Formal Synthesis of (+)-Sinefungin by Way of Sequential Asymmetric Metal Catalysis.

Here, we report a approach toward (+)-sinefungin, a potent inhibitor of the physiological methyl transfer process. A key feature is represented by the sequential metal catalysis combining Pd-catalyzed hydroalkoxylation and ring-rearrangement metathesis. The unique advantage of the method is highlighted by the unprecedented complete control of the C stereocenter.

Organocatalytic Activation of Donor-Acceptor Cyclopropanes: A Tandem (3 + 3)-Cycloaddition/Aryl Migration toward the Synthesis of Enantioenriched Tetrahydropyridazines.

An organocatalytic enantioselective (3 + 3)-cycloaddition reaction of racemic cyclopropane carbaldehydes and aryl hydrazones has been demonstrated for the first time. A wide range of enantioenriched tetrahydropyridazines with an exocyclic double bond were obtained with moderate to good yields and good to excellent enantiomeric excesses. Mechanistic investigations hinted toward a matched/mismatched kinetic resolution, and control experiments and DFT calculations unveiled that 1,3-aryl migration was concerted and intramolecular and proceeds via a four-membered transition state.

Short Synthesis of Molnupiravir (EIDD-2801) a Thionated Uridine Intermediate.

Molnupiravir (MK-4482, EIDD-2801) is an experimental drug that has been demonstrated to be effective for the treatment of COVID-19 in human clinical trials. Herein, we report a concise synthesis of the drug a novel thionated derivative that relies on one-pot methodologies, thus decreasing the number of purification steps required. This route provides the drug in an overall 62% yield and >99% purity and uses cheap and readily available bulk chemicals, thereby providing an affordable synthesis of the drug for cheaper and wider global accessibility.

Relieving the stress together: annulation of two different strained rings towards the formation of biologically significant heterocyclic scaffolds.

Small carbo- and heterocycles have become versatile building blocks owing to their intrinsic ring strain and ease of synthesis. However, the traditional approaches of heterocycle synthesis involved the combination of one strained-carbocycle or heterocycle with one unsaturated molecule. On the contrary, there is an exciting possibility of combining two different strained rings to furnish varieties of heterocycles, where one of the strained rings can act as a valuable alternative to the unsaturated molecule.

Exploitation of Cyclopropane Carbaldehydes to Prins Cyclization: Quick Access to ( E)-Hexahydrooxonine and Octahydrocyclopenta[ b]pyran.

A single-step TiX-mediated Prins-type cyclization of cyclopropane carbaldehydes with 3-buten-1-ol for the highly stereoselective construction of relatively strained ( E)-hexahydrooxonines is reported. Switching the alcohol to 3-butyn-1-ol prompted a similar route, augmented by another cyclization within a nine-membered ring to afford a bicyclized product (4,4-dihalo-5-aryloctahydrocyclopenta[ b]pyran). Easy transformation of the resulting geminal dihalide to a vinyl halide and a ketone further supplemented the substance of this approach.

Lewis Acid Catalyzed Annulation of Cyclopropane Carbaldehydes and Aryl Hydrazines: Construction of Tetrahydropyridazines and Application Toward a One-Pot Synthesis of Hexahydropyrrolo[1,2- b]pyridazines.

In this report, a facile synthesis of tetrahydropyridazines via a Lewis acid catalyzed annulation reaction of cyclopropane carbaldehydes and aryl hydrazines has been demonstrated. Moreover, the generated tetrahydropyridazine further participated in a cycloaddition reaction with donor-acceptor cyclopropanes to furnish hexahydropyrrolo[1,2- b]pyridazines. We also performed these two steps in one pot in a consecutive manner.

Lewis Acid Catalyzed Diastereoselective Cycloaddition Reactions of Donor-Acceptor Cyclopropanes and Vinyl Azides: Synthesis of Functionalized Azidocyclopentane and Tetrahydropyridine Derivatives.

Lewis acid catalyzed [3 + 2]-cycloaddition reaction of donor-acceptor cyclopropanes with vinyl azides has been developed to obtain diastereomerically enriched azidocyclopentane derivatives. In addition, thermal chemoselective ring expansion of azidocyclopentanes to tetrahydropyridine derivatives and further diastereospecific reduction to a substituted piperidine derivative, with an excellent yield, was also achieved.