Cis-fusion

If a tether is attached to the C(3) atom of nitronates (214), the reaction gives rise to spiro systems (215). For these systems, generating a linkage containing three atoms between the six-membered ring and the C,C double bond is a case of choice. It necessarily leads to cis -fusion of two five-membered rings. 

The approach is used to show the shape of cholic acid, one of the bile acids secreted into the gut to emulsify fats and encourage digestion. Cholic acid is characterized by a cis fusion of rings A and B. 

Most natural steroids have the stereochemical features seen in cholesterol, though, as we have seen, there may be some variations, particularly with respect to ring fusions affecting the A and D rings. Note that trans fusion at the hydrindane C-D ring junction is energetically less favourable than a cis fusion (see Section 3.5.2), but most natural steroid systems actually have this trans fusion. 

The cis fusion in which one of the fusion atoms is nitrogen merely indicates that the nitrogen lone pair electrons occupy the remaining part of the tetrahedral array. It does, however, mean that inversion at the nitrogen atom (see Section 3.4.1) is not possible, since that would hypothetically result in formation of the impossible fran -fused system. The ring fusion has thus frozen the nitrogen atom into one configuration. 

Fusion of a four-membered ring onto a six-membered ring is also only possible with a cis fusion cephalosporins provide excellent examples of such compounds, and the comments made above for penicillins are equally valid for these compounds. 

For each ring the other ring can be viewed as 1,2-substituents. For the trans isomer, only the rigid (ee) conformation is possible structurally. As shown in Fig. 9-25, diaxial bonds point 180° away from each other and cannot be bridged by only four C s to complete the second ring. Cis fusion is (ea) and the bonds can be twisted to reverse the (a) and (e) positions, yielding conformation enantiomers. 

Whether cis or trans fusion is observed in nitrone cycloadditions can depend on reaction conditions as first determined by LeBel et al.9 At lower temperature where cycloaddition is irreversible, kinetic control prevails and this usually favors cis fusion. However, at higher temperature equilibration can occur through retrocycloaddition and the more stable product will predominate (i.e. thermodynamic control). The nitrone may also undergo ( )/(Z) isomerization, particularly at elevated temperature, and this complicates the analysis a different kinetically favored ratio might prevail. A recent example of temperature dependence involves formation of isoxazolidines (18) and (19) from aldehyde (17a Scheme 4). At 90 C ds-fused (18) and rrans-fused (19) were formed in 74% and 9% yield, respectively. At 140 C, however, (18) and (19) were formed in 31% and 34% yield. 

The stereochemistry of the epoxidation of A-norsteroids is less predictable than that of the corresponding steroids in view of the flattened nature of ring A and the preferred cis fusion of the hydrindane it has been shown that epoxidation with peroxy acids proceeds predominantly from the fi-face in some norsteroids294. 

The observed exclusive cis fusion and the predominance of the product 355 over 356 was ascribed to the reaction occurring via the preferred transition state 354, wherein steric repulsion between one of the methyl groups of the dioxolane ring and the methylene group f) to nitrogen is minimised. Final introduction of one carbon atom to achieve the crinane skeleton was accomplished with Eschenmoser salt. The product, the O-isopropylidene derivative of the alkaloid, on acid catalysed deketalisation furnished (-)-amabiline with an impressive overall yield of 43%. 

It is easy to see that inversion occurs in these S>j2 reactions if we put the epoxide on the side of another ring. With a five-mem her ed ring only cis- fusion of the epoxide is possible and nucleophilic attack with inversion gives the trans product. As the epoxide is up, attack has to come from underneath. Notice that the new C-N bond is down and that the H atom at the site of attack was down in the epoxide but is up in the product. Inversion has occurred. 

Epimerization at C-14 and 6,7-dimethyl substitution had no pronounced effects on the antagonist potencies of oxilorphan and butorphanol. Similarly, cis fusion of an extra cyclohexane ring to C-6 and C-7 of isobutorphanol (18) (MWR ED50, 23.0 mg/kg) is less detrimental to agonist activity than a trans attachment (MWR ED50, 80 mg/kg).<61)... 

This lignan sub-class of 2,6-diaryl-3,7-dioxabicyclo[3,3.0]octanes, is one of the largest and most widely distributed groups. About 100 members are known, if natural glycoside derivatives are included. As expected, the five-membered heterocyclic rings are constrained in cis fusion. When the aryl groups are identically... 

Hz) [94] was also confirmed by an HMBC experiment. The relative stereochemistry of 46 was established based on NOEDS data. The NOEs observed between Mel4/H2b, Mel4/Mell, M14/H15, HI a/ H5 and Mel3/H9 revealed a trans-anti-cis fusion of A/B/C rings, which was the same as in puupehenone (45), Fig. (21). 

---