Synthesis method of chiral binaphthyl dicarboxylic acid

In the past two or three decades, asymmetric catalytic reactions have been one of the hotspots of scientific researchers in the field of chemistry at home and abroad. As an important catalyst and synthetic intermediate for asymmetric catalytic reaction, studies on chiral carboxylic acids such as chiral binaphthyl dicarboxylic acid and its derivatives have attracted much attention. However, the preparation of chiral binaphthalene dicarboxylic acid and its derivatives is difficult and not commercially available, so the practical application of the substance is greatly limited.

At present, the synthetic methods for chiral binaphthyl dicarboxylic acid mainly include:

1. Chiral resolution of racemic binaphthyl dicarboxylic acid;

2. After chiral 2,2'-bis(trifluoromethanesulfonate)-1,1'-binaphthyl is cyanated, the cyano group is hydrolyzed to a carboxylic acid, or a chiral 2,2'- The bis(trifluoromethanesulfonate)-1,1'-binaphthyl is directly methoxycarbonylated with carbon monoxide to form a chiral binaphthylcarboxylate, which is then hydrolyzed to obtain the target product;

3. Optically active 2-halonaphthalene derivatives are prepared by intermolecular or intramolecular diastereoselective Ullmann coupling reactions.

However, these methods are either disadvantageous in that the route is too long, the reaction conditions are severe, such as high temperature and high pressure, or the raw materials are toxic. In 2004, Hoshi T et al. reported the preparation of chiral binaphthalene dicarboxylic acid using chiral 2,2'-dibromo-1,1'-binaphthalene, ie by chiral 2,2'-dibromo-1 After the 1'-binaphthyl salt is made into a dilithium salt, a chiral 1,1'-binaphthyl-2,2'-dicarboxylic acid is obtained by introducing a CO2 gas into the solution at -72 ° C for carboxylation reaction.

Instruments and reagents

2-naphthol (AR), 80% (mass fraction) hydrazine hydrate (AR), dry ice (homemade), D-( )-10-camphorsulfonic acid (AR), n-BuLi (2.5 mol / L) Alkane solution (AR), N, N, N', N' - tetramethylethylenediamine (TMEDA) (AR, refluxed with CaH2 and then distilled off).

Bruker ARX-400 NMR (TMS is an internal standard), PerkinElmer 341 LC polarimeter, Agilent 1100 High Performance Liquid Chromatograph, X4A Micro Melting Point Tester.

Starting from the cheap and readily available raw material 2-naphthol and 80% hydrazine hydrate, the optically active 2,2'-diamine-1,1'-binaphthyl was synthesized in three steps, and the enantiomer was passed through bromine. The (R)-1,1'-binaphthyl-2,2'-dicarboxylic acid was prepared by substitution, lithiation and carboxylation, and its optical purity was 84%, and the yield was good in each step. Suitable synthesis conditions are:

1. In the preparation of 2-naphthoquinone, m (hydrated hydrazine): m (2-naphthol) = 1.8: 1;

2. In the process of lithium reduction of (R)-2,2'-dibromo-1,1'-binaphthyl, the amount of additive TMEDA is used for the target product (R)-1,1'-binaphthyl-2 The yield and ee value of 2'-dicarboxylic acid have effects. The choice of n(TMEDA): n((R) -2,2'-dibromo-1,1'-binaphthyl) is 2:1. Reaction conditions;

3. In the final step of the carboxylation reaction, instead of introducing CO2 gas at -72 ° C, the solution containing the binaphthyl dilithium salt is directly mixed with dry ice at -20 ° C to obtain a target product having an equivalent ee value. , shortening the carboxylation reaction time and simplifying the operation steps.

Item number

product name

CAS

specification

package

Price¥

C84-4095

--naphthol/2-naphthol

135-19-3

AR

100g

48

D16-1018634

carbon dioxide

124-38-9

0.1mg/ml

100ml

Inquiry

D23-A01341

L-(-) camphorsulfonic acid

35963-20-3

AR, 99%

25g

108

C16-T10695

N-hexane solution, triethyl aluminum

97-93-8

1.0M

25ml

196

D16-1012646

Hydrazine

7803-57-8

90% AR

500ml

144