Trimethylsilyl triflate allylation

Trimethylsilyl triflate itself can not promote allylation reactions of aldehydes with allyltri-methylsilane. By using the more highly reactive system Me3SiB(OTf)4, the reactions proceed smoothly.326 A very small amount (0.2-1 mol.%) of Me3SiB(OTf)4 is enough for the reactions (Scheme 75). Allylation of acetals can be promoted by trimethylsilyl bis(trifluoromethanesulfo-nyl)imide (Me3SiNTf2),327 which is also a reactive catalyst for Diels Alder reactions.328... 

C-Allyl glycosides can be prepared by the reaction of glycal epoxides with allyltributyltin in the presence of tributyltin triflate as a Lewis acid,281 and aldonitrones can be allylated with trimethylsilyl triflate as a catalyst (Equations (101) and (102)).282... 

The Glaxo synthesis of zanamivir (2) started with the esterification of commercially available A-acetyl-neuraminic acid (88) with methanolic HCl to give the methyl ester as shown in Scheme 7.14 (Chandler and Weir, 1993 Chandler et ah, 1995 Patel, 1994 Weir et al., 1994). Global acetylation of all the hydroxyl groups with acetic anhydride in pyridine with catalysis by 4-(dimethylamino)pyridine (DMAP) led to the penta-acetoxy compound 89. Treatment of 89 with trimethylsilyl triflate in ethyl acetate at 52°C introduced the oxazoline as well as the 2,3-double bond to provide 86. Addition of trimethysilyl azide to the activated allylic oxazoline group led to the stereoselective introduction of azide at the C-4 position to afford 83 as in Scheme 7.13. 

Allyl amides (enamides), for example, 225, 228, and 230 cyclize to oxazolines, for example, 226, 229, and 231 when the double bond is activated by an electrophile. The double bond can also be conjugated to a ketone, or present as an allylic epoxide. Reagents commonly used to promote the cyclization include acids,iodine,selenium reagents,and trimethylsilyl triflate (Scheme 8.63). ... 

Homoallyl ethers. Trimethylsilyl triflate catalyzes a reaction between dimethyl ketals and allyltrimethylsilane to form homoallyl ethers. Allylation is not possible with the parent ketones. 

Some of the most useful 2,3-unsaturated C-glycosyl derivatives are the allyl compounds such as 92, made by use of allyltrimethylsilane, and a notable feature of this compound is that it can be produced directly from tri-O-acetyl-D-glucal with DDQ as promoter.111 A further surprising feature of this C-allylation procedure, however, is its applicability to glycals that are not O-substituted. Reactions are carried out in dichloromethane-acetonitrile at low temperatures with trimethylsilyl triflate as catalyst, and almost quantitative yields of 2,3-unsaturated C-allyl glycosyl compounds are recorded, with the a anomers being formed almost exclusively.112... 

Dialkylzincs undergo formal substitution with 4-acetoxy-6-alkyl-l,3-dioxanes in the presence of trimethylsilyl triflate (TMSOTf) with excellent diastereoselectivity (Equations (61) and (62)).123,123a 123c The addition of TMSOTf triggers also the allylic substitution of glycal derivatives, providing the substitution product with excellent regio- and diastereoselectivity (Equation (63)). 

C-AUylated glycopyranosides a-Glycopyranosides or a-glycopyranosyl chlorides arc converted stereoselectively into oc-C-allylated glycopyranosides on reaction with al-lylsilanes catalyzed by trimethylsilyl triflate. lodotrimethylsilane is less effective as the catalyst. 

Use of trimethylsilyl triflate to bring about Piunmeier rearrangement requires the presence of a base such as a tertiary amine (vide supra equations 15 and 26). In some instances, involving attempts to alkylate Pummerer intermediates with silyl enol ethers under such conditions, the base has been found to compete as a nucleophile. In the absence of the silyl enol ether, amine addition can be very efficient. For example, treatment of methallyl phenyl sulfoxide with diisopropylethylamine and trimethylsilyl inflate in dichloromethane (equation 29) at 0 C yields the ammonium triflate indicated in 91% yield. Other tertiary amines which undergo this reaction include niethylamine and Af,Af-diethyltrimethylsiI-amine. In the latter case with allyl phenyl sulfoxide as the substrate and a mildly acidic wotk-up, the Mannich derivative shown in equation (30) can be obtained in 90% yield. ... 

