Cis-fused

In acid solution, the double bond of (203) is hydrogenated to the trans-fused sulfone (204). Presumably, this hydrogenation goes through a cis-fused intermediate that is rapidly epimerized to (204) under the acidic conditions of the reaction. Condensation of the sodium salt of 7,7-ethylenedioxy-3-oxooctanoate (205) with (204) produces (206). Cmde (206) is cyclized, hydroly2ed, and decarboxylated, producing the tricycHc compound (207). Hydrogenation of (207) followed by ketal hydrolysis and cyclization affords (208) in an overall yield of 35% from hydrindandione (203). 

Figure 27.11 Steroid conformations. The three six-membered rings have chair conformations but are unable to undergo ring-flips. The A and B rings can be either cis-fused or trans fused.

The success of intramolecular conjugate additions of carbon-centered radicals in multifunctional contexts is noteworthy. Compound 57 (see Scheme 10), prepared by an interesting sequence starting from meto-toluic acid (54) (see 54 > 55 > 56 > 57), can be converted to the highly functionalized perhydroindane 58 through an intramolecular conjugate addition of a hindered secondary radical.21-22 This radical cyclization actually furnishes a 6 1 mixture of perhydroindane diastereoisomers, epimeric at C-7, in favor of 58 (96 % total yield). It should be noted that a substantially less strained cis-fused bicyclo[4.3.0] substructure is formed in this cyclization. 

The hydroxylation reaction, whose stereochemical course is controlled by the strong inherent preference for the formation of a cis-fused 5,5 ring system, creates a molecule which would appear to be well suited for an intramolecular etherification reaction to give ring E of ginkgolide B (1). Indeed, when a solution of 11 in methylene chloride is exposed to camphorsulfonic acid (CSA), a smooth cycli-zation reaction takes place to give intermediate 10 in an overall yield of 75% from 12. The action of CSA on 11 produces a transient oxonium ion at C-12 which is intercepted intramolecularly by the proximal hydroxyl group at C 4. 

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. ... 

When (62) was treated with ethyl vinyl ether the cycloadduct (63) is afforded. If (62) is reacted with electron donating dienophiles such as allyl alcohols, transesterification and intramolecular cycloaddition occurs in the presence of a catalytic amount of distannoxane catalyst to give cis-fused polycyclic systems such as (64) <96T733>. 

An intramolecular cycloaddition reaction of the ethene sulfonate (57) occurs at high pressure and leads predominantly to the cis fused sultone (58). The minor product is the trans fused diasteieoisomer <96JCS(P1)2297>. 

Epiberberine and berberine were stereoselectively converted to fumaritrine (421) and its analog via 8,14-cycloberbines 216). The cycloberbine 432, derived from epiberberine (431) in the established way, was treated with p-toluenesulfonic acid in methanol and then with methyl iodide to give stereoselectively the cis-fused indenobenzazepine 433 in excellent yield (Scheme 86). Deoxygenation of the hydroxyl group in 433 was accomplished by treatment with methanesulfonyl chloride and subsequent reduction with sodium borohydride in dimethoxyethane to give (+ )-fumaritrine (421) (216). 

It has been assumed that formation of the cis-fused product 2-771 in the domino reaction of aldehyde 2-769 is due to a strongly favored exo-Z-syn transition state 2-770. The endo-E-syn structure is prohibited by the rigidity of the acetonide existing in 2-769, whereas the proximity of the same moiety to the benzyloxymethyl substituent at the double bond disfavors the exo-E-anti transition state, which would be responsible for the formation of the trans-fused diastereomer. 

The configurational differences between 104 and 105 with the partial cis-fused junctions and those of the all trans-fused 95 and 101 (and related compounds) were pointed out [22] and resolved [62] with the determination of the absolute stereochemistry of diisocyanoadociane (95) (vide supra). Selective conversion to, and preparation of, an appropriate formamido-(p-bromobenzamide) derivative for X-ray determination [62], coupled with total synthesis [63], support the lR,2f ,3aS,5S,6/ ,8S,8aS, lOaS, lObS, lOcS absolute configuration. 

In a comparative study, Jacobson et al. have shown that for the cis-fused cyclohexadiene, l,2,3,4,4a,8a-hexahydronaphthalene, the dienophilic reactivity follows the order PTAD > cis-DEAZD > trans-DEAZD, while the order is reversed for their reactivity as enophiles.67 Other studies have produced similar conclusions.21,54 In general, azo compounds give more ene product than the corresponding C=C compounds. 

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. 

It has been shown that an allene acts as a jt-nucleophile and attacks a Jt-allylpalla-dium complex on the face opposite to that of palladium (Scheme 16.90) [98]. An alle-nic allylic pivalate, cis-isomer, undergoes a smooth cyclization in the presence of catalytic amounts of Pd(dba)2 in toluene to give a cis-fused 5,6-ring system. The reaction with the trans-isomer gives no cyclization product and the starting material is recovered. 

Wender et al. s [5 + 2] metal-catalyzed annulation strategy has also been applied to the total synthesis of (+)-aphanamol I (154) [34]. The scope of this method was expanded by using a tetrasubstituted allene that resulted in the stereoselective formation of an angular methyl group. The reaction of allene 149 with 0.5 mol% of rhodium biscarbonyl choride dimer afforded the fused bicyclic product 152 in 93% yield with complete exo/endo and diastereoselectivity (Scheme 19.28). The stereoselectivity of this process was attributed to a preference for formation of the cis-fused metallo-... 

The treatment of the bromoacetal (255) with catalytic amounts ( 10%) of a Co(I) species, generated by the electroreduction of cobaloxime (232) in an Me0H-LiCl04 system at —1.8 V, produces the cis-fused adduct (256) in 60 70% yield (Scheme 96) [392]. Cathodic reduction is used for the synthesis of a [Co(CO)3PBu3] complex in a methanol-methyl formate medium, which catalyzes the alkoxycarbonylation of dichloromethane to dimethyl mal-onate in up to 75% yield [393]. The Co(II) complexes are found to be effective for the homogeneous reduction of gem-dichlorocyclopropanes in the presence of anthracene [394]. The formation of the C—C double bond of (258) may be ascribed to the a-elimination of the Co-H species. Thus, benzalchloride (257) can be converted to a mixture consisting primarily of ds- and trans-stilbenes (258) by the action of electrogenerated Co(I)(salen) (Scheme 97) [395-398]. 

Fused cyclic ethers can be derived from appropriately substituted sugars. An example is given with the stereoselective 5-exo radical cyclization of allylic 2-bromo-2-deoxysugars, in the presence of 1,1,2,2-tetraphenyldisilane as the radical mediator and AIBN in refluxing ethyl acetate. The corresponding cis-fused bicyclic sugars have been prepared in moderate to good yields (Reaction 7.28) [39]. 

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