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. 2019 Aug 2;21(15):6126-6129.
doi: 10.1021/acs.orglett.9b02278. Epub 2019 Jul 12.

Studies Targeting Ryanodol Result in an Annulation Reaction for the Synthesis of a Variety of Fused Carbocycles

Rajdip Karmakar  1 , Arnold L Rheingold  2 , Glenn C Micalizio  1
Affiliations

Studies Targeting Ryanodol Result in an Annulation Reaction for the Synthesis of a Variety of Fused Carbocycles

Rajdip Karmakar et al. Org Lett. .

Abstract

An annulation reaction is described to access a range of polycyclic and highly oxygenated carbocycles. First developed in an approach to the synthesis of ryanodol, metallacycle-mediated annulative diketone-alkyne coupling defines a framework for realization of new retrosynthetic relationships for complex molecule synthesis. In addition to demonstrating this reaction in the context of forging distinct carbocyclic systems, including those featuring a seven-membered ring, the choice of quenching reagent leads to unique reaction outcomes.

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Figures

Figure 1.
Figure 1.
An annulation reaction suitable for a wide variety of fused polyclic carbocycles, including those bearing medium-sized rings.
Figure 2.
Figure 2.
Alkyne–diketone annulation reactions to forge 5-, 6-, and 7-membered rings. Typical annulation reactions are conducted with the combination of Ti(Oi-Pr)4 and c-C5H9MgCl. a Quench with NaHCO3 (half sat. aq.). b t-BuOOH is added for the oxidative quench. c 5 was used as a 1:1 mixture of diastereomers. d Quench with aq. HCl (1N). * Structures of these compounds are supported with X-ray diffraction.
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