Cis-fused rings

In an interesting illustration of these reactions, the two disymmetric trienes (+)-33a and (—)-33b were found to preserve their chirality upon photolysis at 193 K and provide cyclohexadienes 34a and 34b, respectively (Scheme 8)18. Upon warming above 205 K, however, they lose their chiral integrity by competitive disrotatory cyclization to the achiral dienes 35a and 35b. The thermal disrotatory closure to the cis-fused ring isomer is generally found to be extremely facile in these systems. 

Intramolecular cycloadditions of alkenyl-substituted nitrile oxides produce bicyclic isoxazolines. When monocyclic olehns are used, tricyclic structures are obtained. This approach was pioneered by both Kozikowski s and Curran s groups. A typical case involves the cycloaddition of nitro compound 191 [mixture of diastereomers derived from pentenose pyranoside 190], which produced a diaster-eomeric mixture of isoxazolines that contain cis-fused rings (i.e., 192) in near quantitative yield (326) (Scheme 6.85). Further elaboration of this mixture led to epoxycyclopentano-isoxazoline 193, which was then converted to the aldol product in the usual manner. The hydrogenation proceeded well only when rhodium on alumina was used as the catalyst, giving the required p-hydroxyketone 194. This... 

The A-B cis fused rings, the axial methyl group, and ring C form the rigid essential backbone of the structure. 

Moreover, enone 132 reacts with (t-Bu)Me2SiOTf and I its N to give the Diels-Alder adduct 134 in 82% yield via intermediate 133 (equation 54)184. Lactam 134 with a cis fused ring is more stable than the corresponding trans isomer, in which the Me3Si group must rotate into an axial position. The secondary orbital overlap and the steric requirements of the MesSi group on the dienophile moiety in 133 also appear to be critical to the observed stereoselectivity. 

Allyl, pentadienyl, and heptatrienyl anions can in principle undergo electrocyclic rearrangements (81). The thermal conversion of a pentadienyl into a cyclopentenyl anion is predicted to be a disrotatory process. The cyclooctadienyl anion cyclizes to the thermodynamically stable isomer of the bicyclo[3.3.0]octenyl ion having cis fused rings (52,82,83). The acyclic pentadienyl anions, however, do not normally cyclize. On the other hand, heptatrienyl anions cyclize readily at — 30°C by a favorable conrotatory thermal process (41,84). This reaction sets a limit upon the synthetic utility of such anions. 

The Diels-Alder reaction between (2 ,4Z)-hexa-2,4-diene with the dieno-phile 2-methoxycyclohexa-2,5-diene- 1,4-dione yields four stereoisomers. The Diels-Alder reaction is a stereospecific reaction, therefore the configuration of both the starting materials is relocated in the product. Since the reaction is a concerted [4 + 2] cycloaddition, all the products here have always cis-fused rings and because the configuration of (2 ,4Z)-hexa-2,4-diene remains unaltered, both methyl groups in the product will be trans to each other. The various stereoisomers result because the diene and the dienophile may approach each other from both sides and in two distinct orientations. Note that the reaction occurs almost exclusively at the electron poor double bond of the dienophile. In order to deduce the relationships the... 

Before we move on to ris-decalins, here is a sequence of reactions that starts with a symmetrical eight-membered ring with no stereogenic centres and ends with two fused five-membered rings with five stereogenic centres, all controlled by stereospecific reactions, some with stereoselective aspects controlled by cis-fused rings. 

The c/s-alkene dienophile gives stereospecific addition—in each product the CC Me is cis to the alkyl chain (and therefore trans to the H atom). But we get about a 50 50 mixture of endo and exo products. This does not seem to be because there is anything wrong with the transition state for endo addition, which leads in this case to cis-fused rings. 

From the synthetic point of view, oxidative photocyclization of these two types of enamides has a definite advantage in the construction of a polycyclic ring system with a double bond at the ring juncture in one step from the starting compounds. The photocyclized product can be readily converted to the cis-fused ring system by a facile catalytic reduction or to the fully aromatized lactam on dehydrogenolysis (19,20) as in the case of vV-benzoy-lenamines. 

In the electrochemical oxidation of and unsaturated disulfides at Pt electrodes in MeCN, complex mixtures of products are obtained [53]. This situation was circumvented by performing the electrolyses in the presence of bromide salts under either controlled potential or controlled current conditions. A cleavage of the S-S bond occurred and cyclization products were formed. Examples are shown in Eq. (23). The formation of cis fused ring systems indicates high antistereoselectivity for addition to the C-C double bond. 

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. 

The polymers with trans-fused five-membered rings linked with a diisotactic head-to-tail sequence have chirality, although the polymers composed of the cis-fused ring are achiral. Scheme 10 summarizes the structures of the stereoisomeric polymers. The optically active zirconocene complex with a C2 symmetric structure catalyzes the enantioselective cyclopolymerization of 1,5-hexadiene (Eq. 20) [98, 99]. Although the polymer contains not only trans-fused ring but also cis-fused ring units (ca. 68 32), it shows optical rotation due to the main chain chirality. 

Conformational analysis demonstrated that the predominant conformation of the cij-l,4a-H-l-phenyl, cis- and /ran5-3,4a-H-3-methyl, trans-4a,5-H-5-methyl, m-4a,8-H-8-methyl, and trans-4a,7-H-7-ethy derivatives of perhydropyrido[l,2-c][l,3]thiazine is the tram-fused one, whereas for the cw-4a,5-H-5-methyl and ds-4a,7-H-7-methyl derivatives it is the S-inside cw-fused conformation [70T3941 82OMR(20)239]. The chemical shift differences (1.13 and 0.49 ppm) between the C-8 methylene protons of trans-4a,7-H-7-ethyl- and cis-4a,7-H-7-ethylperhydropyrido[l,2-c][l,3]thiazines are in accord with exclusive existence in the tram-fused and in the cis-fused ring conformations, respectively [82OMR(20)239]. 

Bicyclo[4.2.0]octan-2-ones possessing tram ring fusions can be distinguished from cis-fused rings by exposure to base or acid. The /ran.v-adducts are generally readily converted to the cit-isomers under these conditions15. 

A summary of stereoselective reactions that occur on cis-fused rings... 

When two cyclohexane rings are fused—fused rings share two adjacent carbons—one ring can be considered to be a pair of substituents bonded to the other ring. As with any disub-stituted cyclohexane, the two substituents can be either cis or trans. The trans isomer (in which one substituent bond points upward and the other downward) has both substituents in the equatorial position. The cis isomer has one substituent in the equatorial position and one in the axial position. Trans-fused rings, therefore, are more stable than cis-fused rings. 

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