Trimethylsilyl Trifluoromethanesulfonate is generally used following reactions:1. Silylation. TMSOTf is widely used in the conversion of carbonyl compounds to their enol ethers. The conversion is some
109 faster with TMSOTf/triethylamine than with chlorotrimethylsilane.
Dicarbonyl compounds are converted to the corresponding bisenol ethers; this method is an improvement over the previous twostep method.In general, TMSOTf has a tendency toC-silylation which is seen
most clearly in the reaction of esters, whereC-silylation dominates over O-silylation.
2.Carbonyl Activation. 1,3-Dioxolanation of conjugated enals
is facilitated by TMSOTf in the presence of 1,2-bis(trimethylsilyloxy)ethane. In particular, highly selective protection of sterically
differentiated ketones is possible (eq 10).TMSOTf mediates a stereoselective aldol-type condensation
of silyl enol ethers and acetals (or orthoesters). The nonbasic
reaction conditions are extremely mild. The use of TMSOTf in aldol reactions of silyl enol ethers and
ketene acetals with aldehydes is ubiquitous.Stereoselective cyclization of α,β-unsaturated enamide esters is
induced by TMSOTf and has been used as a route to quinolizidines
and indolizidines
4.The often difficult conjugate addition of alkynyl organometallic
reagents to enones is greatly facilitated by TMSOTf. In particular,
alkynyl zinc reagents (normally unreactive with α,β-unsaturated
carbonyl compounds) add in good yield.The formation of nitrones by reaction of aldehydes and ketones
with N-methyl-N,O-bis(trimethylsilyl)hydroxylamine is accelerated when TMSOTf is used as a catalyst; the acceleration is particularly pronounced when the carbonyl group is under a strong electronic influence.5. Methyl glucopyranosides and glycopyranosyl
chlorides undergo allylation with allylsilanes under TMSOTf
catalysis to give predominantly α-allylated carbohydrate analogs.Glycosidation is a reaction of massive importance and widespread employment. TMSOTf activates many selective glycosidation reactions.
5.O-Silylation. The formation of TMS ethers can be achieved by
reacting the requisite alcohol with TMSOTf and an amine (triethylamine, pyridine, or 2,6-lutidine) in dichloromethane;C-Silylation. Depending on the reaction conditions, secondary amides can be either C-silylated or N-silylated;N-Silylation. The N-bis-silylation of α-amino acids with
TMSOTf is only effective for glycine; for other α-amino acids N-mono-silylation prevails because the larger size of the
carbon chain at the α-position hinders bis-silylation;C,O-Bis-silylation. Bis-silylation ofα,β-unsaturated carbonyl
compounds can be achieved by palladium-TMSOTf-catalyzed
addition of disilanes to enones, enals, or aromatic aldehydes via an
η3-silyloxyallylpalladium intermediate;Carbonyl Activation. TMSOTf frequently acts as a Lewis
acid and it is able to activate several functional groups (the carbonyl group, the acetal unit, the nitrone moiety,…) thus facilitating
different kinds of reactions;Acetal Activation. TMSOTf acts as a catalyst for the addition of several nucleophiles (allylsilanes, allylstannanes, silyl enol
ethers, trimethylsilyl cyanide) towardN,O-acetals;Nitrone Activation. The nucleophilic addition to aldonitrones
depends on the nature of the metal involved and the presence/absence of an activator;Epoxide Ring Opening. One-pot alkylation-O-silylation reactions of epoxides take place in excellent yields;Cleavage of Protecting Groups. THP ethers of primary, secondary, and phenolic alcohols can be conveniently deprotected at room temperature; Hypervalent Iodine Chemistry. The formation of hypervalent iodine complexes is often promoted by TMSOTf.
