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. 2023 Feb 16;28(4):1907.
doi: 10.3390/molecules28041907.

Chiral 8-Amino-5,6,7,8-tetrahydroquinoline Derivatives in Metal Catalysts for the Asymmetric Transfer Hydrogenation of 1-Aryl Substituted-3,4-dihydroisoquinolines as Alkaloids Precursors

Giorgio Facchetti  1 , Francesca Neva  1 , Giulia Coffetti  1 , Isabella Rimoldi  1
Affiliations

Chiral 8-Amino-5,6,7,8-tetrahydroquinoline Derivatives in Metal Catalysts for the Asymmetric Transfer Hydrogenation of 1-Aryl Substituted-3,4-dihydroisoquinolines as Alkaloids Precursors

Giorgio Facchetti et al. Molecules. .

Abstract

Chiral diamines based on an 8-amino-5,6,7,8-tetrahydroquinoline backbone, known as CAMPY (L1), or the 2-methyl substituted analogue Me-CAMPY (L2) were employed as novel ligands in Cp* metal complexes for the ATH of a series of substituted dihydroisoquinolines (DHIQs), known for being key intermediates in the synthesis of biologically active alkaloids. Different metal-based complexes were evaluated in this kind of reaction, rhodium catalysts, C3 and C4, proving most effective both in terms of reactivity and enantioselectivity. Although modest enantiomeric excess values were obtained (up to 69% ee in the case of substrate I), a satisfactory quantitative conversion was successfully fulfilled even in the case of the most demanding hindered substrates when La(OTf)3 was used as beneficial additive, opening up the possibility for a rational design of novel chiral catalysts alternatives to the Noyori-Ikariya (arene)Ru(II)/TsDPEN catalyst.

Keywords: 1,2,3,4,5-pentamethylcyclopentadienyl metal complex; alkaloids precursors; cyclic imines; diamine ligand.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Tetrahydroisoquinoline core in biologically relevant natural and non-natural alkaloids.
Figure 2
Figure 2
ATH of different 1-aryl imines using C3 and C4 as catalysts. n.r. = no reaction.
Figure 3
Figure 3
Hypothesis of interaction between the ligand L1 or L2 with the substrate.
See this image and copyright information in PMC

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