2- Azabicyclo octane derivs

Isoquinudidine derivs. 2-azabicyclo[12.2]-octane derivs. retro-synthesis, 212-213 synthesis, 153, 291, 297 Isothioureas, 5-alkyl- thiols from, 168 Isoureas, O-acyl- = carbamimidic anhydrides reactive intermediates, 144-145, 234 —, O-alkyl- carbamimidic esters, 144-145 Isoxazoles, 307—308 —, 4,5-dihydro-, 153 Isoxazolidines, 153... 

The mesoionic 3-oxido-A-alkylpyridinium betaine 13 undergoes 1,3-dipolar cycloadditions as the dipoles a and b. Thus, acetylenedicarboxylate addition via O and C-2 is followed by electrocyclic cleavage of the pyridine N/C-2 bond in the intermediate 16, resulting in the formation of fiiran derivatives 17, In contrast, phenylacetylene and acrylic ester add to the betaine 13 via C-2 and C-6 producing 8-azabicyclo[3.2.1]octane derivatives 14 and 15 [85] ... 

Synthetic approaches to enantiomerically pure 8-azabicyclo[3.2.1]octane derivatives 06CRV2434. 

The mesoionic 3-oxido-N-alkylpyridinium betaine 15-whose electronic description formally corresponds to that of 1,3-dipoles a/b - undergoes cycloadditions with activated alkynes and aUcenes. Thus, phenylacetylene (and analogously acrylate) adds via C-2/C-6 to give 8-azabicyclo[3.2.1]octane derivatives 16. In contrast, dimethyl acetylenedicarboxylate adds via O/C-2 to give as primary product the furo-l,2-dihydropyridine 17, which subsequently is converted to the furan derivative 18 by 67t-electrocyclic N/C-2 opening of the dihydropyridine ring [146] ... 

Scheme 3.39 Asymmetric domino synthesis of 2-azabicyclo[2.2.2]octane derivatives described by Carter.

Heating 3,4-bis(phenylsulfonyl)furoxan with a solution of sodium butoxide in butanol followed by reduction with trimethyl phosphite gives furazan 281 (Scheme 183). Compound 281 was converted into dialkoxy derivative 282 with the lithium salt of ( )-l-azabicyclo[2.2.2]octan-3-ol in 33% overall yield (96W012711, 97EUP773021, 98JMC379). 

The optically active //-amino alcohol (1 / . 3 R. 5 / )-3-(di phenyl hydroxymethyl )-2-azabicyclo[3.3.0]octane [(li ,3i ,5i )-121], can be derived from a bicyclic proline analog. It catalyzes the enantioselective addition of diethylzinc to various aldehydes. Under mild conditions, the resulting chiral secondary alcohols are obtained in optical yields up to 100%. The bicyclic catalyst gives much better results than the corresponding (S )-proline derivative (S )-122 (Scheme 2-47).114... 

As an example of non-enzymatic catalyst using oxazaborolidines [10], Corey and his associates have described an efficient synthesis of (-i-)-l(S),5(R),8(S)-8-phenyl-2-azabicyclo[3.3.0]octan-8-ol (2.) and its enantiomer. The B-methyloxazaborolidine derivatives (3) of these amino alcohols are excellent catalysts -or chemzymes- for the enantioselective reduction of a variety of achiral ketones to chiral secondary alcohols [11]. 

Important improvement in the in vitro activity was obtained when the central proline was replaced by thiaproline (thiaPRO) to give compound 66, suggesting that modification of the central amino acid (of the proline type) could be of importance in modulating the PEP inhibitory activity, Eq. (25) [76]. In fact, replacement of the proline moiety of63 - 66 by non-natural amino acids derived from 2-perhydroindole or from 2-azabicyclo[2.2.2]octane and modulation of the side chain by replacement of the terminal phenyl ring by a dicyclopropyl-carbinyl moiety afforded derivatives such as 67 and 68 with improved activities (IC50 between 10 and 20 nM), Eq. (26). 

