Acetals trimethylsilyl trifluoromethanesulfonate

Considerable efforts have been devoted to the stereoselective introduction of a /(-methyl function in intermediates for the synthesis of 1 jS-methylcarbapenems. While the trimethylsilyl trifluoromethanesulfonate catalyzed reaction of a 4-acetoxyazetidinone derivative with ketene acetals shows no selectivity, ketene thioacetals lead to stereoselective formation of the a-methyl isomer108. The zirconium enolate, however, shows high /(-methyl selectivity. 

High enantioselectivities may be reached using the kinetic controlled Michael addition of achiral tin enolates, prepared in situ, to a,/i-unsaturated carbonyl compounds catalyzed by a chiral amine. The presence of trimethylsilyl trifluoromethanesulfonate as an activator is required in these reactions236. Some typical results, using stoichiometric amounts of chiral amine and various enolates are given below. In the case of the l-(melhylthio)-l-[(trimethylsilyl)thio]ethene it is proposed that metal exchange between the tin(II) trifluoromethanesulfonate and the ketene acetal occurs prior to the 1,4-addition237,395. 

There are relatively few entries in the non-fused dioxepin area, and most of these focus on reactions of these systems. For example the triflic acid-initiated polymerisation of 1,3-dioxepane in the presence of acetic acid and hexanedicarboxylic acid has been studied and mechanistic aspects discussed <00JPS(A)1232>. Biodegradable microspheres for the controlled delivery of drugs have been made from copolymers and homopolymer blends of L-lactide and l,5-dioxepan-2-one <00PP1628>. Ring contraction of 5-methylene-l,3-dioxepanes (eg. Ill) on reaction with trimethylsilyl trifluoromethanesulfonate in the presence of base afforded the exo tetrahydropyrans, in good yields <00TL2171>. 

A diastereoselective synthesis of /3-(iV-acylamino)aldehydes was accomplished via ruthenium-catalyzed isomerization of 0-vinyl-iV,0-acetals followed by rearrangement in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) (Scheme 36).63... 

A special case is the ring-forming reaction in the lactone acetal 568,69. When 5 is treated with trimethylsilyl trifluoromethanesulfonate (trimethylsilyl triflate TMSOTf) in the presence of triethylamine at 0°C the cisjtrans mixture 6a and 6b is formed in ca. 50% yield. In this intramolecular aldol reaction the probable intermediate is the oxonium ion 7. 

The seven-membered phostone 252 was synthesized by the reaction of methyl 2,3-di-0-benzyl-4,6-0-benzyl-idene-a((3)-D-glucopyranoside 251 with triethyl phosphate and trimethylsilyl trifluoromethanesulfonate. Protecting the acetal group of 251 interacted with triethyl phosphite and opened to give 252, which can be further selectively hydrolyzed or deprotected to give 253 or 254 <2003TL8797>. 

Ethers from acetals. Reduction of acetals with trimethylsilane (or tri-ethylsilane) catalyzed by trimethylsilyl trifluoromethanesulfonate gives ethers in 75-95% isolated yield (equation I). 

R. Noyori developed a procedure that avoids migration of the double bond during acetalization of a, 3-unsaturated ketones (enones)A Treatment of the enone with the silylated diol l,2-bis[(trimethylsilyl)oxy]ethane in the presence of a catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf ) affords the acetal without double bond migration (kinetic control). The stability of the Me3Si-0-SiMe3 formed (instead of HjO) drives the reaction to completion. Modifications of Noyori s procedure in which preparation of the silylated diol is circumvented have been reported. ... 

Tsunoda, T., Suzuki, M., Noyori, R. Trialkylsilyl triflates. III. Trimethylsilyl trifluoromethanesulfonate as a catalyst of the reaction of allyltrimethylsilane and acetals. Tetrahedron Lett. 1980, 21,71-74. 

Several different methods have been employed for the preparation of diazo(trimethylsilyl)meth-ane (1). At present, the best synthetic method seems to be the diazo transfer reaction between diphenylphosphoryl azide and (trimethylsilyl)methylmagnesium chloride.However, the product often contains (chloromethyl)trimethylsilane and hexamethyldisiloxane as impurities. This method can also be employed for the synthesis of diazo(triethylsilyl)methane and diazo(di-ethylmethylsilyl)methane. The diazo transfer reaction can also be carried out with (trimethyl-silyl)methyllithium and tosyl azide. Other methods are the silylation of diazomethane with (trimethylsilyl)trifluoromethanesulfonate or chloro(trimethyl)silane and the base-induced cleavage of A-nitroso-A-[(trimethylsilyl)methyl]urea or the related carbamate or acet-amide.2° =... 

