Enol ethers, metal enolate formation

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... 

A concerted mechanism has also been discussed [29,30], involving either a 2+2+1 or 3+2 mechanism. To avoid trimolecular reactions this requires an interaction between Rh(I) and silanes prior to the reaction with a ketone. Interaction of silanes not leading to oxidative addition usually requires high-valent metals as we have seen in Chapter 2. The model is shown in Figure 18.16 it proved useful for the explanation of the enantiomers formed in different instances. The formation of a rhodium-carbon bond is included and thus formation of silyl enol ethers remains a viable side-path. 

Another rhodium vinylidene-mediated reaction for the preparation of substituted naphthalenes was discovered by Dankwardt in the course of studies on 6-endo-dig cyclizations ofenynes [6]. The majority ofhis substrates (not shown), including those bearing internal alkynes, reacted via a typical cationic cycloisomerization mechanism in the presence of alkynophilic metal complexes. In the case of silylalkynes, however, the use of [Rh(CO)2Cl]2 as a catalyst unexpectedly led to the formation of predominantly 4-silyl-l-silyloxy naphthalenes (12, Scheme 9.3). Clearly, a distinct mechanism is operative. The author s proposed catalytic cycle involves the formation of Rh(I) vinylidene intermediate 14 via 1,2-silyl-migration. A nucleophilic addition reaction is thought to occur between the enol-ether and the electrophilic vinylidene a-position of 14. Subsequent H-migration would be expected to provide the observed product. Formally a 67t-electrocyclization process, this type of reaction is promoted by W(0)-and Ru(II)-catalysts (Chapters 5 and 6). 

Next, we considered the activation of 13 towards hydrolysis by K-complexation of a cationic metal unit to the electron-rich diene system. On the basis of the well-known palladium-mediated addition of nucleophiles to alkenamines, it was anticipated that the enol ether function in 13 would add H2O in the presence of Pd(II).21 Interestingly, exposure of 13 to a slight excess of Pd(OAc)2 led to the isolation of 14 (Scheme 8). This material suggested the exploitation of the existing Pd-C linkage for carbon-carbon bond formation with an appropriate A-side chain. In particular, the intramolecular syn insertion of the allylic double bond in the rrans-butenyl substituent in 15b and subsequent syn (3-hydride elimination would give the desired E-alkene 17. This proposal was examined using alkene 15a as a model system, synthesized in a manner similar to 13. Upon exposure to Pd(OAc)2 under the conditions... 

Hydrosilane HSiR.3 behaves similar to H2 toward transition metal complexes in some cases. When HSiR.3 is used instead of hydrogen in hydroformylation, two reactions are expected. One is a hydrocarbonylation-type reaction, by which formation of the silyl enol ethers 62 via the acylmetal intermediate 61, and the acylsilanes 64 via the acyl complex 63, are expected in practice both reactions are observed. The other possibility is silylformylation to form 65, which is unknown, even though silylformylation of alkynes is known. When Co2(CO)8 is used, the silyl enol ether of aldehyde 66 is obtained [36], However, the silyl enol ether 67 of acylsilane 68 is obtained when an Ir complex is used, and converted to the acylsilane 68 by hydrolysis [37],... 

Therefore mercury(II) acetate interacts as an electrophilic transition metal with the nucleophilic alkene to form the three-membered ring 52. This mercurinium ion is opened by relatively feeble nucleophiles like alcohols - or in this reaction water. Similar to a hydroboration the attack happened at the more substituted end of the mercurinium ion according to Markovnikov s rule. To get rid of the metal, solid potassium iodide is added. This means insoluble mercury(Il) iodide is formed, followed by loss of the methoxy group and formation of enol ether 54, which subsequently tautomerizes to the desired aldehyde 55. 

C(2)-C(3) fused polycyclic cephalosporins have received considerable attention as new candidates for /3-lactam antibiotics. An access to tricyclic cephalosporins based on metal-promoted alkenylation of 3-trifloxy-A3-cephem and subsequent Diels-Alder reaction has been published <1996TL5967>. Alternatively, the reaction of a cephalosporin triflate with silyl enol ethers and silylketene acetals has been described to afford tri- and tetracyclic cephalosporins <1996TL7549>. A related process is the formation of fused polycyclic cephalosporins 27 and 28 bearing a wide range of functionalities from the reaction of cephalosporin triflates 26 with unsaturated compounds (alkenes and alkynes) and a base (Scheme 5) <1997JOC4998>. These studies have suggested that the reaction proceeds via the intermediacy of a six-membered cyclic allene which undergoes concerted nZs + K2a cycloaddition with alkenes and acetylenes. 

An alternative mechanism for the formation of the 1,4-addition product could involve olefin coordination to the rhodium metal center followed by hydride transfer and reductive elimination of the silyl enol ether as suggested by a reviewer. 

Hydrogenation of ketones over platinum metals in alcoholic solvents, especially in methanol and ethanol, may be accompanied by the formation of acetals (and also hemiacetals and enol ethers) in the presence of a mineral acid and may lead to the formation of ethers, together with the formation of alcohols and hydrocarbons 98-100 The reactions involved under these conditions are shown in Scheme 5.4 for cyclohexanone. At an equilibrium in acidic methanol, acetals are present predominantly over hemiacetals for most ketones.101... 

By analogy with the mechanistic pathway described for the enol ether 119 (Scheme 44), we believe that the transformation of 123a-c also occurs via the formation of the /J-metalated allenyl intermediate, generated from the -elimination of the corresponding zirconacyclopropane and subsequent rearrange-... 

Dipolar cycloaddition reactions are most commonly applied for the synthesis of five-membered heterocyclic compounds.86 87 [3+2] cycloaddition reactions of transition-metal propargyl complexes have been reviewed.88 Addition of diazomethane to carbene complexes (CO)5Cr= C(OEt)R results in cleavage of the M = C bond with formation of enol ethers H2C = C(OEt)R,3 89 but (l-alkynyl)carbene complexes undergo 1,3-dipolar cycloaddition reactions at the M = C as well as at the C=C bond. Compound lb (M = W, R = Ph) affords a mixture of pyrazole derivatives 61 and 62 with 1 eq diazomethane,90 but compound 62 is obtained as sole... 

Among common carbon-carbon bond formation reactions involving carbanionic species, the nucleophilic substitution of alkyl halides with active methylene compounds in the presence of a base, e. g., malonic and acetoacetic ester syntheses, is one of the most well documented important methods in organic synthesis. Ketone enolates and protected ones such as vinyl silyl ethers are also versatile nucleophiles for the reaction with various electrophiles including alkyl halides. On the other hand, for the reaction of aryl halides with such nucleophiles to proceed, photostimulation or addition of transition metal catalysts or promoters is usually required, unless the halides are activated by strong electron-withdrawing substituents [7]. Of the metal species, palladium has proved to be especially useful, while copper may also be used in some reactions [81. Thus, aryl halides can react with a variety of substrates having acidic C-H bonds under palladium catalysis. 

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