1- azabicyclo decane

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). 

Nitrones derived from 2-azabicyclo[5.3.0]decane give quinolizidine compounds by photochemical Beckmann rearrangement which implies simultaneous ring expansion and ring contraction reactions. Intramolecular Schmidt reactions in 2(4-azidobutyl)-cyclopentanones also give quinolizidinone derivatives by ring expansion. Examples of both types of reactions are given in Sections 12.01.11.1 and 12.01.11.3, respectively. 

Bisher rniBlangen die Versuche, bicyclische Azazulene lierzustellen. Sowohl das von V. Prelog und U. Geyer (107) synthetisierte 8-Aza-bicyclo-(0,3,5)-decan, wie das von J. O. Halford und B. Weissmann (48) beschriebene 4-Azabicyclo-(0,3,5)-decan widerstanden den bekannten Dehydrierungsmoglichkeiten. 

Reduction of lactams to amines resembles closely the reduction of amides except that catalytic hydrogenation is much easier and was accomplished even under mild conditions. a-Norlupinone (l-azabicyclo[4.4.0]-2-oxodecane) was converted quantitatively to norlupinane (l-azabicyclo[4.4.0]decane) over platinum oxide in 1.25% aqueous hydrochloric acid at room temperature and atmospheric pressure after 16 hours [1122]. Reduction of the same compound by electrolysis in 50% sulfuric acid over lead cathode gave 70% yield [1122]. 

The configurations and conformations of cis- and frans-JV-methyl- and /V-benzyl-2-oxa-4-az-abicyclo[4.4.0]decane and 4-oxa-2-azabicyclo[4.4.0]decane, e.g., 8 and 9, have been determined 646 as have the configurations and conformations of diastereomeric tetralins647, e.g., 10-12. 

Several isoxazolidines or their quaternary salts derived from the 1,3-dipolar cycloaddition of rr/i-hcxcnolidcs (6,7-dihydrooxepin-2(5//)-ones) to cyclic nitrones, were converted into the corresponding piperidyl- and pyrrolidyloxepi-nones by reduction of the nitrogen-oxygen bond (Equation 4). These amino alcohols provide a new access to the l-azabicyclo[5.3.0]decane core of the Stemona alkaloids <2004EJ04215>. 

The racemic 2-azabicyclo[2.2.1]heptane-3-carboxylic acid was obtained by alkaline hydrolysis (24 h reflux in 4 N NaOH/MeOH 3/1 yield 78%) of the 4-phenyl-2,4-diazatricyclo[5.2.1.02-5]decane-3,5-dione-(l)- hydantoin obtained... 

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... 

Optimized (6-31G ) ET (without and with Zero-Point Energy and Thermal Corrections) and Selected Geometric Parameters [28] for amides and Lactams (the Carbonyl-Containing Bridge Is Specified e.g. 3.3.2 Signifies l-Azabicyclo[3.3.2]decan-9-one. (See reference 36.)... 

A special type of ring enlargement is found in the electrolytic reduction of bicyclic a-aminoketones (lead cathode, 30% sulfuric acid, 60°C) to monocyclic products.102 103 Thus, 1-ketoquinolizidine (107) under these conditions gave 59% 5-hydroxyazacyclodecane (108) and 4.5% l-azabicyclo[5.3.0]decane (109) (Scheme 13). 

During early studies by May,<24) 6-aryl-2-azabicyclo[4.3.1]decanes (31) were synthesized following the route illustrated in Scheme 5.1, but no analgesic properties were found in the few compounds tested. 

The synthesis of (—)-stemospironine provides another example of the use of aziridinium ions in natural product synthesis <20010L2721>. The Stemona alkaloids are characterized by the l-azabicyclo[5.3.0]decane nucleus. Azide 363 was the key intermediate for the aziridinium-mediated synthesis. Debenzylation at low temperature... 

More recently, the 1,4-disubstituted quinolizidine 275A was reassigned a 4-methyl-9-non)myl-l-azabicyclo[5.3.0]decane structure by comparison with synthetic diastereomers. Fig. (14) [16]. Nevertheless complete characterisation has not yet been reported. 

A synthetic strategy was developed for the typical core structure of the Stemona alkaloids in the laboratory of C.H. Heathcock. " The precursor for the 1-azabicyclo[5.3.0]decane ring system was prepared via the successive double alkylation of the dianion of ethyl acetoacetate. 

Michael additions to acceptor-substituted dienes are often followed by (spontaneous or induced) cyclizations. This was already noted by Vorlander and Groebel" who obtained a substituted 1,3-cyclohexanedione by treatment of 6-phenyl-3,5-hexadien-2-one with diethyl malonate (equation 5). Obviously, the 1,4-addition product which is formed initially then undergoes cyclization, ester hydrolysis and decarboxylation. Similarly, reaction of methyl sorbate with methyl 4-nitrobutyrate gave the 1,6-adduct which was reductively cyclized to 6-methyl-l-azabicyclo[5,3,0]decane (equation 6). 

A/-Alkylgranatanine-3-spiro-5 -hydantoins obtained by the Bucherer-Bergs methods have the a-configuration.68-71 The stereoselectivity of the Bucherer-Bergs and Read reactions of bicyclo[3.2.1]octan-3-one72 and N-methyl-10-azabicyclo[4.3.1]decan-8-one (homogranatanine) has also been... 

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