-conformation is adopted. This makes it the least basic known tertiary amine with purely saturated alkyl substituents. Its pKa, measured in ethanol/water, is only +0.693. Strain effects on amine basicities have been reviewed by Alder88. 

For example, consider the near-planar nitrogen in l-azabicyclo[3.3.3]undecane (manxine), N. J. Leonard, J. C. Coll, A. H. -J. Wang, R. J. Missavage and I. C. Paul, J. Amer. Chem. Soc., 93, 4639 (1971). Regrettably, we know of no enthalpy of formation measurements on either this heterocycle or the corresponding hydrocarbon, manxane. 

Electrochemical perfluorination of 4-methylquinolizidine gives rise to a small amount of by-product perfluoro-l-azabicyclo[5.4.0]undecane (54) (88JFC(38)303). 

Manxine (l-azabicyclo[3.3.3]undecane 60) is an interesting compound which can be prepared in 60% yield by reduction of the quaternary ammonium salt (59) with sodium in liquid ammonia. It has a melting point of 150-152 °C and a remarkably long wavelength absorption [Amax 240 nm, e 2935 (ether)] for a saturated amine. Its pKa (9.9) is one unit... 

Starting from the optically active (S)-proline derivative 159, Clark and Hodgson were able to synthesize azabicyclo[6.3.0]undecane 161 with... 

Leonard and Goode used the hydrogenation of hydroxyimino diesters of the structure I over Copper-Chromium oxide at 250°C and 36 MPa H2 for the synthesis of 1-azabicyclo compounds of the structure II (Scheme 8.8).76 By this method pyrrolizid-ine (Ila), octahydropyrrocoline (lid), quinolizidine (lib), l-azabicyclo[5.3.0]decane (lie), l-azabicyclo[5.4.0]undecane (Ilf) (eq. 8.38), and l-azabicyclo[5.5.0]dodecane (lie) were prepared in 50-60% yields. However, attempts to prepare bicyclic amines... 

Should one ask for direct enthalpy of formation investigations on anti-Bredt enamines, such studies are currently limited to l,6-imino[10]annulene (14) with its gas phase enthalpy of formation of 367.2 7.0 kJ mol-1. How do we affirm the decrease in resonance energy accompanying its geometric constraints There are no enthalpy of hydrogenation measurements for this compound, nor for any other 11-azabicyclo[4.4.1]-undecane (30) derivative71. However, we do know the gas phase enthalpy of formation... 

Spectral investigations of daphnezomines F (42) and G (43), whose molecular formulas are C27H35NO8 and C27H35NO7, respectively, revealed that they are structurally related and possess a l-azabicydo[5.2.2]undecane moiety. The conformation of the l-azabicyclo[5.2.2]undecane ring in 43 was elucidated by a low-temperature NMR study and computational analysis [46],... 

The structure of daphmanidin B (67), C25H36NO6, was elucidated by 2D NM R data to possess a l-azabicydo[5.2.2]undecane moiety, like daphnezomines F and G [46]. The relative stereochemistry was deduced from NOFSY correlations. The conformation of the unit (C-2-C-5, C-18 to C-2, C-19, and N) in the l-azabicyclo[5.2.2]undecane moiety, with a twist-chair form as shown in Figure 18.16, was consistent with the results of a conformational search using MMFF force field [60] implemented in the Macromodel program [59]. 

Two novel alkaloids with an unprecedented fused-pentacyclic skeleton, daphmanidins C (68) and D (69), consisting of l-azabicyclo[5.2.2]undecane, hexahy-dronaphthalen-l-one, and cyclopentane rings, have been isolated from the leaves of D. tdjsmanii [79]. Daphmanidin C elevated the activity of NGF biosynthesis. New daphniphyllum alkaloids, daphmanidins E (70) and F (71), have also been isolated from the leaves of D. teijsmannii, and Daphmanidins E and F showed a moderate vasorelaxant effect on rat aorta [80]. 

This intramolecular hydrogen-hydrogen interaction of methylene group in atranes is implied by NMR data and is similar to that described for l-azabicyclo[3.3.3.]undecane ( manxine ) It is the reason that determines the pronounced physico-chemical... 

There have been reports of l-metalla-5-aza-cyclooctanes of A1 [57], Ga [57], In [57]. Sn [68], P [69], and Si [70] from the reaction MeN(CH2CH2CH2MgX)2 and dihalide compounds. The tri-Grignard reagent N(CH2CH2CH2MgX)3 has been used to make 1-galla- and l-aluma-5-azabicyclo[3.3.3]undecanes 84a-b [Eq. (34)], in addition to l-aza-5-sila-5-methyl-bicyclo[3.3.3]undecane 84c [57,70]. 

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