A definite improvement in the synthesis of A -methoxy aziridines was achieved by substituting boron trifluoride with trimethylsilyl triflate and diethyl ether with dichloromethane"9. In this way, the A -methoxy aziridines were obtained in good yields from a variety of linear and cyclic alkenes, e.g., 6-8. For comparison, the aziridine 8 was obtained in 50% yield by using boron trifluoride- diethyl ether complex in dichloromethane. Complex product mixtures were obtained with allyl and crotyl alcohols and with cyclohexenone. Further transformation of the A -methoxy aziridines into the N-H aziridines was possible using sodium/ ammonia reduction, e.g., 9. 

Conjugate addition to vinylthionium ions is observed in the reaction of allylic sulfoxide (120) with enol silyl ethers in the presence of trimethylsilyl triflate and diisopropylethylamine (Scheme 27). However, in certain cases moderate yields were obtained. This has been traced to a competing reaction of the intermediate (121) with the tertiary amine base to give the quaternary ammonium salt (122). 

Scheme SI presents an entirely different mode of catalyzed [4 2] cycloadditions. Thus trimethylsilyl triflate or triflic acid apparently transform vinyl orthoesters and acrolein acetals to powerful transient allyl cation dienophiles (214) and (219), respectively. The ionic Diels-Alder reactions (213) - (216) and (218) - (220) proceed at low reaction temperatures in a remarkably regio- and em/o-selective man-...

A-Glycosylimidazoles (related to nucleosides) are of interest in the preparation of novel chemotherapeutic agents, hence selective A -glycosylation techniques are of interest. The palladium-catalyzed addition of vinyl epoxides and allyl acetates to imidazoles provides one such route to imidazole nucleoside analogues <91JCS(Pi)2603, 9UOC4990>. The silyl-Hilbert-Johnson method is another in which the imidazole is silylated, then treated with a suitable peracetylated carbohydrate derivative in the presence of trimethylsilyl triflate catalyst. With 4-carbamoylimidazolium-5-olate, for example, the major product is the l-glycosyl-5-carbamoyl isomer with only low yields of the... 

Ring-opening of epoxides by P-elimination, on reaction with strong bases, such as lithium amides, or combinations of trimethylsilyl triflate with diazabicycloundecane, ° is a useful synthetic method to prepare allylic alcohols, particularly as it can be carried out enantioselectively. ... 

The conjugated thionium ylids are prepared by the Pummerer reaction of an allyl sulphoxide, with trimethylsilyl triflate in the presence of ethyl diisopropylamine, and give products of ketone allylation [equation (52)... 

The cross-coupling of o-(trimethylsilyl)phenyl triflate, allyl chloride, and... 

The synthesis of lepimectin (Scheme 29.6.2) is described in the following, as it is published in the patent literature [42-44]. However, it may be assumed that this sequence will be modified in the actual industrial preparation. To introduce the required oxygen functionality at Cl3, milbemycin A3/A4 is first protected as 5-0-trimethylsilyl ether. Reaction with 3-chloroperbenzoic acid results in the ep-oxidation of the double bond between C14 and CIS. The epoxide is rearranged by treatment with a mild Lewis acid (trimethylsilyl triflate), and the product is deprotected. To suitably protect the sensitive allylic C5 hydroxy group, it is oxidized to the ketone. The Cl3 ester substituent is introduced by an acid-mediated... 

Allyl silanes are rather like silyl enol ethers they react with electrophiles, provided they are activated, for example by a Lewis acid. Titanium tetrachloride is widely used but other successful Lewis acids include boron trifluoride, aluminium chloride, and trimethylsilyl triflate. Electrophiles include acylium ions produced from acid chlorides, carbocations from tertiary halides or secondary benzylic halides, activated enones, and epoxides all in the presence of Lewis acid. In each case the new bond is highlighted in black. 

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