Acetylene as a Dicarbene Equivalent for Gold(I) Catalysis: Total Synthesis of Waitziacuminone in One Step

Abstract

The gold(I)‐catalyzed reaction of acetylene gas with alkenes leads to (Z,Z)‐1,4‐disubstituted 1,3‐butadienes and biscyclopropanes depending on the donor ligand on gold(I). Acetylene was generated in situ from calcium carbide and water in a user‐friendly procedure. Reaction of acetylene with 1,5‐dienes gives rise stereoselectively to tricyclo[5.1.0.02,4]octanes. This novel double cyclopropanation has been applied to the one step total synthesis of the natural product waitziacuminone from acetylene and geranyl acetone.

Advances in polycyclization cascades in natural product synthesis

“…28 The Echavarren group recently developed a most impressive Au(I)-catalyzed bis-cyclopropanation of geranyl acetone 61 (Scheme 12), in which acetylene gas itself (generated in situ from calcium carbide) serves as the substrate. 29 This cascade affords the tricyclo[5.1.0.0 2,4 ]octane natural product waitziacuminone in a single step, and in terms of atom and step economy constitutes a 'near-ideal' synthesis. 3 Stereoselectively generating four C-C bonds and three rings, the reaction proceeds via initial cyclopropanation of 61 by the h 2 -acetylene gold(I) complex 62 to form cyclopropyl gold carbene 63; the site-selectivity and diastereoselectivity of this step was determined computationally to favour the terminal alkene by ~1.6 kcal mol -1 .…”

Recent Advances in Construction of Polycyclic Natural Product Scaffolds via One-Pot Reactions Involving Alkyne Annulation

“…Recently, Echavarren's group (Scharnagel et al, 2020) reported a gold(I)-catalyzed double cyclopropanation using acetylene as a unique dicarbene equivalent ( Figure 1B). A 3/6/3 fused tricyclic scaffold can be formed in a diastereoselective way by employing 1,5-dienes as substrates, which can be used for one step total synthesis of waitziacuminone from geranyl acetone.…”

Calcium Carbide: Versatile Synthetic Applications, Green Methodology and Sustainability

“…Acetylene acting as a dicarbene analog has been successfully demonstrated recently. [ 35 ] Calcium carbide reacts with stilbenes 25 giving dienes 26 in moderate yields or bis‐cyclopropanes 27 in good yields; the reaction is catalyzed by gold (Scheme 11). The structure of the product depends on the catalyst: the use of N‐heterocyclic carbene ligands favors formation of bis‐cyclopropanes 27 .…”

“…Under these conditions, 1,5‐dienes are transformed into waitziacuminone derivatives in good to excellent yields. [ 35 ] This methodology has a good perspective for further development using gold‐activated acetylene as a dicarbene equivalent.…”