Seated Rearrangements

As a corollary to the mechanism shown in Chart 12, one would expect facilitation of the rearrangement in structures in which the change (90) to (89) is inhibited. This was fully borne out by the rearrangement of 8- 

Chart 13. Carbocations and quenching products derived from longifolene in fluorosulfonic 

The generation of stable carbonium ions from longifolene in fluoro-sulfonic acid has been investigated 64). The structure of the carbonium ion and consequently that of the end product was shown to be temperature dependent (Chart 13). The activation energies for the rearrangement of cations involved have been estimated to be in the range 15—20 Kcal/mol. 

In a recent study, Suryawanshi and Nayak (65) investigated the rearrangement of methyl- (102) and dimethyl-longifolene (103) with BF3 Et20 to find the anticipated transformations quite facile. 

In a less complex rearrangement, Coates and Chen (66) found that acetolysis of longicamphenilyl tosylate (104) affords, in addition to nor-longicyclene (105) and acetate products, the novel tricyclic olefins (106) and (107). The rearrangement pathway from (104) to (106) is pictured as a C-3 to C-4 hydride shift, followed by methylene migration and then proton elimination. In formic acid, (106) goes over to (107). 

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In a deep-seated rearrangement like this, it s sometimes easier to work backwards from the product. The n bond at C8=C9 in 12 suggests that the last step is deprotonation of C8 of a carbocation at C9, C. Carbocation C might have been formed from carbocation D by a 1,2-alkyl shift of Cl 1 from C9 to C3. Carbocation D might have been formed from carbocation E by a 1,2-alkyl shift of C13 from C3 to C4. Carbocation E might have been formed from carbocation F by attack of a C3=C4 n bond on a C9... 

If the ion is non-classical, nortricyclene may be viewed as the expected deprotonation product, while the hydrolysis products arise from a deep seated rearrangement to a transition state resembling the classical ion and the nucleophile. 

Compound 19 (R = Me, R = H) produced in the above reaction differs slightly in melting point (122° and 116°-117°, respectively) from the dimethylthienothiophene (17) obtained by Friedmann. This supports Horton s assumption that the action of sulfur on the linear Cg hydrocarbons is more likely to lead to thienothiophene 19 (R = Me, R = H) than to its isomer (17), the formation of the latter requiring a deep-seated rearrangement of the skeleton. 

Deep-seated rearrangements have likewise been known to occur during lithium aluminum hydride reduction of epoxides. Among thw is the interesting reaction reported by Barton and Brooke i involving the morolic acid derivative shown in Eq. (402). 

Irradiation of troponoid systems leads to a variety of photochemical reactions which include valence tautomerization, deep-seated rearrangement and dimerization. The photochemical transformations of troponoid systems as a general rule proceed readily in Pyrex vessels and thus must involve excitation of the intense, long wavelength absorption band (320-350 m/t) of the troponoid system. 

In solutions of low nucleophilicity, multiply charged electrophiles can frequently exhibit deep-seated rearrangements and fragmentation reactions. These reactions often stem from the electrostatic repulsive effects involving the charge centers, and they have precluded the observation of... 

The sulfonamide (30) undergoes a clean, uncatalysed deep-seated rearrangement to sulfone (31) via a ketenimine intermediate, a rearrangement in which both the / -toluenesulfonyl (Ts) and p-methoxybenzyl (PMB) groups sequentially migrate from the nitrogen atom on to a neighbouring carbon at the /3-position.51... 

SnCU was used with epoxide (335), and resulted in a deep-seated rearrangement. The mechanism proposed by Scovell and Sutherland is shown in equation (141). 

Thebaine behaves as an active conjugated diene in undergoing addition of maleic anhydride [42-43], benzoquinone [42-43], 1 4-naphthoquinone [42], and acrolein [102], The adduct with benzoquinone undergoes deep-seated rearrangement on heating for three hours with concentrated hydrochloric acid to give flavothebaone [43-44] (see Chap. XXI). 

Substitution with C-N cleavage took place when 4,4-ethylene-l,5,5-triphenyl-4,5-dihydro-l/f-1,2,3-triazole was exposed to hydrochloric acid. The product, 1-benzoyl-1-phenylcyclopropane (8) which was isolated in 97% yield, results from a deep-seated rearrangement envisaged to occur as shown. 

It is noteworthy that irradiation of tetracyclo[6.2.0.0 . 0 ]decan-9-one resulted in cycloreversion and formation of ketene and vinylcyclopropane tricyclo[5.1.0.0 ]oct-5-ene instead of ring cleavage and decarbonylation. A C-C double bond a to a cyclopropane ring also resulted when spiro bicyclo[2.2.1]hept-5-ene-7,l -cyclopropane -2-one eni/o-epoxide underwent a deep-seated rearrangement upon irradiation through Corex to give 5-oxo-spiro[2.4]hept-6-ene-4-ylacetaldehyde in 50% yield. ... 

The mevalonate labelling pattern of the antibiotic pleuromutilin (5.130), which is produced by the Basidiomycete Pleurotus mutilus (Clitopilus scyphoides), suggests that it is formed (Scheme 5.12) by a more deep-seated rearrangement of a copalyl diphosphate (5.131 5.132 5.133). A derivative, tiamulin , is used in animal health and retapamulin (altabax ) has attracted interest because of its activity against resistant organisms where it selectively targets the bacterial ribosome. 

The action of acid on artemisinin (9) and its derivatives gives rise to complex mixtures of products, which are often difficult to analyze. Arteether (95) undergoes deep-seated rearrangement when... 

The biosynthetic pathway is outlined in Figure 1. The thiazole 4 is formed by an oxidative condensation of glycine (1), deoxy-D-xylulose-5-phosphate (DXP, 2), and a sulfide carrier protein with a thiocarboxylate at its carboxy terminus (ThiS-COSH, 3). The pyrimidine phosphate 8 is formed by a deep-seated rearrangement of aminoimidazole ribotide (AIR, 7). It is then pyrophosphorylated and used to alkylate the thiazole to give 10. A final phosphorylation completes the biosynthesis. The entire pathway from glycine, DXP, cysteine, AIR, and ATP has now been reconstituted using purified enzymes. 

The model was also applied to the substitution of alkyl groups by tritium to give the alkanes of lower molecular weight which are observed as products. That these products are not formed by some deep-seated rearrangement is evidenced by the fact that the tritiated alkanes always relate to the parent in a simple way. For example, n-pentane gives only tritiated methane, ethane, propane and butane. Isopentane also gives isobutane ... 

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