Cyclic phosphinate derivatives and method of preparing the same

Patent metadata

Field	Value
Publication number	US-9487547-B2
Application number	US-201514598143-A
Country	US
Kind code	B2
Filing date	Jan 15, 2015
Priority date	May 2, 2014
Publication date	Nov 8, 2016
Grant date	Nov 8, 2016

Abstract

Provided are novel cyclic phosphinate derivatives and a method of preparing the same, and more particularly, cyclic phosphinate derivatives including benzoxaphosphole oxide derivatives and benzoxaphosphorin oxide derivatives, and a method of preparing the same. The cyclic phosphinate derivative according to the present invention may have pharmacological and physiological activities, be used as the basic skeleton of the natural material, and be used in development of a new drug, and synthesis of various medicines. In addition, with the method of preparing a cyclic phosphinate derivative according to the present invention, various cyclic phosphinate derivatives may be prepared with high yield through a simple synthetic process by performing an intramolecular carbon-oxygen coupling reaction on the phosphinic acid derivative in the presence of a palladium (Pd) catalyst, an oxidant, and a base.

First claim

What is claimed is:

1. A cyclic phosphinate compound represented by the following Chemical Formula 1:

in Chemical Formula 1,
R 1 is (C1-C20)alkyl; R 2 to R 4 are each independently hydrogen, (C1-C20)alkyl, halo(C1-C20)alkyl, (C1-C20)alkoxy, (C6-C20)aryl, halogen, (C6-C20)aryloxy, or tri(C1-C20)alkylsilyl;
when X is

 Y is O;
R 5 is (C1-C20)alkyl, (C1-C20)alkoxy, or (C6-C20)aryl;
Z is —CR 11 R 12 —;
R 11 and R 12 are each independently hydrogen or (C1-C20)alkyl, or are linked to each other by (C1-C7)alkylene to form a spiro ring; and
the alkyl and aryl of R 2 to R 5 are optionally substituted with a substituent selected from the group consisting of halogen, (C1-C20)alkyl, (C1-C20)alkoxy, and halo(C1-C20)alkyl.

2. The cyclic phosphinate compound of claim 1 , wherein it is represented by the following Chemical Formula 2:

in Chemical Formula 2, R 1 to R 4 and R 5 have the same definitions as defined in claim 1 ;
Z is —CH2—; and
the alkyl and aryl of R 2 to R 5 are optionally substituted with a substituent selected from the group consisting of halogen, (C1-C20)alkyl, (C1-C20)alkoxy, and halo(C1-C20)alkyl.

3. The cyclic phosphinate compound of claim 2 , wherein R 1 is methyl, ethyl, propyl, butyl, pentyl, or hexyl; R 2 to R 4 are each independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, trifluoromethyl, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, phenyl, naphthyl, fluorenyl, chloro, bromo, fluoro, or trimethylsilyl (TMS), the phenyl, naphthyl, or fluorenyl of R 2 to R 4 are optionally substituted with a substituent selected from the group consisting of chloro, bromo, fluoro, methyl, ethyl, propyl, butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, and trifluoromethyl;
R 5 is methyl, ethyl, propyl, butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, phenyl, or naphthyl, the phenyl or naphthyl of R 5 are optionally substituted with a substituent selected from the group consisting of chloro, bromo, fluoro, methyl, ethyl, propyl, butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, and trifluoromethyl; and
Z is —CH 2 —.

4. The cyclic phosphinate compound of claim 3 , wherein it is selected from the following compounds:

5. A method of preparing a cyclic phosphinate compound characterized by performing an intramolecular carbon-oxygen coupling reaction on a phosphinic acid compound represented by the following Chemical Formula 6 to prepare a cyclic phosphinate compound represented by the following Chemical Formula 2 in the presence of a palladium (Pd) catalyst, an oxidant, and a base:

in Chemical Formulas 2 and 6,
R 1 is (C1-C20)alkyl; R 2 to R 4 are each independently hydrogen, (C1-C20)alkyl, halo(C1-C20)alkyl, (C1-C20)alkoxy, (C6-C20)aryl, halogen, (C6-C20)aryloxy, or tri(C1-C20)alkylsilyl;
R 5 is (C1-C20)alkyl, (C1-C20)alkoxy, or (C6-C20)aryl;
Z is —CH 2 —; and
the alkyl and aryl of R 2 to R 5 are optionally substituted with a substituent selected from the group consisting of halogen, (C1-C20)alkyl, (C1-C20)alkoxy, and halo(C1-C20)alkyl.

