Stereochemistry of fused rings

Where rings are fused together (that is, have a common bond) determination of conformation may allow the determination of ring junction stereochemistry as well. Both isomers of this bicyclic ether were formed as a mixture and then separated. 

One proton at the ring junctions appears clearly in the NMR spectrum as it is next to two oxygen atoms (shown in black on the conformational diagrams alongside). In one compound it is a doublet, = 7.1 Hz, and in the other a doublet / = 1.3 Hz. Which is which  

The coupling is to the green proton in each case and the dihedral angles are 180° for the trans compound but only 60° for the cis one, so the smaller coupling belongs to the cis compound. We shall discuss below why the absolute values are so low this example illustrates how much easier stereochemical determination is if you have both stereoisomers to compare. 

In the next example, unlike the last one, it eventually proved possible to make both compounds in high yield. But first the story reaction of an amino-ketone with benzaldehyde in base gave a mixture of diastereoisomers of the product. 

In unravelling the mechanism of the reaction, chemists protected the nitrogen atom with Boc (Chapter 25) before the reaction with benzaldehyde and found that a new product was formed that was clearly an E-alkene as its NMR spectrum contained 8h 6.73 (1H, d, /16). This is too large a coupling constant even for axial/axial protons and can be only trans coupling across a double bond. They quickly deduced that a simple aldol reaction had happened. 

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Several indium-mediated intramolecular carbonyl allylation reactions have been investigated, and it has been found that these reactions provide an easy access to a variety of cyclic compounds. The intramolecular cyclization of 49a-c mediated by indium in aqueous media proceeds smoothly to afford carbocyclic systems containing y-hydroxy-Q -methylene esters 50a-c, which either spontaneously or readily cyclize to give fused o -methylene-y-butyrolactones 51a-c (Scheme 52). The same cyclization of 49d is too slow to compete with the side-reaction, in which the bromide is substituted by a hydroxy group. The ring junction stereochemistry of fused lactones 51 has been found to be cis in all cases. Of the two possible transition states, the one leading to the m-fused compounds is preferred, because the chair-chair conformation is favored over the chair-boat conformation.209... 

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 fiised-ring system, [njladderanes... 

Subsequent reports by Fleet and co-workers showed that the occurrence and specific type of secondary structure in these furanose-based carbopeptoid foldamers was strongly dependent on both the backbone stereochemistry and the stereochemistry of the ring substituents (Figure 51).355 351 Various ris-linked furanoses mostly exhibit the repeating /3-turn-like conformation mentioned above.360 361 However, one of the cis-linked stereoisomers displayed no indication of secondary structure.359 This surprising result was rationalized in that one methyl group in the isopro-pylidene unit of the fused ring is positioned in a way... 

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 geometry of the TS of these reactions is helpful to understand the stereochemistry of the ring junction. In entry 1, the preferred TS is entfo-boat, which gives the cw-fused product. 

The designations cis and trans are also used to describe the stereochemistry of fused saturated rings at the bridgehead positions. Notice the difference between frans-decalin and m-decaUn with regards to the overall... 

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]. 

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