Trimethylsilylmethyl ketones

Matsuda, I., Okada, H., Sato, S., Izumi, Y. A regioselective enolate formation of trimethylsilylmethyl ketones. Application to the (E)-selective synthesis of a,P-unsaturated ketones. Tetrahedron Lett. 1984, 25, 3879-3882. 

Derivatives. TrimethylsUylacetyl thiolesters, which have been used as precursors to 8-lactams, are prepared by reaction of the appropriate thiol with the acid chloride derivative of (1). Acid (1) has also been used as a precursor to l-diazo-3-trimethylsilyl-acetone, which provides cyclopropyl trimethylsilylmethyl ketones upon reaction with alkenes, through reaction of the acid chloride or a mixed anhydride derivatives of the acid (1) with diazomethane. ... 

Trimethylsilyhex-l-yne, 46 Trimcthylsilylmethyl cyclohexyl ketone, 78-9 Trimethylsilylmethyl lithium, 64,78,79... 

Trimethylsilylmethyl Grignard or lithium reagents 1606 add to ketones such as cyclohexanone to give, via the intermediates 1607, the olefins 1608, often in high yields (Scheme 10.5). 

Our retrosynthesis of (—)-kinamycin F (6) is shown in Scheme 3.20 [45]. It was envisioned that (—)-kinamycin F (6) could be prepared from the protected diazofluorene 114 by conversion of the ketone function of 114 to a trans-], 2-diol, followed by deprotection of the acetonide and methoxymethyl ether protecting groups. The diazofluorene 114 was envisioned to arise from diazo transfer to the hydroxyfulvene 115. The cyclopentadiene substructure of 115 was deconstructed by a two-step annulation sequence, to provide the bromoquinone 116 and the p-trimethylsilylmethyl unsaturated ketone 117. The latter two intermediates were prepared from juglone (118) and the silyl ether 119, respectively. 

The diol function of 130 was protected as its acetonide 131 (88 %). Next, the enone function was installed by a-selenation of the enoxysilane, followed by peroxide oxidation and elimination (57 % over two steps). Finally, the unsaturated ketone 132 was homologated by 1,4-addition of trimethylsilylmethyl magnesium chloride, trapping with chlorotrimethylsilane, and reoxidation, to afford the target 117 (88 %). 

MoC15 promotes the ring-opening transformations of cyclopropyl ketones. Cyclopropyl phenyl ketone 251 is converted to 1-phenyl-1,2,4-trichloro-1-butene 252. Desilylative lactonization of propyl 2-(trimethylsilylmethyl)cyclo-propanecarboxylate 253 yields ds-2-chloro-4-pentanolide 254 stereoselectively [144]. (Scheme 100)... 

For A-(trimethylsilylmethyl)-5-methylisothioureas 262, cycloaddition with carbonyl compounds results in 2-aminooxazolines 263. ° Aliphatic and aromatic aldehydes and ketones can be employed successfully. However, reaction with ketones appears to be poor. Ylide generation with CsF is the method of choice although TBAF and KF have also been used but with lower yields. A polar solvent such as MeCN, DMF, or hexamethylphosphoric triamide (HMPA) is required for a succesful reaction (Scheme 8.73). 

A -Cyano- and A -(p-toluenesulfonyl)-A -(trimethylsilylmethyl)-5-methylisothio-ureas 269a and 269b have also been utilized as synthetic equivalents of azomethine ylides. ° Reaction of 269a and 269b with aromatic aldehydes and aryl ketones, in the presence of CsF, gives 2-iminooxazolines 270a-e in modest-to-good yield. These 2-iminooxazolines apparently are stable to isolation and do not isomerize to 2-aminooxazolines (Scheme 8.76). 

Iodine-Mercury(II) oxide, 149 a-METHYLENE ALDEHYDES AND KETONES 1,4-Diazabicyclo[2.2.2]octane, 92 Dimethyl sulfoxide, 124 Formaldehyde, 136 Methoxyallene, 177 Methylene cycloalkanes By cyclization reactions Diacetatobis(triphenylphos-phine)palladium(II), 91 l-Hydroxy-3-trimethylsilylmethyl-3-butene, 147... 

Irradiation of 49 with methyl vinyl ketone under similar conditions produces two types of compounds, (E)- and (Z)-3-methyl-4-phenyl-5-tri-methylsilyl-1,3-pentadiene and 2,6,6-trimethyl-5-trimethylsilylmethyl-5-phenyl-l-oxa-6-silacyclohexene-2, in 7, 7, and 18% yield, respectively... 

Enantioselective Reduction ofa,P-Ynones. Oxazaborolidine ligands 1 are among the most effective catalysts for the enantioselective reduction of ketones to secondary alcohols. Substitution of the methyl or butyl group on boron by a trimethylsilylmethyl group led to a much improved catalyst for the catecholborane mediated reduction of a, 3-ynones. For example, the enantioselectiv-ities for the reduction of an a, 3-ynone was improved from 60% to 98.5% when the nature of the R group was modified (eq 1). ... 

These have been much less popular, but some examples have been reported. These involve only alkenyltins containing one additional moiety on the G-carbon this substituent can be trimethylsilylmethyl (leading to functionalized allylsilanes [37] or divinyl ketones (Scheme 4-10) [38]) or trifluoromethyl [39]. The substituent can also be in the /3-position (E-geometry) examples have been reported by Parrain et al. [40] and Castano et al., the latter having used the coupling reaction of a jS-stannyl enone as the key step in the preparation of the indolizidine alkaloid ( )-monomorine here the coupling step is followed by an immediate in-situ reduction of the intermediate enone, the mechanism of which is unclear (Scheme 4-11) [41J. 

Kang, H. T., Kim, S. S., Lee, J. C., U, J. S. Synthesis of a-methylenecyclopentanones via silicon-directed Nazarov reaction of a-trimethylsilylmethyl-substituted divinyl ketones. Tetrahedron Lett. 1992, 33, 3495-3498. 

Besides carbon — carbon multiple bonds, carbon —heteroatom double bonds (C = 0 C = NR) are also capable of undergoing metal-catalyzed [3 4- 2] cycloadditions. However, the simplest class of substrates, i.e. ketones and imines, respectively, could so far only be employed when 2-(trimethylsilylmethyl)prop-2-enyl acetate (1) was used as a TMM synthon. These reactions, which additionally require the presence of cocatalysts such as tin or indium compounds when ketones are used as substrates, lead to the selective formation of 3-methylenetetrahydrofurans and 3-methylenepyrrolidines (3, X = O, N), respectively. ... 

Kuroda, C., and Ito, K., Synthesis of cadinanolide type of tricychc a-methylene-y-lactone using intramolecular cychzation of a-trimethylsilylmethyl-a,P-unsaturated ester with cyclic ketone. Bull. Chem. Soc. Jpn., 69, 2297, 1996. 

Intermediate 113 was transformed into the trimethylsilyl methyl ketone 119 in quantitative yield via the acid chloride, followed by the addition of trimethylsilylmethyl lithium (Scheme 2.13). Subsequent Peterson olefination of aldehyde 108 with 119 resulted in the required unsaturated ketone 120 in 95% yield. Subsequent desilylation and thioester hydrolysis afforded a 97% of the seco acid 121. Lactonization was achieved in 32% yield via the phosphoric acid-mixed anhydride, however this procedure also formed about 25% of the dimeric bis lactone. Following removal of the acetonide under the action of acid, a nonselective oxidation with RuCl2(Ph3P)3 produced a 1 1 mixture of the natural... 

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