Phosphinine oxide derivative and preparation method thereof

Patent metadata

Field	Value
Publication number	US-9493494-B2
Application number	US-201414473901-A
Country	US
Kind code	B2
Filing date	Aug 29, 2014
Priority date	May 30, 2014
Publication date	Nov 15, 2016
Grant date	Nov 15, 2016

Abstract

Provided are a novel phosphinine oxide derivative and a preparation method thereof, and more specifically, the phosphinine oxide derivative includes an oxaphosphinine oxide derivative and an azaphosphinine oxide derivative.
The phosphinine oxide derivative according to the present invention may have a pharmacological activity and a physiological activity, and may be used as a basic framework of a natural product and may be used for development of new drug and synthesis of various medical supplies.
In addition, according to the preparation method of the phosphinine oxide derivative according to the present invention, various phosphinine oxide derivatives with a high yield may be prepared by a simple synthesis process using an intramolecular annulation between a phosphinic derivative and an alkyne derivative in the presence of a rhodium (Rh) catalyst or a ruthenium (Ru) catalyst and an oxidant.

First claim

The invention claimed is:

1. A phosphinine oxide derivative represented by the following Chemical Formula 1:

in Chemical Formula (1),
X is NR′ or O;
R′ is C1-C20 alkyl or C6-C20 aryl;
R 1 and R 2 are each independently hydrogen, C1-C20 alkyl or C6-C20 aryl, or R 1 and R 2 may be linked to each other by —CR 11 ═CR 12 —CR 13 ═CR 14 — or -L-CR 15 ═CR 16 — to form a fused ring;
R 11 to R 16 are each independently hydrogen, C1-C20 alkyl, halo C1-C20 alkyl, C1-C20 alkoxy, C6-C20 aryl, halogen, C1-C20 alkylcarbonyl or hydroxyl, or may be linked to an adjacent substituent by C2-C7 alkenylene, C2-C7 alkylenedioxy or —CR 17 ═CR 18 —OC(═O)— to form a fused ring;
R 17 and R 18 are each independently C1-C20 alkyl or C6-C20 aryl;
L is NR″,O or S;
R″ is hydrogen or C1-C20 alkyl;
R 3 and R 4 are each independently C1-C20 alkyl or C6-C20 aryl; and
R 5 is C1-C20 alkoxy, C6-C20 aryl or C3-C20 heteroaryl,
wherein the alkyl and aryl of R 1 , R 2 , R 3 and R 4 , and the alkoxy, aryl, and heteroaryl of R 5 may be further substituted with at least one substituent selected from the group consisting of halogen, C1-C20 alkyl, C1-C20 alkoxy and halo C1-C20 alkyl, respectively;
with a proviso that if R 1 and R 2 are linked to each other by —CR 11 ═CR 12 —CR 13 ═CR 14 — to form a fused ring, X is NR′.

2. The phosphinine oxide derivative of claim 1 , wherein it is represented by the following Chemical Formula 2, 3, or 4:

in Chemical Formulas 2 to 4, X, R 3 , R 4 and R 5 are the same as defined in claim 1 ,
R 1 is C1-C20 alkyl or C6-C20 aryl;
R 11 to R 16 are each independently hydrogen, C1-C20 alkyl, halo C1-C20 alkyl, C1-C20 alkoxy, C6-C20 aryl, halogen, C1-C20 alkylcarbonyl, or hydroxyl, or may be linked to an adjacent substituent by

 to form a fused ring;
L is NR″ or S; and
R″ is hydrogen or C1-C20 alkyl.

3. The phosphinine oxide derivative of claim 2 , wherein X is NR′ or O; R′ is methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl or naphthyl; R 1 is methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, phenyl, naphthyl, fluorenyl, wherein the phenyl, naphthyl or fluorenyl of R 1 may be further substituted with at least one substituent selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, chloro, bromo, fluoro and iodo; R 11 to R 16 are each independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, fluoro, chloro, iodo, bromo, acetyl, trifluoromethyl, phenyl, naphthyl, or hydroxyl, or R 11 to R 14 may be linked to an adjacent substituent by

 to form a fused ring, and R 15 and R 16 may be linked to each other by

 to form a fused ring; R 17 and R 18 are each independently methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl or naphthyl; L is NH or S; R 3 and R 4 are each independently methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl or naphthyl, wherein the phenyl or naphthyl of R 3 and R 4 may be further substituted with at least one substituent selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, chloro, bromo, fluoro and iodo; R 5 is methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, phenyl, naphthyl, thiophenyl, furyl, pyrrolyl, pyridyl, pyrimidinyl, quinolyl, triazolyl, oxazolyl or thiazolyl, wherein the phenyl of R 5 may be further substituted with at least one substituent selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, trifluoromethyl, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, chloro, bromo, fluoro and iodo.

