Recent Progress and Applications of Transition-Metal-Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation of Ketones and Imines through Dynamic Kinetic Resolution

Abstract

Based on the ever-increasing demand for enantiomerically pure compounds, the development of efficient, atom-economical, and sustainable methods to produce chiral alcohols and amines is a major concern. Homogeneous asymmetric catalysis with transition-metal complexes including asymmetric hydrogenation (AH) and transfer hydrogenation (ATH) of ketones and imines through dynamic kinetic resolution (DKR) allowing the construction of up to three stereogenic centers is the main focus of the present short review, emphasizing the development of new catalytic systems combined to new classes of substrates and their applications as well.1 Introduction2 Asymmetric Hydrogenation via Dynamic Kinetic Resolution2.1 α-Substituted Ketones2.2 α-Substituted β-Keto Esters and Amides2.3 α-Substituted Esters2.4 Imine Derivatives3 Asymmetric Transfer Hydrogenation via Dynamic Kinetic Resolution3.1 α-Substituted Ketones3.2 α-Substituted β-Keto Esters, Amides, and Sulfonamides3.3 α,β-Disubstituted Cyclic Ketones3.4 β-Substituted Ketones3.5 Imine Derivatives4. Conclusion

Asymmetric Synthesis of Monofluorinated Carbocyclic Alcohols and Vicinal Difluorinated Heterocycles and Carbocycles

“…[20] Because of the important features of the motif described above, and as a continuation of our work directed towards the preparation of valuable enantioenriched building blocks, [21][22][23][24] we report herein the synthesis of novel families of enantioenriched cis-monofluorinated carbocyclic alcohols and trans-difluorinated indans, 1,2,3,4-tetrahydronaphthalenes, N-Boc tetrahydroquinolines and chromans 8, by deoxofluorination of the corresponding cis-fluoro alcohols 7 (Scheme 1). The enantiomerically enriched 2-fluoro inden-1-ol (7, X = CH 2 , n = 0) and 2-fluoro 1,2,3,4-tetrahydronaphthalen-1-ol (7, X = CH 2 , n = 1) derivatives would result from transition metal-catalyzed asymmetric transfer hydrogenation/dynamic kinetic resolution (ATH/DKR) [25][26][27][28][29][30][31][32] of 2-fluoro-2,3-dihydro-1H-inden-1-ones and 2- www.eurjoc.org fluoro-3,4-dihydronaphthalen-1(2H)-ones 6 whereas we previously achieved the preparation of enantioenriched fluoro chromanols (7, X = O) [33] and N-Boc fluoro hydroxy dihydroquinolines (7, X = NBoc) [34] derivatives.…”

Ru-catalyzed asymmetric hydrogenation of α,β-unsaturated ketones via a hydrogenation/isomerization cascade

“…The stereoselectivities of 5a are controlled by the chiral Ru catalyst via a DKR process. [27][28][29] In conclusion, we have developed a Ru-catalyzed asymmetric hydrogenation of a-substituted a,b-unsaturated ketones for the synthesis of chiral saturated alcohols containing two vicinal stereocenters with excellent stereoselectivities. Mechanistic studies suggest that the reaction proceeds via a metal-base cooperative process, with the former enabling the selective asymmetric hydrogenation of the CQO bond while the latter promotes the isomerization of intermediary allylic alcohols.…”

Asymmetric Hydrogenation of Racemic 2-Substituted Indoles via Dynamic Kinetic Resolution: An Easy Access to Chiral Indolines Bearing Vicinal Stereogenic Centers

“…Hence, DKR has found great potential in constructing chiral molecules with multiple stereogenic centers. DKR-based asymmetric hydrogenation (AH) has been broadly studied and established as an important means to synthesize chiral alcohols or amines with contiguous stereocenters. , With suitable chiral catalytic systems, a remarkable match–mismatch effect is achieved in the reduction process of each enantiomer, which eventually leads to high enantioselectivity and diastereoselectivity of products (Scheme a). The efficiency and practicality of DKR asymmetric hydrogenation have been evidenced in the production of numerous pharmaceuticals, fine chemicals, and agrochemicals. , However, this useful method is mainly limited to enolizable ketones or activated imines, while other types of substrates are rarely explored and thus highly desirable.…”