Azole‐Directed Cobalt‐Catalyzed Asymmetric Hydrogenation of Alkenes

Abstract

The azole‐directed cobalt‐catalyzed asymmetric hydrogenation of alkenes has been developed with high efficiency. With this approach, chiral pyrazole compounds were obtained in quantitative yields and excellent enantioselectivities (up to 99 % ee) under mild conditions, and the hydrogenation was conducted on a gram scale with up to 2000 TON. Several useful applications were demonstrated including the convenient introduction of β‐chirality to a drug intermediate containing an azole ring.

Cobalt-Catalyzed Enantioconvergent Hydrogenation of Minimally Functionalized Isomeric Olefins

“…Based on previous studies on cobalt-catalyzed asymmetric olefin hydrogenation by Chirik, − our group, , and others, − we found that cobalt-catalyzed asymmetric hydrogenation of 1,1-disubstituted alkenes led to a certain amount of undesired E / Z mixtures of thermodynamically more stable trisubstituted alkenes as side-products, which were quite difficult to separate from the desired hydrogenated products. Although this olefin isomerization issue − limited the utility of the protocol, it does offer an opportunity to stereoconvergently convert the alkene isomers.…”

Cobalt-Catalyzed Efficient Asymmetric Hydrogenation of α-Primary Amino Ketones

“…Based on a series of differentiated cobalt catalytic systems, a wide variety of alkene substrates, bearing largely unfunctionalized groups (UFG) as well as functionalized groups (FG) including acylamino, carboxyl, and azolyl, can be hydrogenated with excellent enantioselectivities and yields (Scheme a, up). − From the data recorded, bis­(phosphine) (PP) ligands are more suitable for the latter and often achieve a higher catalytic efficiency (up to 2000 TON). It is important to note that the assisted coordinating groups such as a pyrazolyl with N -coordination are critical for the high efficiency in the cobalt-catalyzed asymmetric hydrogenation of functionalized olefins, which enables the reaction to proceed smoothly at ambient temperature and pressure and to complete quickly within 1 h (Scheme a, down) …”

“…These results coupled with our understanding of the catalytic mechanism propelled us to envisage that cobalt-catalyzed efficient asymmetric hydrogenation of the CO bond may no longer be out of reach. Compared with the traditional acyl and hydroxyl groups using the oxygen atom as the coordinating atom, the imino and amino groups using the nitrogen atom as the coordinating atom are considered to form stronger coordinate bonds . In particular, the simple primary amino group (NH 2 ) has the least steric hindrance and, thus, is more favorable for coordination bond formation.…”

“…In particular, the simple primary amino group (NH 2 ) has the least steric hindrance and, thus, is more favorable for coordination bond formation. This is conducive to improving the stability of cobalt complexes that are relatively sensitive to the coordination space. ,, …”

“…It is important to note that the assisted coordinating groups such as a pyrazolyl with N-coordination are critical for the high efficiency in the cobalt-catalyzed asymmetric hydrogenation of functionalized olefins, which enables the reaction to proceed smoothly at ambient temperature and pressure and to complete quickly within 1 h (Scheme 1a, down). 19 However, for cobalt-catalyzed asymmetric hydrogenation of double bonds containing heteroatoms, the catalytic efficiency is relatively lower, and much fewer achievements have been made, either with relatively lower catalytic efficiency or with harsh conditions (Scheme 1b and c, up). 25−30 To tackle this issue, the assisted coordination strategy has been introduced to enable the cobalt-catalyzed asymmetric hydrogenation of the C�N bond with high efficiency (up to 2000 TON).…”