Silyl derivatives reactions with

Silylation reactions generally proceed very rapidly (within 5 min) with pyridine being the most frequently used solvent. GC columns used for analysis of silyl derivatives are conditioned by HMDS before use to block any acidic sites and avoid possible reactions with silyl derivatives. Many varied... 

Reactions with silyl derivatives Sym. disulfides and trisulfides from alkylthiosilanes... 

The tris(trimethylsilyl)silyl ligands can be easily modified by reactions with silyl chlorides, as shown with a series of phenylated species Mes Ph SiCl (n = 0-3). Furthermore, triisopropyl, thexyldimethylsilyl, or tert-butyldimethylsilyl substitution are all easily possible.190 The crystallographic characterization of some of the alkali metal derivatives indicates a direct correlation between ligand size and resulting structural parameters. 

Both silyl- and alkyl esters derived from primary AN are readily involved in C,C-coupling reactions with silyl ketene acetal (Scheme 3.208, Eq. 1) (484). 

SENAs derived from secondary AN are not involved in catalytic C,C-coupling reactions with silyl ketene acetals. This is possibly due to a decrease in both the effective concentration of the cationic intermediate (the steric effect) and its lower level of electrophilicity (see the lower entry in Table 3.23). 

Reaction of 4a with TiCl4 was carried out in the presence of siloxyalkene 3 as nucleophile and the results are summarized in Table III. In the reaction with ketene silyl acetals 3a and 3e at -78 °C, y-ketoesters 15a and 15e were obtained instead of chloride product 8 which is a major product in the absence of 3. Formation of product 15 is likely to result from trapping of alkylideneallyl cation 5 with 3 at the sp2 carbon. In contrast, the reactions with silyl enol ethers 3f and 3g gave no acyclic product 15, but gave cyclopentanone derivatives 16-18. The product distribution depends on the mode of addition of TiCl4 (entries 4-7). 

Sulfoxides have also been used in the synthesis of nucleoside analogs (Scheme 3.2). Chanteloup and Beau reported the synthesis of ribofuranosyl sulfoxide 13 and its use in the glycosylation of a series of silylated pyrimidine and purine bases.7 Although 16 is not an anomeric sulfoxide, its reaction with cytosine derivative 17 is conceptually related.8... 

Table 12 Mannich-type reaction with silyl enol ethers derived from ketones...

Table 13 Mannich-type reaction with silyl ketene acetals derived from esters or thioesters...

Treatment of 106 with silylated enediols 105 in the presence of TMSOTf gives the corresponding annulated bicyclic diols 107 (equation 82)151. A similar reaction with cyclobutenediol derivative 108 followed by oxidative cleavage of thus formed diol 109 yields a seven-membered ring product (equation 83). 

Sodium cuprate yielded less reduction product and less thiophilic addition product than lithium cuprate at both —50 and 0 °C. In the case of silyl thiones chiral at silicon, the reactions with organolithium derivatives and Grignard reagents produce a-silylsulfides with medium to good levels of asymmetric induction and, interestingly, the asymmetry induced at the a-carbon is retained in the subsequent desilylation431 (equation 118), the process being stereoselective. 

Substitution of the acetate group at the C-3 position of the /3-sultam 105 can occur by reaction with silyl enol ethers in the presence of zinc iodide or zinc chloride. When the diazo compound is used, after desilylation with tetrabutyl-ammonium fluoride (TBAF), photochemical cyclization gives the bicyclic /3-sultam 106 as a mixture of two cis/ fra -diastereoisomers. When silyl enol ethers derived from cyclic ketones are used, the substitution product is stabilized by a retro-Michael-type reaction leading to open-chained sulfonamides 107 (Scheme 31) <1997LA1261>. 

Reactirai with LTA in benzene generates the bisacetoxy derivative (84) analogous to die reaction with silyl enol ethers. Subsequent collapse of the intermediate is however somewhat dendritic (Scheme 16) and consequently of little synthetic value.However it is clear from the nature of the alternative products that enamines possessing no protons at the a-positions could prove to be operable substrates. 

The direct fluorination with elemental fluorine at — 78 "C of trimethylsilyl enol ethers derived from diketones results in the formation of the corresponding monofluoro diketones 11 in moderate yield. The trimethylsilyl ethers from cyclic diketones undergo smooth fluorination to give the enol forms, c.g. 12, and not the keto forms.Higher yields are generally observed for the analogous reactions of silyl derivatives of esters, carboxylic acids, malonates, dimethyl amides and lactones (Table 4). ... 

