Asymmetric Transfer Hydrogenation of Unhindered and Non-Electron-Rich 1-Aryl Dihydroisoquinolines with High Enantioselectivity

Barrios-Rivera, Jonathan; Xu, Ye; Wills, Martin

doi:10.1021/acs.orglett.0c02034

Cited by 27 publications

(9 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…90% and 93% for the conversion to THIQs (72-76) (Figure 18). The proposed mechanism (Figure 19) of this asymmetric reduction supported the extra stabilization of TS state 78 through the interaction of furan moiety of the catalyst with the aryl moiety of substrate [22]. Recently, the pyrazole/phosphine based ruthenium catalyst (1 mol %) also showed high TH activity of a variety of Nheterocyclic substrates.…”

Section: Ruthenium Catalyzed Synthesis Of Heterocyclesmentioning

confidence: 74%

Recent Advances in Ru Catalyzed Transfer Hydrogenation and Its Future Perspectives

Tyagi¹,

Borah²,

Patel³

et al. 2022

Ruthenium - An Element Loved by Researchers

View full text Add to dashboard Cite

Over the past few decades, Ru catalyzed transfer hydrogenation (TH) and asymmetric transfer hydrogenation (ATH) reactions of unsaturated hydrocarbons, imine, nitro and carbonyl compounds have emerged as economic and powerful tools in organic synthesis. These reactions are most preferred processes having applications in the synthesis of fine chemicals to pharmaceuticals due to safe handling as these do not require hazardous pressurized H2 gas. The catalytic activity and selectivity of Ru complexes were investigated with a variety of ligands based on pincer NHC, cyclophane, half-sandwich, organophosphine etc. These ligands coordinate to Ru center in a proper orientation with a labile group replaced by H-source (like methanol, isopropanol, formic acid, dioxane, THF), which facilitate the β-hydrogen transfer to generate metal hydride species (Ru-H) and produce desired reduced product. This chapter describes the recent advances in TH and ATH reactions with homogeneous and heterogeneous Ru catalysts having different ligand environments and mechanistic details leading to their sustainable industrial applications.

show abstract

Section: Ruthenium Catalyzed Synthesis Of Heterocyclesmentioning

confidence: 74%

Recent Advances in Ru Catalyzed Transfer Hydrogenation and Its Future Perspectives

Tyagi¹,

Borah²,

Patel³

et al. 2022

Ruthenium - An Element Loved by Researchers

View full text Add to dashboard Cite

show abstract

“…Several halogenated benzaldehydes were also investigated with dopamine catalysed by the M97V-TfNCS mutant, achieving the desired THIQ derivatives in good to excellent yield and with a high degree of stereoselectivity. Although several other biocatalytic and chemically methodologies have been outlined for the stereoselective synthesis of 1-aryl-THIQs, [155][156][157] this approach generates the desired product in a single step from widely available starting materials.…”

Section: Biocatalytic Pictet-spengler Reactionsmentioning

confidence: 99%

New Trends and Future Opportunities in the Enzymatic Formation of C−C, C−N, and C−O bonds

et al. 2021

View full text Add to dashboard Cite

Organic chemistry provides society with fundamental products we use daily. Concerns about the impact that the chemical industry has over the environment is propelling major changes in the way we manufacture chemicals. Biocatalysis offers an alternative to other synthetic approaches as it employs enzymes, Nature's catalysts, to carry out chemical transformations. Enzymes are biodegradable, come from renewable sources, operate under mild reaction conditions, and display high selectivities in the processes they catalyse. As a highly multidisciplinary field, biocatalysis benefits from advances in different areas, and developments in the fields of molecular biology, bioinformatics, and chemical engineering have accelerated the extension of the range of available transformations (E. L. Bell et al., Nat. Rev. Meth. Prim. 2021, 1, 1-21). Recently, we surveyed advances in the expansion of the scope of biocatalysis via enzyme discovery and protein engineering (J. R. Marshall et al., Tetrahedron 2021, 82, 131926). Herein, we focus on novel enzymes currently available to the broad synthetic community for the construction of new CÀ C, CÀ N and CÀ O bonds, with the purpose of providing the non-specialist with new and alternative tools for chiral and sustainable chemical synthesis.

show abstract

“…To evaluate the tolerance of transfer hydrogenation toward substrates presenting steric hindrance next to the imine moiety, we tested substrates 9 – 11 . 73 Substrate 9 is reduced with good activities but low stereoselectivity ( Table S15 ). The most promising ArM is 2 ·hCAII L60F-N62Y-N67G-E69R-I91C (415 TON, −55% ee , Table 4 , Entry 12).…”

Section: Substrate Screeningmentioning

confidence: 99%

“…The less-hindered substrate 8 gives a high TON but moderate enantioselectivity, with the most enantioselective ArM being 2 ·hCAII N67L‑E69Y‑I91C (500 TON, 59% ee ( S ), Table , Entry 9). To evaluate the tolerance of transfer hydrogenation toward substrates presenting steric hindrance next to the imine moiety, we tested substrates 9 – 11 . Substrate 9 is reduced with good activities but low stereoselectivity (Table S15).…”

Section: Substrate Screeningmentioning

confidence: 99%

A Dual Anchoring Strategy for the Directed Evolution of Improved Artificial Transfer Hydrogenases Based on Carbonic Anhydrase

et al. 2021

View full text Add to dashboard Cite

Artificial metalloenzymes result from anchoring a metal cofactor within a host protein. Such hybrid catalysts combine the selectivity and specificity of enzymes with the versatility of (abiotic) transition metals to catalyze new-to-nature reactions in an evolvable scaffold. With the aim of improving the localization of an arylsulfonamide-bearing iridium-pianostool catalyst within human carbonic anhydrase II (hCAII) for the enantioselective reduction of prochiral imines, we introduced a covalent linkage between the host and the guest. Herein, we show that a judiciously positioned cysteine residue reacts with a p-nitropicolinamide ligand bound to iridium to afford an additional sulfonamide covalent linkage. Three rounds of directed evolution, performed on the dually anchored cofactor, led to improved activity and selectivity for the enantioselective reduction of harmaline (up to 97% ee (R) and >350 turnovers on a preparative scale). To evaluate the substrate scope, the best hits of each generation were tested with eight substrates. X-ray analysis, carried out at various stages of the evolutionary trajectory, was used to scrutinize (i) the nature of the covalent linkage between the cofactor and the host as well as (ii) the remodeling of the substrate-binding pocket.

show abstract

Asymmetric Transfer Hydrogenation of Unhindered and Non-Electron-Rich 1-Aryl Dihydroisoquinolines with High Enantioselectivity

Abstract: Please refer to published version for the most recent bibliographic citation information. If a published version is known of, the repository item page linked to above, will contain details on accessing it.

Cited by 27 publications

References 49 publications

Recent Advances in Ru Catalyzed Transfer Hydrogenation and Its Future Perspectives

Recent Advances in Ru Catalyzed Transfer Hydrogenation and Its Future Perspectives

New Trends and Future Opportunities in the Enzymatic Formation of C−C, C−N, and C−O bonds

A Dual Anchoring Strategy for the Directed Evolution of Improved Artificial Transfer Hydrogenases Based on Carbonic Anhydrase

Contact Info

Product

Resources

About