Silylation configuration

Epimerization at C(5) has not been observed under the conditions discussed for the preparation of C(6) epimers (see Section 5.11.3.8.4). It is possible to prepare 5 -epipenicillins, however, as shown in Scheme 28. Note particularly the successful removal of the phthaloyl group (step iii) in this sequence, a procedure which leads to /3-lactam cleavage when C(5) is the R, or natural, configuration. Silylation of (35) followed by DBN treatment afforded (36), which corresponds to epimerization at C(3), and (37), which corresponds to epimerization at C(3) and C(6). No product corresponding to only C(6) epimerization was observed (76JOC2561). 

In the presence of catalytic amounts of Pd(0), silicon-substituted vinyloxiranes can rearrange into the corresponding ot-silyl- 3,y-unsaturated aldehydes (Scheme 9.34) [151]. Treatment of 80 with Pd(OAc)2 and P(OPh)3 results in the formation of 7t-allylpalladium complex 81. Bond rotation to give 82, followed by migration of the silyl moiety, affords aldehyde 83, which is trapped in situ to provide the Felkin-Anh product 84. The reaction proceeds with retention of configuration and the ee of the starting material is retained in the product. The size of the silicon substituents is critical for the outcome of the reaction, as is the choice of ligands on palladium. 

On the other hand, the fluorine-induced addition of the diastereomeric silyl-subsliluted sulfides 36 A and 36B to benzaldehyde proceeds without loss of stereochemical information and with retention of configuration32. Since, however, the anionic reagent 35A/35B is known to be configurationally labile, the observed retention of configuration in the fluorine-induced desi-lylative hydroxy alkylation lends experimental evidence to the notion that these reactions proceed via hypervalent silicon species rather than anionic reagents. 

Symmetric allylsilanes and unsymmetric allylsilanes, in which the silyl substituent is at the less substituted end of the allyl fragment, are available from allyl halides and trimethylsilylmetal reagents13. 2-Chloro-l-cyclohexenes react with inversion of configuration and a 1,3-shift, with better results in the presence of coppcr(l) iodide14. 

Diisopropylamino(dimethyl)silyl]-2-propenyl]lithium adds to aromatic and x-branched aldehydes in the presence of anhydrous zinc chloride with essentially complete anti stereoselectiv-ity3s. as expected from the chair-like pericyclic transition state formed by the ( -intermediate. The addition products are not isolated, but after O-silylation, oxidative desilylation with retention of configuration forms the rmft-diols. 

Diastereoselection is also observed in the catalyzed [titanium tetrachloride (TiCI4)13, trimethyl-silyltrifluoromethanesulfonate (TMSTf)l4, zinc iodide (Znl2)15] reactions of silyl ketene acetal 1 with imines 2, The ami configuration of the product 3 dominates. 

An interesting example from carbohydrate chemistry is the boron trifluoride-diethyl ether complex catalyzed nucleophilic addition of silyl enol ethers to chiral imines (from n-glyceralde-hyde or D-serinal)22. This reaction yields unsaturated y-butyrolactones with predominantly the D-arabino configuration (and almost complete Cram-type erythro selectivity). 

This excellent method of oxidative cleavage (/) of carbon-silicon bonds requires that the silane carry an electronegative substituent (2), such as alkoxy or fluoro. Either hydrogen peroxide or mcpba may be used as oxidant, and the alcohol is produced with retention of configuration (3). Fluoride ion is normally a mandatory additive in what is believed to be a fluoride ion-assisted rearrangement of a silyl peroxide, as shown below ... 

Diene 265, substituted by a bulky silyl ether to prevent cycloaddition before the metathesis process, produced in the presence of catalyst C the undesired furanophane 266 with a (Z) double bond as the sole reaction product in high yield. The same compound was obtained with Schrock s molybdenum catalyst B, while first-generation catalyst A led even under very high dilution only to an isomeric mixture of dimerized products. The (Z)-configured furanophane 266 after desilylation did not, in accordance with earlier observations, produce any TADA product. On the other hand, dienone 267 furnished the desired macrocycle (E)-268, though as minor component in a 2 1 isomeric mixture with (Z)-268. Alcohol 269 derived from E-268 then underwent the projected TADA reaction selectively to produce cycloadduct 270 (70% conversion) in a reversible process after 3 days. The final Lewis acid-mediated conversion to 272 however did not occur, delivering anhydrochatancin 271 instead. 

