Asymmetric Total Synthesis of Cryptorigidifoliol I.

An efficient asymmetric total synthesis of cryptorigidifoliol I based on an unusual Luche reduction leading to bicyclic etherification and acid hydrolysis to a thermodynamically less stable 4-hydroxy-2,6-trans-disubstituted-THP moiety has been achieved. The easy setup of trans-2,6-substitution on the core pyran ring through bicyclic etherification would enable the synthesis of various THP and bicyclic-THP-lactone natural products.

Unanticipated Bicyclic Etherification in Luche Reduction: Asymmetric Total Syntheses of Diospongins A and B and Tetraketide.

In the synthesis of diospongin B based on rearrangement of δ-hydroxyalkynone to 2,3-dihydro-4H-pyran-4-one, we discovered an unanticipated beguiling reaction giving a thermodynamically less stable 4-hydroxy-2,6-trans-disubstituted-THP moiety via bicyclic etherification under Luche reduction conditions and simple acid hydrolysis. The practical applicability of this method is exemplified by the asymmetric total syntheses of diospongins A and B, several analogues, and tetraketide.

Asymmetric total synthesis of diosniponols A and B.

A concise asymmetric total synthesis of diosniponols A and B has been achieved based on an enantioselective Jacobsen kinetic resolution of racemic epoxide and the important 2,3-dihydro-4H-pyran-4-one moiety being installed by the metal-free δ-hydroxyalkynone rearrangement catalyzed by p-TsOH. A diastereoselective catalytic hydrogenation set the required all-syn stereochemistry leading to diosniponol A, which then, under the Mitsunobu inversion conditions, provided diosniponol B. The structure and absolute stereochemistry of the natural products were further confirmed.

Metal-Free Brønsted Acid-Catalyzed Rearrangement of δ-Hydroxyalkynones to 2,3-Dihydro-4 H-pyran-4-ones: Total Synthesis of Obolactone and a Catechol Pyran Isolated from Plectranthus sylvestris.

A metal-free, Brønsted acid, pTsOH-catalyzed intramolecular rearrangement of δ-hydroxyalkynones to substituted 2,3-dihydro-4 H-pyran-4-ones was developed. The rearrangement occurs with high regioselectivity under mild and open-air conditions. The scope of work was illustrated by synthesizing an array of aliphatic and aromatic substituted 2,3-dihydro-4 H-pyran-4-ones in up to 96% yield, 100% atom economy, and complete regioselectivity. Some of the dihydropyranones are utilized for vinylic halogenations and to complete the total synthesis of bioactive natural products, obolactone and a catechol pyran isolated from Plectranthus sylvestris ( Labiatae) .