KR101621754B1 - PROCESS OF PREPARING α-KETO (CYANOMETHYLENE)TRIPHENYLPHOSPHORANES USING XANTHATE COMPOUNDS - Google Patents

Abstract

The present invention relates to a preparation method of an α-keto (cyanomethylene)triphenylphosphorane compound using a novel xanthate compound and an olefin compound. According to the present invention, an α-keto (cyanomethylene)triphenylphosphorane compound which is a core intermediate product to introduce α-keto amide and α-keto ester functional groups can be simply prepared with a high yield by using substances commercially and synthetically simply accessible. The preparation method of an α-keto (cyanomethylene)triphenylphosphorane compound comprises the steps of: (i) conducting an addition reaction of S-[3-cyano-2-oxo-3-(triphenyl-λ^5-phosphanylidene)propyl] O-ethyl carbamodithioate with an olefin compound to obtain a xanthate side product represented by chemical formula 8; and (ii) conducting a radical reduction reaction of the xanthate side product represented by chemical formula 8.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a process for preparing an α-keto (cyanomethylene) triphenylphosphorine compound using a zantate compound,

The present invention relates to a process for producing an? -Keto (cyanomethylene) triphenylphosphorine compound using a zantite compound. More specifically, the present invention relates to a method for preparing an? -Keto (cyanomethylene) triphenylphosphorine compound using a novel zirconate compound and an olefin compound as starting materials, a novel zirconate compound S- [3-cyano-2-oxo-3- (triphenyl-? ⁵ -phosphanylidene) propyl] O -ethylcarbododioate and a process for producing the same.

The α-keto amide and α-keto ester functional groups are important functional groups directly linked to the pharmacological activities frequently found in many natural materials with physiological activity, Is an important electron-deficient electrophilic functional group that has been attracting much attention in the field of organic synthesis and pharmacy, such as being utilized as a reaction intermediate, and more recently, being artificially introduced for pharmacological action to a synthetic peptide compound [Otto, HH; Schirmeister, T. Chem. Rev. 1997 , 97 , 133; Babine, RE; Bender, SL Chem. Rev. 1997 , 97 , 1359; Cooper, AJE; Ginos, JZ; Meister, A. Chem. Rev. 1983 , 83 , 321]. Thus, many synthetic methods for introducing alpha -ketoamides and alpha -ketoester functionalities have been reported in the literature, and in particular in U.S. Patent No. 5,834,588, alpha -keto (cyanomethylene) triphenylphosphor A synthesis method has been reported in which? -Ketoamides and? -Ketoester functional groups are introduced by using? -Keto (cyanomethylene) triphenylphosphoranes, 3 ' as core intermediates (Wasserman, HH; Ho, W.-B. J. Org. Chem. 1994 , 59 , 4364-4366].

[Reaction Scheme 1]

The synthesis method is an excellent method for introducing? -Ketoamides and? -Ketoester functional groups in consideration of mild reaction conditions, excellent convergence, a wide range of application, and excellent reaction yield. However, the synthesis of α-keto (cyanomethylene) triphenylphosphorine ( 3 ' ), an essential intermediate in the synthesis method, requires acyl chlorides derived from carboxylic acids or carboxylic acids, Acids are often not commercially available, and acyl chloride is very difficult to make and use, such as readily hydrolyzed to highly reactive reagents.

In order to overcome such a problem, ( 10 ) diethyl [3-cyano-2-oxo-3- (triphenylphosphoranylidene) propyl] phosphonate (Horner-Wadsworth-Emmons Wittig Reagent) (Cyanomethylene) triphenylphosphorane ( 11 , 3 '' ) by reacting with a carbonyl compound (aldehyde or ketone) under mild conditions Kieseung Lee, Bull. Korean Chem. Soc., 2007 , 28, 1641-1642; Kieseung Lee, Bull. Korean Chem. Soc., 2010 , 31, 2776-2782; Korean Patent No. 10-0911357].

[Reaction Scheme 2]

The present inventors have also found that the novel sulfinyl compound ( 12 ) is treated with an appropriate base under mild reaction conditions and reacted with alkyl bromides as shown in Reaction Scheme 3 below to perform a simple pyrolysis reaction. (Cyanomethylene) triphenylphosphorane ( 11 ' , 3''' ) through an electron transporting method (Kieseung Lee, Bull. Korean Chem. Soc., 2009 , 30, 2521-2522; Korean Patent No. 10-1085202].

