Acetal elimination, enol

As mentioned earlier, metal complexation not only allows isolation of the QM derivatives but can also dramatically modify their reactivity patterns.29o-QMs are important intermediates in numerous synthetic and biological processes, in which the exocyclic carbon exhibits an electrophilic character.30-33 In contrast, a metal-stabilized o-QM can react as a base or nucleophile (Scheme 3.16).29 For instance, protonation of the Ir-T 4-QM complex 24 by one equivalent of HBF4 gave the initial oxo-dienyl complex 25, while in the presence of an excess of acid the dicationic complex 26 was obtained. Reaction of 24 with I2 led to the formation of new oxo-dienyl complex 27, instead of the expected oxidation of the complex and elimination of the free o-QM. Such reactivity of the exocyclic methylene group can be compared with the reactivity of electron-rich enol acetates or enol silyl ethers, which undergo electrophilic iodination.34... 

Most ir-nucleophiles employed in iminium ion cyclizations have a predetennined postcyclization destiny. For example, aromatic terminators will rearomatize, organosilanes will eliminate silicon through anticipated pathways and acetals and enol ethers will produce carbonyl compounds. However, the cyclizations of simple alkenes have supplied products that are the formal results of eliminations, additions and Wagner-Meerwein rearrangements. Almost exclusively Mannich-type cyclizations of unsaturated amines have been employed to prepare piperidines. 

The majority of preparative methods which have been used for obtaining cyclopropane derivatives involve carbene addition to an olefmic bond, if acetylenes are used in the reaction, cyclopropenes are obtained. Heteroatom-substituted or vinyl cydopropanes come from alkenyl bromides or enol acetates (A. de Meijere, 1979 E. J. Corey, 1975 B E. Wenkert, 1970 A). The carbenes needed for cyclopropane syntheses can be obtained in situ by a-elimination of hydrogen halides with strong bases (R. Kdstcr, 1971 E.J. Corey, 1975 B), by copper catalyzed decomposition of diazo compounds (E. Wenkert, 1970 A S.D. Burke, 1979 N.J. Turro, 1966), or by reductive elimination of iodine from gem-diiodides (J. Nishimura, 1969 D. Wen-disch, 1971 J.M. Denis, 1972 H.E. Simmons, 1973 C. Girard, 1974),... 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

The unsaturated c.vo-enol lactone 17 is obtained by the coupling of propargylic acetate with 4-pentynoic acid in the presence of KBr using tri(2-furyl)-phosphine (TFP) as a ligand. The reaction is explained by the oxypalladation of the triple bond of 4-pentynoic acid with the ailenyipailadium and the carbox-ylate as shown by 16, followed by reductive elimination to afford the lactone 17. The ( -alkene bond is formed because the oxypalladation is tnins addition[8]. 

The cyclic enol ether 255 from the functionalized 3-alkynoI 254 was converted into the furans 256 by the reaction of allyl chloride, and 257 by elimination of MeOH[132], The alkynes 258 and 260, which have two hydroxy groups at suitable positions, are converted into the cyclic acetals 259 and 261. Carcogran and frontalin have been prepared by this reaction[124]. 

Olefins may be obtained by elimination from the organoboron intermediates formed from enol derivatives and diborane. " As in the reaction with a,jS-unsaturated ketones (section IX), the conversion is carried out in two parts first formation of the diborane adduct and second, decomposition in refluxing acetic anhydride. 

Only in 1961 did Woodward and Olofson succeed in elucidating the true mechanism of this interesting reaction by making an extensive use of spectroscopic methods. The difficulty was that the reaction proceeds in many stages. The isomeric compounds formed thereby are extremely labile, readily interconvertible, and can be identified only spectroscopically. The authors found that the attack by the anion eliminates the proton at C-3 (147) subsequent cleavage of the N—0 bond yields a -oxoketene imine (148) whose formation was established for the first time. The oxoketene imine spontaneously adds acetic acid and is converted via two intermediates (149, 150) to an enol acetate (151) whose structure was determined by UV spectra. Finally the enol acetate readily yields the W-acyl derivative (152). 