4. The phosphinine oxide derivative of claim 3 , wherein it is selected from the following compounds:

5. A preparation method of a phosphinine oxide derivative represented by the following Chemical Formula 1, by an intramolecular annulation between a phosphinic derivative represented by the following Chemical Formula 5 and an alkyne derivative represented by the following Chemical Formula 6, in the presence of a catalyst and an oxidant:

in Chemical Formulas 1, 5, and 6,
X is NR′ or O;
R′ is C1-C20 alkyl or C6-C20 aryl;
R 1 and R 2 are each independently hydrogen, C1-C20 alkyl or C6-C20 aryl, or R 1 and R 2 may be linked to each other by —CR 11 ═CR 12 —CR 13 ═CR 14 — or -L-CR 15 ═CR 16 — to form a fused ring;
R 11 to R 16 are each independently hydrogen, C1-C20 alkyl, halo C1-C20 alkyl, C1-C20 alkoxy, C6-C20 aryl, halogen, C1-C20 alkylcarbonyl or hydroxyl, or may be linked to an adjacent substituent by C2-C7 alkenylene, C2-C7 alkylenedioxy or —CR 17 ═CR 18 —OC(═O)— to form a fused ring;
R 17 and R 18 are each independently C1-C20 alkyl or C6-C20 aryl;
L is NR″, O or S;
R″ is hydrogen or C1-C20 alkyl;
R 3 and R 4 are each independently C1-C20 alkyl or C6-C20 aryl; and
R 5 is C1-C20 alkoxy, C6-C20 aryl or C3-C20 heteroaryl, wherein the alkyl and aryl of R 1 , R 2 , R 3 and R 4 , and the alkoxy, aryl, and heteroaryl of R 5 may be further substituted with at least one substituent selected from the group consisting of halogen, C1-C20 alkyl, C1-C20 alkoxy and halo C1-C20 alkyl;

with a proviso that if R 1 and R 2 are linked to each other by —CR 11 ═CR 12 —CR 13 ═CR 14 — to form a fused ring, X is NR′.

6. The preparation method of claim 5 , wherein the catalyst is a rhodium (Rh) catalyst or a ruthenium (Ru) catalyst.

7. The preparation method of claim 6 , wherein
the rhodium (Rh) catalyst is one or two or more selected from the group consisting of [RhCl(cod)] 2 (cod=1,5-cyclooctadiene), [RhCl(C 2 H 4 ) 2 ] 2 , Rh(acac) 3 , RhCl 3 , RhCl 3 .xH 2 O, RhBr 3 .xH 2 O, Rh 2 O 3 , Rh 2 O 3 .xH 2 O, [Rh(C 5 Me 5 )Cl 2 ] 2 , (H 2 NCH 2 CH 2 NH 2 ) 3 RhCl 3 .3H 2 O, chlorobis(2-phenylpyridine)rhodium(III) dimer, dichloro(dimethylglyoximato)(dimethylglyoxime)rhodium(III)), trichloro [1,1,1-tri (diphenylphosphino methyl)ethane]rhodium(III), RhI 3 , rhodium(III)2,4-pentene dionate and Rh 2 (SO 4 ) 3 .4H 2 O; and
the ruthenium (Ru) catalyst is one or two or more selected from the group consisting of [RuCl 2 (p-cymene)] 2 , [RuCl 2 (benzene)] 2, (C 5 Me 5 )RU(CH 3 CN) 3 PF 6 , Ru(CO) 2 (PPh 3 ) 3 , RuH 2 (CO)(PPh 3 ) 3 , Ru 3 (CO) 12 , [Ru(COD)Cl 2 ] (COD=1,5-cyclooctadiene), RuCl 2 (PPh 3 ) 3 , RuH 2 (PPh 3 ) 4 , RuH 2 (H 2 ) 2 (PCy 3 ) 2 (Cy =cyclohexyl), RuCl 3 , RuCl 3 .3H 2 O an

Assignees

• Knu Industry Cooperation Found

Inventors

• Lee Phil Ho
• Park Young Chul
• Jeon In Cheol
• Seo Jung Min
• Seo Bo Ram

Classifications

• C07F9/65846 Primary

  the phosphorus atom being part of a six-membered ring which may be condensed with another ring system · CPC title

• C07F9/657172

  the ring phosphorus atom and one oxygen atom being part of a (thio)phosphinic acid ester: [IMAGE cpc-sch-C07F-1008.gif] (X = O, S) · CPC title

• C07F9/657181

  the ring phosphorus atom and, at least, one ring oxygen atom being part of a (thio)phosphonic acid derivative · CPC title

• C07F9/657163

  the ring phosphorus atom being bound to at least one carbon atom · CPC title