Bridged Carbocycles

If whole heterocyclic systems appear as bridges they are treated like analogous carbocyclic bridges. 

The Ti coordination via the carbocycle prevails for indole and carbazole, although the species were also found in organomanganese and -iridium chemistry. Osmium carbonyls tend to produce the species with the bridging indole function. Some illustrations of the ti N) coordination exist. 

Mascarenas developed a synthetic method to 1,5-oxygen-bridged medium-sized carbocycles through a sequential ruthenium-catalyzed alkyne-alkene coupling and a Lewis-acid-catalyzed Prins-type reaction (Eq. 3.45). The ruthenium-catalyzed reaction can be carried out in aqueous media (DMF/H20 = 10 1).181... 

Moreover, the authors were able successfully to apply this process to the synthesis of the antibiotic (+)-CP-263,114 (2-912) (Scheme 2.203) [454]. Transformation of the bromide 2-908 into the vinyl Grignard reagent 2-909, followed by addition to the ketone 2-910, led to the bridged carbocyclic compound 2-911 which was then transformed into the target compound within a few steps. 

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. 

The same "heuristic principles" which are applied to carbocyclic compounds also hold true for simple heterocyclic compounds containing one heteroatom. However, in the case of bridged heterocyclic molecules a modified strategic bond selection must be applied. Besides the strategic bonds which meet Corey s six rules, the bonds directly attached to nucleophilic heteroatoms -such as O, S and N-are also strategic Cf. heuristic principle HP-7), provided that they satisfy rules 2B, 4, 5 and 6. For instance, in compound 31a besides the five strategic bonds determined by rules 1-6 (cf. compound 26), the sixth darkened C-N bond in 31b is also a strategic bond. 

Polycyclic parent hydrides. These are classified as bridged polyalkanes (also known as von Baeyer bridged systems, from the nomenclature system developed to name them), spiro compounds, fused polycyclic systems and assemblies of identical rings. The four systems may be either carbocyclic or heterocyclic. In developing their names, the following principles are used. 

Singlet oxygen reacts with many carbocyclic 1,3-dienes to form the corresponding bridged endoperoxides, which can be further transformed into miscellaneous polyoxy functionalized carbocycles . The rate of photooxygenation of n-cyclic 1,3-dienes is gradually decreasing in the order n = 5) >6>7 8 While the rate... 

Phanes are compounds with at least one aromatic nucleus and at least one bridge 28 Such structures can incorporate a great number of arenes — carbophanes contain carbocycles such as benzene or naphthalene, heterophanes heteroaromatic rings including metallocenes — and a wide variety of bridges spanning the ring (s) in different positions from one to several simple alkylidene residues (e.g. hexamethylene or... 

In contrast, the closely related palladium acetate-promoted intramolecular alkylation of alkenes by tri-methylsilyl enol ethers (Scheme 4)6,7 has been used to synthesize a large number of bridged carbocyclic systems (Table 1). In principle, this process should be capable of being made catalytic in palladium(II), since silyl enol ethers are stable to a range of oxidants used to carry the Pd° -> Pd11 redox chemistry required for catalysis. In practice, catalytically efficient conditions have not yet been developed, and the reaction is usually carried out using a full equivalent of palladium(II) acetate. This chemistry has been used in the synthesis of quadrone (equation 2).8 With the more electrophilic palladium(II) trifluoroace-tate, methyl enol ethers underwent this cyclization process (equation 3).9... 

Macro carbocyclic rings can be constructed by cyclization of nitrile oxides derived from oj-nitro-l-al-kenes (Scheme 22). If the intervening bridge is not longer than seven atoms, only fused bicyclic products are obtained. Thus, the nitrile oxide derived from nitro compound (75a) is cyclized in 44% yield to the 5,9-fused bicyclic isoxazoline (76a).38 10-Nitro-l-decene (75b) also cyclized to (76b) in unspecified yield.39 It should be noted that these results go counter to the usual regiochemistry of an intermolecular nitrile oxide cycloaddition where the five-substituted isoxazoline is usually,27 although not always,40 heavily preferred from reaction of a terminal alkene. Thus, geometric constraints have won out over the normal electronic control. 

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