Enantioselective Cobalt‐Catalyzed Intermolecular Hydroacylation of 1,6‐Enynes

Abstract

We report a cobalt‐catalyzed hydroacylation of 1,6‐enynes with exogenous aldehydes in a domino sequence to construct enantioenriched ketones. The products were obtained in good yields with excellent regio‐, diastereo‐, and enantioselectivity. Furthermore, the chiral products served as valuable precursors to access complex spirocyclic scaffolds with three contiguous stereocenters. The asymmetric hydroacylation process exhibited no C−H crossover and no KIE, thus indicating that the C−H bond cleavage was not involved in the turnover‐limiting step.

Mechanism and origins of enantioselectivity of cobalt-catalyzed intermolecular hydroacylation/cyclization of 1,6-enynes with aldehydes

“…1). The wellprecedented cationic cobalt(I) species, which was suggested to be generated in the presence of zinc and NaBARF, 10 was taken as the active catalyst species for the reaction. To be noted, both singlet and triplet spin states of all species were computed and the spin-crossover mechanistic scenario was established.…”

“…11 In this context, Co complexes have shown particular promise for the hydrofunctionalization/cyclization of 1,6-enynes. 10 For instance, RajanBabu and co-workers developed the Co-catalyzed regiodivergent hydroalkenylation/cyclization of 1,6-enynes with alkenes 10b and Cheng et al realized the Co-catalyzed hydroacylation/cyclization and hydroarylation/cyclization of 1,6-enynes with aldehydes by a careful choice of ligands. 10c Very recently, Lautens and co-workers reported an elegant example of the cobalt-catalyzed intermolecular hydroacylation/ cyclization of 1,6-enynes (Scheme 1).…”

Cobalt-Catalyzed Enantioselective Intramolecular Reductive Cyclization via Electrochemistry

“…In order to better understand the reaction pathway, particularly which pathway is more favorable, DFT calculations were carried out to probe the proposed mechanism. To reduce the computational cost, the calculations were performed on a model reaction using carbon tethered enyne: methyl (E)-non-2-en-7ynoate and (dppe)Co(I) (singlet or triplet) as the starting complex 15,16,[18][19][20] .…”

“…1a). Known methods include [3+2] cyclization 15,16 , hydrosilylation 17 , homo-ene cyclization 18 , hydroarylative 19 and hydroacylative cyclization 20 , depending on the functional groups and the experimental conditions. Most of these reactions are proposed to be initiated by the formation of low-valent cobalt species, which promotes the alkyne/alkene oxidative cyclization to form a cocbaltacyclopentane intermediate, followed by the subsequent transformation.…”

Transition-Metal-Catalyzed Enantioselective Synthesis of Indoles from 2-Alkynylanilines

“…42 Inspired by this work, Lautens­ and co-workers developed a palladium-catalyzed asymmetric domino-Heck reaction/aminopalladation using Pd 2 (dba) 3 / L17 as the catalyst, and obtained bis-heterocyclic frameworks in generally good yields and excellent enantio­selectivities (Scheme 16 ). 43 Mechanistically, alkylpalladium(II) intermediate 90 was achieved by oxidative addition and insertion of the C=C double bond. Coordination of 90 with the triple bond of the 2-alkynylaniline followed by trans -aminopalladation and reductive elimination delivered the product.…”