Vinylic lithium reagents (26) react with silyl peroxides to give high yields of silyl enol ethers with retention of configuration. Since the preparation of 26 from vinylic halides (12-37) also proceeds with retention, the overall procedure is a... 

Figure 4.85 Flow configuration for the aldol reaction of silyl enol ethers in a mixing-tee chip micro reactor [15],...

The most fundamental issues of the structures of heavier group 14 element-centered anionic derivatives R3EM (R = alkyl, aryl, silyl E = Si, Ge, Sn, Pb M = alkali or alkaline earth metals) turned out to be the questions of their aggregation states (monomeric, dimeric, or oligomeric), nature of the E-M bond (covalent or ionic), and configuration of the anionic centers E (tetrahedral, pyramidal, or planar). The most important experimental techniques that are widely used to clarify these questions are NMR spectroscopy and X-ray diffraction analysis. 

Scheme 2.2 illustrates several examples of the Mukaiyama aldol reaction. Entries 1 to 3 are cases of addition reactions with silyl enol ethers as the nucleophile and TiCl4 as the Lewis acid. Entry 2 demonstrates steric approach control with respect to the silyl enol ether, but in this case the relative configuration of the hydroxyl group was not assigned. Entry 4 shows a fully substituted silyl enol ether. The favored product places the larger C(2) substituent syn to the hydroxy group. Entry 5 uses a silyl ketene thioacetal. This reaction proceeds through an open TS and favors the anti product. 

Initial stereochemical studies suggested that the Mukaiyama-Michael reaction proceeds through an open TS, since there was a tendency to favor anti diastereoselec-tivity, regardless of the silyl enol ether configuration.312... 

Silyl acetals of thiol esters have also been studied. With TiCl4 as the Lewis acid, there is correspondence between the configuration of the silyl thioketene acetal and the adduct stereochemistry.314 L-Isomers show high anti selectivity, whereas Z-isomers are less selective. 

Unsaturated acyl derivatives of oxazolidinones can be used as acceptors, and these reactions are enantioselective in the presence of chiral to-oxazoline catalysts.321 Silyl ketene acetals of thiol esters are good reactants and the stereochemistry depends on the ketene acetal configuration. The Z-isomer gives higher diastereoselectivity than the Zf-isomer. 

The silyl ketene acetal rearrangement can also be carried out by reaction of the ester with a silyl triflate and tertiary amine, without formation of the ester enolate. Optimum results are obtained with bulky silyl triflates and amines, e.g., f-butyldimethylsilyl triflate and (V-methyl-Af, /V-dicyclohcxylaminc. Under these conditions the reaction is stereoselective for the Z-silyl ketene acetal and the stereochemistry of the allylic double bond determines the syn or anti configuration of the product.243... 

The stereoselectivity of silyl ketene acetal Claisen rearrangements can also be controlled by specific intramolecular interactions.246 The enolates of a-alkoxy esters adopt the Z-configuration because of chelation by the alkoxy substituent. 

In this context, it is interesting to note that the first synthesis of 2, 3 -0,0-cyclic phosphorothioate 22a was reported by Eckstein in 1968 [25], He also isolated pure Rp diastereomer by fractional crystallization of the triethylammonium salts [26] and used it as reference to determine the absolute configurations of the other phosphorothioate analogues [27], 2, 3 -0,0-Cyclic H-phosphonate 20a was used as a key substrate for the synthesis of uridine 2, 3 -0,0-cyclic boranophosphate 27. Silylation of H-phosphate 20a gave the phosphite triester 25 (two diastereomers). Its boronation, with simultaneous removal of the trimethylsilyl group, was achieved by its reaction with borane-A.A-diisopropylethylamine complex (DIPEA-BH3). 

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