One‐Step Synthesis of Chiral Azamacrocycles via Palladium‐Catalyzed Enantioselective Amination of 1,5‐Dichloroanthraquinone and 1,5‐Dichloroanthracene

Abstract

Asymmetric amination of 1,5-dichloroanthraquinone and 1,5-dichloroanthracene with di-and trioxadiamines catalyzed by palladium complexes with various chiral phosphine ligands gave chiral macrocycles with ee values of up to 60%. The dependence of the chemical yields and enantiomeric excess on the nature of the starting compounds and the phosphine ligands employed was demonstrated. An unexpected spontaneous resolution upon crystallization of the macrocycle comprising anthraquinone and dioxadiamine moieties was observed while in the case of the macrocycle with a trioxadiamine linker racemic monocrystals were obtained. Crystallization of the enantiomerically enriched mixtures afforded chiral macrocycles with 88-99% ee.

Pd(0)-Сatalyzed Amination in the Synthesis of Planar-Chiral Macrobicyclic Compounds Comprising 1,5-Disubstituted Anthraquinone Moiety

“…The macrocyclization was catalyzed by Pd(dba) 2 /rac-BINAP to form racemic mixtures of the macrocycles 3 or by Pd(dba) 2 /Josiphos SL-J002-2 which was found out by us previously to be the best for ensuring the enantiomeric induction in such processes. [16] The reactions were run in boiling dioxane in the presence of Cs 2 CO 3 as base for 30-40 h using 0.02 M concentration of the reagents (Scheme 1). Usually the reactions were first run with 0.2-0.25 mmol of starting compounds and in the case of success they were scaled up to 2-3 mmol of the starting reagents.…”

“…[14] Almost all these reactions were accomplished using non-catalytic methods, and a rare exception is the synthesis of several planar-chiral macrocycles using metathesis reaction at the macrocyclization step. [15] Several years ago we have proposed a direct route to planar-chiral macrocycles using Pd(0)-catalyzed macrocyclization in the presence of chiral phosphine ligands, [16] and further the possibility to synthesize planarchiral macrobicycles comprising cyclam central moiety was also shown. [17] In this connection the present research is aimed at the synthesis of macrobicycles based on the central planar-chiral macrocycle formed around 1,5-disubstituted anthraquinone.…”

Contribution of I. P. Beletskaya in the Twentieth Year Successful Russian-French Cooperation in Catalytic Syntheses

“…The best enantiomeric excess reached 60 %. [21] Another research direction was the synthesis of colorimetric detectors for metal cations using cyclic and non-cyclic polyamino derivatives of anthraquinone, this became possible due to intensive absorption of such compounds in visible region (ca 520-530 nm). The decoration of the compounds with amidophosphonate arms in order to provide solubility in water resulted in the creation of several selective molecular sensors for Cu(II) and Pb(II) cations (Figure 1).…”

Synthesis of Macrocycles Containing Endocyclic Chiral BINAM Moieties

“…planar-chiral macrocycles, [1][2][3] and our previous works contributed to this field. [4,5] Also we elaborated a new type of macrocycles with endocyclic chiral cholane fragments. [6][7][8][9] Macrocyclic compounds containing fragments with C2 chirality are known for quite a long time, and the majority Macrocycles Containing Endocyclic Chiral BINAM Moieties of them possess 2,2'-binaphthol (BINOL) moiety.…”