Cobalt-catalyzed highly enantioselective hydrogenation of α,β-unsaturated carboxylic acids

Abstract

Asymmetric hydrogenation of α,β-unsaturated acids catalyzed by noble metals has been well established, whereas, the asymmetric hydrogenation with earth-abundant-metal was rarely reported. Here, we describe a cobalt-catalyzed asymmetric hydrogenation of α,β-unsaturated carboxylic acids. By using chiral cobalt catalyst bearing electron-donating diphosphine ligand, high activity (up to 1860 TON) and excellent enantioselectivity (up to >99% ee) are observed. Furthermore, the cobalt-catalyzed asymmetric hydrogenation is successfully applied to a broad spectrum of α,β-unsaturated carboxylic acids, such as various α-aryl and αalkyl cinnamic acid derivatives, α-oxy-functionalized α,β-unsaturated acids, α-substituted acrylic acids and heterocyclic α,β-unsaturated acids (30 examples). The synthetic utility of the protocol is highlighted by the synthesis of key intermediates for chiral drugs (6 cases). Preliminary mechanistic studies reveal that the carboxy group may be involved in the control of the reactivity and enantioselectivity through an interaction with the metal centre.

Synthesis of fluorinated leucines, valines and alanines for use in protein NMR

“…Notably, asymmetric hydrogenation methods of 34 have been published, which allow the synthesis of either enantiomer of 35 and consequently provide selective access to either diastereomer of 4-fluoro- l -valine ( 42 or 43 ). 29 Common functional group manipulations allowed conversion of 35 to alkyl-fluoride 36 in 81% overall yield. Ruthenium-mediated oxidative degradation of 36 afforded carboxylic acid 37 in 73% yield.…”

Ni-catalyzed asymmetric hydrogenation of N-aryl imino esters for the efficient synthesis of chiral α-aryl glycines

“…1b) [28][29][30] . In view of current interest in the development of earthabundant metal catalysts in asymmetric hydrogenation [31][32][33][34][35][36][37][38][39][40][41] , which are inexpensive and environmentally friendly, the use of nickel has drawn increasing attention 24,[31][32][33][34][35][36][37][38][39][40][41] . Although Nicatalyzed asymmetric reduction has seen rapid development, the asymmetric hydrogenation of imines is still in its infancy 24,[42][43][44] .…”

Asymmetric hydrogenation and transfer hydrogenation in the enantioselective synthesis of flavonoids

“…With the goal to develop efficient methodologies based on cheaper Earth-abundant metals, X. Zhang and co-workers reported, recently, a Co-catalysed AH of a wide range of α,β-unsaturated carboxylic acids. 66 Under 60 atm of hydrogen pressure using 1 mol% of the commercially available diphosphine ligand ( L3 ) combined with the cobalt salt and 10 mol% of Zn as an additive, the α-arylcinnamic acid 10g , the key intermediate in Zhou's enantioselective synthesis of ( S )-equol ( S )- 9 , 63 was reduced with 90% yield and 94% ee after 48 h in MeOH at 50 °C (Scheme 11). Other seven different types of α,β-unsaturated carboxylic acids were hydrogenated (30 examples) with high enantioselectivities showing a wide utility of this methodology in the synthesis of chiral natural products and pharmaceuticals.…”