Ethers Benzyl trichloroacetimidate

Dimethylthexylsilyl trifluorometh-anesulfonate, 74 using other methods Allyl chloroformate, 9 Benzyl trichloroacetimidate, 32 Bromodimethylborane, 47 Chloromethyl ethyl ether, 75 2,3-Dihydro-1,4-dioxin, 112 p-Methoxyphenol, 181 of aldehydes and ketones as acetals or dithioacetals... 

Cerium(IV) ammonium nitrate, 67 Dimethyl sulfate, 239 Other ethers Allyltrimethylsilane, 11 Benzyl trichloroacetimidate, 32 (E)-(Carboxyvinyl)trimethylammonium betaine, 67... 

Benzylation with benzyl trichloroacetimidate and a catalytic amount of triflic acid (TfOH) is a mild and efficient procedure (Scheme 2.1c).5 The acid protonates the nitrogen of the imidate moiety converting it into a very good leaving group. Nucleophilic attack by an alcohol introduces a benzyl ether. The procedure is often compatible with base- and acid-sensitive functionalities with esters, (7-isopropylidene and (7-benzylidene acetals. Benzyl trichloroacetimidate is commercially available but can easily be prepared by reaction of benzyl alcohol with trichloroacetonitrile in the presence of a mild base. 

Acid-Catalyzed Benzylation. Benzyl trichloroacetimidate, Cl3CC(=NH)OBn, reacts with hydroxyl groups under acid catalysis to give the con-esponding benzyl ethers in good yield. The method is particularly useful for the protection of base-sensitive substrates (i.e., alkoxide-sensitive), such as hydroxy esters or hydroxy lactones, as exemplified below. 

When W-aceCyl-protected sugar amines were under investigation the A -acetyl group was observed to undergo transformation to the O-benzyl imidate in competition with OH benzylation (eq 3). It appears for best yields at least 1 equiv of reagent per OH and NAc group is needed, and subsequent hydrolysis and reacetylation of the amine are necessary to obtain are the originally desired material. Similar problems were encountered with the morpholine derived lactams (eq 4), where mixed products were obtained, but with p-lactams with yV-amide protection (eq 5), t -benzylation with benzyl trichloroacetimidate proceeded smoothly. BTCA has recently been used to convert diketopiperazines into their bis-benzyl imino ethers. ... 

A solution of trichloroacetimidate 9 (2.06 g, 3 mmol) and 1,3,5-trimethoxybenzene 10 (0.50 g, 3 mmol) in dichloromethane (20 mL) was treated with 0.5 M boron trifluoride etherate in anhydrous dichloromethane (6 mL, 3 mmol) at room temperature. After 3 h, excess saturated solution of NaHC03 in water was added. The organic layer was separated, dried (Na2S04), and evaporated. The oily residue was purified on silica gel by flash chromatography (4 1 v/v, petroleum ether-ethyl acetate) gave 2,4,6-trimethoxy-l-(2,3,4,6-tetra-0-benzyl-(3-D-glucopyranosyl)benzene 11 (1.55 g, 76%) [a]J7g + 5.4° (c 1.0, chloroform). 

A solution of trichloroacetimidate 2-azido-3-0-benzyl-4,6-0-benzylidene-2-deoxy-n-glucopyranoside (3.217mmol) and l-D-l,2-0-(r.-l,7,7-trimethy][2.2.1 -bicyc]ohept-2-ylidene)-3,4-0-(l,l,3,3-tetraisopropyldisiloxanyl)-myo-inositol (4.507mmol) in 50 ml diethyl ether at —20°C was treated with 29 ml trimethylsilyl trifluromethanesulfonate, then gradually warmed over 5 hours to ambient temperature. The mixture was then quenched with 0.5 ml triethylamine and concentrated. The residue was purified by flash chromatography using a hexane/EtOAc gradient of 95 5-75 25 and the a(l-6) product isolated in 55% yield as a white solid. 

Benzyl 2,2,2-trichloroacetimidate (bp 106-114 °C/0.07 kPa) alkylates alcohols in the presence of trifluoromethanesulfomc acid.311 Esters, imides, isopropylidene and benzylidene acetals are unaffected. This method allows the formation of benzyl ethers in molecules that are base-sensitive. In the example [Scheme 4,167],312 benzylation of the P-hydroxy ester 167.1.1 under the usual basic conditions would lead to retro-aldol reactions and/or elimination. A synthesis of the cellular messenger L-a-phosphatidyl-D-myo-inositol 3,4-bisphosphate exemplifies the use of trityl cation-promoted benzylation of two adjacent hydroxyls [Scheme 4.168].313314... 

Acid-catalysed alkylation of an alcohol with O-alkyl trichloroacetimidate prepared from allyl alcohol and trichloroacetonitrile is readily accomplished Scheme 4.233]440 as previously discussed for the preparation of benzyl and tert-butyl ethers.311 However, these conditions are not compatible with many of the protecting groups employed in oligosaccharide synthesis. For such cases, two methods for 0-allylation under essentially neutral conditions have been devised. The first method takes advantage of the mild conditions and regioselectivity of stannylene alkylations (see section 4.3.3). The method is illustrated by the selective O-allylation of o-lactal, which began with stannylene formation on an 0.8 mole scale [Scheme 4.234].441... 

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