CIS-ANTI-

The mixture of diastereomers has been separated into its two principal components by Izatt, Haymore, Bradshaw and Christensen who had previously identified the two principal diastereomers as the cis-syn-cis and cis-anti-cis isomers. Their previous separation technique involved a protracted chromatography on alumina but the new method relied upon the difference in water solubility between the lead perchlorate and hydroniur perchlorate complexes. The lead perchlorate complex is essentially insoluble in aqueous solution and precipitates from it. Using this method, one may obtain 39% of the high-melting polymorph (mp 83—84°) and 44% of the low-melting compound (mp 62—63°). Note that the former also exists in a second crystalline form, mp 69—70°. 

The conversion of octachloronaphthalene to octafluoronaphthalene with potassium fluoride and either 18-crown-6, dibenzo-18-crown-6, cis,j>m,cis-dicyclohexano-18-crown-6, cis,anti,cis-dicyclohexano-l 8-crown-6, or irons,syn,trails-dicyclohexano-18-crown-6 demonstrates that 18-crown-6 or dibenzo-18-crown-5 increases the yield and selecuvity and decreases the reaction time [55] Treatment of 3,4-dichloro-],2,5-thiadiazole with potassium fluonde in sulfolane with and without 18-crown-6 present shows that less severe conditions can be used with either 18-crown-6 or dibenzo-18-crown-6 to form 3,4-difluoro-l,2,5-thiadiazole (equation 34)... 

It is important to note here that both of the 5-exo radical cyclizations (133—>132—>131, Scheme 27) must proceed in a cis fashion the transition state leading to a strained mms-fused bicy-clo[3.3.0]octane does not permit efficient overlap between the singly occupied molecular orbital (SOMO) of the radical and the lowest unoccupied molecular orbital (LUMO) of the alkene. The relative orientation of the two side chains in the monocyclic radical precursor 134 is thus very significant because it dictates the relationship between the two outer rings (i. e. syn or anti) in the tricyclic product. The cis-anti-cis ring fusion stereochemistry of hirsutene would arise naturally from a cyclization precursor with trans-disposed side chain appendages (see 134). 

The influence of 1,2-asymmctric induction on the exchange of diastereotopic bromine atoms has also been investigated22,23. Thus, treatment of the / -silyloxydibromo compound 15 with butyllithium at — 110°C in the presence of 2-methylpropana led to products 17-19 after the reaction mixture was warmed to 20 °C. The distribution of the products indicates that the diastereomeric lithium compounds 16 A and 16B were formed in a ratio of 84 16, with 16A being kinetically favored by 1,2-asymmetric induction. Formation of the m-configurated epoxide (cis,anti-18) was slowed to such an extent that its formation was incomplete and a substantial amount of the parent bromohydrin 17 remained. The analogous m.yyn-configurat-ed epoxide was not observed. Presumably for sterie reasons, the parent bromohydrin did not cyclize to the epoxide but instead led to the ketone 1923. 

The epoxyketone 3 is a versatile precursor for a variety of tricycloundecane systems having a p,y-unsaturated carbonyl chromophore, which are not so readily accessible. The contiguous epoxy ketone functionality and the double bond present in the five-membered ring provide opportunities for further manipulation. Adduct 3 may be transformed into a variety of molecular frameworks such as linearly fused cis anti cis tricyclopentanoids, protoilludanes, and marasmanes in a stereoselective fashion after suitable chemical and photochemical manipulation.13... 

It is clear from the foregoing that ring closure to five-membered rings fused to the isoxazolidine, regardless whether part of a pyrrolizidine or of an indolizidine system, led mainly to the cis-anti isomers (see 243 a, b and 246 a, b)... 

