Highly Enantioselective Cobalt‐Catalyzed (3+2) Cycloadditions of Alkynylidenecyclopropanes

Abstract

Low-valent cobalt complexes equipped with chiral ligands can efficiently promote highly enantioselective (3+ +2) cycloadditions of alkyne-tethered alkylidenecyclopropanes. The annulation allows to assemble bicyclic systems containing five-membered rings in good yields and with excellent enantiomeric ratios.W ea lso present am echanistic discussion based on experimental and computational data, whichsupport the involvement of Co I /Co III catalytic cycles. Scheme 1. Enantioselective cycloadditions of ACPs.

Co‐Catalyzed Asymmetric Intramolecular [3+2] Cycloaddition of Yne‐Alkylidenecyclopropanes and its Reaction Mechanism

“…In addition, substrates with substituted alkynes, whicha re aliphatic groups such as methyl (1l), cyclopropyl( 1m), and functionalized alkyl group bearing aO TBS substituent (1n), generated the desired products( 2l, 2m, 2n)i ng ood yields (72-90 %) and enantioselectivities (71-87% ee). It should be pointed out that, in some cases, more equivalents of AlMe 2 Cl (1.0 equiv)a nd ah igher reaction temperature (60 8C) were neededt oa cceleratet he transformations and ensure efficient conversions( entries [7][8][9][10][11][12][13][14][15][16][17][18]. Interestingly,t he protocolw ed eveloped can not only afford the fused 5,5-bicyclic ring systems but also generate the bicyclo [4.3.0]nonadiened erivatives 2o (83 %, 74 % ee), 2p (68 %, 55 % ee), and 2q (95 %, 59 % ee).…”

“…For example, using sterically hindered bisphospine ligand (S)-Xyl-BINAP( L 5 ) provided the desired product 2a in 85 %y ield and 89 % ee (entry 11). It was interesting to observe that using axial chirall igands (L 6 -L 10 ;e ntries [12][13][14][15][16] and other types of ligands( L 11 -L 13 ;e ntries [17][18][19] can all realize the reaction. However,p oorer enantioselectivities were obtained compared to the L 5 ligand.…”

“…[11] It is interesting to find that using Zn/ZnI 2 as activator instead, the oxygen-tethered substrate 1s and carbon-tethered substrates 1t and 1u can participate in the [3+ +2] reactions, affording the desired product 2s (90 %, 87 % ee), 2t (81 %, 88 % ee), and 2u (92 %, 88 % ee), respectively. [12] We also tested the substrate 1v with an aryl group as tether,f inding that the reactiont ook place in high yield of 85 %, but almost no ee wasobtained.…”

“…We expect that the present reaction will become au seful toolf or synthetic chemists and the mechanism here will be inspiring for understanding/designing of known/new Co-catalyzed reactions. [12] ComputationalMethods DFT calculations with the Gaussian 09 program [19] were used to explore the mechanism of the reaction. The B3LYP functional [20] was used to optimize the geometries of all stationary points in the gas phase with the LANL2DZ basis set [21] for cobalt and 6-31G(d) basis set [22] for the other atoms.…”

Cobalt‐Catalyzed Intramolecular Cycloadditions of Alkenylidenecyclopropanes with Alkenes and Dienes

“…Moreover, we discovered that the cobalt‐catalyzed annulation exhibits a different mechanism than those promoted by noble metals, which usually entail an initial oxidative addition cleavage of the cyclopropane ring. In the case of cobalt chemistry, the reaction prefers to start with the coordination of the enyne to a cationic Co(I) species to deliver a highly stable intermediate I , that undergoes an oxidative cyclization to the key spirocobaltacyclopentene intermediate II (Scheme 1a) [7c–d] …”