2,6-Lutidine as reagent

Alternatively, the NM2 silyl triflate 7 can be used as a very powerful silylating reagent capable of silylating even tertiary alcohols under mild reaction conditions (2,6-lutidine as base, ambient temperature, 2 h, aqueous work-up). The NM2 silyl triflate can be simply prepared by reacting neat silane NM2 3 with triflic acid 6 at 60 °C for 10 h. The triflate is a colorless liquid that can be purified by direct distillation (bp 100 - 105 °C/1 mbar) from the reaction flask in 83% yield. The transformation from chloride to triflate does not alter the exo/endo ratio according to GC/NMR. 

Triisopropylsilyl ethers are formed under essentially the same conditions as TBS ethers — i.e. primary or unhindered secondary alcohols are treated with triisopropylsilyl chloride (bp 198 °C/98.5 kPa) in dichloromethane or DMF in the presence of imidazole or DMAP [Scheme 4.85J.138 The TIPS group is too bulky to react with a tertiary alcohol and protection of hindered secondary alcohols can be very slow in which case triisopropylsilyl triflate in the presence of 2,6-lutidine is used.100 However, even with the triflate as the silylating reagent, the reaction can be slow as illustrated by the reaction in Scheme 4.86.61 Triisopropylsilyl triflate is commercially available and it can be easily prepared on a large scale from triisopropylsilane and triflic acid in 97% yield. 

Deprotonation of 7 in DMF by base (i.e., triethylamine, N-methylmorpholine, imidazole, or 2,6-lutidine) was characterized by NMR. The chemical shifts were recorded vs. acetone-dg, the shift of which was assumed to be 2.0 ppm. The dried reagent of DMF (water content is less than 0.005% ) was used as a solvent. 

In conjunction with proton sponge, the activated phosphate 256 turned out to be an effective reagent in the direct synthesis of peptides and branched amides from carboxylic acids (equation 21). In this process, diamine 1 surpassed in its efficiency for such bases as triethylamine, V,iV-dimethylaniline, 2,6-lutidine and Hiinig bases225. 

Triethylsilyl triflate. This has become a popular reagent for the preparation of TES ethers. Commonly used bases are pyridine and 2,6-lutidine. The most frequently used solvent is CH2CI2, but others such as CH3CN have also been used. 

The unambiguous regioselective synthesis of chiral polysiloxane-containing CyDs as chiral stationary phases, with the mono-octamethylene spacer in either the 02, 03, or 06 position was performed and the products applied to enantio-selective GC separations [99]. Subtle differences in the chemistry of the hydroxyl groups at the 2-, 3-, and 6-positions of CyDs can be exploited to direct an electrophilic reagent to the desired site. Selective monoalkylation at the primary side of a-CyDs involves the reaction of a-CyD with 4-methylamino-3-nitrobenzyl chloride in 2,6-lutidine. Monoalkylation at the 2-position of j8-CyD is accomplished by the reaction of yS-CyD with l -bromo-4-methylamino-3-nitroacetophenone [100]. 

The same combination of reagents (TMSOTf/2,6-lutidine) has been employed to deprotect (V-ferf-butoxycarbonyl groups from substrates in the solid phase synthesis of several peptides, without cleaving the substrates from the support as would occur in the case of using TFA with TFA-sensitive resins (such as Rink s amide resin) (eq 100). This method has great potential for the solid-phase synthesis of small molecule libraries. Such a reagent combination had been previously developed for solution phase reactions of nonpeptidic substrates. ... 

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