A new methodology for the construction of novel and uniquely shaped 3-azabicyclo[4.2.0]octan-4-one derivatives 166 by combining the Ugi multi-component reaction with [2 + 2] enone-olefin photochemical transformations was recently reported [132] (Fig. 32). The additional functional groups are in this case an enone (165) and a C=C double bond. Although the overall sequence is capable of creating up to five stereocentres, in most cases only two diastereomers are observed, which are epimeric at the exocyclic stereogenic centre. 

Hoechst has reported an enantioselective approach toward the key azabicyclo[3.3.0] octane-3-carboxylic acid 46 that preserves the stereochemistry of the L-serine-derived starting material (Urbach and Henning, 1991). L-Serine methyl ester (48) was alkylated... 

In an extension to this work, treatment of the template with 5-hexynal under the standard dehydrating conditions furnished the cycloadduct 301 in good yield (68). However, structural analysis of both the product and the azabicyclo[3.3.0]octane-3-carboxylic acid, derived by hydrogenation of the double bond, followed by... 

The cephalosporins, discovered in the 1950s, are produced by various species of the mold Cephalosporium. Cephalosporin C (9.46) is the prototype of these antibiotics, and its structure shows a close similarity to the penam stmcture. The 5-thia-l-azabicyclo[4.2.0] octane ring system is therefore called the cepham ring. The parent compound carries the aminoadipate side chain, which can be cleaved to supply the 7-amino-cephalosporanic acid. This amine can easily be acylated and thus forms the basis of many useful derivatives. The 3-acetoxymethyl substiment is also amenable to modifications. 

Conversion of oximes derived from cyclobutyl ketones to amides represents the classic Beckmann rearrangement. One example of this reaction is the formation of optically active 7,7-dimethyl-2-azabicyclo[4.1.1]octan-3-one (1) from 6,6-dimethylbicyclo[3.1.1]heptan-2-one oxime, which is readily derived from /3-pinene.40... 

Azabicyclo[4.2.0]octan-l-ols were converted to azocinone derivatives 4 and 5 on photolysis in the presence of an excess of red mercury(II) oxide and iodine.189 A similar ring enlargement is reported for 2-azabicyclo[4.2.0]octan-6-ol to give 6.190... 

The biochemical properties of epibatidine have been Modifications to the compared to the ring-enlarged 8-azabicyclo[3.2.1]octane azabicycioaikane skeleton derivative homoepibatidine and several 2-azabicyclo-[2.2.1]heptanes (Cox et al., 2001). 

Quinuclidine (l-azabicyclo[2.2.2]octane) is a heterocyclic system which is part of the structure of a number of natural physiologically active compounds and synthetic drugs.1 Among the natural alkaloids, the following quinoline and indole derivatives contain the quinuclidine ring cinchonine, cinchonamine (alkaloids of Cinchona species),8-12... 

The kinetics of the reaction of 3-azabicyclo[3.3.0]octane with chloramine have been studied in the pH range 8-13.25 Two competitive bimolecular reactions lead to the formation of A -amino and A-eh loro derivatives, by reaction between neutral species in the former case and by reaction between chloramine and protonated aza compound in the latter case. 

From the reaction mixture of 3-methyl-2-/er/-butyl-6,7,8,9-tetrahy-dropyrido[l,2-a]pyrimidin-4-one 653 in a 1 2 mixture of acetic acid and acetonitrile under argon at 0°C, after photolysis with a high-pressure mercury lamp, 6-acetoxy-l-azabicyclo[4.2.0]octan-8-one 654, 1-azabicyclo [4.2.0]oct-5-en-8-one 655, and piperidone derivative 656 could be isolated in 72%, 7%, and 1% yields, respectively [88JCS(P1)2653]. 

Oxa-3-azabicyclo[3.2.1]octan-2-one (65) derived from methyl furoate was allowed to polymerize in bulk with its N-acetyl derivative as the initiator, and... 

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