Halogenation-induced C–N bond activation enables the synthesis of 1,2-cis C-aryl furanosides via deaminative cyclization

Abstract

1,2-cis C-Aryl furanosides are prevalent in nature and exhibit significant biological activities. The 1,2-cis configuration is less favorable in terms of stereoelectronic and steric effects, making the synthesis of this type of skeleton highly challenging. Traditional methods for the synthesis of 1,2-cis C-aryl furanosides usually require complicated protection manipulations, resulting in lengthy synthetic routes and low overall efficiency. Here, we report a simple and highly applicable procedure for the synthesis of 1,2-cis C-aryl furanosides from unprotected aldoses via Petasis reaction and subsequent deaminative cyclization. Unprotected aldose mediated Petasis reactions yield linear 1,2-trans 1-aryl polyhydroxy amines. Halogenation of the amine motif activates the conventionally inert C–N bond and triggers the key stereoinvertive intramolecular substitution process, affording 1,2-cis C-aryl furanosides with excellent chemo- and diastereoselectivity. This procedure does not require the use of any sensitive reagents, and can be conducted in one-pot without precautions against oxygen or moisture, offering a streamlined approach to 1,2-cis C-aryl furanoside natural products and bioactive agents.