Ketone, silyl vinyl

Enals vinyl silyl ketones.1 The anion of I reacts smoothly with va rious electrophiles (alkyl halides, epoxides, carbonyl compounds). The products are converted to (E)-enals by oxidation with 30% H202. 

The selenium group can be removed under very mild oxidative conditions (Scheme 44). Treatment of the anion of (65) with TMS-Cl gives another reagent that can be deprotonated and used with various electrophiles to prepare vinyl silyl ketones (Scheme 45). Therefore, (65) can be used as synthons of (6) and (66), like the 1,3-di(methylthio)allyl anions. ... 

Vinyl silyl ketones have been prepared from alkoxyallenes as shown in Scheme 17. Eleprotonation and silylation afford the corresponding allenylsilanes, which are hydrolyzed to vinyl silyl ketones. - - The regioisomeric organoaluminum reagents react with aldehydes to give furans after acid hydrolysis (Scheme 18). ... 

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. 

Two consecutive enolate alkylations were utilized to generate the quaternary carbon atom (Scheme 38). Alcohol 238 was transformed into the protected hydroxy enone 244. Regioselective deprotonation at the a-position of the ketone 244 led to a cross-conjugated enolate that was alkylated with the allylic iodide 245. The vinyl silyl moiety in 245 represents a masked keto group [127]. The choice of the TBS protecting group for the hydroxyl group at of 244 was crucial in order to prevent the deprotonation at the y-posi-... 

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. 

Clearly the course of these cyclization reactions is dependent upon the silicon group. In this regard, cyclization of (82) affords the steroid nucleus (83 Scheme 40). The formation of (83) was attributed, in part, to a transition state preference for the formation of the linear vinyl carbocation (84b) rather than the bent vinyl cation (84a), which would be produced in an endocyclic cyclization. The formation of (81) was controlled by the generation of the -silyl carbocation (85a), which may be a precursor to an a-silyl ketone, which undergoes protodesilylation. It is not known whether the formation of (81) as the major cyclization product occurs through a kinetic pathway or by Wagner-Meerwein rearrangement of the kinetically prefened linear carbocation (85b). 

Metal-mediated additions of silyl enolates to alkynes also are valuable for intra-and intermolecular vinylation of ketones. The Hg(II)-induced cychzation of alky-nyl-branched SEE provides regio- and stereochemicaUy homogeneous exocychc vinyl mercurial products that can be converted into a variety of functionahzed alkenes [265-267]. Two plausible mechanisms for the intramolecular carbomercura-tion have been proposed, as in the above Pd(II)-mediated cycloaUcenylation-nu-cleophihc enolate addition to the Hg(II)-activated alkyne and concerted addition of an a-keto mercurial species generated by Si-Hg transmetalation. Forsyth et al. have determined that carbomercuration occurs in an anti fashion by the former... 

Directed lithiation. 2-Arenesul gioselective fashion, furnishing thio 157-96%). 3-Halopyridines, includm lithiation and regioselective reaction that 3-chloro-4-iodopyridine generate t-BuLi. Halogen dance is also obsersx Vinyl esters are silylated at the esters of silyl ketones. The regiosel and the ability of the lithio derivative tion with suitable acceptors are expio cyclopentenones. ... 

The use of a-silylated vinyl ketone is another approach to overcome drawbacks of the standard Robinson annulation conditions such as polymerization of the vinyl ketone. The a-silylated vinyl ketones are stable and can undergo Michael addition in standard aprotic conditions (conditions that induces polymerization for vinyl ketones), as well as protic conditions. Synthesis of the octalone 21 can be used as an example of this variation. The silylated ketone 20 reacts with lithium enolate 13 (generated by methyllithium from its corresponding enol silyl ether in THE) in /-butyl... 

TMS-alkynes are oxidized at the terminal carbon to carboxylic acids by hydroboration/oxidation (dicyclohexylborane/NaOH, H2O2). This does not work with TIPS-alkynes. Instead, TIPS-alkynes are cleanly monohydroborated at the internal carbon by 9-borabicyclo[3.3.1]nonane dimer to give (Z)- -borylvinyl-silanes. These can be oxidized in high yields to a-silyl ketones, or cross coupled with a bromide R Br (R = aryl, benzyl, dimethyl-vinyl) in the presence of NaOH and tetrakis(triphenylphos-phine)palladium(0) to give /3,/3-disubstituted vinylsilanes (Suzuki reaction eq 14). The same nucleophilic substituted vinylsilane can be added to an aromatic aldehyde to provide access to ( )-3-silyl allyl alcohols. ... 

Anionic Additions to Aldehydes. The addition of l,3-bis(silyl)-propenes to aldehydes and ketones to yield the vinyl silyl alcohol was explored. This was done using TBAF and good to excellent yields were achieved (eq 11). A further extension of this work was the addition of the (l,3-bis(silyl)allyl)lithium to ketones and aldehydes (eq 12). In this reaction, the substituted silyl diene was isolated in moderate to good yields. These substrates were then explored as ligands for both iron and manganese complexes. 

Silyl ketones are hydrolytically unstable and can be converted to the desilylated ketone by simple acid or base treatment, or used in a Peterson alkenation reaction to provide enones. They are also precursors to silyl enol ethers by rearrangement. Reaction of the /3-silyl ketone with a vinyl Grignard reagent provides a rapid entry to 2-substituted 1,3-dienes by a Peterson protocol. ... 

A combination of a Pd-catalyzed arylation of a ketone followed by intramolecular cyclization of the formed enolate with an allylic silyl ether moiety in one of the substrates led to the direct formation of a 1-vinyl-lH-isochromene, as described by Wills and coworkers [164]. 

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