Determining stereoisomeric excess, concentration and absolute configuration

Patent metadata

Field	Value
Publication number	US-10012627-B2
Application number	US-201414777264-A
Country	US
Kind code	B2
Filing date	Mar 15, 2014
Priority date	Mar 15, 2013
Publication date	Jul 3, 2018
Grant date	Jul 3, 2018

Abstract

The present invention is directed to analytical methods for determining the concentration, and/or stereoisomeric excess, and/or absolute configuration of chiral analytes in a sample.

First claim

What is claimed:

1. An analytical method comprising:
providing a sample potentially containing a chiral analyte that can exist in stereoisomeric forms;
providing a racemic mixture of a probe having the formula A m -MR n —Y o , wherein:
each A is independently a chiral stereodynamic ligand that undergoes rapid stereoisomeric interconversion at room temperature,
M is a metal,
each R is independently a metal coordinating ligand,
each Y is independently a displaceable ligand,
m is an integer from 1 to 6, and
n and o are each independently an integer from 0 to 6, wherein the sum of m, n, and o is from 1 to 6;

contacting the sample with the racemic mixture under conditions effective to form probe-analyte complexes; and
determining, based on the probe-analyte complexes that form, the stereoisomeric excess of the analyte in the sample and/or the concentration of the analyte in the sample.

2. The analytical method according to claim 1 , wherein A is selected from the group consisting of 1,1′-bis(diphenylphosphino)ferrocene (DPPF), 2,2′-bis(diphenylphosphino)diphenyl ether (BDPDE), 2,2′-bis(diphenylphosphino)-1,1′-biphenyl (BIPHEP), BIPHOS, 2,2′-diaminobiphenyls, 2,2′-dihydroxybiphenyls, and analogues of each of the preceding compounds.

3. The analytical method according to claim 1 , wherein M is selected from the group consisting of palladium, magnesium, boron, aluminum, copper, zinc, iron, cobalt, nickel, platinum, gold, titanium, vanadium, manganese, chromium and cobalt.

4. The analytical method according to claim 3 , wherein M is Pd(II).

5. The analytical method according to claim 1 , wherein each Y is independently selected from the group consisting of H, OH, NH 2 , NCCH 3 , CF 3 SO 3 − , alkyls, alkenyls, alkynyls, halogens, halides, halogen-containing anions, haloalkyls, haloalkenyls, hydroxyls, alcohols, hydrides, carbonyls, aldehydes, carbonate esters, carboxylates, carboxyls, esters, alkoxyls, alkoxides, ethers, hemiacetals, hemiketals, acetals, ketals, orthoesters, orthocarbonate esters, amides, amines, imines, imides, azides, diimides, cyanates, cyanides, nitrates, nitriles, nitrites, nitrosos, pyridyls, thiols, thioethers, disulfides, sulfoxides, sulfones, sulfonates, thiocyanates, thiones, phosphines, phosphoric acids, phosphates, aryls, heteroaryls, arylalkyls, heterocycles, cycloalkyls, cycloalkenyls, and acyls.

6. The analytical method according to claim 1 , wherein the probe is selected from the group consisting of

7. The analytical method according to claim 1 , wherein the analyte is a compound selected from the group consisting of amines, alcohols, amino alcohols, carboxylic acids, amino acids, thiols, aldehydes, ketones, amides, esters, and any combination thereof.

8. The analytical method according to claim 7 , wherein the analyte is a diamine or an amino alcohol.

9. The analytical method according to claim 1 , wherein the stereoisomeric excess of the probe-analyte complexes is determined.

10. The analytical method according to claim 9 , wherein the analyte is a reaction product and the stereoselectivity of the reaction is determined by determining the stereoisomeric excess of the analyte.

11. The analytical method according to claim 1 , wherein the concentration of the probe-analyte complexes is determined.

12. The analytical method according to claim 11 , wherein the analyte is a reaction product and the yield of the reaction is determined by determining the concentration of the analyte.

13. The analytical method according to claim 1 , wherein the stereoisomeric excess of the probe-analyte complexes and the concentration of the probe-analyte complexes are both determined.

14. The analytical method according to claim 13 further comprising:
determining the individual concentration of any particular stereoisomers present in the sample based on the determined concentration of the analyte and the determined stereoisomeric excess.

Assignees

• Univ Georgetown

Inventors

• Wolf Christian
• Zhang Peng

Classifications

• G01N21/19 Primary

  Dichroism · CPC title

• G01N31/10 Primary

  using catalysis · CPC title