In Kiyooka s approach to acetate aldols by use of a stoichiometric amount of 3f, the enantiomeric excess obtained in the reaction with silyl ketene acetals derived from a-unsubstituted acetates was much lower (ca 10-20 %) than that obtained in the reaction with l-ethoxy-2-methyl-l-(trimethylsiloxy)-l-propene (> 98 % ee). Introduction of an removable substituent, e.g., a methylthio or bromo substituent, after aldol reaction at the a-position of chiral esters, resolved this problem [43e], Asymmetric synthesis of dithiolane aldols was achieved in good yield by using the silyl ketene acetal derived from l,3-dithiolane-2-carboxylate in the 3f-promoted aldol reaction, and desulfurization of the dithiolane aldols resulted in production of the acetate aldols in high enantiomeric purity (Eq. 56). 

Carreira employed a chiral BINOL-derived Schiff base-titanium complex as a catalyst for aldol reactions with acetate-derived ketene silyl acetals (Sch. 38) [100]. The catalyst was prepared in toluene in the presence of salicylic acid, which was reported to be crucial to achieving high enantioselectivity. A similar Schiff base-titanium complex is also applicable to the carbonyl-ene type reaction with 2-methoxypropene (Sch. 39) [101]. Although conducting the reaction in toluene or ether solution provided no addition product, excellent chemical yield and enantioselectivity were attained by the use of 2-methoxypropene as a solvent. 

By contrast, reactions with silyl phosphites do not give the phosphazenes (26), for the silyl group readily migrates to nitrogen, leaving (27). The same tendency for migration of the silyl group has also been noted for intermediates derived from azides. ... 

Halogeno-derivatives.— The usefulness of t.l.c. has been adequately demonstrated for the analytical separation of bromocyclophosphazenes (NPBr2) ( = 3—16). Compounds (76 X=Cl or F Y=Cl) have been fluorinated by antimony trifluoride to give (76 X=Cl or F Y=F). The latter compounds undergo reactions with silyl-... 

One of these resins (546) was then subjected to Mannich-type reactions with silyl nucleophiles in the presence of 20-40 mol% of Sc(OTf)3. a-Amino add derivatives were thus prepared in excellent yields, after NaOMe-mediated cleavage (548) (Scheme 112). 

Reaction with silyl enol ethers. Derivatives from ketones and esters behave to- ards arenediazonium salts according to their relative nucleophilicities. a-Arylation, 9 ketones by a free radical pathway and nonradical a-amination of esters are. bserved. 

Six-membered chiral acetals, derived from aliphatic aldehydes, undergo aldol-type coupling reactions with silyl ketene acetals in the presence of TiCU with high diastereoselectivity (eq 15). This procedure, in combination with oxidative destructive elimination of the chiral auxiliary, has been applied to the preparation of (i )-(+)-Q -lipoic acid and mevinolin analogs. ... 

Paterson et al. [98] in their attempt used a similar disconnection for rhizopodin as described by Menche (fragments 144 and 149) (Scheme 2.151). However, unlike, Menche, they used silyl ketene acetal 16 in an asynunetric VMAR for the addition to ( )-iodoacrolein (142) to obtain dioxinone 143 in 94% ee. Methanolysis removed the aceto-nide, and the subsequent Narasaka reduction [99] provided the syn-diol 144 in 80% yield and a 10 1 selectivity for the desired isomer. The synthesis of segment 149 started with aldehyde 145, which was ultimately derived from Roche ester. Carbon chain extension was achieved through a chelation-controlled Mukaiyama aldol reaction with silyl ketene acetal 146, which installed the new chiral center with excellent stereocontrol (20 1 dr). For the installation of the third secondary alcohol, six-membered lactone 148 was obtained by treatment with K COj in methanol. Subsequent borane reduction provided stereospecifically the desired alcohol, which was then further transformed to the desired acid (149). 

Cinchona alkaloid-derived ammonium phenoxides as Lewis base catalysts have been appUed to asymmetric vinylogous Mukaiyama-type aldol reactions (Scheme 14.8) [30]. In the first step of this reaction, silyl compound 14 reacts with ammonium phenoxide to produce ammonium dienolate 15 with generation of trimethyl(phenoxy) silane. The latter part of this reachon mechanism is basically simQar to the reaction mechanism of ammonium fluoride-catalyzed reactions with silyl nucleophiles as shown in Scheme 14.7. This reaction system was also appUed to other asymmetric transformations [6a, 31]. 

The catalytic [2-1-2] cycloaddition reactions are an essential and important tool for the syntheses of cyclobutane derivatives. In particular, the catalytic cycloaddition reactions of silyl enol ethers, which are the most easily prepared ketone equivalents, have been an attractive method for cyclobutane syntheses. A number of catalytic methods that give high stereoselectivities and yields have been developed. Recently, several studies on the synthetic utilization of the [2-1-2] cycloaddition have been reported [43]. Further improvements are required for more practical and large scale syntheses. We look forward to further developments of the [2-1-2] cycloaddition reaction with silyl enol ethers in the near future. 

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