Robert Lett

Epoxidations with 30% hydrogen peroxide catalyzed by tungstic acid in buffered media

Abstract The scope of the tungstic acid catalyzed hydrogen peroxide epoxidation of olefinic alcohols is examined, at room temperature, in buffered protic media. Epoxidation occurs with complete retention of configuration for both cis and trans alkenes. Chemoselectivity is discussed with respect to the olefinic alcohol structure and olefin substituents.

Convergent stereospecific total synthesis of monochiral Monocillin I related macrolides

Abstract The first total synthesis of Monocillin I related macrolides has been achieved by a convergent and stereospecific route involving the palladium - catalyzed coupling of a functionnalized chiral vinylstannane with the appropriate dimethoxy bromomethyl isocoumarin. Cleavage conditions of the isocoumarin ring were then found for the preparation of a precursor hydroxy acid. The 14-membered macrolide was obtained in the Mitsunobu reaction conditions, and the required natural conjugated dienone epoxide system of Monocillin I was generated stereospecifically from that macrocyclic precursor.

Stereoselective expoxidation of allylic and homoallylic alcohols with 30% hydrogen peroxide catalyzed by tungstic acid in buffered media

Abstract The aqueous tungstic acid-catalyzed hydrogen peroxide epoxidation of allylic alcohols affords the same major diastereoisomer as the VO(acac) 2 /tBuOOH system with quite comparable stereoselectivities. In contrast, epoxidation of homoallylic alcohols appears to be much less stereoselective.

Convergent stereospecific total synthesis of Monocillin I and Monorden (or Radicicol)

Abstract The first total syntheses of the antifungal resorcylic macrolides Monocillin I and Monorden (or Radicicol) have been achieved by a convergent stereospecific route. TBDMS phenol ethers were found to be suitable for all the scheme and were removed in the ultimate step under mild conditions (aqueous borax/THF/methanol), hence allowing to get the natural macrolides in good yields, with no degradation. An efficient conversion of di-OTBMDS Monocillin I into Monorden is also reported.

Total synthesis of forskolin — Part III studies related to an asymmetric synthesis

Abstract A modification of the Corey CBS methodology for the asymmetric reduction of the dienone 3 A affords the dienol 4 A with an ee = 98% (92% yield). The intramolecular Diels-Alder reaction of the derived tetrolate 7 yields the tricyclic lactone 8 (48–56%) with no significant loss of ee (less than 1%), thus demonstrating the feasibility of a total synthesis of forskolin in enantiomerically pure form according to our route. The present synthesis of the optically active lactone 8 (ee=98%) is the shortest and the most efficient.

Synthesis of 14,15-dehydroforskolin via dimethyl diazomethylphosphonate anion reaction with an aldehyde

Abstract 14,15-Dehydroforskolin is prepared by the reaction of the dimethyl diazomethylphosphonate anion with 13 α-carboxaldehydes obtained from forskolin. Isolation of a by-product gives the first evidence of the reactivity of the primary phosphonate adduct, by intramolecular quenching, before its evolution into carbenoid or carbene intermediates.

Retrosynthetic studies with forskolin

Abstract New preparations of some dihydro-γ-pyrones derived from forskolin 1 are reported. Conjugate addition of cuprates is shown to occur on these compounds, in good yield, in the presence of BF3-Et2O: dimethyl and vinyl cuprates add with major α stereoselectivity, whereas dibutylcuprate adds mostly β. Some other reaction conditions or copper reagents failed.