Increasing the Structural Span of Alkyne Metathesis

Abstract

A new generation of alkyne metathesis catalysts, which are distinguished by high activity and an exquisite functional group tolerance, allows the scope of this transformation to be extended beyond its traditional range. They accept substrates that were previously found problematic or unreactive, such as propargyl alcohol derivatives, electron-deficient and electron-rich acetylenes of various types, and even terminal alkynes. Moreover, post-metathetic transformations other than semi-reduction increase the structural portfolio, as witnessed by the synthesis of a annulated phenol derivative via ring-closing alkyne metathesis (RCAM) followed by a transannular gold-catalyzed Conia-ene reaction. Further examples encompass a post-metathetic transannular ketone-alkyne cyclization with formation of a trisubstituted furan, a ruthenium-catalyzed redox isomerization, and a Meyer-Schuster rearrangement/oxa-Michael cascade. These reaction modes fueled model studies toward salicylate macrolides, furanocembranolides, and the cytotoxic macrolides acutiphycin and enigmazole A; moreover, they served as the key design elements of concise total syntheses of dehydrocurvularin (27) and the antibiotic agent A26771B (36).

A New Method for the Preparation of Non‐Terminal Alkynes: Application to the Total Syntheses of Tulearin A and C

“…To meet the high chemical demands of the final deprotection, (EtO) 3 SiH was used in lieu of BnMe 2 SiH for the subsequent trans-hydrosilylation of 51, which had again to be performed under solvent-free conditions. Protodesilylation of the resulting alkenylsiloxanes 52 was now achieved with the aid of AgF in protic medium at ambient temperature.…”

“…[1] To fully harness the potential of this transformation, however, it is also necessary to develop new and effective gateways to the required starting materials. Although the recent past has seen the first successful metathesis reactions of terminal acetylene derivatives, [2][3][4][5] the use of non-terminal alkynes still dominates the field. Therefore improved access routes to alkynes in general and methyl-capped alkynes in particular are on high demand.…”

In SituGeneration of Molybdenum-Based Catalyst for Alkyne Metathesis: Further Developments and Mechanistic Insights

“…Since more than four decades, tremendous efforts have been devoted to the search of new catalysts for metathesis reactions in general, in particular via the synthesis and use of well-defined, active metathesis catalysts, essentially based on ruthenium, tungsten and molybdenum. In that context, a strong interest has been devoted within the last decade to the synthesis of molecular initiators for alkyne metathesis, as revealed by recent publications in the field [4][5][6][7]. However, the use of in situ catalysts still remains of interest both from academic and industrial point of views, as they are generally prepared using procedures that are less sensitive to oxygen and water, whereas the synthesis and uses of well-defined and active carbenes or carbynes would require their prior synthesis and working under more specific experimental conditions.…”

Concise Total Synthesis of Enigmazole A

“…[12] We conceived that the most likely explanation [28] for this striking difference is the fact that the possible p-complexes [29] formed upon initial coordination of the catalyst to the alkyne in 33 are diastereomeric.I fo nly one …”

“…However,asimple feasibility study encouraged us to pursue this route. [12] If successful, the projected sequence provides opportunities for late-stage modification of the region carrying the distinctive phosphate ester,o nce the project enters into the phase of diverted total synthesis.F rom the purely chemical vantage point, it would help illustrate the prowess of p-acid catalysis,which remains surprisingly underrepresented in total synthesis compared with the overall activity in this topical field of research. [13,14] An oxazole of type H had already been used by the group of Molinski, [5] but our route to this building block represents ac onvenient short cut (Scheme 2).…”