[Reaction Scheme 3]

In addition, the present inventors have found that, as shown in Reaction Scheme 4 below, the novel sulfonyl compound ( 13 ) can be used for alkylation and reductive desulfonylation of various types of halogenated alkyl compounds to form α-keto (Cyanomethylene) triphenylphosphorane ( 3 ''' ) (Kieseung Lee, et al. Chan-Yeon Hwang, Bull. Korean Chem. Soc., 2013 , 34, 2953-2958; Korean Patent Publication No. 10-2014-0131677].

[Reaction Scheme 4]

Although the method of preparing α-keto (cyanomethylene) triphenylphosphorine from the carbonyl compound and the halogenated alkyl compound overcomes the limitations of the Wasserman synthesis method and broadens the application range , It is urgently required to develop a novel synthetic method which can be commercially obtained at a low cost and which can be easily produced at the same time, and which can prepare? -Keto (cyanomethylene) triphenylphosphorane using an olefin compound as a starting material come.

U.S. Patent No. 5,834,588 Korean Patent No. 10-0911357 Korean Patent No. 10-1085202 Korean Patent Publication No. 10-2014-0131677

The inventors of the present invention have conducted intensive studies to develop a method for more effectively producing alpha -keto (cyanomethylene) triphenylphosphorane. As a result, they have found that a novel zanthate compound and various forms of It has been found that various α-keto (cyanomethylene) triphenylphosphorane can be effectively prepared by using olefinic compounds as a starting material, thereby completing the present invention.

Accordingly, an object of the present invention is to provide a process for preparing an? -Keto (cyanomethylene) triphenylphosphorine compound using a novel zonate compound and an olefin compound.

It is another object of the present invention to provide a novel zonate compound for the preparation of alpha -keto (cyanomethylene) triphenylphosphorane.

It is a further object of the present invention to provide a process for preparing the abovementioned zantite compounds.

One embodiment of the present invention relates to a process for producing an? -Keto (cyanomethylene) triphenylphosphorine compound represented by the following formula (3) using a novel zirconate compound and an olefin compound,

(i) reacting an S- [3-cyano-2-oxo-3- (triphenyl-? ⁵ -phosphanylidene) propyl] O- ethylcarbodioate with an olefin compound represented by the following formula An addition reaction to obtain a side chain adduct of the formula (8); And

(ii) subjecting the azide adduct of the formula (8) to a radical reduction reaction.

(3)

[Chemical Formula 1]

(2)

[Chemical Formula 8]

In this formula,

Xa is -SC (= S) OEt,

R is a C ₁ -C ₆ alkyl group, a C ₃ -C ₁₀ cycloalkanonyl group, an aryl group, a -OCOR ₁ , a cyano or an aryloxy group,

R ₁ is a C ₁ -C ₆ alkyl group or an aryloxy group which is unsubstituted or substituted by cyano.

Alkyl group of C ₁ -C _6, as used herein, means a straight-chain or branched hydrocarbon group having 1 to 6 carbon atoms and composed of pieces, such as methyl, ethyl, n - propyl, i - propyl, n - butyl, n - Pentyl, n -hexyl, and the like.

As used herein, a C ₃ -C ₁₀ cycloalkanonyl group means a simple or fused ring hydrocarbon having 3 to 10 carbon atoms having at least one carbonyl group and includes, for example, cyclopentanonyl, cyclohexanonyl, etc. But is not limited to these.

As used herein, an aryl group includes both an aromatic group and a heteroaromatic group and a partially reduced derivative thereof. The arometric group is a simple or fused ring group of 5 to 15-ary, and the heteroaromatic group means an arometric group containing at least one of oxygen, sulfur or nitrogen. Exemplary aryl groups include, but are not limited to, phenyl, naphthyl, pyridinyl, furanyl, thiophenyl, indolyl, quinolinyl, imidazolinyl, But are not limited to, oxazolyl, thiazolyl, tetrahydronaphthyl, and the like.

In the present specification, an aryloxy group means an oxygen functional group mono-bonded to an aryl group, and includes, but is not limited to, phenoxy, benzyloxy, and the like.

