Regioselective 1,2-dearomatization of functionalized azines by organolanthanide catalysts

Patent metadata

Field	Value
Publication number	US-9862732-B2
Application number	US-201514961472-A
Country	US
Kind code	B2
Filing date	Dec 7, 2015
Priority date	Dec 5, 2014
Publication date	Jan 9, 2018
Grant date	Jan 9, 2018

Abstract

A 1,2-regioselective organolanthanide-catalyzed azine dearomatization process using pinacolborane is disclosed.

First claim

What is claimed is:

1. A method for dearomatizing an aromatic azine ring compound, said method comprising treating an azine ring compound comprising at least one nitrogen atom with at least one main-group element hydride in the presence of an organolathanide catalyst to afford a 1,2-dearomatized azine.

2. The method according to claim 1 , wherein the 1,2-dearomatized azine is regioselective.

3. The method according to claim 2 , wherein the regioselective 1,2-dearomatized azine is a regioselective 1,2-dihydropyridine.

4. A method according to claim 1 , wherein the at least one main-group element hydride is pinacolborane.

5. A method according to claim 1 , wherein the organolanthanide catalyst has a formula of (L) x Ln-H, wherein L is an ancillary ligand selected from a group consisting of Cp, Cp* and CGC, Cp″; Ln is a lanthanide element; X is an integer selected from a group consisting of 1 and 2; and H is hydrogen.

6. A method according to claim 5 , wherein the lanthanide element is selected from a group consisting of Sc, Y, La, Sm, Nd, Yb and Lu.

7. A method according to claim 1 , wherein the azine is a substituted with one or more subsituents.

8. A method according to claim 7 , wherein the one or more substituents are independently selected from a group consisting of halogen, CF 3 , OMe, (2S)-1-methyl-2-pyrrolidinyl, 1-piperidinyl, phenyl, vinyl, SnMe 3 , Bpin and fused ring systems and combinations thereof.

9. A method according to claim 1 , wherein the azine is pyridine.

10. A method according to claim 1 , wherein the azine and the at least one main-group element hydride are present in equimolar quantity.

11. A method according to claim 10 , wherein the catalyst is present in less than equimolar quantity relative to the azine and the at least one main-group element hydride.

12. A method according to claim 11 , wherein the catalyst is present in about 1% stoichiometric quantity relative to the azine and the at least one main-group element hydride.

13. A method according to claim 1 , wherein the treating of the azine with at least one main-group element hydride in the presence of an organolathanide catalyst is performed in a solvent comprising benzene.

14. A method according to claim 3 , wherein the regioselective 1,2-dihydropyridine is selected from a group consisting of:
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-phenyl-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-methyl-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-fluoro-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-methyl-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,5-methyl-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-methoxy-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydroquinoline;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydroisoquinoline;
1,4-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydropyrazine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-iodo-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-methoxy-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-piperidino-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-vinyl-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-trimethylstannyl-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-chloro-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-chloro-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-bromo-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-bromo-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-iodo-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-iodo-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-phenyl-1,2-dihydropyridine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-phenyl-1,2-dihydropylidine;
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-[(2S)-1-methyl-2-pyrrolidinyl-1,2-dihydropyridine; and
1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-[(2S)-1-methyl-2-pyrrolidinyl-1,2-dihydropyridine (3s).

Assignees

• Univ Northwestern

Inventors

• Marks Tobin J
• Delferro Massimiliano
• Dudnik Alexander S
• Weidner Victoria L

Classifications

• C07F5/025 Primary

  Boronic and borinic acid compounds · CPC title

• C07F7/2208

  Compounds having tin linked only to carbon, hydrogen and/or halogen · CPC title

• B01J2231/344

  Boronation, e.g. by adding R-B(OR)2 · CPC title

• B01J2531/37

  Lanthanum · CPC title

• B01J2531/38

  Lanthanides other than lanthanum · CPC title