3-Enol-17,21 -triacetate

Chemoselective C-alkylation of the highly acidic and enolic triacetic acid lactone 104 (pAl, = 4.94) and tetronic acid (pA, = 3.76) is possible by use of DBU[68]. No 0-alkylation takes place. The same compound 105 is obtained by the regioslective allylation of copper-protected methyl 3,5-dioxohexano-ate[69]. It is known that base-catalyzed alkylation of nitro compounds affords 0-alkylation products, and the smooth Pd-catalyzed C-allylation of nitroalkanes[38.39], nitroacetate[70], and phenylstilfonylnitromethane[71] is possible. Chemoselective C-allylation of nitroethane (106) or the nitroacetate 107 has been applied to the synthesis of the skeleton of the ergoline alkaloid 108[70]. 

Figure 4.11. Examples of redox-initiated radical reactions. Samarium diiodide reduction of the bromide gives a radical that cyclizes faster than the second reduction reaction. Manganese triacetate oxidation of the P-keto ester gives an enol radical that is not further oxidized by the manganese reagent. The IBX oxidizes anilides to the corresponding radicals. Hexamethylphosphoramide = HMPA and Tetrahydrofuran = THE.

Alkenyl(alkoxy)-allenylidenes, in Ru and Os half-sandwich tj-arenes, 6, 619 Alkenylation C-H bonds, 10, 221 Ge-H bonds, 3, 726 via lead triacetates, 9, 400 silyl enolates, 9, 328... 

Known bicyclo[4.3.1]enone 15758 was converted into vinylsilane 158 with bis(trimethylsilyl)methyl lithium.55 Diene 158 underwent selective ozonolysis at the cis-olefin under conditions to produce differentially oxidized termini 90 alde-hydo-ester 159 was homologated with a phosphine oxide anion91 to enol 160. Subsequent hydrolysis of 161 provided substrate 162, which after tandem ozonolysis-acidification gave racemic 6,9-desmethyl analogue 155. Unfortunately, initial efforts failed to resolve 155 into its two optical isomers with cellulose triacetate.92 However, the antimalarial activity of racemate 155 is intriguing, as discussed in a later section. 

Racemic colchiceine was obtained by Corrodi and Hardegger by a base-catalyzed equilibration of the Schiff base obtained by reacting deacetyl-colchiceine with benzaldehyde (34). Aldimine-ketimine isomerization was found to be the mechanism by which the racemization had occurred (35). The optical resolution of deacetylcolchiceine was accomplished with cam-phorsulfonic acids, affording, after O-methylation with diazomethane, separation of the enolate isomers and after N-acetylation, unnatural (+)-and natural (-)- colchicine (Fig. 1). Racemization of colchicine in refluxing acetic anhydride followed by mild hydrolysis of the intermediate triacetate represents a much improved method of preparing ( )-colchicine (36). The Blade-Font procedure was later extended to the preparation of ( )-3-demethylcolchicine and other racemic analogs (5). 

Hydroxycoumarins are cyclic, completely enolized /3-ketoesters. In their reactions with aryllead triacetates, they behave more like phenols than like /3-ketoesters bearing two a-hydrogens. Indeed monoarylation took place... 

Pyridine is an important cofactor in the reaction system that leads to cleaner reactions and better yields of products than in its absence.15 It can act either as a u-donor for Pb(rv) or as a base catalyzing the keto-enol tautomerism. The u-donor effect was evidenced spectroscopically by the formation of adducts of pyridine with lead tetraacetate.45,4511 Moreover, pyridine catalyzed the ligand redistribution of twcfc-methoxyphenyllead triacetate to bis( r/ -mcthoxy-phenyl)lead diacetate. Other u-donor catalysts can be used and their nature is highly important for the success of the reaction. NaOMe and HOBT showed a modest effect, but a thousand-fold increase in rate over the uncatalyzed reaction was observed when 1,10-phenanthroline was employed and near quantitative yields of arylation products were obtained (Equation (16)).44... 