The C ₁ -C ₆ alkyl group, the C ₃ -C ₁₀ cycloalkanonyl group, the aryl group and the aryloxy group may be substituted by one or more hydrogen atoms selected from the group consisting of C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, a haloalkyl group of C ₂ -C ₆ alkynyl group, C ₃ -C ₁₀ cycloalkyl, C ₃ -C ₁₀ heterocycloalkyl group, heterocycloalkyl alkyloxy group of _{C 3 -C 10, C 1 -C} 6 of the, C ₁ thioalkoxy group of -C ₆ alkoxy group, C ₁ -C ₆ of, aryl, acyl, hydroxy, thio (thio), halogen, amino, alkoxycarbonyl, carboxy, carbamoyl, cyano, nitro, And the like.

In an embodiment of the present invention,

R is a C ₁ -C ₆ alkyl group, a C ₃ -C ₁₀ cycloalkanonyl group, phenyl, -OCOR ₁ , cyano or benzyloxy,

R ₁ is a C ₁ -C ₆ alkyl group which is unsubstituted or substituted by cyano or phenoxy.

In an embodiment of the present invention,

R is n -pentyl, cyclohexanonyl, phenyl, -OCOR < _{1 &} gt ;, cyano or benzyloxy,

R < ₁ > is methyl, cyanomethyl or phenoxy.

Hereinafter, the production method of the present invention will be described in more detail with reference to the following Reaction Scheme 5. The method described below exemplifies the representative method, but the reaction reagent, the reaction conditions, and the like may be changed as required.

[Reaction Scheme 5]

Glass Tate adduct 8 S - [3- cyano-2-oxo-3- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) propyl] O - ethyl carbonyl nodi the olefin thio benzoate (1) The compound ( 2 ). Specifically, the glass Tate compound (1), an olefin compound (2) when refluxed in a radical reaction condition with a glass Tate compound (1) up the glass Tate radicals transferred to the olefin compound (2) glass Tate adduct 8 in the .

The addition reaction may be carried out using a catalytic amount of a radical initiator, and examples of the radical initiator include dilauroyl peroxide (DLP), dibenzoyl peroxide (BPO), dicumyl peroxide dicumyl peroxide: CPO), di - t - butyl peroxide (di- t -butyl peroxide: DTBP), but such can be used, and the like.

As the reaction solvent, 1,2-dichloroethane (DCE), benzene, chlorobenzene, cyclohexane, diisopropyl ether, toluene and the like can be used, but the present invention is not limited thereto.

In this process, the reductant dexanthation occurs partially in the side reaction as the zatate adduct 8 is generated, and a small amount of? -Keto (cyanomethylene) triphenylphosphorane ( 3 ) may be generated.

The α-keto (cyanomethylene) triphenylphosphorane ( 3 ) can be obtained by radical reduction reaction of the zetate adduct ( 8 ). Specifically, when the zirconate adduct ( 8 ) is subjected to a radical reduction reaction, a reductive amination reaction is carried out to produce α-keto (cyanomethylene) triphenylphosphorane ( 3 ).

The radical reduction reaction may be carried out in the presence of dilauroyl peroxide (DLP) or in the presence of hypophosphorous acid (H ₃ PO ₂ ), triethylamine (Et ₃ N) and azobisisobutyronitrile (AIBN) And the like.

Examples of the reaction solvent include i -propyl alcohol (IPA), 1,4-dioxane, benzene, 1,2-dichloroethane (DCE), diisopropyl ether ether) may be used, but the present invention is not limited thereto.

Another aspect of the present invention is of formula (1) to a novel glass Tate compound S - [3- cyano-2-oxo-3- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) propyl] O - ethyl carbonyl Nodithioate.

[Chemical Formula 1]

The quaternate compound of the present invention can be usefully used as a starting material for preparing the? -Keto (cyanomethylene) triphenylphosphorine compound of Formula 1 above.

Another embodiment of the present invention is a process for producing S- [3-cyano-2-oxo-3- (triphenyl-? ⁵ -phosphanylidene) propyl] O -ethylcarbodioate of Formula 1 , And the manufacturing method of the present invention

(a) to the formula (4) (triphenyl Fora alkylpiperidinyl) acetonitrile and ethyl chloride to the formula (5) to condensation reaction of 4-chloro-3-oxo-2-chloride of formula (6) (triphenyl -λ ⁵ - Phosphanylidene) butanenitrile; And

(b) reacting 4-chloro-3-oxo-2- (triphenyl-? ⁵ -phosphanylidene) butanenitrile of Formula 6 with potassium O -ethylate of Formula 7 below.

