TBDMS triflate

Substituents can be introduced even at the lateral 4-position (1993JCS(P1)625). In the example shown in Scheme 122, the reactive 5-position is first protected by silylation effected by abstraction of the proton at C5 using a strong non-nucleophilic base like LiTMP, followed by treatment with TMS chloride. With the 5-position thus protected subsequent O-silylation of 431 to give 432 activates the lateral proton at the 4-position, which is removed by a second equivalent of base. The lateral anion 433 is then quenched with an electrophile like ferf-butyldimethylsilyl (TBDMS) triflate that produces 434. The entire sequence 430 -> 434 can be preformed in one pot. 

Harman and coworkers have explored the reactivity of -osmium complexes of pyrroles. These complexes can react as nonaromatic species in which the Os has localized two of the Ji-electrons. For example, the complex of 1-methylpyrrole gives a conjugate addition product with methyl vinyl ketone in the presence of TBDMS triflate <93JOC4788>. Decomplexation by reaction with a base gives a 3-substituted pyrrole (Scheme 131). 

In the absence of TBDMS-triflate, a [3 + 2] cycloaddition occurs. This is attributed to reaction through a minor isomer which is in dynamic equilibrium with the major complex (Scheme 132). 

TBDMSCl is very effective in the more convenient solvent acetonitrile and under our conditions it is superior to TBDMS triflate for silylating sterically hindered phenols. Minor disadvantages of lb are that it cannot be used for alcohol protection with TMSCl (because of an interesting side reaction that is under current investigation) or for the silylation of tertiary alcohols with TBDPSCl. 

Two other trialkylsilyl trifluoromethanesulphonates, the TBDMS and tri-isopropylsilyl (TIPS) compounds, have been prepared and used in silylation reactions catalysed by 2,6-lutidine " TBDMS triflate allows formation of TBDMS ethers from tertiary and unreactive secondary alcohols, and TIPS triflate reacts effectively with primary and secondary alcohols. Use of the perfluorinated resin sulphonic acid trimethylsilyl ester Nafion-TMS , an immobilized TMS triflate, as a silylating agent for alcohols cf. 5,167) is discussed in a publication on applications of TMS triflate in synthesis. ... 

Preparative Method to 24 g (0.16 mol) of l-butyldimethyl-chlorosilane at 23 °C under argon is added 14 mL (0.16 mol) of trrfluoromethanesulfonic acid dropwise. The solution is heated at 60 °C for 10 h, at which time no further hydrogen chloride evolves (removed through a bubbler). The resulting product is distilled under reduced pressure 34 g (80% yield) of TBDMS triflate bp 60 °C77 mmHg. 

Silylation of Alcohols. Primary, secondary, and tertiary alcohols are silylated by reaction with TBDMS triflate in excellent yields. For instance, treatment of r-butanol with 1.5 equiv of TBDMS triflate and 2 equiv of 2,6-lutidine in CH2CI2 at 25 °C for 10 min gives a 90% yield of (r-butoxy)-r-butyldimethylsilane. The following alcohols are similarly silylated in excellent yields (70-90%) 2-phenyl-2-propanol, ewufo-norbomeol, c/s-2,2,4,4-tetramethylcyclobutane-l,3-diol, and 9-O-methylmaytansinol (converted to the 3-TBDMS derivative) (eq I). ... 

Formation of Enol Silyl Ethers. Various sterically hindered ketones have been converted into enol silyl ethers by treatment with 1-2 equiv of TBDMS triflate and 1.5 equiv of tri-ethylamine in CH2CI2 or 1,2-dichloroethane at rt. A representative example is depicted in eq 2. ... 

Reactions of chiral -keto sulfoxides with 1.1 equiv of lithium diisopropylamide in THF at —78°C followed by 1.2 equiv of TBDMS triflate at —78°C produce the corresponding (Z)-enol silyl ethers (eq 3). 

Lactones have also been transformed into silyl ketene acetals upon treatment with TBDMS triflate and triethylamine in CH2CI2 (eqs 4 and 5). In the case of 8a-vinyl-2-oxooctahydro-2W-l,4-benzoxazine, the resulting silyl ketene acetal undergoes Claisen rearrangement to provide the octahydroquinoline (eq 6). ... 

Phosphoniosilylation. Cyclic enones treated with TBDMS triflate and triphenylphosphine in THF at it provide the corresponding l-(3-f-butyldimethylsilyloxy-2-cycloalkenyl)triphenyl-phosphonium triflates (eq 8) which, upon lithiation with n-butyllithium followed by Wittig reaction with aldehydes, afford various conjuated dienes. ... 

Sily lation of Chromones. The preparation of 4-f-butyldime-thylsilyloxy-1-henzopyrylium triflate is carried out by heating chromone and TBDMS triflate at 80 °C for 1 h (without solvent) under nitrogen (eq 9). The silylated chromones undergo addition reaction with enol silyl ethers and 2,6-lutidine, and [4 + 21-type cycloaddition reactions with a, 8-unsaturated ketones in the presence of TBDMS triflate and 2,6-lutidine. An example of the cycloaddition reaction is shown in eq 10. ... 

Activation of Pyridine. Al-(f-Butyldimethylsilyl)pyridinium triflate, prepared from pyridine and TBDMS triflate in CH2CI2 at rt, undergoes addition reactions with alkyl and aryl Grignard reagents to give 4-substituted pyridines after oxidation with oxygen (eq 12). Only about 1% of the 2-substituted pyridines were formed in the cases studied. 

An intramolecular silylative aldol reaction has been effectively employed as a key step in the synthesis of a variety of carbasugars (eq 19). The TBDMS triflate plays a dual role in this chemistry, forming an enol silane and activating the aldehyde toward nucleophilic attack. 

