Selective Pathway To Small-Ring Aldehydes

Formylcyclopropanes—three-membered rings with a pendant aldehyde substituent—are some of the most sought-after building blocks in synthetic chemistry. The compounds have the benefit of being biologically active, and the aldehyde functionality can be readily transformed into other useful groups. There are a variety of established synthetic approaches to prepare these compounds, including cycloaddition reactions or by starting with substituted cyclopropanes, but a new approach developed by William M. Sherrill and Michael Rubin of the University of Kansas is the first reported catalytic diastereo- and enantioselective hydroformylation of cyclopropenes to make chiral formylcyclopropanes (J. Am. Chem. Soc., DOI: 10.1021/ja805059f). The researchers reacted various substituted cyclopropenes with synthesis gas (CO and H₂) under mild conditions (60 °C and 150 psi) in toluene. The reactions in general required only small amounts of the standard hydroformylation precatalyst, Rh(acetylacetonate)(CO)₂), which was coupled with a rigid phosphinoferrocene ligand in situ to impart diastereoselectivity or chiral phosphine ligands to enhance enantioselectivity. The method represents "a convenient, atom-economic approach toward optically active cyclopropylcarboxaldehydes from readily available prochiral cyclopropenes," the researchers write.