[Chemical Formula 4]

[Chemical Formula 5]

[Chemical Formula 6]

(7)

Hereinafter, the production method of the zanthate compound will be described in more detail with reference to the following Reaction Scheme 6. The method described below exemplifies the representative method, but the reaction reagent, the reaction conditions, and the like may be changed as required.

[Reaction Scheme 6]

4-chloro-3-oxo-2- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) butane nitrile (6) is (triphenylphosphoranylidene Fora alkylpiperidinyl) condensation of acetonitrile (4) and a chloride acid chloride (5) Followed by reaction.

The condensation reaction is N, O - bis (trimethylsilyl) acetamide may be performed by using the (N, O -bis (trimethylsilyl) acetamide BSA).

Examples of the reaction solvent include, but are not limited to, methylene chloride (CH ₂ Cl ₂ ), diethyl ether (Et ₂ O), tetrahydrofuran (THF), and the like.

S - [3- cyano-2-oxo-3- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) propyl] O - ethyl nodi thio carbonyl benzoate (1) is 4-chloro-3-oxo-2- ( triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) potassium butane nitrile (6) O - it may be prepared cup of ethyl lactate (potassium O -ethyl xanthate, 7) and by the reaction.

As the reaction solvent, acetone, diethyl ether (Et ₂ O), tetrahydrofuran (THF) and the like may be used, but it is not limited thereto.

The (triphenylphosphoranylidene) acetonitrile ( 4 ) and the chloroacetic acid chloride ( 5 ) are commercially available.

According to the production method of the present invention, α- keto amides and keto esters α- key intermediate, α- keto for introducing a functional group (cyano-methylene) triphenyl Faure a novel glass Compound lactate compound is S - [3 -cyano-2-oxo-3- (triphenyl -λ ^{5-phosphazene-alkylpiperidinyl)} propyl] O-ethyl carbonyl nodi thio benzoate with commercially purchased and manufacturing can be easily manufactured with high yield from readily olefin compound have.

In addition, S -3- [3-cyano-2-oxo-3- (triphenyl-λ ⁵ -phosphanylidene) propyl] O -ethylcarbododioate Can be easily produced at a high yield using one of the reagents.

Hereinafter, the present invention will be described in more detail with reference to Examples. It should be apparent to those skilled in the art that these embodiments are for illustrative purpose only and that the scope of the present invention is not limited to these embodiments.

Preparation Example 1: 4-Chloro-3-oxo-2- (triphenyl-l ⁵ (4-Chloro-3-oxo-2- (triphenyl-l ⁵ -phosphanylidene) butanenitrile, 6)

(CH ₂ Cl ₂ , 30 mL) containing acetonitrile ( 4 , 2.59 g, 8.60 mmol) was cooled to 0 ^° C and N , O -bis (trimethyl ( 5 , 0.69 mL, 1.0 eq.) Was added to the reaction mixture, and the mixture was stirred at 0 ^° C for 1 hour, at room temperature for 12 hours, Lt; / RTI > Subsequently, water (20 mL) was added to the reaction solution. After shaking, the two layers were separated with a separatory funnel, and the aqueous layer was further extracted twice with methylene chloride (5 mL x 2). The separated organic layers were combined, and anhydrous magnesium sulfate (5 g) was added to remove moisture. After filtration, the solvent was removed under reduced pressure. The resulting residue was purified by flash chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 20/1) to give the pure title compound ( 6, 2.66 g, 82%) as a pale brown solid Respectively.

mp 185-187 ^o C;

IR (KBr) 2180, 1594 cm < ^{-1 &} gt ;;

¹ H NMR (CDCl ₃ , 400 MHz)? 4.44 (s, 2H), 7.49-7.72 (m, 15H).

Example 1: S - [3- cyano-2-oxo-3- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) propyl] O - ethyl nodi thio carbonyl benzoate (S - [3-Cyano- 2-oxo -3- (triphenyl-λ ⁵ -phosphanylidene) propyl] O- ethyl carbonodithioate, 1)

4-chloro-3-oxo-2- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) butane nitrile (4-Chloro-3-oxo -2- (triphenyl-λ 5 -phosphanylidene) butanenitrile) ( 6 , 868.3 mg, 2.30 mmol) in anhydrous acetone (20 mL) was cooled to 0 ^° C and added to a cooled acetone solution containing potassium O -ethyl zetate ( 7 , 387.1 mg, 1.05 eq) 15 mL, 0 ^° C), and the mixture was stirred at 0 ^° C for 30 minutes and at room temperature for 2 hours under argon gas. The solvent acetone was removed under reduced pressure, water (20 mL) was added to the remaining residue and the organic product was extracted with CH ₂ Cl ₂ (20 mL x 3). The residue was purified by flash chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 20) to obtain a residue. The residue was purified by silica gel column chromatography / 1) to give the pure title compound ( 1 , 1.013 g, 95%).

