Application of 2-Substituted Benzyl Groups in Stereoselective Glycosylation

Abstract

The use of 2-O-(2-nitrobenzyl) and 2-O-(2-cyanobenzyl) groups controls stereoselective formation of 1,2-trans-glycosidic linkages via the arming participation effect. The observed stereoselectivity likely arises from the intramolecular formation of cyclic intermediate between the electron-rich substituent and the donor oxacarbenium ion providing the expected facial selectivity for attack of the glycoside acceptor. The stereodirecting effect of the 2-nitro- and 2-cyanobenzyl groups attached at the remote position (C-3, C-4, and C-6) of the donor molecule have also been investigated. To prove the postulated mechanism based on the participation effect of 2-substituted benzyl groups in the glycosylation stereoselectivity we used DFT theoretical calculation methodology.

Bimodal Glycosyl Donors Protected by 2-O-(ortho-Tosylamido)benzyl Group

“…Aimed at achieving stereocontrolled glycosylation, nonclassical NGP strategies involving C2 chiral auxiliaries (Figure , 2 ) or the 2- O- picolyl group ( 3 ) have been developed. , More recently, the use of 2- O - ortho -substituted benzyl groups such as o -nitrobenzyl ( 4 ) and o -cyanobenzyl ( 5 ) have shown to be effective for the formation of 1,2- trans -glycosides (Figure , donor 4 and donor 5 ).…”

Mechanisms of Stereodirecting Participation and Ester Migration from Near and Far in Glycosylation and Related Reactions

“…Indeed, stereodirecting participation by halides, ethers, thioethers, nitrogen heterocycles, and an array of o-functionalized benzyl ethers, through cyclic ions of varying size, has been invoked on many occasions in the literature of glycosidic bond formation, with important work by the Boons, 203,204 Fairbanks, [205][206][207][208] Demchenko, 209,210 and Turnbull [211][212][213][214] laboratories, among many others. [215][216][217][218][219] As the focus of this review is on the mechanisms of stereodirecting participation by esters, and as a review has recently appeared on participation by ether type groups, 220 this extensive area is not covered here other than to note the parallels with participation by esters. Thus, important issues involve the possible involvement of fused and bridging ions versus that of glycosyl oxocarbenium ions and/or reactive intermediates such as glycosyl triflates in the transition state for glycosidic bond formation, with evidence presented both for, and against, dependent on the system and conditions under study.…”

“…The advancement of participation by a proximal or distal functionality as a rationale for stereocontrol is by no means limited to esters. Indeed, stereodirecting participation by halides, ethers, thioethers, nitrogen heterocycles, and an array of o -functionalized benzyl ethers, through cyclic ions of varying size, has been invoked on many occasions in the literature of glycosidic bond formation, with important work by the Boons, , Fairbanks, − Demchenko, , and Turnbull − laboratories, among many others. − As the focus of this review is on the mechanisms of stereodirecting participation by esters, and as a review has recently appeared on participation by ether type groups, this extensive area is not covered here other than to note the parallels with participation by esters. Thus, important issues involve the possible involvement of fused and bridging ions versus that of glycosyl oxocarbenium ions or reactive intermediates such as glycosyl triflates in the transition state for glycosidic bond formation, with evidence presented both for, and against, dependent on the system and conditions under study. ,,− This delicate balance between stereodirecting participation and alternative mechanisms is a prominent feature of the involvement of esters in glycosylation and apparent from the comparison of a recent study on 1,2- trans -glycosylation directed by the presence of 2- O -alkoxymethyl methyl groups, and one of the many instances of intramolecular aglycone delivery, a common strategy for 1,2- cis glycoside formation (Scheme ).…”

Absence of Stereodirecting Participation by 2-O-Alkoxycarbonylmethyl Ethers in 4,6-O-Benzylidene-Directed Mannosylation

“…13 With certain notable exceptions for which cyclic intermediates have been demonstrated spectroscopically or crystallographically, 14–21 the evidence for such effects typically is limited to often modest changes in anomeric selectivity and comparisons with selectivities observed in the presence of non-participating groups. 13,22–31 Alternative explanations are always available for such examples, most notably protecting group-induced changes in: i) conformation; 32–34 ii) through space stabilization of oxocarbenium ions; 35–41 iii) in the degree of association of the leaving group with the anomeric carbon; 42–43 iv) and the extent of pre-association of the donor and acceptor through hydrogen bonding. 44–45 By means of isotopic labelling experiments Wilen demonstrated in simple model systems that participation by esters through six- and even seven-membered ring intermediates is possible albeit significantly retarded with respect to neighboring group participation through five-membered dioxalenium ions.…”