Two epimerisations in the formation of oxetanes from l-rhamnose: towards oxetane-containing peptidomimetics

Oxetane cis- and trans-β-amino-acid scaffolds from l-rhamnose by efficient SN2 reactions in oxetane rings; pseudoenantiomeric analogues of the antibiotic oxetin

“…The conversion of L L-rhamnose 8 to benzylidene oxetane 11 was performed with minor modifications to the previously reported procedure 6 higher yield (60% overall yield on a 5 g scale). In the case of the L L-rhamnose triflate 10, however, the triflate of the c-lactone is cis to the C-3 substituent.…”

“…The organic fractions were combined, dried over magnesium sulfate and the solvent removed to give benzylidene oxetane 11 (4.20 g, 89% yield), mp 126-127°C [Lit. 6 …”

“…The crude product was purified by flash chromatography (EtOAc/hexane, 1:1) to give triflate 10 (14.78 g, 92%) as a white solid, with physical properties identical to those previously described. 6 Mp 139-140°C; ½a 22 D ¼ À63:9 (c 0.98 in MeCN).…”

“…The solid was then filtered and washed with Et 2 O. The washings were re-concentrated, and more material was crystallised out to give, after three re-crystallisations, the benzylidene lactone 9 (45.8 g, 72%), with physical properties identical to those previously described, 6 Pyridine (17.46 mL, 5 equiv) was added to a solution of benzylidene lactone 9 (10.52 g, 42 mmol) in THF (220 mL) under nitrogen at À78°C. Trifluoromethanesulfonic (triflic) anhydride (14.63 mL, 2 equiv) was added dropwise.…”

“…1:1) afforded diol 12 as a clear oil, which solidified upon standing and had identical physical properties to those previously described. 6 Mp 52-54°C; ½a and pyridine (153 lL, 1.89 mmol) in dichloromethane (5 mL) at À78°C under nitrogen. The reaction mixture was stirred at À78°C for 20 min, and then at 0°C for 1 h after which time TLC showed the formation of one major product (R f 0.64, EtOAc/hexane, 1:3).…”