Atropisomers and methods of altering enantiomeric excess

Patent metadata

Field	Value
Publication number	US-10584077-B2
Application number	US-201715854885-A
Country	US
Kind code	B2
Filing date	Dec 27, 2017
Priority date	Dec 27, 2016
Publication date	Mar 10, 2020
Grant date	Mar 10, 2020

Abstract

Provided herein are methods of altering enantiomeric excess. The methods may include irradiating an atropisomer that includes at least one chiral substituent to alter the enantiomeric excess of the atropisomer. The at least one chiral substituent may be removed following irradiation.

First claim

We claim:

1. A method of altering enantiomeric excess, the method comprising:
providing an atropisomer having an enantiomeric excess of 0% to 100%, wherein the atropisomer comprises at least one chiral substituent; and
irradiating the atropisomer to alter the enantiomeric excess;
wherein the atropisomer comprises a compound of formula (I), (II), (III), or (IV)—

wherein (i) R 1 is the at least one chiral substituent, (ii) R 2 is independently selected from hydrogen, a C 1 -C 30 hydrocarbyl, or a halogen, (iii) R 3 is independently selected from hydrogen, a C 1 -C 30 hydrocarbyl, or a halogen, and (iv) R 4 is independently selected from hydrogen or a halogen.

2. The method of claim 1 , wherein R 1 is a C 1 -C 30 hydrocarbyl comprising at least one chiral atom.

3. The method of claim 1 , wherein R 1 is an N-protected amino acid substituent.

4. The method of claim 3 , wherein the N-protected amino acid substituent has a structure according to formula (1), (2), (3), (4), (5), or (6):

5. The method of claim 1 , wherein R 1 is a substituent selected from formula (A) or (B);

6. The method of claim 1 , wherein R 2 is independently selected from the following substituents:

4-β-naphthylphenyl, 4-t-BuC 6 H 4 , or 3,5-t-Bu 2 C 6 H 3 .

7. The method of claim 1 , wherein R 3 is independently selected from the following substituents:

4-β-naphthylphenyl, 4-t-BuC 6 H 4 , or 3,5-t-Bu 2 C 6 H 3 .

8. The method of claim 1 , wherein the enantiomeric excess is 0% to about 5% prior to the irradiating of the atropisomer, and the atropisomer is a racemic atropisomer.

9. The method of claim 1 , wherein the enantiomeric excess is about 95% to 100% prior to the irradiating of the atropisomer, and the atropisomer is an enantiopure atropisomer.

10. The method of claim 1 , wherein the providing of the atropisomer comprises:
contacting an unsubstituted atropisomer with a chiral substituent precursor to form the atropisomer,
wherein the unsubstituted atropisomer comprises a hydroxyl functional group, and the chiral substituent precursor comprises an ester functional group or an acyl halide functional group.

11. The method of claim 10 , wherein the chiral substituent precursor comprises an N-protected amino acid.

12. The method of claim 10 , wherein the unsubstituted atropisomer comprises a compound of formula (I′), (II′), (III′), or (IV′):

wherein (i) R 2 is independently selected from hydrogen, a C 1 -C 30 hydrocarbyl, or a halogen, (ii) R 3 is independently selected from hydrogen, a C 1 -C 30 hydrocarbyl, or a halogen, and (iii) R 4 is independently selected from hydrogen or a halogen.

13. The method of claim 12 , wherein R 2 is independently selected from the following substituents:

4-β-naphthylphenyl, 4-t-BuC 6 H 4 , or 3,5-t-Bu 2 C 6 H 3 .

14. The method of claim 12 , wherein R 3 is independently selected from the following substituents:

4-β-naphthylphenyl, 4-t-BuC 6 H 4 , or 3,5-t-Bu 2 C 6 H 3 .

15. The method of claim 1 , wherein the irradiating of the atropisomer comprises exposing the atropisomer to electromagnetic radiation comprising one or more wavelengths of about 10 nm to about 900 nm.

16. The method of claim 1 , wherein the atropisomer is contacted with a base during at least a portion of the irradiating of the atropisomer.

17. An atropisomer according to formula (I), (II), (III), or (IV):

wherein (i) R 1 is a C 1 -C 30 hydrocarbyl comprising at least one chiral atom, (ii) R 2 is independently selected from hydrogen, a C 1 -C 30 hydrocarbyl, or a halogen, (iii) R 3 is independently selected from hydrogen, a C 1 -C 30 hydrocarbyl, or a halogen, and (iv) R 4 is independently selected from hydrogen or a halogen; and
wherein R 3 is independently selected from a C 1 -C 30 hydrocarbyl when the atropisomer is of formula (III).

18. The atropisomer of claim 17 , wherein R 1 is an N-protected amino acid substituent.

19. The atropisomer of claim 17 , wherein (i) R 2 is independently selected from the following substituents:

4-β-naphthylphenyl, 4-t-BuC 6 H 4 , or 3,5-t-Bu 2 C 6 H 3 ; and
(ii) R 3 is independently selected from the following substituents:

4-β-naphthylphenyl, 4-t-BuC 6 H 4 , or 3,5-t-Bu 2 C 6 H 3 .

Assignees

• Univ Florida State Res Found

Inventors

• Hanson Kenneth
• Ayad Suliman A
• Posey Victoria A

Classifications

• C07C68/06

  from organic carbonates · CPC title

• C07C69/96

  Esters of carbonic or haloformic acids · CPC title

• C07B55/00 Primary

  Racemisation; Complete or partial inversion · CPC title

• C07C2601/14

  The ring being saturated · CPC title

• C07D209/18

  Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title