Domino access to highly substituted chromans and isochromans from carbohydrates

Abstract

Herein we describe the synthesis of highly substituted chromans and isochromans using carbohydrates as starting materials. Our approach makes use of a Pd-catalyzed domino reaction consisting of oxidative addition, followed by two carbopalladation steps and completed by a cyclization to annelate the benzene moiety. The versatility of this route has been demonstrated by a small library of highly substituted chromans and isochromans.

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

“…After having established several methods of domino carbopalladation reactions which employ dialkynyl-substituted bromoglycals [17–20] or bromoarenes [21], we envisioned to apply a similar procedure for the preparation of anthracycline derivatives. Therefore, the D-ring was exchanged for a pyranose, as described in our previous synthetic approaches for the syntheses of chromans, isochromans and biphenyls, respectively.…”

“…Therefore, the D-ring was exchanged for a pyranose, as described in our previous synthetic approaches for the syntheses of chromans, isochromans and biphenyls, respectively. These 2-bromoglycals 15 are well-known compounds and their synthesis was accomplished according to literature-known procedures [17–18]. The dialkyne unit provides both the A-ring and the information for the formation of the B and C-ring within the palladium-catalyzed domino transformation [22–27].…”

Sonogashira–Hagihara reactions of halogenated glycals

“…Our recent interest in domino reactions starting with 2-brominated glycals [26–28] motivated us to investigate also the behaviour of peracetylated 2-bromogalactal 10 in Sonogashira–Hagihara reactions (Table 2). We found that 10 is much less reactive than 7 .…”

High-Throughput Synthesis of Diverse Compound Collections for Lead Discovery and Optimization

“…Using a Pd-catalyzed domino reaction under microwave irradiation, Werz and coworkers prepared a library of chromans and isochromans from bromoglycal as a starting material (Leibeling et al 2010). This study opens doors for the generation of highly functionalized scaffolds for libraries from carbohydrates in high-throughput synthesis.…”