Trans-fused 5,6-ring junction

Of special interest for practical applications, as well as for future receptor studies, are the structure-activity relationships of the brassinosteroids. As postulated (6) the structural requirements for a high activity are the following (22R.23R)-vicinal diol moiety (24S)-methyl- or ethyl group 7-oxa-lactone or 6-oxo functionality 3a-hydroxy group, 2a,3a-vicinai diol or 3a,4a-vicinal diol and A/B-trans-fused ring junction. 

Note that cAMP has a trans 6,5-fused ring junction. 

This Pd-catalyzed cascade bis-cyclization reaction can also be applied to trans linear substrates 40 and 41. It was possible to effect either 5-exo or 6-endo cyclizalion selectively by an appropriate choice of the electron-withdrawing substituents of the nucleophile, as illustrated in Scheme 20. Ero-cyclizations were observed when sterically encumbered nucleophiles were employed. Cyclopentanes were obtained as a result of steric interactions between the nucleophile and one of the allylic hydrogens of the linear substrate. Endo-cyclizations leading to trani-octahydrophenanthrene were the only reactions observed when less sterically demanding nucleophiles were employed. Notably, these cyclizations proceed in a completely stereoselective trans manner. Attack of the carbon nucleophile onto a double bond electrophilicaUy activated by the palladium species results in a trans configuration of the fused ring junction. This stereochemistry is defined by that of the double bond in the initial substrate the relative configuration of compound 42 or 43 is hereby controlled. 

For the bicyclo[2.2.0] system (a four-four fusion), only cis compounds have been made. The smallest known trans junction when one ring is three membered is a six-three junction (a bicyclo[4.1.0] system). An example is 74. When one ring is three membered and the other eight membered (an eight-three junction), the trans-fused isomer is more stable than the corresponding cis-fused isomer. ... 

In the case of ring-fused systems the cis/trans notation is used to designate the geometric nature of the ring junction. Structures (25) and (26) represent partial structures of the ring-fused compounds (13) and (14) respectively, which emphasise that the ring junctions utilise cis- or frans-orientated bonds. 

The molecules in question form a series of trans fused bicyclo[4.//.,0]ketones, where n = 4,3, 2. As n decreases, the dihedral angle forming the junction with the right-hand ring closes and the left-hand ring opens ... 

Anionic cascade cyclisations can be stereoselective (just like their simpler counterparts see below). The cyclisation of 289, for example, gives solely the trans ring-junction product 292 (stereochemistry is determined in the first cyclisation to 290) despite the fact that the cis 5,5-fused system is nearly 30 kJ mol-1 more stable.149 This argues against the reversibility of the cyclisation. Because the cyclisation of 290 is rather slow, trapping the product organolithium 291 with electrophiles other than a proton can pose problems, and considerable amounts of material protonated by the ether solvent are obtained. This can be overcome by decreasing the proportion of ether from 40% to 10% of the solvent volume.150... 

Just as in the decalin system, each ring junction could be cis or trans, but it turns out that all steroids have all trans-junctions except where rings A and B join which is sometimes cis. Examples are cholestanol (all trans) and coprostanol (A and B fused cis). 

A 6/6 fused system will prefer a trans ring junction as /rans-decalins (Chapter 18) have a 11-chair structures with every bond staggered from every other bond, as yon can see from the diagram alongside. We can show... 

Finally, after ester hydrolysis, HC1 decarboxylates the product and removes the protecting group. As we saw earlier, it is not easy to get a trans-fused 5/6 system. In this sequence the molecule is effectively tricked into making the trans ring junction by the work done with the blocking lactone bridge. 

Both ring systems are trans-fused, and both hydrogens at the ring junctions are axial. 

Treatment with base enolizes the ketone and changes the ring junction from trans to cis. A cis ring fusion is less strained when a six-membered ring is fused to a five-membered ring. 

The pattern of formation of fused-ring diacetals of glycitols having a trans junction of the rings conforms to expectations, the known stable acetals of this type all having the residues in equatorial positions. 

Six-membered acetal rings fused to seven-membered rings are found in acetals formed directly from mannitol and certain of its derivatives. The 1,3 2,5 4,6-structure has been proved for the tri-O-methylene " and tri-0-ethylidene " derivatives of mannitol, and the 1,3 2,5-structure for the di-O-methylene derivative of 6-deoxy-L-mannitol. " These acetals are markedly more stable than the 2,4 3,5-diacetals discussed above. Their stability has been related to the probable mechanism of formation,"" but is also understandable on conformational grounds. " The ring junctions are trans, and the triacetals LXI have the trans-anti-trans configuration, which... 

When rings are fused through adjacent atoms, the fusion may be cis or trans, as illustrated by the steroid structure (Fig. 16). In the naturally occurring steroids the ring junctions are all trans, except in the case of... 

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