Enantioselective synthesis of heteroaromatic epoxyketones under phase-transfer catalysis using d-glucose- and d-mannose-based crown ethers

Sugar-based Crown Ethers in Enantioselective Syntheses

“…The synthesis of one of the key compounds (16) involves the opening of the benzylidene acetal ring of 2,3-anhydro derivative 13 that was performed with N-bromosuccinimide (NBS). The benzoyl group of the intermediate was removed by reaction with sodium methylate in methanol to provide bromo sugar 14.…”

“…The bromo function of intermediate 14 was removed by hydrogenolysis in the presence of Pd/C to give species 15. The regioselective reductive ring opening was accomplished by LiAlH 4 in THF to afford methyl 2,6-dideoxy-α-d-ribo-hexopyranoside (16).…”

“…5). The trans-epoxyketone (32) was obtained in general in a diastereomeric excess (de) of >98 %, with a configuration of (-)-(2R,3S) [5,8,14,[16][17][18]. The aromatic unit (Ar 1 ) of the α-chloro-carbonyl compounds (30) were phenyl-, 2-furyl-, 2-thiophenyl-, 2-pyrroyl.…”

“…The use of d-glucose-based lariat ether 1d (R=(CH 2 ) 3 OH) as the catalyst gave the best results. The results of the reaction of a few aromatic aldehydes in the presence of the catalyst 1d were summarized in Table 3 [14,16].…”

“…The α,β-epoxyketones with a furan (Table 3, entries 6-7) or a thiophene (Table 3, entries 8-10) moiety were obtained in good enantioselectivities (up to 86 % ee) as well as excellent diastereoselectivities (up to 98:2), but the epoxyketone with a pyrrole ring was formed in a low yield and enantioselectivity (Table 3, entry 11). The mannose-based crown ethers 2 generated lower enantioselectivities and promoted the formation of the enantiomer with a positive optical rotation [16].…”