Trimethylsilyl chloride ketone synthesis

Treatment of em-dibromocyclopropanes with one equivalent of alkyllithium at low temperature generates 1-bromocyclopropyllithiums, which have proved to be very versatile intermediates for the synthesis of various cyclopropyl derivatives. Thus, the reactions of the bromolithium compounds with disulfides ketones, alkyl ha-lides , methyleneammonium salts and trimethylsilyl chloride provide the corresponding 1-bromocyclopropyl derivatives (equation 124). A neighbouring ether... 

For the linear synthesis of spheroidene (97) [20] that is described in Section B.4, the Cig-ketone 51 is used as starting material. This is prepared (Scheme 17) from commercially available (5jF)-6,10-dimethylundeca-5,9-dien-2-one (geranylacetone) (52). This ketone 52 is coupled in an Horner-Emmons reaction with the commercially available triethyl phosphonocrotonate (53), in the presence of BuLi as base. Yields for this reaction are almost doubled (from 45 to 85%) when HMPA is added. The ester 54 is converted in one step into the Ci8-ketone 51 by addition of an excess of MeLi (55) in the presence of five equivalents of trimethylsilyl chloride at -100°C, giving, after acidic work-up, the all-E" Cig-ketone 51 in 69% yield [20]. 

The reaction of the ester 51 with MeLi (55) in the presence of trimethylsilyl chloride cannot be performed on a large scale in a reproducibly high yield. For the synthesis of the Ci8-ketone 51 on a large scale, an alternative, a three-step route is used (Scheme 18). First the geranylacetone (52J is coupled in an Horner-Emmons reaction with diethyl cyano-methylphosphonate (4) with NaH as a base. Reduction of the nitrile by DEB AH then gives the aldehyde 56 in 73% yield. Aldol condensation of 56 with acetone (57) in the presence of a... 

A new two-step procedure for the preparation of cyanohydrins from ketones is particularly useful for the synthesis of highly hindered cyanohydrins [equation (38)]. Note that potassium cyanide and trimethylsilyl chloride can be used in place of trimethylsilyl cyanide in the above reaction. ... 

Trimethylsilyl [ C]cyanide is conveniently accessible from trimethylsilyl chloride, Na CN and Nal in the presence of lutidine or pyridine ". In carbon-14 synthesis it is normally generated in situ and used immediately in subsequent Lewis acid catalyzed chemical transformations. It is useful for some reactions in which alkah metal [ " C]cyanides normally fail, such as cyanide addition to acetals and aromatic and heteroaromatic aldehydes and ketones. Examples include the Znl2-catalyzed addition of TMS " CN to 2-furaldehyde followed by hydride reduction of the resultant silylated cyanohydrin to the aminoalcohol 96 " and the SnCLj-catalyzed formation of D-[l- " C]allonitrile 98, obtained from reaction of TMS " CN to the 0-acetylated hemiacetal 97 (Figure 7.26). Subsequent addition of H2Se to the nitrile group, cyclocondensation of the intermediate selenoamide in situ with ethyl bromopymvate and deprotection yielded 99, precursor to [2- " C]CI-935, a compound with... 

Additionally, acetylene itself is a useful two-carbon building block but is not very convenient to handle as it is an explosive gas. Trimethylsilyl acetylene is a distillable liquid that is a convenient substitute for acetylene in reactions involving the lithium derivative as it has only one acidic proton. The synthesis of this alkynyl ketone is an example. Deprotonation with butyl lithium provides the alkynyl lithium that reacted with the alkyl chloride in the presence of iodide as nucleophilic catalyst (see Chapter 17). Removal of the trimethylsilyl group with potassium carbonate in methanol allowed further reaction on the other end of the alkyne. 

Silyl, germanyl and stannyl alk-l-ynyl ketones have been prepared from 2-lithio-2-(trimethylsilylethynyl)-l,3-dioxolane 448. The deprotonation of the dioxane 447 with n-BuLi at — 65 °C afforded the acyl anion 448 which, after reaction with trimethylsilyl, trimethylgermanyl and trimethylstannyl chloride, gave the expected derivatives (Scheme 117)658. Hydrolysis of these products with 0.01 M sulfuric acid at room temperature in aqueous acetone gave the corresponding acyl derivatives 449. On the other hand, the reaction of the intermediate 448 with alkyl halides allows the synthesis of acetylenic ketones659. 

In a similar fashion, chromium tricarbonyl complexes of aryl ketones are exclusively alkylated and reduced from the exo face relative to the metal. For example, addition of vinyl magnesium chloride to the substituted tetralone complex (42) affords the alcohol (43) exclusively with an antirelationship between the incoming nucleophile and the chromium tricarbonyl group (Scheme 83). This was used in a synthesis of 11-epi-helioporin B. 2-Trimethylsilyl-substituted benzaldehyde complexes undergo an interesting... 

The synthesis of terminal alkenes entails addition of either (trimethylsilyl)methyl-magnesium chloride (Me3SiCH2MgCl) or (trimethylsilyl)methyllithium (Me3SiCH2Li) to an aldehyde or a ketone to yield the corresponding P-hydroxysilane, which undergoes base- or acid-mediated elimination to furnish the alkene, as exemplified below. " ... 

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