Trimethylsiloxy lithium

Surprisingly, the size of the silyl protecting group significantly influences the stereochemical outcome of aldol additions performed with the lithium enolates of (S )-l-trimethylsiloxy-and (S)-l-f< rt-butyldimethylsiloxy-l-cyclohexyl-2-butanone. Thus, the former reagent attacks benzaldehyde preferably from the Si-face (9 1), which is the opposite topicity to that found in the addition of the corresponding titanium enolates of either ketone ... 

Stereodivergent aldol addition is also possible when (.S,)-5,5-dimethyl-4-trimethylsiloxy-3-hexanonc (16) is chosen as the enolate precursor. Thus, the lithium enolate generated from 16 by treatment with lithium diisopropylamide and tetramethylethylenediamine leads predomi-... 

The potential for coordination depends on the oxy substituents.82 Alkoxy substituents are usually chelated, whereas highly hindered silyloxy groups usually do not chelate. Trimethylsiloxy groups are intermediate in chelating ability. The extent of chelation also depends on the Lewis acid. Studies with a-alkoxy and (3-alkoxy aldehydes with lithium enolates found only modest diastereoselectivity.83... 

Several enolates of 4,4-dimethyl-3-(trimethylsiloxy)-2-pentanone have been investigated.106 The lithium enolate reacts through a chelated TS with high 2,2 -anti stereoselectivity, based on the steric differentiation by the f-butyl group. 

The reactions of 1-TMS-cyclohexene oxide are similar (112). Treatment78,82 with sulfuric acid/water (in acetone), concentrated hydrobromic acid, sulfuric acid/ methanol, lithium aluminum hydride afford the corresponding compounds 1,2-di-hydroxy- (113)-, l-bromo-2-hydroxy- (114)-, l-methoxy-2-hydroxy- (115)-, 1-hydroxy-2-TMS-cyclohexane (117). Application of base to 115 yields 1-methoxy-l-cyclohexene (116). Pyrolysis of 112 gives a mixture of 1-trimethylsiloxy-l-cyclo-hexene (118) and 3-trimethylsiloxy-1-cyclohexene (ii9)77 (Scheme 13). 

With respect to the mechanism just discussed, the statement of Cowley et al. [25] that merely Z-isomeric [2,2-dimethyl-l-(trimethylsiloxy)propylidene]trimethylsilylphosphane can eliminate hexamethyldisiloxane, does need further verification. From our point of view the E- and Z-isomer of the mesomeric enolate anion are readily interconverted by a rotation around the P-C bond of the keto form (Eq. 6) which is supposed to be an easily accessible transition state. At any rate, we were not able to confirm their results as the reaction of lithium bis(trimethylsilyl)phosphanide with 2,2-dimethylpropionyl chloride at -78 °C in cyclopentane solution gives exclusively the -isomeric phosphaalkene, whereas at room temperature the Z-isomer prevails. 

In order to understand the formation of compounds now being discussed one has to realize that tris(trimethylsilyl)phosphane originating in the desilylation of [l-(trimethylsiloxy)benzylidene]-trimethylsilylphosphane (Scheme 1) reacts slowly with lithium ethanolate to give lithium bis(trimethylsilyl)phosphanide again (Eq. 13). This compound must then be considered a continuous source for the phosphaalkyne H5Q-C P, provided that a sufficient amoimt of ethyl benzoate is present in solution. 

Stereoselective aldol condensation. Heathcock and Buse have previously employed 2-methyl-2-trimethylsiloxy-3-pentanone (1) in a highly stereoselective route to 3-hydroxy-2-methylcarboxylic acids (8, 295). Aldol condensation of the lithium enolate derived from 1 with a chiral aldehyde yields ery//iro-aldols, which are cleaved with periodic acid to -hydroxy carboxylic acids. However, when 1 is condensed with a chiral aldehyde such as 2, two eryt/iro-products (3 and 4) are produced. Heathcock and co-workers now report that the 1,2-diastereoselectivity of these aldol condensations can be enhanced by use of the ketone 5. Reaction of racemic 5 with racemic aldehyde 2 furnishes a single (racemic) adduct 6. 

CYCLOHEPTENONES 3-Bromo-3-methyl-2-trimethylsiloxy-I-butene. Lithium phcnylthiol 2-vinylcyclopropyl)-cuprate. 

The most systematically investigated acyl anion equivalents have been the IMS ethers of aromatic and heteroaromatic aldehyde cyanohydrins, TBDMS-protected cyanohydrins, - benzoyl-protected cyanohydrins, alkoxycaibonyl-protected cyanohydrins, THP-protected cyanohydrins, ethoxyethyl-protect cyanohydrins, a-(dialkylamino)nitriles, cyanophosphates, diethyl l-(trimethylsiloxy)-phenyimethyl phosphonate and dithioacetals. Deprotonation di these masked acyl anions under the action of strong basie, usually LDA, followed by treatment with a wide varies of electrophiles is of great synthetic value. If the electrophUe is another aldehyde, a-hydroxy ketones or benzoins are formed. More recently, the acyl caibanion equivalents formed by electroreduction of oxazolium salts were found to be useful for the formation of ketones, aldehydes or a-hydroxy ketones (Scheme 4). a-Methoxyvinyl-lithium also can act as an acyl anion equivalent and can be used for the formation of a-hydroxy ketones, a-diketones, ketones, y-diketones and silyl ketones. - - ... 

