Scientists from the ZIOC have proposed an updated "isoxazoline route" for the synthesis of aldols

Aldol condensation is one of the most common and widely used transformations to construct carbon-carbon bonds. However, versatile regio- and diastereoselective methods of aldol condensation still do not exist. At the end of the 20th century, an alternative method for obtaining aldols was proposed — the "isoxazoline route", which includes the [3 + 2]-cycloaddition of nitrile oxides to alkenes followed by hydrogenolysis. This method has found application in the total synthesis of a number of natural compounds, but it still has problems with regioselectivity.

Researchers from the Laboratory of Organic and Metal–Organic Nitrogen–Oxygen Systems of ZIOC have proposed an alternative regioselective route to isoxazolines, consisting of [4 + 1]-annulation of nitroalkenes with sulfur ylides and subsequent Boekelheide rearrangement. Hydrogenolysis of the isoxazoline ring leads to the formation of α'-acyloxy-substituted aldols, which are difficult to access by known synthetic routes. In the course of the research, the applicability of the obtained aldols for the assembly of stereochemically complex frameworks of natural compounds was also demonstrated. The developed approach can be used in the stereoselective total synthesis of pharmaceutically important molecules.

Source:

Pavel Yu. Ushakov, Sema L. Ioffe, Alexey Yu. Sukhorukov Regio- and diastereoselective access to densely functionalized ketones via the Boekelheide rearrangement of isoxazoline N-oxides Org. Biomol. Chem., 2022, 20, 5624-5637. DOI: 10.1039/D2OB00787H.