Trans Ring Fusion

In general, epoxidation of steroids with trans-anti-trans ring fusions leads to exclusive formation of the a-oxirane. Steroid Reactions lists examples of exclusive a-epoxide formation from 2-, 4-, 6-, 7-, 8(9)-, 14-, 16- and 17(20)-unsaturated steroids. Further examples of a-epoxidation of steroid 1-enes, 3-enes, 8-enes, 9(ll)-enes, 8(14)-enes and 16-enes have been reported. The preferred attack by the reagent on the a-side of the steroid nucleus can be attributed to shielding of the -side of the molecules by the two angular methyl groups. 

In this experiment, advantage is made of the fact that lithium-ammonia reduction usually proceeds to give trans-fused Decalins 4). Thus, hydrogenation of A -octal one-2 over palladium catalyst gives essentially cw-2-decalone as the product, whereas the lithium-ammonia reduction of the octalone gives the trans ring fusion. 

With two y,8 double bonds, two a,/3 double bonds, and the possibilities of cis and trans ring fusions with syn and anti configurations, 20 isomeric dimers are possible. Surprisingly, only one product is formed in a head-to-tail fashion. The sole product of the irradiation of the 3,5-diene-7-ketosteroid (76), however, is the head-to-head dimer. The specificity and mode of addition arise presumably through the effect of the specific environment of the chromaphore. The dimerization of (75) is believed to involve the addition of the a,fi double bond of a photoexcited molecule to the less hindered y,8 double bond of a ground state molecule. The photocondensation of (76) with cyclopentene, in which steric hindrance should not be a controlling factor, was found to yield a cyclobutane product involving the a,/ bond of the steroid in contrast to dimerization across the y,8 bond. 

When small rings are fused to other rings, the cis ring fusion is almost always much more stable than the trans ring fusion. The opposite is true only for saturated 6-6 or larger ring systems. (Make models to confirm this.) The order of stability of the three possible products shown above is cis-6-5 > trans-1 A > trans- 8-3. 

E. J. Corey recently described (Organic Lett. 2005, 7,2699, 2703) an even more elegant approach to the y-lactam. Exposure of 5 to the Kulinkovich conditions followed by iodination delivered 18, presumably by way of the titanacycle 17. Although all-carbon trans-5,5 systems are strained, the trans ring fusion is the expected stereochemical outcome with (RO),Ti in the ring. Complexation of the ester to the Ti may explain the observed facial selectivity. Brief exposure of 18 to Et,N followed by silylation converted it to 6. The preparation of several more analogues in this series is also reported in these two articles. 

Camphor (11), and cholesterol (14), are conformationally rigid, in the former case because of the bridged-ring structure, and in the latter because of the all-trans ring fusions. 

Ring reversal can give only one twist form of relatively low energy(because of the trans ring fusion (Dreiding models)) in which the values of Js p and J5"p are essentially interchanged. 

The neotropical dart poison frogs contain a remarkable diversity of alkaloids, and the 2,5-disubstituted decahydroquinolines represent, a major class of these amphibian alkaloids[21]. Isolation of these alkaloids from some ants strengthens a dietary hypothesis for the origin of the above alkaloids that have been detected in extracts of frog skin[22]. In addition, these alkaloids containing both cis and trans ring fusion have been identified as well as diastereomers at the C-2 and C-5 position. 

Isomorphinans possess a B/C-trans ring fusion and in this they differ from B/C cis morphine geometry. Such geometry, however, may be related stereochemically to endo-ethanotetrahydrooripavines. Opioid activity tends to be increased in B/C trans series, and a compound such as 3-hydroxy-N-methylisomorphinan is several times more potent than morphine in rat analgesic tests. 

At least 11 compounds (and there are probably more) can be theoretically conceived during the acid treatment of I by way of rearrangement pathway D alone. Route A may not be all that relevant since it leads to unstable cations vicinal to carbonyl groups. Also, not all the intermediates contrived in the previous scheme are stable entities, owing chiefly to those stereochemical restrictions imposed by the bicyclic system. For example, the trans-ring fusion of the cyclopentanone ring and its adjacent bicyclic structures have considerable ring strain. This becomes visible in the three-dimensional representation of structure VIII, that is, XVI that would be the epimer of the observed product (IV). 

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