Recent improvements in the standard synthetic procedure using haloacetates have featured the use of trialkyi phosphites and activated acetates in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as activating reagent. " This reaction has proved to be of great value in constructing complex sugar phosphonates. For example, in the presence of TMSOTf, the Michaelis-Arbuzov reaction between protected ketose acetates and triethyl phosphite takes place in ( 1 FC F at room temperature to produce, after deprotection, the expected diethyl l-(methoxycarbonyl)alkyl-phosphonates in high yields. -" ... 

Zerth, H.M., Leonard, N.M., Mohan, R.S. (2003) Synthesis of homoallyl ethers via alkylation of acetals in ionic liquids catalyzed by trimethylsilyl trifluoromethanesulfonate. Org. Lett., 5,55-57. 

Polymer-bound reagents for silylation have been reported. Murata and Noyori treated Nation, a perfluorinated resin-sulfonic acid, with trimethylsilyl chloride to afford a polymer-bound trimethylsilyl ester that functions as a polymer-bound equivalent of trimethylsilyl trifluoromethanesulfonate, converting alcohols, eth-anethiol and diethylamine into the corresponding silylated compounds in high yields (Scheme 6.16) [70]. Acetic acid could also be silylated, albeit with moderate conversion. The corresponding polystyrene-bound reagent is commercially available. 

Aldol-type condensation of enol silyl ethers and acetals or orthoesters can be accontplished by the use of trimethylsilyl trifluoromethanesulfonate (TMSOTf). In these reactions, TMSOTf acts as a true catalyst and is required in 1-S ntol %. The reactions show interesting chemoselectivity in that acetals are highly reactive receptors of enol silyl ethers but the parent aldehydes and ketones do not react under these conditions (Scheme 37). Similarly, trityl perchlorate is found to be an efficient catalyst to promote the reaction between enol silyl ethers and acetals. 

Cyclizations can be initiated by an oxonium ion generated from a carbonyl, acetal or ketal precursor. When dimethylacetal is treated with trimethylsilyl trifluoromethanesulfonate in dichloromethane. 6-exo cyclization takes place forming piperidine 11 with the methyl and vinyl group stereoselectively synls. The remaining methoxy substituent gives a mixture of diastereomers. 

A bifunctional allylsilane reagent has been developed in which an initial nucleophilic attack at an acetal centre, mediated by trimethylsilyl trifluoromethanesulfonate(TMSOTf). is followed by cyclization of the allylsilane portion onto an electrophilic site, mediated by titanium(IV) chloride11. 

A gentle method for the formation of trifluoromethanesulfonate salts of some condensed triazine systems, e.g. 6, involves treatment of the free bases 5 with trimethylsilyl trifluoromethanesulfonate followed by methanol or ethyl acetate containing water,31... 

Electrophilic attack by aldehydes can also take place at positions 3 and 4 in suitably substituted thiophenes. Thus, 2,5-bis(trimethylsilyloxy)thiophene reacts with aromatic aldehydes in the presence of the Lewis acid trimethylsilyl trifluoromethanesulfonate (0.1-1.0%) to form 3,4-disubstituted thiosuccinic anhydrides (88) in quantitative yield. With aliphatic aldehydes, the yields are lower, the catalyst being ZnBry, the products so obtained have been hydrolyzed in the presence of lead acetate to form the lactones (89) in 30-40% yields. 2,5-Bis(trimethylsilyloxy)thiophene also reacts with orthoesters in the presence of trimethylsilyl triflate to form (90) <87C152,92LA615>. 

The reaction with acetals does not always need the acetal itself to be synthesized it can be made in the same flask by mixing the allylsilane, the aldehyde, the silyl ether of the alcohol, and a catalytic amount of an acid such as diphenylboryl trifluoro-methanesulfonate, trimethylsilyl trifluoromethanesulfonate, or fluorosulfuric acid. ... 

SILYLATION Bis(trimethylsilyl)urea. t-Butyldimethylchlorosilane. t-Butyldimethylsilyl trifluoromethanesulfonate. Chlorotrimethylsilane. Dimethyl(2,4,6-tri-f-butylphenoxy)chlorosilane. Ethyl trimethylsilylacctate. Ketene t-butyldimethylsilyl methyl acetal. N-Methyl-N-(/-... 

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