_{^{1 H NMR (CDCl 3, 400}} MHz) δ 1.39 (t, 3H, J = 7.1 Hz), 4.39 (s, 2H) 4.62 (q, 2H, J = 7.1 Hz), 7.48-7.68 (m, 15H).

Example 2 Synthesis of S- [11-cyano-10-oxo-11- (triphenyl-? ⁵ -phosphanylidene ) undecan-7-yl] O -ethylcarbododioate ( S- [ Preparation of Cyano-10-oxo-11- (triphenyl-λ ⁵ -phosphanylidene) undecan-7-yl] O- ethyl carbonodithioate, 8a)

S- [3- cyano-2-oxo-3- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) propyl] O - ethyl nodi thio carbonyl benzoate (1, 185.4 mg, 0.4 mmol ) and 1-octene (2a , 188.3 [mu] L, 3.0 eq.) Was refluxed under argon gas for 15 min. To this reaction solution, dilauryl peroxide (DLP) (15.9 mg, 0.1 equivalent) was added periodically every hour while stirring under an argon atmosphere for 3 hours, and then the reaction solution was cooled to room temperature, ( 8a , 177.3 mg, 77%) was obtained by separation of the resulting residue by flash chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 40/1) .

_{^{1 H NMR (CDCl 3, 400}} MHz) δ 0.86 (t, 3H, J = 6.8 Hz), 1.17-1.49 (m, 11H), 1.60-1.77 (m, 2H), 1.87-2.01 (m, 1H), 2H), 3.70-3.80 (m, 1H), 4.64 (qd, 2H, J ₁ = 7.1 Hz, J ₂ = 3.2 Hz), 7.47-7.67 (m, 15H).

Further, the title compound ( 3a , 12.8 mg, 7%), in which the zeta-functional group was removed as a by-product during the separation, was obtained at the same time.

Example 3: S - [6- cyano-5-oxo-1-phenyl-6- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) hexane-2-yl] O - ethyl nodi thio carbonyl benzoate (S - Preparation of [6-Cyano-5-oxo-1-phenyl-6- (triphenyl-λ ⁵ -phosphanylidene) hexan-2-yl] O- ethyl carbonodithioate,

S- [3- cyano-2-oxo-3- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) propyl] O - ethyl nodi thio carbonyl benzoate (1, 185.4 mg, 0.4 mmol ) and allyl benzene (2b, 159.0 [mu] L, 3.0 eq.) In DCE (2 mL) was refluxed under argon gas for 15 min. To this reaction solution was added DLP (15.9 mg, 0.1 equivalent) periodically every hour while stirring under argon gas for 3 hours. The reaction solution was cooled to room temperature and the solvent was removed by rotary evaporation to remove the residue. The pure title compound ( 8b , 160.5 mg, 69%) was obtained by chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 40/1).

_{^{1 H NMR (CDCl 3, 400}} MHz) δ 1.40 (t, 3H, J = 7.1 Hz), 1.84-1.97 (m, 1H), 2.02-2.12 (m, 1H), 2.76-2.96 (m, 3H), 3.10 (dd, 1H, J ₁ = 14.1 Hz, J ₂ = 6.8 Hz), 3.92-4.03 (m, 1H), 4.60 (qd, 2H, J ₁ = 7.1 Hz, J ₂ = 1.6 Hz), 7.17-7.31 (m, 5H), 7.48-7.66 (m, 15H).

Also, the title compound ( 3b , 12.9 mg, 7%), in which the zetate functional group was removed as a byproduct during the separation, was obtained at the same time.

