Recent developments in the stereoselective synthesis of polysubstituted cyclopropanes nowadays allow chemists to easily access these strained rings with high diastereo-and enantiomeric ratios. In turn, this development has created a paradigm shift for the synthesis of stereodefined acyclic molecules though selective carbon−carbon bond cleavage. Through chosen illustrative examples, we aim to show in this review that the cleavage of cyclopropane is a powerful approach to reveal sp 3 stereocenters in acyclic systems. The application of these concepts was illustrated by the total syntheses of several natural products and other important molecules, further showing the power of these strategies as a powerful tool in organic synthesis.

The development of a modular and diastereodivergent approach to acyclic products bearing two distant stereocenters in a 1,5 relationship is reported. Remarkably, it was accomplished in just three catalytic steps from commercially available alkynes. This sequence generates the desired distant stereocenters efficiently and with high diastereocontrol and a perfect E:Z ratio. The approach was used for a noniterative formal synthesis of the α-tocopherol side chain.

The preparation of a new class of alkenyl cyclopropyl diols, easily available through a copper-catalyzed carbometalation reaction of cyclopropenes, has enabled the study of key mechanistic aspects of the tandem Heck–cyclopropane ring-opening reaction. Utilizing these substrates containing two distinct hydroxyl groups allowed us to examine parameters affecting the reaction outcome and selectivity. The combination of these experimental results with detailed DFT studies shed light on the mechanism governing the regio- and stereoselectivity of the cyclopropane ring-opening. A thorough investigation displayed the dual roles fulfilled by the hydroxyl group during the reaction, which is key to this remarkable transformation. In addition to its mechanistic implication, the reaction granted access to various lactones possessing up to four stereocenters as a single diastereomer, conveniently prepared in only two catalytic steps from easily accessible achiral cyclopropenes.

The diastereoselective double carbometalation reaction of cyclopropenes provides, in a single-pot operation, two ω-ene-[1,1]-bicyclopropyl ester derivatives. One regioisomer then undergoes a Pd-catalyzed addition of aryl iodide to provide skipped dienes possessing several distant stereocenters including two congested quaternary carbon centers with excellent diastereoselectivity.

We report the directed diastereoselective Simmons−Smith cyclopropanation and vanadium-catalyzed epoxidation reactions of alkenyl cyclopropyl carbinol derivatives. The reaction furnished densely substituted stereodefined bicyclopropanes and cyclopropyl oxiranes as a single diastereomer in each case. The remarkable selectivity is obtained thanks to the rigidity of the cyclopropyl core, allowing diastereoselective reactions on the alkenyl moiety. This emphasizes the uniqueness of the cyclopropyl ring as a central platform in stereoselective synthesis.