Chelate-Assisted Ring-Closing Metathesis: A Strategy for Accelerating Macrocyclization at Ambient Temperatures.

Ring-closing metathesis (RCM) offers versatile catalytic routes to macrocycles, with applications ranging from perfumery to production of antiviral drugs. Unwanted oligomerization, however, is a long-standing challenge. Oligomers can be converted into the cyclic targets by catalysts that are sufficiently reactive to promote backbiting (e.g., Ru complexes of N-heterocyclic carbenes; NHCs), but catalyst decomposition limits yields and selectivity. Incorporation of a hemilabile o-dianiline (ODA) chelate into new catalysts of the form RuCl2(NHC)(ODA)(=CHPh) accelerates macrocyclization, particularly for dienes bearing polar sites capable of H-bonding: it may also inhibit catalyst decomposition during metathesis. Significant improvements relative to prior Ru-NHC catalysts result, with fast macrocyclization of conformationally flexible dienes at room temperature.

Stereoselective Total Syntheses of Polyacetylene Plant Metabolites via Ester-Tethered Ring Closing Metathesis.

Total syntheses of five naturally occurring polyacetylenes from three different plants are described. These natural products have in common an E,Z-configured conjugated diene linked to a di- or triyne chain. As the key method to stereoselectively establish the E,Z-diene part, an ester-tethered ring-closing metathesis/base-induced eliminative ring opening sequence was used. The results presented herein do not only showcase the utility of this tethered RCM variant but have also prompted us to suggest that the originally assigned absolute configurations of chiral polyacetylenes from Atractylodes macrocephala should be revised or at least reconsidered.

Stereoselective Total Synthesis of Atractylodemayne A, a Conjugated 2(E),8(Z),10(E)-Triene-4,6-diyne.

The first total synthesis of the polyacetylene natural product atractylodemayne A is reported. Stereoselective construction of the conjugated 8(Z),10(E)-diene moiety was achieved through a tethered ring-closing metathesis approach, comprising a Ru-catalyzed RCM followed by a base-induced elimination. A Pd-catalyzed Cadiot-Chodkiewicz coupling was used for the synthesis of the diyne. Overall, atractylodemayne A was synthesized in nine steps for the longest linear sequence.