Tris silyl-substituted ketones

Of course, the use of tris(trimethylsilyl) phosphite213 214 provides facile access to the free a-hydroxyphosphonic acids. These silyl reagents have been used for the preparation of a wide range of a-substituted phosphonates and -phosphonic acids, starting with ketene,215 a-ketophosphonates,216 ketoesters,217 218 and a,P-unsaturated carbonyl compounds,207/219-221 as well as simple aldehydes and ketones.205 210/219 224 Their use for the preparation of compounds of significant biological interest has been reviewed.125... 

The ruthenium carbene catalysts 1 developed by Grubbs are distinguished by an exceptional tolerance towards polar functional groups [3]. Although generalizations are difficult and further experimental data are necessary in order to obtain a fully comprehensive picture, some trends may be deduced from the literature reports. Thus, many examples indicate that ethers, silyl ethers, acetals, esters, amides, carbamates, sulfonamides, silanes and various heterocyclic entities do not disturb. Moreover, ketones and even aldehyde functions are compatible, in contrast to reactions catalyzed by the molybdenum alkylidene complex 24 which is known to react with these groups under certain conditions [26]. Even unprotected alcohols and free carboxylic acids seem to be tolerated by 1. It should also be emphasized that the sensitivity of 1 toward the substitution pattern of alkenes outlined above usually leaves pre-existing di-, tri- and tetrasubstituted double bonds in the substrates unaffected. A nice example that illustrates many of these features is the clean dimerization of FK-506 45 to compound 46 reported by Schreiber et al. (Scheme 12) [27]. 

Di- and tri-substituted enamines of aldehydes have been generated under mild conditions (1 h, 0°C, 1.2 equiv. of amine).278 Although easily isolable, they can be conveniently employed in situ. The reaction is chemoselective (ketones present are not affected), it tolerates sensitive groups such as acetals and silyl ethers, and it works for both aliphatic and aromatic aldehydes. 

Allyl cyanides can be added across alkynes in the presence of a nickel catalyst prepared from (COD)2Ni and (4-CF3CeH4)3P in situ to give functionalized di- or tri-substituted acrylonitriles in a highly stereoselective manner, presumably via n-allylnickel intermediates. a-Siloxyallyl cyanides also react at the y -position of a cyano group with both internal and terminal alkynes to give silyl enol ethers, which can be converted into the corresponding aldehydes or ketones upon hydrolysis.70... 

A further example of the use of 2//-thiopyrans as surrogates for m-substituted dienes involves the use of the protected 3,4-dihydio-3-(3-oxobutyl)A//-thiopyranA-onc, 3-[2-(2-methyl-l,3-dioxolan-2-yl)ethyl]-4-[tris(l-methy-lethyl)silyl)oxy-2//-thiopyran 328 as an equivalent of l-ethenyl-2-methylcyclohexene in Diels-Alder reactions. The thiopyran reacted with various maleimides to yield the endo cycloadducts and with methyl propenoate to give the exo adduct under either thermal or Lewis-acid-catalyzed conditions. In the latter case concomitant release of the protected ketone functions occurs, acid-catalyzed cyclization of which generates a fused cyclohexenone ring (Scheme 67). Desulfurization, preferably before the aldol cyclization, leads to derivatives of 2,3,4,4a,5,6,7,8-octahy-dro-4a-methylnaphthalenes < 1997CJC681 >. 

We might consider using the lithium enolate or the silyl enol ether. As we need the kinetic enolate (the enolate formed on the less substituted side of the ketone), we shall be using the lithium enolate to make the silyl enol ether, so it would make sense to try that first. 

As shown in Scheme 38, several primary alkyl-substituted cyclohexanones have been prepared by Lewis acid catalyzed phenylthioalkylation of the TMS enol ether of cyclohexanone followed by reductive removal of a phenylsulfenyl group. The two-step neopentylation sequence is particularly noteworthy. This methodology has been used to prepare numerous a-alkylated cyclic and acyclic ketones. a-Alkylated aldehydes can be produced in a like manner. a-Alkylidenation can also be accomplished by oxidative removal of sulfur. Lee and coworkers have found that TMS triflate-catalyzed reactions of silyl enol ethers of cyclic ketones and aldehydes with saturated and unsaturated l,l-dimethoxy-(i>-tri-methylstannanes, followed by addition of titanium tetrachloride, provide novel routes to fused and spiro-cyclic ring systems. Phenylthiomethylstannylations of silyl enol ethers have also been reported. ... 

The experimental results and the known facility of O-desilylation of silyl enol ethers, such as 3-acetoxy-2-trimethylsiloxypropenes, under the given reaction conditions led Trost ° to suggest the intermediacy of an oxatrimethylenemethanepalladium complex 4 addition to the alkene at the less-substituted terminal carbon atom of 4 followed by tautomerism and ring closure would give rise to the cyclopropane. Since the palladium complex that is prepared from tris(dibenzylideneacetone)palladium(0)-chloroform complex [Pd2(dba)j CHClj] and triphen-ylphosphane also catalyzes the Brook rearrangement of an a-silyl ketone to a silyl enol ether, (2-oxo-3-silylpropyl) acetates can also serve as precursors of intermediate palladium complexes 4, and the same cyclopropanation reactions as with 3-acetoxy-2-trimethylsiloxypropenes can be carried out. 

Silyloxy-substituted alkyl radicals, which are generated via addition of tris(trimethylsilyl)silyl radicals to chiral ketones, abstract hydrogen from thiols with moderate diastereoselectivitics37. The svnjunti ratio is dependent on the steric bulk of the neighboring alkyl substituents. 

In general, ruthenium catalysts 86 are less active than 85 with respect to the formation of tri- and tetra-substituted alkenes. Although molybdenum catalyst 85 is appreciably sensitive to air and moisture, ruthenium catalysts 86 are not significantly affected. Both catalysts are tolerant of functionality in the substrate for example, ketones, esters, amides, epoxides, acetals, silyl ethers, amines, sulfides, and alcohols. 

Although it has been stated that di- and tri-haloketones and a-haloaldehydes (irrespective of the degree of halogen substitution) tend to yield only enol phosphate esters, further qualification of this statement is appropriate. The formation of silyl ethers from aldehydes or ketones and silyl phosphites has already been noted (see section III.A). Reactions between silyl phosphites and trifluoroacetaldehyde or perfluoroacetone and other similar compounds initially lead to silyl ethers of (a-hydroxyalkyl)phosphonic diesters in which all the fluorine is retained, although subsequent change leads to fluorinated enol phosphate esters. Sekine et also observed the formation of (a-silyloxyalkyl)phospho-... 

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