4-Methoxybenzyl-2,2,2-trichloroacetimidate

The imidate can be prepared from the sodium alkoxide ion of benzyl alcohol and trichloroacetonitrile according to procedures based on those developed by Cramer in the late 1950s. Substituted benzyl ethers have also been prepared this way, for example using 4-methoxybenzyl trichloroacetimidate, 3,4-dimethoxybenzyl trichloroacetimidate, and 2,6-dichlorobenzyl trichloroacetimidate, and the method has also been applied for the synthesis of allyl and r-butyl ethers, as well as for 2-phenylisopropyl esters for peptide synthesis. The benzyl and 4-methoxybenzyl 2,2,2-trichloroacetimidates are available commercially. 

O-Dechloroacetylation of IV.61 by treatment with thiomea gave IV.62, which was subsequently reprotected as the hydrogenolyzable 4-methoxybenzyl ether with 4-methoxybenzyl trichloroacetimidate and triflic acid under phase transfer catalysis conditions [104]. Saponification of the benzoate and methyl esters with lithium hydroperoxide followed by methanolic sodium hydroxide and acidification then gave the acid IV.63. O-Sulfonation of IV.63 was achieved with the sulfur trioxide-tri-methylamine complex to give the disulfate IV.64 as the sodium salt. Finally, hydro-genolysis of IV.64 with Pd/C in aqueous methanol afforded the target disaccharide IV.51. 

Startg. alcohol in ether treated with p-methoxybenzyl trichloroacetimidate and a little (0.3 mol%) trifiuoromethanesulfonic acid at room temp, for 10 min - product. Y 77%. The method is mild, applicable to sterically hindered hydroxyl groups, and tolerates a wide range of both acid- (epoxide, bisspiroketal, acetonide, silyl) and base-sensitive (ester, mesyl, silyl) functions, even in 1,2- and 1,3-diol systems furthermore, there is no epimerization at the a-position of carbonyls or P-elimination of P-hydroxy compds. F.e.s. N. Nakajima et al.. Tetrahedron Letters 29,4139-42 (1988). 

The most frequently employed acid catalyst is TfOH Trifluo-romethanesulfonic Acid, or triflic acid), but others that have been used include BF3 0Et2, TMSOTf, /7-TsOH, and TFA. Camphorsulfonic acid, pyridinium p-toluenesulfonate, and trityl perchlorate have also been investigated in conjunction with the more reactive 4-methoxybenzyl trichloroacetimidate. ... 

By combining the CM and cuprate methodologies, an advanced intermediate 37 containing the key aspects of the dolabehde family was constructed (Scheme 4.13) [24]. Hence, phosphate-mediated coupHng of (R,R)-2A with 1,1-dimethylallyl alcohol afforded the bicycHc phosphate 33 over a three-step sequence. CM of the latter with but-3-en-l-ol in the presence of [Ru]-III and subsequent hydrogenation of the exocychc olefin of 34 furnished an extended side chain bearing the C15-C19 structure of dolabehde. After benzylation of the primary alcohol in 35 with p-methoxybenzyl trichloroacetimidate, addition of a methyl cuprate, methy-lation of the phosphate acid (TMSCHN2), and removal of the phosphate ester (Red-Al) yielded advanced intermediate 37, a key synthon toward the synthesis of dolabehde C [4b]. 

A number of other catalysts have been used in conjunction with p-methoxyben-zyl trichloroacetimidate for the synthesis of p-methoxybenzyl ethers such as tri-fluoroborane etherate,358 tin(II) triflate [Scheme 4.193]359 and triphenylcarbe-nium tetrafluoroborate [Scheme 4.194].313 360 361... 

BenzybUion. The reagent is much more stable than the corresponding trichloroacetimidate. It is obtained by reaction of trifluoroacetonitrile, which is the dehydration product of trifluoroacetamide under Swem oxidation conditions, with 4-methoxybenzyl alcohol. Even tertiary alcohols form 4-methoxybenzyl ethers with this reagent. 

Procedure, The alkyl trichloroacetimidate can be prepared as follows. To a stirred suspension of sodium hydride (0.50 g, 21.0 mmol) in anhydrous diethyl ether (20 ml) add dropwise via cannula a solution of para-methoxybenzyl alcohol (29.0 g, 210 mmol) in diethyl ether (30 ml). After the solids have dissolved, cool the reaction vessel in an ice-salt bath and add trichloroacetonitrile (20.0 ml, 200 mmol) over a period of 15 min, then allow the reaction mixture to warm to room temperature. After 1 h concentrate the solution in vacuo to afford a syrup, then add pentane (20 ml) containing anhydrous methanol (0.8 ml) and stir vigorously. Filter off the precipitate and wash with pentane (2 X 20 ml) concentrate the filtrate and washings in vacuo to yield the alkyl trichloroacetimidate. 

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