1‐exo‐Alkylidene‐2,3‐anhydrofuranoses: Valuable Synthons in the Preparation of Furanose‐Based Templates

Abstract

Highly functionalized 1‐exo‐alkylidene‐2,3‐anhydro‐, and 1′‐halo‐1‐exo‐alkylidene‐2,3‐anhydrofuranoses can be prepared in four or five steps, respectively, from D‐mannose. These compounds feature a variety of functionalities, including a double bond, an oxirane, an allylic oxirane and (in the case of the 1′‐halo derivative) an alkenyl halide. The reactivity of each functionality in these derivatives has been explored, and the usefulness of these substrates has been demonstrated with the preparation of furanose‐based carbohydrate templates with up to four sites of molecular diversity.

Furanose-based templates in the chemoselective generation of molecular diversity

“…27 Early attempts at hydrogenation of 4a (H 2 , Pd/C, EtOH, 25 psi) led to the formation of furan derivative 13 (Scheme 5a) under a variety of hydrogenation conditions. 28 These results were in line with previous results from our laboratory that already pointed to the easiness with which aromatization takes place in these systems. 29 In our opinion the aromatization process is favored by the allylic oxirane moiety.…”

Tetrasubstituted C‐Glycosylidenes and C‐Glycosyl Compounds from Di‐ and Monobromo‐Substituted exo‐Glycals

“…A mixture of Z and E isomers was obtained in each case, in sharp contrast with the halogenation of methylene-exo-glycals which gave single Z isomers as described by Lopez's group. [23] These results could be explained by the mechanism depicted in Figure 2. Bromine addition to the double bond leads to a bromonium ion (intermediate A).…”

“…In the case of methylene-exo-glycal, elimination of hy- drogen bromide from B occurs by a E2 mechanism on the most favoured rotamer, leading to the corresponding Z derivative. [23] In our case the acidity of the proton is strongly enhanced by the carboxyl group and this proton is abstracted by the NEt 3 base. The initial double bond stereochemistry is lost in the intermediate enolates C and D. Elimination leads, through an E 1CB mechanism, to a mixture of Z and E isomers in slightly different ratios, depending on the starting double bond configuration of the exo-glycal and the sugar configuration.…”

“…Lopez's group's elegant works based on chemoselective transformations of functionalized exo-glycals opened the way to exoglycal manipulation. [23,24] In particular, Suzuki and Stille cross-coupling reactions have been successfully applied to 1Ј-halo-substituted exo-glycals obtained by halogenation of methylene-exo-glycals. [25] Various aryl, heteroaryl, vinyl or alkynyl groups have been introduced stereoselectively onto exo-glycal vinyl halide functionalities.…”

Ferrier–Nicholas pyranosidic cations: application to diversity-oriented synthesis

“…On the other hand, our research group focused in an approach to appendage diversity consisting on "decorating" the carbohydrate moiety with additional functionalities that could be exploited in synthetic transfomations aimed at the formation of C-C, C-N, and C-O bonds [16,17]. In this context, we designed a furanose epoxy exo-glycal endowed with an exocyclic (enol-ether type) olefin and an oxirane moiety, i.e., 1 (Scheme 1).…”