Asymmetric Preparation of Polysubstituted Cyclopropanes Based on Direct Functionalization of Achiral Three-Membered Carbocycles

Abstract

In addition to the appealing synthetic transformations that cyclopropanes present, they are also part of larger molecular structures that possess a wide range of biological properties. Therefore, the preparation of enantiomerically enriched cyclopropanes has consistently been a very interesting research topic in organic synthesis. In this Focus Review, we are presenting new methods for the synthesis of these target compounds through catalytic and asymmetric direct functionalization of simple achiral three-membered carbocycle precursors. These convergent and very flexible approaches allow the preparation of a large variety of polysubstituted alkyl-, vinyl-, alkynyl-, and arylcyclopropanes but also cyclopropanols and cyclopropylamines in very high diastereo- and enantiomeric ratios from a single precursor, underlining the power of this synthetic route.

Rhodium(III)‐Catalyzed Enantio‐ and Diastereoselective C−H Cyclopropylation of N‐Phenoxylsulfonamides: Combined Experimental and Computational Studies

“…[4c] Therefore,the development of efficient synthetic methods for rapid construction of the highly valuable cyclopropane core is an important research objective.C onsequently,n otable synthetic progress has been made, [6][7][8][9][10] including classical metal-catalyzed decomposition of diazoalkanes, [6] Simmons-Smith type cyclopropanations, [7] Michael addition initiated ring closure, [8] and enzymatic synthesis. [9] Cyclopropenes [11] are versatile and reactive electrophilic cyclopropylating reagents owing to ring strain (approximately 54 kcal mol À1 ). Metal-catalyzed cis-selective carbofunctionalization of cyclopropenes has been realized through insertion of main group organometallics,terminated by an electrophile (Scheme 1a).…”

Controllable Si−C Bond Activation Enables Stereocontrol in the Palladium‐Catalyzed [4+2] Annulation of Cyclopropenes with Benzosilacyclobutanes

“…Cyclopropenes are unique three-membered compounds and extremely important building blocks in organic synthesis owing to their inherent ring strain and unusual electronic properties similar to those of (benzo)silacyclobutanes and cyclopropenones.Inthe past years,numerous transformations based on the direct functionalization of prochiral or achiral cyclopropenes has consistently been ah ot research topic in synthetic chemistry and organometallic catalysis. [12] However, there are few reports on the functionalization or cycloaddition of cyclopropenes by aS i ÀCb ond-cleavage-initiated tandem reaction process. [12x] Until now,t he transition-metalcatalyzed cycloaddition of silabutanes with alkenes,including three-membered cyclopropenes,has not been explored.…”

Cobalt‐Catalyzed Diastereo‐ and Enantioselective Hydroalkenylation of Cyclopropenes with Alkenylboronic Acids

“…[6] However,t hese protocols require incorporation of specific functional groups and have limited substrate scope.Amore general strategy to access alkenylcyclopropanes is catalytic enantioselective hydroalkenylation of cyclopropenes.T he advantage is that ab road range of enantioenriched multisubstituted cyclopropanes can be rapidly synthesized through as ingle set of transformations without requirement of pre-installation of as pecific functional group,s tarting from easily accessible materials and catalysts. [7] Although direct CÀHf unctionalization of cyclopropyl rings constitutes another straightforward way to chiral multisubstituted cyclopropanes,only intramolecular reactions and intermolecular C À Ha rylation in the presence of ad irecting group have been achieved. [8] Introduction of an alkenyl group through C À Hf unctionalization of cyclopropanes in high efficiency and stereoselectivity with broad substrate scope remains scarce.…”

“…Thec hallenge for such ap rocess is the lower reactivity compared with other organometallic reagents.E levated reaction temperatures might be required to enhance the efficiency. Although only Co complexes derived from phosphines 4g and 4h promoted the reaction, the desired product 3a was afforded in high diastereo-and enantioselectivities (entries [7][8]. [28] Herein, we disclosed the first Co-catalyzed enantioselective hydroalkenylation of cyclopropenes,u sing awide range of alkenylboronic acids,todeliver products with high diastereo-and enantioselectivities (Scheme 1c).…”

“…[29] We commenced our studies with the reaction of the 3,3disubstituted cyclopropene 1a with the alkenylboronic acid 2a in the presence of various phosphine/Co complexes (Table 1). Although only Co complexes derived from phosphines 4g and 4h promoted the reaction, the desired product 3a was afforded in high diastereo-and enantioselectivities (entries [7][8].…”