Homogeneous Hydrogenation Catalysts in Organic Synthesis

Abstract

During recent years, studies of the activation of hydrogen by soluble catalysts have been intensely pursued. The scope of this chapter has been limited to those catalysts utilizing hydrogen gas in the reduction of organic substrates. The first hydrogenation of an organic molecule using a soluble catalyst rather than classical divided metal catalysts was reported in 1938. Other catalyst studies followed. Homogeneous and heterogenous catalysts employ a similar range of metals, but soluble complex catalysts are uniform and therefore show more clearly defined activity and selectivity. Variations of ligands in a soluble catalyst, resulting in arrange of properties, may be likened to poisoning of metal surfaces; but use of different ligands in theory makes possible precise control of a range of properties in soluble catalysts. Many developments are to come and with them the increasing utility of soluble catalyst in general organic synthesis.

Convergent (De)Hydrogenative Pathways via a Rhodium α-Hydroxylalkyl Complex

“…The transfer of hydrogen from metals to ketones and, through reversibility, from alcohols to metals is of fundamental importance to (de)­hydrogenation reactions mediated by metal catalysts . Such reactions involve metal hydride intermediates and can proceed via two distinct pathways involving hydride transfer to either the electrophilic carbon or the nucleophilic oxygen of the carbonyl group (Scheme ).…”

Invention of MK-8262, a Cholesteryl Ester Transfer Protein (CETP) Inhibitor Backup to Anacetrapib with Best-in-Class Properties

“…The third-generation approach that was designed to access intermediate 58 with high selectivity starts with a racemic addition of vinyl Grignard to the same commercially available aldehyde 53 , and subsequently to benefit from a catalytic double-stereodifferentiation kinetic resolution promoted by Hartwig or Helmchen iridium catalysts using chiral 60 , yielding a highly functionalized single enantiomer 61 in nearly quantitative yield. A Schrock- or Grubbs-type (Zhan 1B) catalyst-mediated ring-closing metathesis (RCM) of 61 , followed by hydrogenation of olefin 62 with Wilkinson catalyst yielded 58 in just four linear steps, a 40% overall yield, and with full control of enantio- and stereo-selectivity in all steps. Versatile bromide 58 can be readily converted to final candidates under Suzuki conditions with the desired boronic-acid – coupling partner.…”

Regularity of Deuteration in Linear Polyethylene Prepared by Saturation of Polycyclopentene over Homogeneous Catalysts

“…The hydrogenation process begins with Wilkinson’s catalyst losing one PPh 3 ligand and adding H 2 to form a rhodium dihydride complex (Rh–H 2 ), the active form of the catalyst. Then, the σ-metalalkyl intermediate is formed via the 1,2-insertion of Rh–H 2 to the olefin substrate, and the remaining H on the Rh center is transferred to complete the hydrogenation and regenerate the inactive form of the catalyst. ,, Scheme a shows the analogous deuteration mechanism, where H 2 is replaced with D 2 , and with the PCP repeat unit as the substrate. H/D exchange between the catalyst and polymer then becomes possible, as shown in Scheme b, where Rh–D 2 first coordinates with the PCP double bond and forms a σ-metalalkyl intermediate by 1,2-insertion.…”

“…Then, the σ-metalalkyl intermediate is formed via the 1,2insertion of Rh−H 2 to the olefin substrate, and the remaining H on the Rh center is transferred to complete the hydrogenation and regenerate the inactive form of the catalyst. 45,47,48 ) is ∼20 times more abundant than all HD that could potentially be released from all olefinic H on the polymer (a limit which is not approached over either catalyst). Thus, the coordination of the "inactive" form of Wilkinson's catalyst with "free" HD is not considered as a significant pathway to form Rh−HD.…”