Trimethylsilyl methyl vinyl ketone

Palladium-catalyzed bis-silylation of methyl vinyl ketone proceeds in a 1,4-fashion, leading to the formation of a silyl enol ether (Equation (47)).121 1,4-Bis-silylation of a wide variety of enones bearing /3-substituents has become possible by the use of unsymmetrical disilanes, such as 1,1-dichloro-l-phenyltrimethyldisilane and 1,1,1-trichloro-trimethyldisilane (Scheme 28).129 The trimethylsilyl enol ethers obtained by the 1,4-bis-silylation are treated with methyllithium, generating lithium enolates, which in turn are reacted with electrophiles. The a-substituted-/3-silyl ketones, thus obtained, are subjected to Tamao oxidation conditions, leading to the formation of /3-hydroxy ketones. This 1,4-bis-silylation reaction has been extended to the asymmetric synthesis of optically active /3-hydroxy ketones (Scheme 29).130 The key to the success of the asymmetric bis-silylation is to use BINAP as the chiral ligand on palladium. Enantiomeric excesses ranging from 74% to 92% have been attained in the 1,4-bis-silylation. 

When trimethylsilyl substituted diyne 607 was reacted with methyl vinyl ketone, the reaction proceeded with complete regioselectivity and without aromatization to afford 608 with 56% yield (equation 174). The regioselectivity observed was considered to result from a metallacyclopentene intermediate which was built up of the nickel atom, the double bond of methyl vinyl ketone and the less substituted triple bond of 607. 

The same research group has further performed radical carbonylation reactions on the same microreactor system [36]. First, alkyl halides were initiated and effectively reacted with pressurized carbon monoxide to form carbonyl compounds. The principle was subsequently successfully extrapolated to the multicomponent coupling reactions. 1-Iodooctane, carbon monoxide and methyl vinyl ketone were reacted in the presence of 2,2 -azobis(2,4-dimethylvaleronitrile) (V-65) as an initiator and tributyltin hydride or tris(trimethylsilyl)silane (TTMSS) as catalyst (Scheme 15). 

The copper-catalyzed conjugate addition of methyl magnesium iodide to cyclohexenone and trapping the enolate as its trimethylsilyl enol ether, followed by a trityl hexachloro-antinomate-catalyzed Mukaiyama reaction, is apphed to / -(—jcarvone. C-2, C-3 functionalized chiral cyclohexanones are converted into their a-cyano ketones, which are submitted to Robinson annulation with methyl vinyl ketone. Highly functionalized chiral decalones are obtained that can be used as starting compounds in the total synthesis of enantiomerically pure clerodanes (equation 70). 

Reaction of (trimethylsilyl)vinyl selenide 122 with methyl vinyl ketone catalyzed by SnCLt gives the [2 + 2] adduct 123 in 66% yield (equation 51)176. Replacement of the MegSi group with a hydrogen atom or a methyl group produces a complex mixture. Thus, the MesSi group can suppress side reactions by its steric effect. 

Intermediate A reacts with conjugated carbonyl compounds to give 1 1 adducts (92). Reaction of the intermediate produced from p-tolylpenta-methyldisilane with methyl vinyl ketone affords 2-trimethylsilyl-4-methyl(methylallyloxydimethylsilyl)benzene in 51% yield as the sole volatile product. Acrolein also reacts with phenylpentamethyldisilane under similar photolysis conditions to give 2-trimethylsilyl-4-methyl(allyloxydi-... 

It was found that methyl vinyl ketone could be converted into 2-trimethylsilyl-1,3-butadiene by reaction with chlorotrimethylsilane (TMSC1) in the presence of triethylamie (TEA) and lithium bromide in tetrahydrofuran solution [33]. 

This is a mild, simple and practical procedure for 1,4-addition of an aldehyde to methyl vinyl ketone, without converting the aldehyde into an enamine or a silyl enol ether. The products, substituted 5-ketoaldehydes, are important compounds, especially for the preparation of substituted 2-cyclohexen-1-one derivatives, which have been versatile starting materials for syntheses of natural products such as terpenoids. These 5-ketoaldehydes have been prepared previously by the 1,4-addition of modified aldehydes, i.e., morpholinoenamines of aldehydes,trimethylsilyl enol ethers of aldehydes in the presence of a Lewis acid, or diethylallylamine in the presence of a catalytic amount of a Ru complex, to methyl vinyl ketones. 

The role of the trimethylsilyl group is to stabilize the intermediate carbanion formed by conjugate addition. The silyl group is removed under conditions similar to those required for the dehydration the removal occurs by nucleophilic attack on silicon, resulting in displacement of the ketone. The advantage of the substituted methyl vinyl ketone is that it permits the annelation reaction to be carried out in aprotic solvents under conditions where enolate equilibration does not take place. The annelation of unsymmetrical ketones can therefore be controlled by using specific enolates generated by the methods described in Chapter 1. 

Annulation. 3-Trimethylsilyl-3-buten-2-one has been employed as a methyl vinyl ketone homolog in an improved method for the annulation of ketones. Based on work by Stork and Ganem, who employed 3-triethylsilyl-3-buten-2-one as a Michael acceptor in the Robinson annulation reaction, Suzuki and co-workers prepared a functionalized bicyclic ketone via a silyl enol ether as shown in eq 1. In general, the annulation of 2-alkylcycloketones with methyl vinyl ketone and its homologs produces rather poor yields of the desired cyclized products. 

As shown in Scheme 17,180 was available from the common, totally synthetic, intermediate 17. Using reported methodology for the introduction of vinylsilanes,57 17 was reacted smoothly with (methoxy dimethylsilyl) trimethylsilyl methyl-lithium in pentane to afford (EIZ) vinyl silane 220 in 54% yield. The main by-product in this reaction was ketone 17, which could be recycled thus, based on recovered 17, the yield of 220 was 93%. Hydrolysis of ketal 220 occurred without protodesilylation upon exposure to aqueous oxalic acid absorbed onto silica gel to give ketone 221 in 80% yield. Upon low-temperature ozonolysis of 221 in methanol, a remarkably stable dioxetane 223 was produced, as evidenced in the H NMR... 

A majority of reaction sequences rely on the use of nucleophilic (metalated) variants of 1. However, the electrophilic character of the sterically congested methine carbon has been successfully exploited via displacement reactions with sodium azide.Ogata and Shimizu have also reported that 1 undergoes nucleophilic attack by 1,2,4-tiiazole in the presence of potassium carbonate to provide l-[bis(trimethylsilyl)methyl]-1,2,4-triazole (3) (eq 2). Subsequent introduction of TBAF results in desilylation of 3 to afford an a-sUyl carbanion intermediate that provides 1-vinyl-1,2,4-triazole products upon condensations with aldehydes or ketones (eq 3). While high yields of the alkene products are generally obtained, mixtures of 7Z-isomers are observed in all cases. 

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