Asymmetric Copper-Catalyzed Carbozincation of Cyclopropenes en Route to the Formation of Diastereo- and Enantiomerically Enriched Polysubstituted Cyclopropanes

Abstract

The enantioselective synthesis of cyclopropylzinc reagents has been achieved via a copper-catalyzed carbozincation of 3,3-disubstituted cyclopropenes with diorganozinc reagents. The obtained organozinc compounds can be easily functionalized with a broad range of electrophiles, including palladium-catalyzed cross-couplings, affording highly substituted cyclopropanes. The operationally simple procedure using very low quantities of a commercially available and inexpensive copper catalyst provides a new tool for the synthesis of highly enantioenriched cyclopropanes as single diastereoisomers.

Asymmetric Catalytic Preparation of Polysubstituted Cyclopropanol and Cyclopropylamine Derivatives

“…As reported, [14] the catalytic diastereo-and enantioselective carbometalation of cyclopropenes 1 was easily achieved by addition of 1.5 equiv of Grignard reagent R 1 MgBr in the presence of acatalytic amount of copper salt Cu(CH 3 CN) 4 PF 6 (2 mol %) and chiral catalyst (R,S)-Josiphos (2.2 mol %) in Et 2 OatÀ5 8 8Cin30min (Scheme 2). As reported, [14] the catalytic diastereo-and enantioselective carbometalation of cyclopropenes 1 was easily achieved by addition of 1.5 equiv of Grignard reagent R 1 MgBr in the presence of acatalytic amount of copper salt Cu(CH 3 CN) 4 PF 6 (2 mol %) and chiral catalyst (R,S)-Josiphos (2.2 mol %) in Et 2 OatÀ5 8 8Cin30min (Scheme 2).…”

Synthesis of Chiral Aminocyclopropanes by Rare‐Earth‐Metal‐Catalyzed Cyclopropene Hydroamination

“…The nature of the solvent (polar (fluorobenzene,c hlorobenzene, and THF) vs.non-polar (benzene and toluene)) did not have as ignificant influence on this reaction (entries 6a nd [8][9][10][11]. )i n8 5% yield in 48 h, but the enantioselectivity was rather poor (45 % ee,entry 2).…”

“…Extensive studies on the asymmetric hydroamination of alkenes have already been reported, but mostly focused on intramolecular reactions. [4] Regarding the asymmetric functionalization of cyclopropenes,v arious types of nucleophilic addition reactions,s uch as hydroboration, [5] hydrostannation, [6] hydroacylation, [7] hydroformylation, [8] and carbozincation, [9] have recently been reported. [4] Regarding the asymmetric functionalization of cyclopropenes,v arious types of nucleophilic addition reactions,s uch as hydroboration, [5] hydrostannation, [6] hydroacylation, [7] hydroformylation, [8] and carbozincation, [9] have recently been reported.…”

Copper mediated carbometalation reactions

“…79 Following the pioneering work by Nakamura and Lautens they were able to identify two chiral copper catalysts which efficiently furnished highly enantioenriched polysubstituted cyclopropanes. 80,81 Several features of the method are noteworthy: (1) the combination of highly encumbered phosphine ligand ( R )-DTBM-SEGPhos with Cu(CH 3 CN) 4 PF 6 or CuTC (copper( i ) thiophene-2-carboxylate) completely suppressed dimeric side products which appeared otherwise in significant amounts (typically 15–20%).…”