Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

The prochiral 4-(allyloxy)hepta-1,6-diynes, optionally modified in the positions 1 and 7 with an alkyl or ester group, undergo a chemoselective ring-closing enyne metathesis yielding racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans. Among the catalysts tested, Grubbs 1st generation precatalyst in the presence of ethene (Mori conditions) gave superior results compared to the more stable Grubbs or Hoveyda–Grubbs 2nd generation precatalysts. This is probably caused by a suppression of the subsequent side-reactions of the enyne metathesis product with ethene. On the other hand, the 2nd generation precatalysts gave better yields in the absence of ethene. The metathesis products, containing both a triple bond and a conjugated system, can be successfully orthogonally modified. For example, the metathesis product of 5-(allyloxy)nona-2,7-diyne reacted chemo- and stereoselectively in a Diels–Alder reaction with N-phenylmaleimide affording the tricyclic products as a mixture of two separable diastereoisomers, the configuration of which was estimated by DFT computations. The reported enediyne metathesis paves the way to the enantioselective enyne metathesis yielding chiral building blocks for compounds with potential biological activity, e.g., norsalvinorin or cacospongionolide B.

Recent Advances in One-Pot Enyne Metathesis Processes for the Preparation of Biologically and Medicinally Relevant Compounds

Enyne metathesis reactions are powerful tools for the preparation of a wide range of synthetic and natural chemical substances with increasing efficiency and environmental sustainability. The driving force of the reaction is the formation of a stable conjugated system, i.e., a diene, which through further functionalization steps can be used for the construction of skeletally complex molecular architectures. These concepts are exploited to design cascade reaction sequences, where multiple rings can be formed in a one-pot fashion by combining metathetic protocols with various chemical transformations. The strong correlation between synthetic organic chemistry and medicinal chemistry prompted us to review the most notable approaches for the synthesis of biologically relevant compounds via enyne metathesis-based one-pot processes. With the aim to provide a modern and practical overview, by taking into consideration the scientific literature on this topic, we have focused the majority of our attention on the research performed in the last decade. This review covers the literature from 2003 to 2020.1 Introduction2 Ethylene-Mediated Processes3 RCEYM/CM and CEYM/RCM Processes4 Enyne Metathesis/Diels–Alder-Based Processes5 RCM of Dienynes6 RCM of Tethered Dienynes7 Relay Metathesis8 Ring-Rearrangement Metathesis9 RCEYM/Transition-Metal-Catalyzed C–C Bond-Forming Processes10 Conclusions11 List of Acronyms

Ring closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

Prochiral 4-(allyloxy)hepta-1,6-diynes, optionally modified in the positions 1 and 7 with an alkyl or ester group, undergo chemoselective ring closing enyne metathesis yielding racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans. Among the catalysts tested, Grubbs 1st generation precatalyst in the presence of ethene (Mori conditions) gave superior results compared to more stable Grubbs or Hoveyda-Grubbs 2nd generation precatalysts. This is probably caused by suppression of subsequent side-reactions of the enyne metathesis product with ethene. On the other hand, 2nd generation precatalysts gave better yields in the absence of ethene. The metathesis products, containing both triple bond and conjugated system, can be successfully orthogonally modified. For example, metathesis product of 5-(allyloxy)nona-2,7-diyne reacted chemo- and stereoselectively by Diels-Alder reaction with N-phenylmaleimide affording tricyclic products as the mixture of two separable diastereoisomers, the configuration of which was estimated by DFT computations. The reported enediyne metathesis paves the way to enantioselective enyne metathesis yielding chiral building blocks for compounds with potential biological activity, e.g. norsalvinorin or cacospongionolide B.