Activating group methoxycarbonyl

The effect of substituents on the reactivity of heterocyclic nuclei is broadly similar to that on benzene. Thus mem-directing groups such as methoxycarbonyl and nitro are deactivating. The effects of strongly activating groups such as amino and hydroxy are difficult to assess since simple amino compounds are unstable and hydroxy compounds exist in an alternative tautomeric form. Comparison of the rates of formylation and trifiuoroacetylation of the parent heterocycle and its 2-methyl derivative indicate the following order of sensitivity to substituent effects furan > tellurophene > selenophene = thiophene... 

Iron complexes can also catalyze allylic amination [31,32]. Enders et al. have demonstrated the nucleophilic addition of various acyclic and cyclic amines to the optically active l-methoxycarbonyl-3-methyl-(T)3-allyl)-tetracarbonyliron cation 49 formed in high yield from reaction of 48 with iron carbonyls. Oxidative removal of the tetracarbonyliron group by reaction with CAN gives 50 with high optical purity and retention of the stereochemistry (Eq. (12)) [31]. The reaction proceeds well for the different amines, and has been used for the synthesis of a compound showing cytotoxic activity against diverse cell lines [31b]. 

The crucial quaternary C-9 stereocenter was installed by methoxycarbo-nylation of the lactam carbonyl a-position of 53, followed by stereoselective alkylation of the resulting 1,3-dicarbonyl derivative with 2-(3-bromopropyl)-l,3-dioxolane. The methoxycarbonyl group not only acts as an activating group and an element of stereocontrol in the alkylation... 

Another series of antiinflammatory carboxyhc acids that ate derived from cortienic acid (107), a minor adrenal metabohte, has been described (104,105). Esterification of both the 17a-hydroxyl group and the carboxyhc acid of (107) were requited to develop a compound of high topical potency with low systemic activity. Peak activity was generally associated with a 17a-propionoxy group and a 17P- uoromethoxy carbonyl (eg, (108)), or 17P-methoxycarbonyl residue. 

In a like manner the 6/3-isocyano group can be utilized to activate the C(6) proton (79JCS(P1)2455), an example of which is shown in Scheme 43. It was also possible to introduce the 6a-methylthio substituent by reacting the intermediate anion with methyl methoxycarbonyl disulfide The 6a-methylthio group could subsequently be converted to the 6a-methoxy group by treatment with CI2 and MeOH. 

Interaction of a carbonyl group with an electrophilic metal carbene would be expected to lead to a carbonyl ylide. In fact, such compounds have been isolated in recent years 14) the strategy comprises intramolecular generation of a carbonyl ylide whose substituent pattern guarantees efficient stabilization of the dipolar electronic structure. The highly reactive 1,3-dipolar species are usually characterized by [3 + 2] cycloaddition to alkynes and activated alkenes. Furthermore, cycloaddition to ketones and aldehydes has been reported for l-methoxy-2-benzopyrylium-4-olate 286, which was generated by Cu(acac)2-catalyzed decomposition of o-methoxycarbonyl-m-diazoacetophenone 285 2681... 

The iminophosphoranes of methyl arylhydrazono acetates (338) possessing a keto function in an o-position afford l//-l,2,4-benzotriazepines (339) upon heating (Scheme 123). The yield depends on the substituents and solvents employed. Methoxycarbonyl-, 4-pyridyl-, and 3-pyridyl groups activate the carbonyl function and improve the yield. Reactions of alkyl ketones and aldehydes proved to be unsuccessful [91JCR(S)2],... 

The enantioselective a-alkylation of /i-oxo esters, e.g., 2-methoxycarbonyl-l-oxoindane and 2-methoxycarbonylcyclohexanone, with optically active alkyl or aryl(cthyl)methyIselenonium and -sulfonium camphorsulfonates or perchlorates, which possess a stereogenic center at the selenonium or sulfonium group, led to a mixture of a-methylated and a-ethylated compounds (Table l)7-10. 

Vincristine (26b) and vinblastine (26a) are representative of the so-called dimeric indole alkaloids which arise in the plant by combination of non-identical monomeric alkaloids. Vincristine in particular has important clinical activity both as a single agent and in combination chemotherapies (B-77MI30614). Recently, a semi-synthetic derivative vindesine (26c) in which the C-16 methoxycarbonyl group has been converted to a primary amide... 

The synthesis of the starting aminoacyl nitrile 39 was carried out by the modified method of Lowe and Yuthavong 91,92 as shown in Scheme 19. The dipeptide derivative 43 was produced by simple chloroformate-mediated condensation of 42 with aminoacetonitrile formally derived from Gly. This example uses the TV-methoxycarbonyl protection group, presumably to avoid steric interference in the target enzyme active site. 

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