The reactivity of ketones toward aryllead(iv) triacetates is quite different from the reaction of these ketones with lead(iv) tetraacetate, which gives the a-acetoxyketones. Under the usual conditions for arylation (pyridine, CHCI3), simple ketones remain unaffected. Only ketone enolates and some specially activated ketones have been successfully... 

Alkynylation of enolates was used to prepare optically active 13,14-didehydroisocarbacyclin. Preparation of the optically active (Ai-alkynyllead triacetate was compatible with the lithium-lead tetraacetate metal-metal exchange (Scheme 11 and Equation (66)).91... 

The a-arylation of ketones, such as cyclohexanone, can be achieved using different methods. A convenient route by Pinhey et al.89), reacts cyclohexanone-2-carboxylic esters with aryllead triacetates in pyridine. The protection of the P-carboxylic ester prevents a,a-di- or even higher arylations in a -positions. The ester group can be removed by basic hydrolysis and mild thermal decarboxylation or by heating in wet dimethylsulfoxide with sodium chloride (120-180 °C)90). Barton et al. 91) have found a similar a-arylation route using the less electrophilic triphenylbismuth carbonate. In both cases probably the lead- or bismuth-enolates, respectively, are the first inter-... 

Salts of other transition metals including vanadium, cerium, chromium and manganese have been used for a-oxygenation, although rarely applied in synthesis. Manganese triacetate has been used for the efficient a -oxidation of enones (Section 2.3.2.2.1.i), but appears not to have been used for the a-hydrox-ylation of saturated ketones des]Hte its known ability to form the corresponding a-keto radicals. Similarly the use of Lewis acid assisted enolization in the oxidative process appears to have been limited to the LTA-mediated examples. 

Direct treatment of a free acid with thallium triacetate provides the a-acetoxy adds via intramolecular reductive reanangement of the derived thallium enolate. Only simple adds have been used and the necessity to use a large excess of the substrate acid limits the syndetic usefiilness of the procedure. 

Enamines [42] and potassium enolates of ketones [43] can also he employed in the arylation reaction wifh aryllead triacetate to give a-arylated ketones (Scheme 13.14). 

Two mechanisms have been suggested. A radical mechanism was first proposed and its involvement is supported by the presence of dimeric products. However, the ligand coupling mechanism is now generally accepted. An enol-lead (IV) triacetate intermediate (7) is first formed by reaction of lead tetraacetate with the enol form. Its formation is accelerated by catalysis by boron trifluoride. 14,33 Treatment of the preformed enolate with lead tetraacetate performs a-acetoxylation at lower temperature and more rapidly than in the reaction with the corresponding enol. 4 Ligand coupling then takes place on this intermediate to lead to the a-acetoxycarbonyl derivative. 

Trimethylsilyl enol ethers of acetophenone derivatives (8) react with lead tetraacetate in benzene at room temperature to give unstable phenacyllead triacetate intermediates (9), which decompose to the a-acetoxyacetophenones (10) in high yields (90-95%), when a 1 1 ratio of the enol ether to lead tetraacetate is used. However when a 2 1 ratio is used and the reaction performed in CH2CI2 or in THF at - 78°C, only small amounts of the a-acetoxyacetophenone derivatives (11) are formed, the main product being the 1,4-diketone dimers of acetophenone (40-60%). 

The silyl enol ethers of ketones react with aryllead triacetates to afford completely different types of product, depending on the nature of the substrate. The reaction of cyclohexanone trimethylsilyl enol ether with 4-methoxyphenyllead triacetate (15) afforded a mixture of 2-p-anisylcyclohexanone (44%) and 2-acetoxycyclohexanone (32%). ... 

The possible involvement of vinyllead tricarboxylates has been suggested by Corey and Wollenberg and by Larock et as reactive intermediates. Their existence is supported by NMR studies and by the isolation of cyclopent-l-enyllead triacetate. 2 Vinyllead triacetates are extremely unstable compounds which generally decompose by formation of vinyl cations and afford acetylenes or enol acetates, depending on the precursor and the substitution pattern. 

Attempts to produce the analogous carbon-lead compounds by reaction of silyl enol et p-dicarbonyl compounds with aryllead triacetates under similar conditions were unsuccessf only products which were detected were the a-arylated P-dicarbonyl derivatives. 

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