Cyclic phosphinate derivatives and method of preparing the same

Patent metadata

Field	Value
Publication number	US-9670240-B2
Application number	US-201615286408-A
Country	US
Kind code	B2
Filing date	Oct 5, 2016
Priority date	May 2, 2014
Publication date	Jun 6, 2017
Grant date	Jun 6, 2017

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 compound represented by the following Chemical Formula 3:

in Chemical Formula 3,
R 1 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;
R 11 and R 12 are each independently (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 1 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 compound of claim 1 , wherein R 1 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 1 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
R 11 and R 12 are each independently methyl, ethyl, propyl, butyl, pentyl, or hexyl, or are linked to each other by butylene or pentylene to form a spiro ring.

3. The compound of claim 2 , wherein it is selected from the following compounds:

4. A method of preparing a compound characterized by performing an intramolecular carbon-oxygen coupling reaction on a phosphinic acid compound represented by the following Chemical Formula 7 to prepare a compound represented by the following Chemical Formula 3 in the presence of a palladium (Pd) catalyst, an oxidant, and a base:

in Chemical Formulas 3 and 7,
R 1 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;
R 11 and R 12 are each independently (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 1 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.

5. The method of preparing a compound of claim 4 , 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 .

6. The method of preparing a compound of claim 4 , 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 7.

7. The method of preparing a compound of claim 4 , 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).

8. The method of preparing a compound of claim 4 , 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 7.

9. The method of preparing a compound of claim 4 , 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.

10. The method of preparing a compound of claim 4 , wherein a use amount of the base is 0.5 to 3.0 equivalents with respect to the phosphinic acid compound derivative-represented by Chemical Formula 7.

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

• C07F9/657181 Primary

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

• C07F9/65744

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