Highly Chemo‐ and Enantioselective Hydrogenation of Linear α,β‐Unsaturated Ketones

Abstract

Asymmetric hydrogenation of olefins is one of the most powerful transformations in asymmetric catalysis. In reductions of unfunctionalized substrates, chiral iridium complexes with N-heterocyclic carbene ligands or P,N-ligands have revealed high activities and excellent enantioselectivities under relatively mild reaction conditions.[1] Catalytic asymmetric hydrogenations of functionalized olefins such as a-(acylamino) acrylic acids, enamides, a,b-unsaturated carboxylic acids and esters, allylic and homoallylic alcohols have also been widely investigated, and they can most successfully be performed with chirally modified ruthenium, rhodium and iridium complexes. [2] In contrast, enone-toketone hydrogenations are less studied, which is surprising considering the synthetic importance of compounds with stereogenic centers at the a-or b-position to a carbonyl group. [3] Generally, the chemoselectivity is a key issue in the hydrogenation of a,b-unsaturated ketones, since both double bonds can react. Commonly, in catalytic hydrogenations C= C double bonds are more reactive than C=O ones.[4] Important exceptions are Noyoris Ru II -diamine-diphosphine [5a-c] and Takayas Ir I -BINAP [5d] catalyst systems, which preferentially reduce carbonyl groups faster than C=C double bonds. Effective catalysts for enantioselective C=C bond hydrogenations of unsaturated ketones, especially those applicable for linear substrates, are still rare.[6] The following examples shall illustrate the current status.As early as 1983, Maux and Simonneaux investigated asymmetric hydrogenations of a,b-unsaturated ketones catalyzed by chiral [Co 2 (CO) 8 ]/phosphine complexes giving saturated ketones with 1-16 % ee.[7] Later, the enantioselectivity was improved to 62 % ee by using a chiral ruthenium complex as the catalyst, [8] but only 2 % ee were achieved in asymmetric hydrogenations of linear a,b-unsaturated ketones. In 1995, Takaya and co-workers employed Ru II -BINAP complexes as catalysts to hydrogenate exo-cyclic enones, and they obtained 2-alkyl-substituted cyclic ketones with up to 98 % ee.[9] However, the conversion of a 2-arylsubstituted substrate provided a product with only 9 % ee, and furthermore, to achieve full conversion, it was necessary to employ both high pressure (100 bar) and elevated temperature (50 8C). A few selected examples of hydrogenations of endo-cyclic enones were reported by Consiglio [10] and Genet.[11] The former obtained (two) products with up to 76 % ee and the latter focused on a synthesis of (+)-cismethyl dihydrojasmonate, which was finally prepared with 88 % ee. In 2005, Hilgraf and Pfaltz investigated the hydrogenation of 3-methyl cyclohexenone using iridium/P,Nligand complexes as catalysts, and a moderate enantioselectivity (58 % ee) was obtained under high pressure (100 bar) using a 4 mol % catalyst loading.[12] Subsequently, MacMillan [13] and List [14] found organocatalytic transfer hydrogenation of enones using Hantzsch esters as hydrogen sources. Excellent enantioselectivities (up to 98 % ee) were...

Asymmetric Hydrogenation of Olefins Using Chiral Crabtree-type Catalysts: Scope and Limitations

“…Interestingly, when β,β-disubstituted enones were reduced by the same complex, significant amounts of the saturated alcohol were obtained. 163 Using [Ir(cod)(5d)][BAr F ], both aryl-and alkyl-substituted alkenes could be reduced in 3 hours and using only 2 bar H 2 ( and S206 with dichloromethane and close to identical results were observed (Table 10, entries 7 and 8). 165 Recently, a catalytic system featuring phosphinite-oxazoline ligand 72, developed by Kazmaier and co-workers, was shown to give excellent enantioselecivities (>99% ee) in the hydrogenation of two α,β-disubstituted enones (Table 10, entries 9 and 10).…”

“…149 Ligands 69a and 69b both exhibited high selectivity but the former was significantly faster and thus used for further studies of both alkyl-(S161- 163) and aryl-substituted (S160) derivatives (Scheme 23). COOH COOH S157 S158 S159…”

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

“…Hence, optically active compounds based on 2 have been utilized in the synthesis of pseudopeptides [20–24], and they have found widespread application in auxiliary-assisted diastereoselective transformations or as chiral ligands in enantioselective metal catalysis [25–33]. With respect to the latter field we have recently demonstrated that various ligands bearing a sulfonimidoyl moiety lead to excellent stereoselectivities in transition metal-catalyzed hydrogenations and carbon–carbon bond formations [34–36]. …”

Synthesis of ligands based on naphthalene peri-substituted by Group 15 and 16 elements and their coordination chemistry

“…The resulting complexes 66 are air/moisture stable and were purified by column chromatography. They were used as catalysts in a range of asymmetric hydrogenations [50,52,53].…”