Access to chiral tertiary amines via the iridium-catalyzed asymmetric hydrogenation of enamines

Asymmetric Hydrogenation of Unfunctionalized Enamines Catalyzed by Iridium Complexes of Chiral Spiro N,N‐Diarylphosphoramidites

“…Entries 15-18). The hydrogenation of enamine 3a can also be carried out at 1×10 6 Pa of hydrogen, giving a comparable result (Entry 19). It is worthy noting that the catalyst loading can be lowered to 0.1 mol% without diminishing the enantioselectivity of reaction (Entry 20).…”

“…4,5 By using chiral spiro monophosphoramidite ligand (R)-2a with two phenyl groups on nitrogen atom, the enamine 3a was quantitatively hydrogenated under 5×10 6 Pa of hydrogen in THF, and chiral amine (S)-4a was obtained in 97% yield with 87% ee (Table 1, Entry 1). This result was better than those obtained by using Ir catalysts with P,N-ligands reported in the literatures (33% ee and 44% ee), 6,7 and encouraged us to study the effect of N-aryl group of the ligands on the enantioselectivity of the hydrogenation of enamines 3. A series of spiro phosphoramidite ligands (R)-2 with different N-aryl or N,N-diaryl groups were synthesized by our previous method.…”

“…However, the enamine 3c with a morpholine moiety was reluctant to be hydrogenated under standard conditions. It was only hydrogenated under 5×10 6 Pa of hydrogen at 50 ℃, providing chiral amine 4c with 34% ee (Entry 3). The enamines 3d and 3e, both having an acyclic amino group, also showed low reactivity in the hydrogenation, requiring 24 h or 40 h at 5×10 6 Pa of hydrogen for full conversion (Entries 4 and 5).…”

“…3 We also demonstrated that iridium complexes of chiral spiro phosphoramidite ligands (R a ,S,S) or (S a ,R,R)-SIPHOSpe were excellent catalysts for the enantioselective hydrogenation of cyclic enamines such as 1-alkyl-2-arylpyrrolines (up to 97% ee) 4 and N-alkyl-1-alkylidenetetrahydroisoquinolines (up to 98% ee) 5 ( Figure 1). Andersson 6 and Pfaltz 7 independently introduced chiral iridium complexes of chiral P,N-ligands into the asymmetric hydrogenation of enamines, giving the corresponding tertiary amines with up to 87% ee and 92.5% ee, respectively.…”

Asymmetric Hydrogenation

“…Therefore, not only unfuctionalized alkenes but also alkenes with functional groups connected to their C=C double bonds have been hydrogenated with high to excellent enantioselectivity. Figure 6 shows examples of the [61], furan rings [62], -dehydroamino acid derivatives [63], ,β-unsaturated ketones [64],,β-unsaturated carboxylic acid esters [61], -alkoxy ,β-unsaturated acids [65], vinylphosphine oxides [66], enol phosphinates [67], vinyl boronates [68], and enamines [69,70]. Notably, substituted furans, vinyl boronates, and even enamines are hydrogenated with full conversion in high to excellent enantioselectivity.…”