Silyl enol ethers dimerization

Dimerization of silyl enol ethers or of lithium enolates... 

Schafer reported that the electrochemical oxidation of silyl enol ethers results in the homo-coupling products. 1,4-diketones (Scheme 25) [59], A mechanism involving the dimerization of initially formed cation radical species seems to be reasonable. Another possible mechanism involves the decomposition of the cation radical by Si-O bond cleavage to give the radical species which dimerizes to form the 1,4-diketone. In the case of the anodic oxidation of allylsilanes and benzylsilanes, the radical intermediate is immediately oxidized to give the cationic species, because oxidation potentials of allyl radicals and benzyl radicals are relatively low. But in the case of a-oxoalkyl radicals, the oxidation to the cationic species seems to be retarded. Presumably, the oxidation potential of such radicals becomes more positive because of the electron-withdrawing effect of the carbonyl group. Therefore, the dimerization seems to take place preferentially. 

Silyl enol ethers (Scheme 2, Y = OSi ( 113)3) can be dimerized to 1,4-dicarbonyl compounds in good yields. To suppress the methanolysis of the silyl enol ethers, MeCN-5% MeOH is used as solvent and the electrolysis is conducted within one hour by the use of a capillary gap cell, which allows high currents (Table 7, numbers 6 and 7) [59]. 

Dimerization of Silyl Enol Ethers or of Lithium Enolates 3/O-De-trimethylsilyM / C-coupling... 

Silyl enol ethers can be dimerized to symmetrical 1,4-diketones by treatment with Ag20 in dimethyl sulfoxide or certain other polar aprotic solvents.465 The reaction has been performed with R2, R-1 = hydrogen or alkyl, though best yields are obtained when R2 = R1 = H. In certain cases, unsymmetrical 1,4-diketones have been prepared by using a mixture of two silyl enol ethers. Other reagents that have been used to achieve either symmetrical or cross-coupled products are iodosobenzene-BFy-EtiO.466 ceric ammonium nitrate,467 and lead tetraacetate.m If R1 = OR (in which case the substrate is a ketene silyl acetal), dimerization with TiCL, leads to a dialkyl succinate (32, R1 = OR).4 9... 

Products of the type (24) also result from enolizable ketones without the formation of silyl enol ethers if the reaction is carried out in the presence of tertiary phosphines. The proposed mechanism involves the betaine R3P—SiMe2 as the silylene transfer agent. In preventing a 1,3-hydrogen migration, the phosphine may well induce dimerization prior to oxasilacyclopropane formation. The dioxadisilacyclohexane (24) can be reduced with LiAIHU to give dimethylsilyl-substituted carbinols, so the reaction is of synthetic value (Scheme 34) (78JA7074). 

Since silyl enol ethers have a silyl group ji to the jr-system, anodic oxidation of silyl enol ethers takes place easily. In fact, anodic oxidation of silyl enol ethers proceeds smoothly to provide the homo-coupling products, 1,4-diketones (equations 37 and 38)42. This dimerization of the initially generated cation radical intermediate is more likely than the reaction of acyl cations formed by two electron oxidation of unreacted silyl enol ethers in these anodic reactions. 

Another carbon-carbon bond forming reaction mediated by (difluoroiodo)benzene-boron trifluoride was reported using silyl enol ethers which underwent oxidative dimerization to 1,4-diketones [58] (see also Sections 5.2.2 and 12.2.2). 

Triplex catalysis.1 1,3-Cyclohexadiene does not undergo cycloadditions under usual conditions although it is known to dimerize on irradiation in the presence of a sensitizer. Actually, 1,3-cyclohexadiene can undergo both [2 + 2]- and [4 + 2]cycloaddition with a silyl enol ether such as 1-trimethylsiloxy-l-phenylethyl-ene (1). Similar results obtain with trimethylsilylketene acetal. These sensitized... 

The corresponding silyl enol ethers are likewise readily available carbonyl umpolmg substrates which can be oxidized by a variety of chemical oxidants and also by cathodic oxidation. If not trapped by nucleophiles, the radical cations can dimerize and subsequently hydrolyze to give 1,4-dicarbonyl (homo)coupling products [195]. 

Silyl enol ethers can be dimerized to symmetrical 1,4-diketones by treatment with Ag20 in DMSO or certain other polar aprotic solvents.The reaction has been performed with R, = hydrogen or alkyl, although best yields are obtained... 

Aliphatic amines are mainly converted to a-substituted products [99,100], whereby especially the a-methoxylation leads to valuable reagents for synthesis. The intermediate iminium salts can be directly trapped by silyl enol ethers to form Mannich bases [108]. If the a-position is blocked or steric conditions favor it, N,N coupling to hydrazo or azo compounds occurs (Table 5, numbers 17-19). 1,1-Disubstituted hydrazines are dimerized to tetrazenes in fair to excellent yields (Table 5, numbers 20-24). The intermediate diaze-nium ions can attack enolizable carbonyl compounds to form aza-Mannich bases [109]. Arylazonaphthols undergo anodic oxidation, producing radical cations. These couple to biphenylbisazo compounds (up to 34%) or can be trapped by anisidine to form azodiphe-nylamines (up to 74%) [110a]. 

