Trans fused bicyclic rings

G. Synthesis of trans-Fused Bicyclic Ring Systons... 

A base-promoted reaction between L-threitol and tetraethylene glycol di-tosylate afforded (165) the chiral bis(15-ctown-5) derivative l-146 as well as the trans-fused bicyclic system l-147 containing 15-crown-5 and 17-crown-5 rings. These constitutional isomers, which were separated chromatographically, were characterized by preparing l-147 unequivocally by a stepwise route from 2,3-O-isopropylidene-L-threitol. 

Another case of increased strain is found with the trans-fused bicyclic cyclopropanes. With an eight-membered ring, the cis- and trans-fused compounds have essentially the... 

For a starting material containing a seven-membered ring, i.e., cyclohepta-dienyl carboxylate-allene 104, both the cis isomer and the trans isomer can be cyclized to afford the cis- or trans-fused bicyclic product 105 highly stereo-selectively depending on the solvent applied (Scheme 49). The formation of the trans-fused product 105 is made possible due to the flexibility of the seven-membered ring [31]. 

More recent work by van Boom and co-workers has seen the use of this method in the synthesis of cis- and tran -fused bicyclic ethers via a ring closing metathesis... 

In general, enolates of cis-fused 5,6 bicyclic ring systems display strong tendencies to undergo alkylation from the less hindered convex side [15]. An example demonstrating this trend was reported by Marshall, who obtained lactone 35 in 91 % yield as the only observed diastereomer in the methylation of 34 (Equation 6) [48], For trans-fused bicyclic systems, prediction of the stereochemical outcome becomes more complicated, as the inherent stereogenic centers may exhibit mutually opposing biases consequently, the situation has to be carefully evaluated for each particular enolate. The diastereomeric trans-lactone 36 (Equation 7) thus furnished methylated product 37 in 97 % yield and dr >97 3 [49]. 

This result should be compared to the cydization of the more advanced intermediate 49 (4 1 mixture of isomers at the acetal position Scheme 9.25), which afforded the bicyclic oxepane 50 as the sole product in excellent yield. It was suggested that this result was due to the presence of a trans-fused five-membered ring, which restricts the rotation around the C7-C8 bond and thus promotes the 7-endo cydization. 

Fused bicyclic systems are those in which two rings share two and only two atoms. In such systems there is no new principle. The fusion may be cis or trans, as illustrated by cis- and /ran -decalin. However, when the rings are small enough, the trans configuration is impossible and the junction must be cis. The smallest trans junction that has been prepared when one ring is four-membered is a four-five... 

A number of intramolecular cycloadditions of alkene-tethered nitrile oxides, where the double bond forms part of a ring, have been used for the synthesis of fused carbocyclic structures (18,74,266-271). The cycloadditions afford the cis-fused bicyclic products, and this stereochemical outcome does not depend on the substituents on the alkene or on the carbon chain. When cyclic olefins were used, the configuration of the products found could be rationalized in terms of the transition states described in Scheme 6.49 (18,74,266-271). In the transition state leading to the cis-fused heterocycle, the dipole is more easily aligned with the dipolarophile if the nitrile oxide adds to the face of the cycloolefin in which the tethering chain resides. In the trans transition state, considerable nonbonded interactions and strain would have to be overcome in order to achieve good parallel alignment of the dipole and dipolarophile (74,266). 

All of-cyclononatriene (53) cyclizes in the predicted disrotatory manner at measurable rates at 25-50°C to the bicyclic diene 54.115 The nine-membered ring is large enough to accommodate a trans double bond trans-cis-cis-cyclo-nonatriene (55), obtained by conrotatory photochemical opening of 54, cyclizes to the trans fused bicyclononadiene 55.116... 

The increased basicity of pyrrolizidine (pKa= 11.68) compared with indolizidine (pKa = 10.15) and quinolizidine (pKa= 10.19) has been attributed to ring fusion, the basicity of the c/s-fused N-bridgehead aza bicycles being larger than that of the trans-fused bases. The basicity of hydroxyindolizidines has been helpful in assigning the conformation of these compounds. 

Of the theoretically possible bicyclic systems arising via combinations of five- and six-membered rings, we discuss only three of the most common in carbohydrate chemistry here. These are the 5 + 5, 5 + 6 and 6 + 6 variations, in which the two fused rings have only two adjacent common atoms, representing the [3,3,0]octane, the [4,3,0]nonane and the [4,4,0]decane systems. Theoretically, all three can form cis or trans fused systems, but because of the high steric strain of a trans fused 5 + 5 bicyclic system, this combination can be disregarded (Figure 2.30). 

Hanessian, S, Liak, T J, Dixit, D M, Synthesis of trans-fused perhydrofuropyrans and related a-methylene lactones bicyclic ring-systems present in the ezomycins, the octosyl acids, and certain antitumor terpenoids, Carbohydr. Res., 88, C14-C19, 1981. 

The intramolecular acid-catalyzed reacdon of 2-propargylsilanes of structural type (117) with N-acy-liumion ion precursors leads to bridged azabicyclic ring systems (118 Scheme 33) which contain an a-allenic amide fimcdon. These bicyclic products serve as intermediates to highly funcdonalized trans-fused ring systems possessing a 1,3-diene moiety. 

Lastly, there are two types of bicyclic ring system that must be considered. The first is the fused ring system, e.g. decalin, which has two isomers, cis and trans. 

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