Further Investigation of the 2‐Azido‐phenylselenylation of Glycals

Abstract

Derivatives of 2‐azido‐2‐deoxysugars are widely applied as precursor of 2‐amino‐2‐deoxysugars in the synthesis of various oligosaccharides of bacterial, fungal and mammalian origin. Heterogeneous or homogeneous azidophenylselenylation (APS) of glycals, i. e., reaction of glycals with Ph2Se2, PhI(OAc)2 and NaN3 or TMSN3 as azide radical donors, is a straightforward way to phenyl 2‐azido‐2‐deoxy‐1‐selenoglycosides that can be directly used as glycosyl donors. However, heterogeneous APS is characterized by insufficient reproducibility and scalability. We have studied the effect of reaction conditions on the product distribution in heterogeneous APS of 3,4,6‐tri‐O‐acetyl‐d‐galactal and found the conditions that enabled reliable preparation of crystalline phenyl 2‐azido‐2‐deoxy‐1‐seleno‐α‐d‐galactopyranoside triacetate in yield of 58 % on the 3.7 mmol scale. APS of 3,4,6‐tri‐O‐acetyl‐d‐glucal under those conditions produced a ∼1 : 1 mixture of phenyl 2‐azido‐2‐deoxy‐1‐seleno‐α‐d‐gluco‐ and mannopyranosides in total yield of 78 %. Acetoxyphenylselenylation of differently protected galactals and 3,4,6‐tri‐O‐acetyl‐d‐glucal under the action of Ph2Se2 and PhI(OAc)2 has been shown to be a convenient method for the synthesis of 1‐O‐acetyl‐2‐seleno‐2‐deoxy derivatives, valuable intermediates in chemistry of 2‐deoxysugars. 2‐Seleno‐2‐deoxy sugars were characterized in detail by NMR data including 77Se chemical shifts and nJSe−H coupling constant values.

Thiourea-Cu(OTf)2/NIS-synergistically promoted stereoselective glycoside formation with 2-azidoselenoglycosides or thioglycosides as donors

“…Moreover, the regioselectivity and stereoselectivity of 2-selenoglycoazidation can be satisfactorily achieved. 9 At present, several activator systems are known for their efficient application in the synthesis of 2-azidoglycosides. For example, Hagen's group studied the stereoselectivity of fucosylation using a series of phenyl 2-azido-selenofucosides as glycosyl donors in the presence of Ph 2 SO-Tf 2 O.…”