Indirect replacement of the a-hydrogen atom of carboxylic esters by the nitroso group is remarkable. This procedure uses ketene 0-alkyl O -silyl acetals (1), generated from carboxylic esters, which are treated with nitric oxide or isopentyl nitrite in the presence of titanium(IV) chloride. In the absence of an a-hydrogen a-nitroso esters (2) are obtained. a-Nitroso esters with an a-hydrogen undergo isomerization to oximes of a-keto esters (3 equation 1). Similarly, silyl enol ethers of aldehydes or ketones can be used instead of the carbonyl compound itself for nitrosation. Thus, treatment of enol ether (4) with nitro-syl chloride gives the a-nitroso aldehyde (5 equation 2), which is quite stable at 0 C, but dimerizes at room temperature. 

The total synthesis of (+)- -onocerin via four-component coupling and tetracyclization steps was achieved in the laboratory of E.J. Corey. The farnesyl acetate-derived acyl silane was treated with vinyllithium, which brought about the stereospecific formation of a (Z)-silyl enol ether as a result of a spontaneous Brook rearrangement. In the same pot, the solution of I2 was added to obtain the desired diepoxide via oxidative dimerization. 

Jauch, J. Stereochemistry of the Rubottom oxidation with bicyclic silyl enol ethers synthesis and dimerization reactions of bicyclic a-hydroxy ketones. Tetrahedron 1994, 50,12903-12912. 

The occurrence of two competing pathways was also observed in the reaction of some enol silyl ethers with diphenyliodonium fluoride (19), which afforded the mono- or the di-phenylated products in moderate to good yields. This C-phenylation reaction is likely to occur by a ligand coupling process. However, with some hindered silyl enol ethers, for example (20), diketone dimers (21) were also isolated, indicative of a free-radical component in the overall mechanistic picture. ... 

For these reasons, this variation is not as widely used as the anionic reaction (the aldol condensation). The base catalyzed reaction often leads to dimers, polymers, self-condensation products or a, 5-unsaturated carbonyl derivatives, as described in Section 9.4.A. Mukaiyama and co-workers modified the acid-catalyzed reaction to include silyl enol ethers. He found that they react with carbonyl compounds to produce aldol-like... 

The air stable and storable zirconium catalyst, formed from Zr(0 Bu)4, 3,3 -diiodo-l,l -binaphthalene-2,2 -diol (3,3 -l2-BINOL), -propanol and water, with the putative dimeric structure (7.33) also catalyses auft -selective asymmetric aldol reactions. While this process is beheved to proceed through an acyclic transition state, as depicted in Figure 7.2, it is postulated that the greatest steric interaction is now between the silyl enol ether substituent R3 and the bulky Lewis acid resulting in the formation of the fluft -diastereomer predominantly. 

Oxidative Coupling. Both intermolecular and intramolecular oxidative coupling reactions can be effected using Cu(OTf)2. Examples of dimerization include one-pot syntheses of 1,4-diketones from ketone enolates or from silyl enol ethers (eqs 1 and 2), and coupling of allylstannanes with TMS-enol ethers... 

Lewis acid promoted reactions of silicon enolates, /.e., silyl enol ethers and ketene silyl acetals with various electrophiles have yielded a wealth of novel and selective synthetic methods. This combination of reagents has been used in the past to perform such reactions as aldol-condensations with aldehydes and acetals, imine-condensations, conjugate additions to a,P-enones, alkylations, electrophilic aminations, and Diels-Alder/cyclocondensations. Our own interest in this field has involved the use of titanium tetrachloride to promote the reaction of ketene silyl acetals with non-activated imines as an efficient route to P-lactams. This reaction has been applied to the asymmetric synthesis of P-lactams via a chiral imine-titanium tetrachloride template. We have also found that both ketene silyl acetals and vinylketene silyl acetals oxidativelly dimerize or cross-couple, in the presence of titanium tetrachloride to conveniently yield various diesters . Our present study concerns reactions of vinylketene silyl acetals with non-activated imines and vinylimines promoted by titanium and zirconium tetrachlorides. 

Reactions of various activated alkenes with Mg/TMSCl in DMF system have been explored as well. When treated with this reduction mixture, a-substituted arylvinyl sulfones affords ( )-/3-substituted st)renes in high stereoselectivity and reasonable yields, through the desulfonation reaction (eq 83). Under the reaction conditions, Q ,/3-unsaturated ketones undergo facile and regioselective reductive dimerization to afford the corresponding bis(silyl enol ethers), that is, l,6-bis(trimethylsilyloxy)-1,5-dienes (eq 84) In contrast, Q ,/3-unsaturated esters or a,/3-epoxy... 

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