Advances in the Asymmetric Synthesis of BINOL Derivatives

Abstract

BINOL derivatives have shown relevant biological activities and are important chiral ligands and catalysts. Due to these properties, their asymmetric synthesis has attracted the interest of the scientific community. In this work, we present an overview of the most efficient methods to obtain chiral BINOLs, highlighting the use of metal complexes and organocatalysts as well as kinetic resolution. Further derivatizations of BINOLs are also discussed.

Keywords: BINOL; chirality transfer; kinetic resolution; metal-mediated enantioselective coupling; organocatalysis.

Figure 1

Enantiomers of the biaryl 6,6’-dinitro-2,2’-diphenic acid.

Figure 2

Examples of biologically active compounds with axial chirality.

Scheme 1

Chiral Cu-amine catalytic systems employed in the construction of BINOL derivatives with axial chirality [39,40,41,42,43,44,45,46,47].

Scheme 2

Chiral V, Fe, and Ru catalytic systems employed in the construction of optically pure C2-symmetric BINOL derivatives [50,51,52,53,54,55,56,57,58,59].

Scheme 3

General aspects of the mechanism for aerobic radical–anion coupling of 2-napthols in the presence of metallic chiral complex catalysts (Mⁿ⁺). DG: coordination aids. Adapted from Brunel et al [57].

Scheme 4

Recent synthetic protocols for the construction of axially chiral BINOL derivatives.

Scheme 5

Mechanistic proposal for the enantioselective aerobic coupling of 2-naphthols based on a ligand catalytic system containing a spirocyclic skeleton of pyrrolidine oxazoline/CuBr.

Scheme 6

Enantioselective coupling between 2-naphthols (3c) mediated by an iron/bisquinolyldiamine ligand complex.

Scheme 7

(Aqua)ruthenium (salen) catalyzed enantioselective aerobic coupling between 2-naphthols for access to C1-symmetric BINOL derivatives.

Scheme 8

Asymmetric oxidative coupling of 2-naphthols mediated by a macrocyclic Cu(II) complex.

Scheme 9

Chiral diphosphine oxide-iron(II) complex catalyzed enantioselective aerobic coupling between 2-naphthols to access C1-symmetric BINOL derivatives.

Scheme 10

Copper-catalyzed asymmetric oxidative coupling of 2-naphthols for the synthesis of 6,6′- disubstituted BINOLs.

Scheme 11

Atroposelective synthesis of (R)- and (S)-BINOLs (1) via mono- and binuclear vanadium catalysts.

Scheme 12

Electrochemical synthesis of (S)-BINOL (1) using a TEMPO-modified graphite electrode.

Scheme 13

Enantioselective Ni-promoted electrochemical synthesis of (R)-BINOL derivatives (1).

Scheme 14

Palladium-catalyzed kinetic resolution of 2,2’-dihydroxy-1,1’-biaryls using 6.

Scheme 15

(A): Enantioselective intramolecular multi-step transformation catalyzed by chiral guanidine 9. (B): synthesis of (R)-11 through optical resolution using chiral diamine (S,S)-12.

Scheme 16

Kinetic resolution of a BINOL derivative promoted by a DMAP-type (14) catalyst through O-acylation.

Scheme 17

Kinetic resolution of a BINOL derivative promoted by a NHC catalyst 18.

Scheme 18

Synthesis of binaphthyl derivatives through an intramolecular aldol condensation using catalyst 21.

Scheme 19

Asymmetric synthesis of BINOL derivatives 25 via O-alkylation using catalyst 24.

Scheme 20

Synthesis of (S)-29 via atroposelective aldol condensation using catalyst 27.

Scheme 21

Kinetic resolution of BINOL mediated by catalyst 32.

Scheme 22

Enantiospecific hydrolysis catalyzed by cholesterol esterase.

Scheme 23

Kinetic resolution by lipase (Candida antarctica).

Scheme 24

Kinetic resolution with immobilized Pseudomonas sp. lipoprotein lipase.

Scheme 25

Preparation of chiral quaternary ammonium bromide as a phase transfer catalyst from (S)-BINOL (1).

Scheme 26

Synthesis of (S)-3,3’,6,6’-tetrakis(trifluoromethyl)-BINOL (42) from (S)-BINOL (1).

Scheme 27

Synthesis of BINOL derivatives containing phosphoric acid.