Trimethylsiloxy cyanohydrins (9) derived from an a,3-unsaturatied aldehyde form ambident anions (9a) on deprotonation. The latter can react with electrophiles at the a-position as an acyl anion equivalent (at -78 C) or at the -y-position as a homoenolate equivalent (at 0 C). The lithium salt of (9) reacts exclusively at the a-position with aldehydes and ketones. The initial kinetic product (10) formed at -78 C undergoes an intramolecular 1,4-silyl rearrangement at higher temperature to give (11). Thus the initial kinetic product is trapped and only products resulting from a-attack are observed (see Scheme 11). The a-hydroxyenones (12), -y-lactones (13) and a-trimethylsiloxyenones (11) formed are useful precursors to cyclopentenones and the overall reaction sequence constitutes a three-carbon annelation procedure. 

Studies pertaining to diastereoselectivity in Lewis acid catalyzed alkylations of enol derivatives have been limited. Reetz has reported that r-butylation of l-trimethylsiloxy-4-f-butylcyclohex-l-ene gave an 8S 1S mixture of cis- and frafu-2,4-di-f-butylcyclohexanone, which could result from kinetic equatorial and axial alkylation, respectively. However, equilibration of the products, which would favor formation of the former isomer, was not ruled out. Titanium tetrachloride promoted phenylthiomethylation of the more-substituted TMS enol ether of 1-decalone gave a 4 1 mixture of cis- and rranj-fused 1-deca-lones. In this case, where equilibration of the product could not occur, the diastereoselectivity was similar to that of methylation of the corresponding lithium enolate (49). ... 

The second step in the above sequence, deprotonation followed by silylation of the resulting enolate, was not successful under standard lithium diisopropylamide (LDA) conditions, presumably because silylation of the lithium enolate was slow. The deprotonation/silylation can be carried out effectively using KHMDS, which is available from Aldrich Chemical Company, Inc., as a 0.5 M solution in toluene. This protocol is quite general for the preparation of various dienes containing different silyl and amino groups as illustrated in Table I.5-7 For preparative scale reactions, such as that described above, the use of NaHMDS was preferred as it is available from Aldrich Chemical Company, Inc., as 1.0 M solution in THF. The procedure described here also provides a convenient and high-yielding preparation of Danishefsky s diene (1-methoxy-3-trimethylsiloxy-1,3-butadiene).8... 

Lithium diisopropylamide itself has the potential to open the ring in trimethylsiloxy-substituted cydopropanes by desilylation. The ring-opened intermediate can be trapped by alkylation with various alkyl halides. When this reaction was performed in the presence of phenyl isocyanate and iodomethane, highly substituted A -phenylpyrrole derivatives were obtained after treatment with trifluoroacetic acid. ... 

Pachybasin, 2-methyl-4-hydroxyanthra-9,10-quinone has been obtained in 73% yield by Diels-Alder addition from 2-bromonaphthoquinone and the vinylketene mixed acetal, 1-trimethylsiloxy-1-methoxy-3-methylbuta-1,3-diene, by reaction in dichloromethane containing potassium carbonate, heating with sodium acetate and finally aromatisation of the crude product by refluxing in ethanol The diene was accessible from methyl senecioate (methyl 3-methylbut-2-enoate) by treatment with lithium diisopropylamide and trimethylchlorosilane (ref.25). 

Bis(trimethylsiloxy)cyclohexadienes. LDA and related lithium dialkyl-amides appear to be specific for generation of the anion of keto trimethylsilyl enol ethers reaction of these anions with (CHajaSiCI gives the disiloxycyclohexa-dienes 1 and 2, which cannot be prepared directly from the 1,2- and 1,3-dike-... 

Hexamethylcyclotrisilazane Hexylsilane Hydrazine Hydrazine carbonate Hydrazine monohydrate Hydrazine monohydrochloride Hydrazine sulfate Hydriodic acid Hydroxylamine hydrochloride Hydroxylamine sulfate Hypophosphorous acid Isocyanatopropyltriethoxysilane Lithium Magnesium 2-Mercaptoethanol 3-Mercaptopropylmethyldimethoxysilane 3-Methacryloxypropyltris (trimethylsiloxy) silane N-Methylaminopropyltrimethoxysilane Methylcyclohexyldichlorosilane Methylcyclohexyldimethoxysilane Methyidichlorosilane Methyidiethoxysilane N-Methyl-N-trimethylsilyltrifluoroacetamide Octadecyidimethylsilane Octadecyidimethyl [3-(trimethoxysilyl) propyl] ammonium chloride Octadecylsilane Octylsilane Octyltrichlorosilane 1,1,1,3,3-Pentamethyl-3-acetoxydisiloxane 2-... 

Treatment of the siloxysilane 4 with LiOSiMc3 leads to the lithium bis(trimethylsiloxy)hydrido-silanolate (17) (Eq. 6). The yield has been determined by trapping of 17 with chlorodimethylsilane. 

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