Dimers (73) and (74) were formed in approximately equal amounts in all cases, although, as in the cases of 2-cyclopentenone and 2-cyclohexenone, the relative amount of (72) (either cis-syn-cis or cis-anti-cis) was found to vary substantially with solvent polarity. As in 2-cyclopentenone, this increase in the rate of head-to-head dimerization was attributed to stabilization of the increase in dipole moment in going to the transition state leading to (72) in polar solvents. It is thought that the solvent effect in this case is not associated with the state of aggregation since a plot of Stem-Volmer plot and complete quenching with 0.2 M piperylene indicate that the reaction proceeds mainly from the triplet manifold. However, the rates of formation of head-to-head and head-to-tail dimers do not show the same relationship when sensitized by benzophenone as in the direct photolysis. This effect, when combined with different intercepts for head-to-head and head-to-tail dimerizations quenched by piperylene in the Stem-Volmer plot, indicates that two distinct excited triplet states are involved with differing efficiencies of population. The nature of these two triplets has not been disclosed. 

It could be shown that the stereochemical outcome of such radical polycycliza-tions is influenced by the nature of the substituents (H, Me, C02R). For instance, as in the example 3-225, the all-( )-methyl-substituted polyene 3-228 also gave the corresponding all-trans-anti polycycle 3-229 in the presence of Bu3SnH and AIBN. However, the ester-substituted polyene 3-230 led to the cis-anti-cis-anti-cis tetracycle 3-231 under similar reaction conditions (Scheme 3.60). A certain degree of preorganization of the precursor is assumed to be the reason for this result [97]. 

Asymmetric [2 + 2] photocycloadditions. Acid-catalyzed condensation of t-butyl acetoacetate with (— )-menthone (1) results in two dioxacyclohexenones, 2 and 3, which are easily separable. Photocycloaddition of ( — )-2 with methylcyclo-butene gives mainly the adduct (4) which has the cis, anti, cis-configuration at the... 

Photodissociation of the polyamides (Figures 4 and 5) was carried out in the solid films. Polymer films (1-2 U m) were cast onto quartz substrates and were exposed to monochromatic 250 nm light from a spectroirradiator. The dissociation of the thymine photodimers was followed by monitoring the absorbance at 270 nm. The results obtained for the polyamide prepared from the reaction of propane diamine and the isomers of the thymine photodimer (cis-syn(17a), cis-anti(17b), and... 

Both butenolides 50 and 51, one tethered to an a, -unsaturated ester, the other to an unsaturated nitrile, failed to undergo cyclization. Instead, the C=C 7i-bond of the butenolide was reduced, leading cleanly and efficiently to saturation of that bond, and to compounds 54 and 55, respectively. In contrast, the corresponding alkylidene malonate 52, as well as the alkylidene malononitrile 53, both cyclize to afford a mixture of the cis-anti-cis and cis-syn-cis linearly fused lactones 56 and 57. 

Catalytic hydrogenation of the triple bond (Pd/C) and oxidation of the acetal in acid medium led to lactone 13. which could be cyclised directly to the tricyclic intermediate 5. according to a Dieckmann condensation induced by sodium methylsulphinylmethylide in DMSO. The cyclisation takes place through intermediate 14. Compound 5 was a diastereomeric mixture still, but on treatment with aqueous alkali, at room temperature, gave a crystalline compound in about 30-35% yield, to which the cis-anti-cis- configuration was assigned (in fact an equilibration through the intermediate A may take place). 

Figure 2 depicts the relevant cyclopentane conformations for either di-astereomeric alcohol 48. Conformations A and C would lead to the desired cis-anti-cis tricyclodecane skeleton of kelsoene whereas conformations B and D would be responsible for the formation of the undesired cis-syn-cis product. We were convinced that the influence of the stereogenic center to which the hydroxymethyl group is attached (" ) was marginal as compared to... 

With 2-diazopropane, two stereoisomers of the resulting tricyclic product 116 (cis, anti, cis and cis, syn, cis) were obtained (183). Formation of 116 can be rationalized by N2 extrusion from the cycloaddition product 114 and a subsequent [34 + 22 ] cycloaddition of the resulting 3-alkylidene-l,2,3-diazaphosphole 115 with the remaining heterophosphole 110. When an excess of 2-diazopropane was used, 115 was trapped by 1,3-dipolar cycloaddition across the exocyclic P=C bond. 

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