Bicyclo octane, rings

Two possible intramolecular disconnections are available for the [2.2.2] bicyclo-octane ring system (path A and path B, Scheme 1.4). The choice between the initial [4+2] disconnections A and B at first appears inconsequential leading to idealized intermediates of comparable complexity (54 and 57). However, when the [4+2] and [3+2] disconnections are considered in sequence, the difference becomes clear. For path A, retrosynthetic [3+2] disconnection of intermediate 54 leads to the conceptual precursor 56, which embodies a considerable simplification. In contrast, path B reveals a retrosynthetic [3+2] disconnection of intermediate 57 to provide the precursor 59, a considerably less simplified medium-ring bridged macrocycle. Thus, unification of the [3+2]/[4+2] dual cycloaddition strategy, using the staging... 

A bicyclo[3.3.0]octane ring system 164 can be conveniently prepared by refluxing an acetonitrile solution of the azo compound 163 in the presence of excess of phenyl vinyl... 

Intramolecular cycloadditions are among the most efficient methods for the synthesis of fused bicyclic ring systems [30]. From this perspective, the hetisine skeleton encompasses two key retro-cycloaddition key elements. (1) a bridging pyrrolidine ring accessible via a [3+2] azomethine dipolar cycloaddition and (2) a [2.2.2] bicyclo-octane accessible via a [4+2] Diels-Alder carbocyclic cycloaddition (Chart 1.4). While intramolecular [4+2] Diels—Alder cycloadditions to form [2.2.2] bicycle-octane systems have extensive precedence [3+2], azomethine dipolar cycloadditions to form highly fused aza systems are rare [31-33]. The staging of these two operations in sequence is critical to a unified synthetic plan. As the proposed [3+2] dipolar cycloaddition is expected to be the more challenging of the two transformations, it should be conducted in an early phase in the forward synthetic direction. As a result, a retrosynthetic analysis would entail initial consideration of the [4+2] cycloaddition to arrive at the optimal retrosynthetic C-C bond disconnections for this transformation. 

As in the case of the bicyclo-octane the isomerizations must occur by a disrotatory process. It is clear that, owing to the rigid nature of these bicyclobutenes, considerable stretching of the bridgehead bond is necessary before appreciable twisting of the cyclobutene ring can... 

Alongside these developments has arisen an increased awareness that the bicyclo-[3.3.0]octane ring system can serve as a versatile template in the synthetic elaboration of nonquinane compounds of nature. Although this work necessarily builds on many of the phenomena described earlier, it is generally exciting for its conceptual originality. 

Adcock, W. Abeywickrema, A. N. Substituent effects in the bicyclo[2.2.2]octane ring system. A carbon-13 and fluorine-19 nuclear magnetic resonance study of 4-substituted bicyclo[2.2.2]oct-l-yl fluorides, / Org. Chem 1982,47,2957-2966. Laube, T Ha, T. K. Detection of hyperconjugative effects in expaimentaUy dete-mined structures of neutral molecules, J. Am. Chem. Soc. 1988,110, 5511-5517. Rozeboom, M. D. Houk, K. N. Stereospecific alkyl group effects on amine lone-pair ionization potentials Photoelectron spectra of alkylpiperidines, / Am Chem Soc. 1982,104,1189-1191. 

In an asymmetric approach to the bicyclo[2.2.2]octane ring system, a double Michael addition has been employed using phenylmenthyl acrylate as the initial Michael acceptor. The condensation of the dienolate, generated with Lithium Diisopropylamide, reacts with the acrylate to afford the bicyclo[2.2.2]octane derivative (eq 6). The de for the reaction is only 50% however, it is highly endo selective (>95%). ... 

Bicyclo[3J.0]octane and Bicyclo[3.2.1]octane Ring Formation... 

Two groups have reported syntheses of the bicyclo[3.2.1]octane ring system found in certain tetracyclic diterpenes in which the key step is an intramolecular carbenoid insertion reaction. Thus decomposition of the diazoketone (4) in the presence of copper(II) sulfate gives the cyclopropyl ketone (5) in 48% yield. Acid hydrolysis of the acetal grouping is accompanied by concomitant fragmentation to the substituted bicyclo[3.2.1]octanone derivative (6).3... 

Intramolecular conjugate addition is most common with a readily enoUzable Michael donor, such as a 1,3-dicarbonyl compound. For example, the mild base K2CO3 promotes the cyclization of the p-keto-ester 36 by a 5-exo ring closure (1.48). The product 37 contains two five-membered rings fused cis to each other, as would be expected on the basis of the thermodynamic stability of such bicyclo[3.3.0]octane ring systems. 

A hetero-Diels-Alder reaction between the imine (115) and the cyclohexadiene (116) produces the aza-bicyclo-octane (117), which after Baeyer-Villiger ring expansion followed by reduction, gave the triol (1l8), an advanced intermediate with all three chiral centres in their correct relative stereochemistry, for the synthe-... 

The Pd-catalyzed cascade Heck reaction of 5-methylenecycloheptene precursor 108 was utilized to construct the scopadulan ring system and chiral centers at C9 and C12 of the bicyclo-octane 109 and 110 for the first total synthesis of scopadulcic acid B, which is a powerful inhibitors of H+, K+ -adenosine triphosphatase and have potential for the treatment of peptic ulcers, gastritis, and esophagitis. (Scheme 55) (103,104). 

The Weiss-Cook reaction entails the formation of c/5-bicyclo[3.3.0]octane ring systems from the condensation of 1,2-dicarbonyl compounds with 3-oxoglutarate diester derivatives. Decarboxylation of the immediate reaction product affords access to the parent carbon scaffold. 

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