6. The method of preparing a cyclic phosphinate compound of claim 5 , wherein the palladium (Pd) catalyst is one or two or more selected from the group consisting of PdCl 2 , PdBr 2 , Pd(OAc) 2 , Pd(dba) 2 , Pd 2 (dba) 3 , Pd 2 dba 3 .CHCl 3 , Pd(PPh 3 ) 4 , Pd(OTf) 2 , Pd(OTf) 2 .2H 2 O, Pd(TFA) 2 , PdCl 2 (MeCN) 2 , PdCl 2 (PPh 3 ) 2 , Pd(dppf)Cl 2 , and [PdCl(C 3 H 5 )] 2 .

7. The method of preparing a cyclic phosphinate compound of claim 5 , wherein a use amount of the palladium (Pd) catalyst is 0.01 to 0.5 equivalents with respect to the phosphinic acid compound represented by Chemical Formula 6.

8. The method of preparing a cyclic phosphinate compound of claim 5 , wherein the oxidant is one or two or more selected from the group consisting of CuCl, Cu 2 O, CuO, Cu(OAc) 2 , Cu(OTf) 2 [OTf: trifluoromethanesulfonate], CuCl 2 , CuBr, CuI, Cu(acac) 2 , Ag 2 O, AgO, AgOAc, Ag 2 CO 3 , Na 2 S 2 O 8 , K 2 S 2 O 8 , NaOAc, BQ [BQ: benzoquinone], FeCl 3 , Mn(OAc) 3 .2H 2 O, V 2 O 5 , PhI(OAc) 2 , PhI(TFA) 2 , IOAc, ozone, oxygen, (PhCO 2 ) 2 , and 2,2,6,6-tetramethyl-1-piperidinyloxy (free radical, TEMPO).

9. The method of preparing a cyclic phosphinate compound of claim 5 , wherein a use amount of the oxidant is 0.1 to 5.0 equivalents with respect to the phosphinic acid compound represented by Chemical Formula 6.

10. The method of preparing a cyclic phosphinate compound of claim 5 , wherein the base is one or two or more selected from the group consisting of KH 2 PO 4 , Na 2 HPO 4 .2H 2 O, Na 2 HPO 4 , Na 2 CO 3 , NaH 2 PO 4 , LiOAc, Li 2 CO 3 , NaOAc, K 2 HPO 4 , K 3 PO 4 , K 2 CO 3 , CsF, KHCO 3 , KOH, KF, KPF 6 , KOAc, NaF, CsOAc, CsOPiv, LiPF 6 , Li 3 PO 4 , LiF, and LiI.

11. The method of preparing a cyclic phosphinate compound of claim 5 , wherein a use amount of the base is 0.5 to 3.0 equivalents with respect to the phosphinic acid compound represented by Chemical Formula 6.

12. The method of preparing a cyclic phosphinate compound of claim 5 , wherein a ligand is further used.

13. The method of preparing a cyclic phosphinate compound of claim 12 , wherein the ligand is one or two or more selected from the group consisting of N-acetyl-L-leucine, Boc-Val-OH [N-(tent-butoxycarbonyl)-L-valine], N-Boc-L-isoleucine, Boc-L-leucine, Ac-Gly-OH [N-acetylglycine], N-Boc-L-isoleucine-hemihydrate, Ac-Ala-OH [N-acetyl-L-alanine], Ac-Phe-OH [N-acetyl-L-phenylalanine], pivalic acid, 2-methyl-2-phenylpropanoic acid, adamantane-1-carboxylic acid, (4-CF 3 —C 6 H 4 ) 3 P, (4-MeO—C 6 H 4 ) 3 P, (4-MeO—C 6 H 4 ) 3 P, (2,6-di-MeO—C 6 H 3 )3P, (2,4,6-tri-MeO—C6H2)3P, Xantphos [4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene], XPhos [2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl], CyJohnphos [(2-biphenyl)dicyclohexylphosphine], SPhos [2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl], Johnphos [(2-biphenyl)di-tert-butylphosphine], DPEphos [bis[(2-diphenylphosphino)phenyl]ether], DPPP [1,3-Bis(diphenylphosphino)propane], DPPE [1,2-Bis(diphenylphosphino)ethane], DPPF [1,1′-Bis(diphenylphosphino) ferrocene], tri-o-tolylphosphine, and tri-2-furylphosphine.

14. The method of preparing a cyclic phosphinate compound of claim 12 , wherein a use amount of the ligand is 0.1 to 1.0 equivalent with respect to the phosphinic acid compound represented by Chemical Formula 6.

Assignees

• Knu Industry Cooperation Found

Inventors

• Lee Phil Ho
• Shin Seo Hyun
• Kang Dong Jin
• Eom Da Han
• Kim Yea Rin
• Jeong Yeon Seok
• Choi Won Seok

Classifications

• 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

• C07F9/65744

  condensed with carbocyclic or heterocyclic rings or ring systems · CPC title

• C07F9/657181 Primary

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