Selective silylation

TBDMSCl, DMAP, Et3N, DMF, 25°, 12 h. " These conditions were used to silylate selectively a primaiy over a secondary alcohol. Besides DMAP, other catalysts such as 1,1,3,3-tetramethylguanidine, 1,8-diazabicy-clo[5.4.0]undec-7-ene(83-99%), l,5-diazabicyclo[4.3.0]non-5-ene, and ethyldiisopropylamine have been used. ... 

Methyl- and 2-phenyl-triazole 1-oxide (207) are silylated selectively at the 5-position with trimethylsilyl triflate to afford stable 5-trimethylsilyl derivatives (208) (Scheme 35). If the 5-position is blocked with a substituent, the 4-position is silylated. Thus, 5-chlorotriazole 1-oxide is converted to 5-chloro-4-trimethylsilyl-l,2,3-triazole 1-oxide in the presence of lithium tetramethylpiperidine. 

Hindered secondary and tertiary alcohols can be silylated with TBSOTf (bp 60 C/0.9 kPa) using 2,6-lutidine as the base as illustrated by the silylation of the secondary alcohol 61.1 in a synthesis of the diterpene Zoapatanol [Scheme 4,61] and the tertiary alcohol 62.1 [Scheme 4.62] originating in a synthesis of Erythronolide A. The reactions can be run at molar concentrations using dichloromethane as a co-solvent and the recommended ratio of reactants is alcohol TBSOTf 2,6-lutidine = 1 1.5 2. TBSOTf is both expensive and very moisture sensitive and in our experience commercial samples do not store well consequently, it may be best to prepare it fresh from the reaction of /er/-butyldi-methylsilyl chloride and triflic acid. For the silylation of p-hydroxybutyrolac-lones, which are prone to dehydration during silylation with TBSOTf under the standard conditions, 2,6-di-/m-butylpyridine has been recommended as the base. Owing to their higher acidity, phenols can be silylated selectively in the presence of alkanols [Scheme 4.63]. ... 

TIPS Protection for Oxazoles/Regioselective Trapping of C-2 Oxazole Anions. Deprotonation of oxazoles occurs selectively at the C-2 position, and reaction with either TIPS triflate or TIPS chloride gave completely opposite C-silylation or O-silylation selectivity (eq 11). The same remarkable trend was observed for the other, less hindered silyl chloride and -triflates however, the stability of those products did not allow facile isolation and characterization. The C-2 TIPS oxazole derivative was shown to be stable to strongly basic reactions that allowed further oxazole functionalization (eq 12). Removal of the TIPS group was then achieved with dilute acid. 

Trimethylsilylacetate esters may he converted to the enolate by treatment with lithium dialkylamide bases (LDA in Eq. 7.28) in THF at -78°C. These will add to ketones or aldehydes quickly at -78°C, followed by elimination of MOjSiOLi and formation of a,p-unsaturated esters in high yields, uncontaminated by p,y-unsaturated isomers [47]. This is known as the Peterson reaction [48, 49]. The requisite ethyl trimethylsilylacetate is made by the reaction of cldorotrimethylsilane, ethyl bromoacetate, and zinc [50]. Esters of longer-chain acids give mostly 0-silylation under these conditions, but diphenylmethylchlorosilane gives C-silylation selectively. These diphenyl-methylsilylated esters also give the Peterson reaction (Eq. 7.29) [51]. 

Alkyl halides and sulfonates are the most frequently used alkylating acceptor synthons. The carbonyl group is used as the classical a -synthon. O-Silylated hemithioacetals (T.H. Chan, 1976) and fomic acid orthoesters are examples for less common a -synthons. In most synthetic reactions carbon atoms with a partial positive charge (= positively polarized carbon) are involved. More reactive, "free carbocations as occurring in Friedel-Crafts type alkylations and acylations are of comparably limited synthetic value, because they tend to react non-selectively. 

Various bicyclic and polycyclic compounds are produced by intramolecular reactions] 127]. In the syntheses of the decalin systems 157 [38] and 158 [128], cis ring Junctions are selectively generated. In the formation of 158, allyhc silyl ether remains intact. A bridged bicyclo[3.3. l]nonane ring 159 was constructed... 

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

The effect of the AK = 1 selection rule, compared with AK = 0 for an transition, is to spread out the sets of P, Q, and R branches with different values of K. Each Q branch consists, as usual, of closely spaced lines, so as to appear almost line-like, and the separation between adjacent Q branches is approximately 2 A — B ). Figure 6.29 shows such an example, E — A band of the prolate symmetric rotor silyl fluoride (SiH3F) where Vg is the e rocking vibration of the SiH3 group. The Q branches dominate this fairly low resolution specttum, those with AK = - -1 and —1 being on the high and low wavenumber sides, respectively. 

Silyl Ethers. The preparation of per- O-trimethyl silyl ethers of sucrose is generally achieved by reaction with chi orotrimethyl sil ane and/or hexamethyldisila2ane in pyridine (25,26). However, this reaction is not selective and in general per-trimethyl silyl ethers are only used as derivatives for gas chromatographic studies. 

Me3SiNEt2- Trimethylsilyldiethylamine selectively silylates equatorial hydroxyl groups in quantitative yield (4-10 h, 25°). The report indicated no reaction at axial hydroxyl groups. In the prostaglandin series the order of reactivity of trimethylsilyldiethylamine is Cii > Ci5 C9 (no reaction). These trimethylsilyl ethers are readily hydrolyzed in aqueous methanol containing a trace of acetic acid. The reagent is also useful for the silylation of amino-acids. ... 

TBDPSCl, DMAP, Pyr. Selective silylation of a primary hydroxyl was achieved under these conditions. 

TBDPSCl, DMAP, triethylamine, CH2Cl2. This combination of reagents was shown to )e very selective for the silylation of a primary hydroxyl in the presence of a secondary hydroxyl. 

Titanium(IV) is a powerful but selective Lewis acid which can promote the coupling of allylsilanes with carbonyl compounds and derivatives In the presence of titanium tetrachlonde, benzalacetone reacts with allyltnmethylsilane by 1,4-addition to give 4-PHENYL-6-HEPTEN-2-ONE. Similarly, the enol silyl ether of cyclopentanone is coupled with f-pentyl chloride using titanium tetrachlonde to give 2-(tert-PENTYL)CYCLOPENTANONE, an example of a-tert-alkylation of ketones. 

Selective fluonnation in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

Systems usually fluonnated by electropositive fluorine reagents include acti-vated alkenes (enol ethers, enol acetates, silyl enol ethers, and enamines), activated aromatic systems, certain slightly activated carbon-hydrogen bonds, and selected organometallics. 

Fluoroalkyl ketones may be used as the electrophilic partners in condensation reactions with other carbonyl compounds The highly electrophilic hexafluo-roacetone has been used in selective hexafluoroisopropyhdenation reactions with enol silyl ethers and dienolsilyl ethers [f] (equation 1)... 

The Lewis acid-catalyzed addition of silyl kelene acetals occurred m high yield, and when the ketene acetal bore a substituent, the reactions occurred with modest diastereofacial selectivity [d] (equation 7) (Table 3)... 

T. D. Nelson and R. D. Crouch, Selective Deprotection of Silyl Ethers, Synthesis, 1031 (1996). 

An excellent review is available that discusses the selective cleavage of numerous silyl derivatives. ... 

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