Hydroxy-substituted iron-acyl complexes 1, which are derived from aldol reactions of iron-acyl enolates with carbonyl compounds, are readily converted to the corresponding /i-methoxy or /1-acetoxy complexes 2 on deprotonation and reaction of the resulting alkoxide with iodomethane or acetic anhydride (Tabic 1). Further exposure of these materials to base promotes elimination of methoxide or acetate to provide the a,/ -unsaturated complexes (E)-3 and (Z)-3 (Table 2). 

Enol (9) comes from available dkione (10) and the synthesis was performed on the enol acetate (11) rather than enol (9). Elimination with strong base gave (6) and the synthesis was completed by Wolf-Kishner removal of the carbonyl group. 

Silyl enol ethers and silyl ketene acetals also offer both enhanced reactivity and a favorable termination step. Electrophilic attack is followed by desilylation to give an a-substituted carbonyl compound. The carbocations can be generated from tertiary chlorides and a Lewis acid, such as TiCl4. This reaction provides a method for introducing tertiary alkyl groups a to a carbonyl, a transformation that cannot be achieved by base-catalyzed alkylation because of the strong tendency for tertiary halides to undergo elimination. 

Giomi s group developed a domino process for the synthesis of spiro tricyclic nitroso acetals using a, 3-unsaturated nitro compounds 4-163 and ethyl vinyl ether to give the nitrone 4-164, which underwent a second 1,3-dipolar cycloaddition with the enol ether (Scheme 4.35) [56]. The diastereomeric cycloadducts formed, 4-165 and 4-166 can be isolated in high yield. However, if R is hydrogen, an elimination process follows to give the acetals 4-167 in 56% yield. 

A one-pot reaction between a tryptophan ester, benzotriazole, and 2,5-dimethoxytetrahydrofuran in acetic acid gives the diastereomeric benzotriazolyl tetracycles, 349, in good yield. Substitution of the benzotriazole by reaction with silyl enol ethers and boron trifluoride etherate gives the corresponding ketones 350 and 351, and reaction with allylsilanes gives the corresponding alkenes 352 and 353. If the boron trifluoride etherate is added to the mixture before the silane, elimination of benzotriazole from 349 is also observed (Scheme 83) <1999T3489>. 

The acetate function of 98 was then cleaved by treatment with samarium diiodide in methanol in high yield (81 %) [44], A potential mechanism for this transformation is shown in Scheme 3.18. Reduction of the ketone function forms a samarium ketyl radical (103). Transfer of a second electron forms a carbanion (104) which undergoes p-elimination of acetate to generate the samarium enolate 105. Protonation and tautomerization then affords the observed product 107. 

Furans.2 Enol ethers, p-dicarbonyl compounds, and Mn(III) acetate (2 equiv.) react in acetic acid (25°) to form l-aIkoxy-l,2-dihydrofurans, which form furans readily on acid-catalyzed elimination of ROH. 

Azidation.1 Arylsulfonyl azides generally react with enolates to effect net diazo transfer, but this hindered and electron-rich azide can effect azide transfer at the expense of diazo transfer. The nature of the enolate counterion also plays a role, with K being more effective than Na. In addition, acetic acid (or KOAc) is required as the quench for decomposition of the triazine intermediate to the azide with elimination of the arylsulfinic acid, ArS(0)0H. By use of these conditions, chiral N-acyloxazolidones such as 2 undergo diastereoselective azidation to give the azides 3 in 75-90% yield and in high optical purity (>91 9). These... 

Another major problem in oxidative carbonylation is the presence in the reaction medium of water, which, as we have seen, is even formed as a co-product when oxygen is used as reoxidant for Cu(I) or for M(X-2). In fact, in the presence of water, competitive M-promoted oxidation processes, such as oxidation of CO to C02, may take place, which reduce the activity of the catalyst towards the desired carbonylation reaction. The oxidation of CO to C02 may be promoted by Ir(IV), Pt(IV, II), Rh(III), and especially by Pd(II), and can be stoichiometric (Eq. 8) or catalytic (working in the presence of an oxidant such as 02, Cu(II) or quinone, Eq. 9). In the case of particularly water-sensible oxidative carbonylation processes, a dehydrating agent has proven necessary to achieve acceptable catalytic efficiencies and/or product yields. Several systems have been envisaged to eliminate water, such as acetals, enol ethers,... 

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