Carbonyl Activation. The high oxaphilicity and Lewis acidity of TBDMS triflate activates carbonyl compounds toward nucleophilic attack. Examples of heteroatom- and carhon-hased nucleophiles have been reported. 

TBDMS triflate has been used in place of the more commonly employed TMS triflate as a catalyst in the Noyori protocol for the formation of cyclic acetals from ketones and l,2-his(trimethyl-siloxy)ethane (eq 16). ... 

The intermolecular addition of 5-valerolactam to 2,3-0-isopro-pylidene-D-glyceraldehyde is promoted hy a combination of 3 equiv each of TBDMS triflate and i-PrNEt2 (eq 17). Addition of nucleohases such as th3nnine, uracil, and 6-chloropurine is also effective under these conditions, with a similar preference for the awh -diastereomer. ... 

O-Acyl mandelamides undergo highly stereoselective intramolecular cyclization reactions in the presence of TBDMS triflate to give stable 2-silyloxy-l,3-oxazolidin-4-ones (eq 18). ... 

TBDMS triflate-activated carbonyl compounds have also been trapped intramolecularly with carbon-carbon double bonds, such as in the intramolecular Friedel-Crafts alkylation of a furan (eq 20).i ... 

A highly stereoselective intramolecular Prins double cycUza-tion catalyzed by TBDMS triflate has been reported (eq 21). The more bulky TBDMS triflate was used in preference to TES triflate to discourage competing protection of the tertiary alcohol. ... 

Conjugate Addition. TBDMS triflate has been used to promote the conjugate addition of carbon- and heteroatom-based nucleophiles to a range of a./S-unsaturated carbonyl compounds, in both stoichiometric and catalytic quantities. In some cases, the silyl enol ether is isolated, in other cases, it is implied as an intermediate but hydrolyzed either in situ or by addition of an acid or a reagent known to cleave a carbon-silicon bond e.g., TBAF. Examples of carbon-based nucleophiles are shown in eqs 22-26. 

TBDMS triflate promotes the addition of organoaluminates, generated in situ from the corresponding organolithium compound and trimethylaluminum, to Q ,/3-unsaturated carbonyl compounds (eq 22). The greater hydrolytic stability of TBDMS enol ethers compared with TMS enol ethers made TBDMS triflate preferable to TMS triflate in this chemistry, although additions to -disubstituted Q ,/3-unsaturated ketones and Q ,/3-unsaturated esters could not be achieved. 

The addition of a stoichiometric amount of TBDMS triflate resulted in the best yields and ee values in the asymmetric copper-catalyzed conjugate addition of trimethylaluminum to a cyclohexa-2,5-dienone (eq 23). ... 

The first step in a one-pot formation of a phenanthrene ring system from an enantiomericaUy pure rhenium-bound naphthalene is a TBDMS triflate-promoted Michael addition to 3-penten-2-one (eq 26). Electron-rich rhenium-bound naphthalenes also undergo TBDMS triflate-promoted conjugate addition reactions to less-activated Michael acceptors such as methyl acrylate, leading to the formal Diels-Alder cycloaddition product of naphthalene with this dienophile. ... 

The addition of heteroatom nucleophiles to Q , -unsaturated carbonyl compounds has also been promoted using TBDMS triflate. An intermolecular aza-double Michael reaction has been developed as a route to functionalized piperidin-2-ones (eq 27). Due to its relative ease of handling, TBDMS triflate was generally preferred to TMSI-HMDS as an additive in such reactions. 

TBDMS triflate promotes the conjugate addition of formaldehyde hydrazones to a,)3-unsaturated ketones and lactones (eq 24). Another bulky silylating agent, dimethyl(l,2,2-tri-methylpropyl)silyl (TDS) triflate, has also been used to the same effect with enones. ... 

TBDMS triflate was the most selective and efficient catalyst for the addition of f-butyldimethylsilyl ketene acetal to iV-tosyl-2-pyridone (eq 25). ... 

Acetal Activation. Activated carbonyl derivatives are also obtained by treatment of acetals with TBDMS triflate. In the case of oxygen nucleophiles, this results in the formation of a new acetal... 

Addition of carbon-based nucleophiles to acetals activated with TBDMS triflate has been reported. In a Mukaiyama aldolization-type reaction, oxygen-, sulfur-, and nitrogen-based heterocyclic silyloxydienes add to chiral electrophilic species derived from the same building blocks (eq 32). All nine possible combinations of nucleophile and electrophile have been achieved. ... 

Oxonium species derived from the combination of TBDMS triflate and acetals have been used as electrophiles in carbon-carbon bond forming reactions with r-basic transition metal complexes of aromatic rings, such as the rhenium-bound naphthalene in eq 26. ... 

Epoxide Opening. Epoxides undergo stereospecific opening reactions when treated with a combination of trimethylaluminum, EtsN, and TBDMS triflate in CH2CI2 at —50 °C to give the corresponding alkylation-silylation products in excellent yield (eq 34). TMS triflate and TES triflate are equally effective and have been used in combination with other trialkylaluminum reagents. ... 

Activation of C=N Double Bonds. TBDMS triflate has been used to promote additions to, and for the isomerization of, a number of systems containing carbon-nitrogen double bonds. TBDMS triflate is the optimal silyl triflate to promote the Mukaiyama-type vinylogous imino-aldol (Mannich-type) addition of 2-[(f-butyldimethylsilyl)oxy]furan to the IV-benzyl imine derived from (25)-2,3-0-isopropylideneglyceraldehyde (eq 36). ... 

---