Chaykovsky Reaction Research Articles

Asymmetric and Regiospecific Synthesis of Isotopically Labelled Cyclopropane Fatty Acid (9R,10S)-Dihydrosterculic Acid: Overcoming Spontaneous Protonation During Lithium-Sulfoxide Exchange­

The total synthesis of isotopically labelled (9R,10S)-dihydro­sterculic acid, a usual cyclopropane fatty acid with biologically relevant toxicity upon desaturation in vivo, is reported. A diastereoselective Corey­–Chaykovsky reaction was employed to form the cyclopropane ring. Rapid quenching of a lithium-sulfoxide exchange was required to achieve the requisite high levels of deuterium incorporation.

A Scalable Synthesis of an Azabicyclooctanyl Derivative, a Novel DPP-4 Inhibitor

A practical synthetic strategy to a chiral azabicycclooctanyl derivative (1), a potent DPP-4 inhibitor, starting from a commercially available nortropine is described. The stereogenic center of 1 was established employing a modified protocol of Ellman's diastereoselective addition of a benzylic nucleophile to tert-butanesulfinimine. Other key steps include Corey-Chaykovsky reaction, Meinwald rearrangement, and CDMT-promoted amide bond formation involving a sterically hindered amine 2.

A Potential Intermediate for the Aza-Corey−Chaykovsky Reaction: Synthesis, Structure, and Thermolysis of a Pentacoordinate 1,2-Thiazetidine 1-Oxide

Thermolysis of a pentacoordinate 1lambda(6),2-thiazetidine, which was synthesized for the first time and characterized by X-ray crystallographic analysis, gave the corresponding aziridine and a cyclic sulfinate almost quantitatively. The potential intermediacy of a 1lambda(6),2-thiazetidine was suggested in the aza-Corey-Chaykovsky reaction.

Stereoselective Synthesis of Medium-Sized Cyclic Compounds by Means of Tandem Reactions of a Cyclic Oxosulfonium Ylide with Acetates of Baylis−Hillman Adducts

Treatment of a five-membered cyclic oxosulfonium ylide 3 with β-acetoxy-α-methylene ketones in the presence of two equimolar amounts of base afforded the cycloheptene oxide derivatives 7a−i as single stereoisomers in 19−77% yields. The products were considered to form through a Michael-type addition of the ylide, followed by elimination of the acetoxy group and an intramolecular Corey−Chaykovsky reaction. On the other hand, the same treatment, when using a six-membered oxosulfonium ylide, gave the corresponding cyclooctene oxide derivatives in moderate yields, with the products formed in a ca. 4:1 mixture of stereoisomers, a fact correlated with differences in the configuration of the sulfur atom in the sulfinyl group.

Origins of Stereoselectivity in the Corey-Chaykovsky Reaction. Insights from Quantum Chemistry.

Reaction pathways of the Corey-Chaykovsky epoxidation reaction have been compared quantum chemically. Of the concerted, torsional rotation and anti addition pathways the latter two were found to be favored both in the gas phase and in CH(2)Cl(2) in a model system. Several theoretically previously uncharacterized stationary points were located, and selective solvent effects were observed. On the anti addition pathway the C-C bond formation transition state A, suitably substituted to allow comparison with published experimental data, was able to predict both the absolute stereochemistry of the main product and, qualitatively, the distribution of its other stereoisomers. The quantum chemical protocol reported here is useful in designing new sulfides for the Corey-Chaykovsky reaction.