Fused ring systems, stereochemistry

The reaction of the allylic acetate with a diene system 784 affords the poly-fused ring system 785 by three repeated alkene insertions[487]. An even more strained molecule of the [5.5.5.5] fenestrane 788 has been constructed by a one-pot reaction in a satisfactory yield by the Pd-catalyzed carbonylation-cycliza-tion of 786 without undergoing elimination of /3-hydrogen in the cr-alkylpalla-dium intermediate 787 owing to unfavorable stereochemistry for syn elimination[488]. 

During ACV formation, the stereochemistry of the valine component is changed. ACV is the linear tripeptide that leads to isopenicillin N, the first intermediate with the fused ring system found in the penicillins. Note, we are using the d and l convention for amino acid stereochemistry rather than the fully systematic R and S (see Section 3.4.10). This is one occasion where use of d and l is advantageous, in that the sulfur atom in L-cysteine means this compound has the R configuration, whereas the other L-amino acids have the S configuration. 

Any method of making such bicyclic compounds will automatically form this stereochemistry. An important method of stereochemical control that we have not used so far in this chapter is catalytic hydrogenation of alkenes, which adds a molecule of hydrogen stereospecifically cis. If the reaction also makes a fused ring system, it may show stereoselectivity too. Here is an example with 5/5 fused rings. 

The second step is now rather important. Ethoxide will form the enolate of the ester reversib and turn it to the outside, the convex face, of the molecule. Though nitrogen is not normally a fixec chiral centre because it undergoes rapid pyramidal inversion, here it is fixed by the need of the five five fused ring system to have a cis ring junction. The last step is just the reduction of the ester wif-no change in the stereochemistry. 

In the example shown above, halolactonization controls the relative stereochemistries of three contiguous stereocenters ( ) the two newly created stereocenters (C-0 and C-I) are trans to each other and the lactone is by necessity part of a cis-fused ring system. 

From the extensive chemical experience of the last decade in the stereochemistry and synthesis of fused ring systems related to steroids, alkaloids, resin acids, and terpenes and in the synthesis and reactions of tropolones, one might be led to the erroneous conclusion that the total synthesis of colchicine should not be difficult. Preliminary studies in this direction have been reported by many workers, but the ultimate goal has yet to be reached. 

The simplest member of the class is the [l]-ladderane, a small and familiar strained molecule known as cyclobutane. The strain in a [n]-ladderane increases with the number of fused rings and the introduction of multiple bonds. The [2]-ladderane derivative, Dewar benzene, is highly unstable and converts readily to the conjugation-stabilized counterpart, benzene. Depending on the stereochemistry of bridgehead atoms in the fused-ring system, [ ]ladderanes... 

The butyrolactones can also be obtained from bicyclic lactones. For example, (2) can be obtained on solvolysis of either (1) or (3). This synthesis is stereoselective the stereochemistry of the fused ring system is apparently controlled by the C3 /C4 steric arrangement and not by the configuration of the hydroxyl group. 

Paquette and co-workers were interested in using the Hajos-Wiechert reaction to prepare 6-7 fused ring system analogs such as 28. ° After screening several amino acids, the best yield was obtained with L-phenylalanine (86% yield, 48% ee). The methyl group stereochemistry at the ring junction was inverted from that typically observed in the preparation of the fused 5,5- or 5,6-bicyclic analogs. 

Most steroids share a common tetracyclic ring system, but are adorned differently in terms of oxidation state at various carbons. The three targets we will consider are only the tip of the iceberg. Fused ring systems with different ring juncture stereochemistry (cis vs trans), different sidechains, and different oxidation patterns are common. A few examples are shown here (see problems for some questions about fiisidic and cholic acids). 

A large variety of N-benzoylenamines have been subjected to photochemical cychzation. Mostly trans fused ring systems were obtained from the cychzation of N-benzoylenamines such as 25 derived fi om cychc amines, especiaUy cyclohexylamines (Scheme 5). The stereochemistry can be explained by a photochemical conrotatory cychzation leading to intermediate F. A thermal 1,5-suprafacial H shift leads then to the final product 26. In this way, the aromaticity of the benzoyl moiety is reestablished. Frequently, the formation of a cis-isomer as a byproduct was observed. These products resulted from a consecutive photochemical or thermal isomerization of the trans product. When the reaction was carried out in the... 

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