Application of an Enyne Metathesis/Diels–Alder Cycloaddition Sequence: A New Versatile Approach to the Syntheses of C‐Aryl Glycosides and Spiro‐C‐Aryl Glycosides

Abstract

An efficient approach for the synthesis of a variety of C-aryl and spiro-C-aryl glycosides is described. This diversity-oriented strategy employed here relies on a sequential enyne metathesis to generate the 1,3-diene moiety and Diels-Alder reaction with different dienophiles followed by aromatisation. Whereas cross-enyne metathesis with ethylene gas is used to install the 1,3-diene moiety at the anomeric centre for the synthesis of C-aryl glycosides, an intramolecular enyne metathesis on the sugar enyne is performed to generate the 1,3-diene moiety for the synthesis of spiro-C-aryl glycosides. Efforts to extend this strategy to the synthesis of the core structure of natural C-aryl glycoside gilvocarcin are also described. A combination of both C-aryl and spiro-C-aryl glycosides in the same moiety to combine the features thereof has also been accomplished. A tandem enyne metathesis/Diels-Alder reaction/aromatisation has also been attempted to directly access the C-aryl glycosides in one pot albeit in low yield.

Synthesis of 5,6- and 6,6-Spirocyclic Compounds

“…This approach has most recently been exploited for the synthesis of (+)-aigialospirol 400. Most recently, papulacandin-like spiroacetals have been accessed using this method [192] to provide a spiroacetal-diene 402, which can then be converted to the benzannulated spiroacetal 404 via cycloaddition with electron-deficient alkynes, e.g., 404 (Scheme 97).…”

“…Scheme 96 RCM strategy in the synthesis of aigialospirol [191] Scheme 97 RCM strategy in the synthesis of papulacandin-like spiroacetals [192] Scheme 98 Blanchard et al's ring-rearrangement metathesis strategy for the synthesis of spiroacetals [193] Scheme 99 Application of RRM in the synthesis of bis(spiroacetals) [193] …”

Metathesis Reactions of Carbohydrates: Recent Highlights in Alkyne Metathesis

“…Along this line, a recent contribution by Kaliappan and co‐workers focused on the RCEYM reaction of more reactive allyl ketosides aiming at the preparation of spiro‐ C ‐aryl glycosides 42…”

“…As previously pointed out, RCEYM reactions yield 1,3‐dienes which may undergo Diels–Alder cycloaddition with dienophiles to give bi(poly)cyclic derivatives (see Section 3.5). On the other hand, Diels–Alder cycloaddition reactions have also been performed on 1,3‐dienes, for example, 151 , arising from EYCM of C ‐alkynyl glycosides, for example, 150 , with ethylene, and this approach has been applied to the synthesis of C ‐aryl glycosides, for example, 152 (Scheme ) 42,90…”

Synthesis and antifungal properties of papulacandin derivatives

“…1) [3–4]. They contain a benzannulated spiroketal unit, which has been the signature of a wide series of bioactive natural products [5] and has inspired ample synthetic activity [5–8]. The papulacandins A–E were isolated from the fermentation broths of Papularia sphaerosperma [3].…”