Example 4: S - [6- cyano-5-oxo-1- (2-oxo-cyclohexyl) -6- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) hexane-2-yl] O - ethyl carbonyl Preparation of (- - [phosphanylidene) hexan- 2-yl 6-Cyano-5-oxo-1- (2-oxocyclohexyl) -6- (triphenyl-λ 5] O -ethyl carbonodithioate, 8c S) nodi thio benzoate

S- [3- cyano-2-oxo-3- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) propyl] O - ethyl nodi thio carbonyl benzoate (1, 185.4 mg, 0.4 mmol ) and 2-allyl cyclohexanone A solution of DCE (2 mL) containing rice ( 2c , 178.9 [mu] L, 3.0 eq) was refluxed under argon gas for 15 min. To this reaction solution was added DLP (15.9 mg, 0.1 equivalent) periodically every hour while stirring under argon gas for 3 hours. The reaction solution was cooled to room temperature and the solvent was removed by rotary evaporation to remove the residue. Chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 20/1) afforded the pure title compound ( 8c , 187.8 mg, 78%).

_{^{1 H NMR (CDCl 3, 400}} MHz) δ 2H), 1.75-2.13 (m, 5H), 2.17-2.41 (m, 3H), 2.45-2.60 (m, 1H), 2.78-2.92 (m, , 2H), 3.73-3.86 (m, 1H), 4.53-4.68 (m, 2H), 7.45-7.67 (m, 15H).

Further, the title compound ( 3c , 9.6 mg, 5%) in which the zetate functional group was removed as a by-product in the separation process was obtained at the same time.

Example 5: 6-cyano-2 - [(ethoxycarbonyl phenothiazine O'Neill) sulfanyl] -5-oxo-6- (triphenyl -λ ^{5-phosphazene-alkylpiperidinyl)} hexyl acetate (6-Cyano-2- Preparation of [(ethoxycarbonothionyl) sulfanyl] -5-oxo-6- (triphenyl-? ⁵ - phosphanylidene) hexyl acetate, 8d)

S- [3- cyano-2-oxo-3- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) propyl] O - ethyl nodi thio carbonyl benzoate (1, 185.4 mg, 0.4 mmol ) and allyl acetate (2d, 129.5 [mu] L, 3.0 eq.) In DCE (2 mL) was refluxed under argon gas for 15 min. To this reaction solution was added DLP (15.9 mg, 0.1 equivalent) periodically every hour while stirring under argon gas for 3 hours. The reaction solution was cooled to room temperature and the solvent was removed by rotary evaporation to remove the residue. The pure title compound ( 8d , 140.0 mg, 62%) was obtained by chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 40/1).

¹ H NMR (CDCl ₃ , 400 MHz)? 1.41 (t, 3H, J = 7.1 Hz), 1.77-2.20 (m, 5H), 2.81-2.93 (m, 2H), 3.88-4.02 4.15-4.32 (m, 2H), 4.63 (bq, 2H, J = 7.1 Hz), 7.42-7.68 (m, 15H).

In addition, the title compound ( 3d , 16.0 mg, 9%) in which the zetate functional group was removed as a byproduct in the separation process was obtained at the same time.

Example 6 Synthesis of S- [1,6-dicyano-5-oxo-6- (triphenyl-? ⁵ -phosphanylidene ) hexan-2-yl] O -ethylcarbodioate ( S- [ , 6-Dicyano-5-oxo-6- (triphenyl-λ ⁵ -phosphanylidene) hexan-2-yl] O- ethyl carbonodithioate, 8e

S- [3- cyano-2-oxo-3- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) propyl] O - ethyl nodi thio carbonyl benzoate (1, 185.4 mg, 0.4 mmol ) and allyl cyanide when (2e , 96.5 [mu] L, 3.0 eq.) In DCE (2 mL) was refluxed under argon gas for 15 min. To this reaction solution was added DLP (15.9 mg, 0.1 equivalent) periodically every hour while stirring under argon gas for 3 hours. The reaction solution was cooled to room temperature and the solvent was removed by rotary evaporation to remove the residue. The pure title compound ( 8e , 127.3 mg, 60%) was obtained by chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 40/1).

¹ H NMR (CDCl ₃ , 400 MHz)? 1.42 (t, 3H, J = 7.1 Hz), 1.98-2.28 (m, 2H), 2.78-3.05 (m, 4H), 3.85-3.98 4.65 (qd, 2H, J ₁ = 7.1 Hz, J ₂ = 2.2 Hz), 7.47-7.72 (m, 15H).

In addition, the title compound ( 3e , 14.8 mg, 9%), in which the zetate functional group was removed as a by-product during the separation, was obtained at the same time.

Example 7: Synthesis of 6-cyano-2 - [(ethoxycarbonothionyl) sulfanyl] -5-oxo-6- (triphenyl- ⁵ -phosphonylidene) hexyl cyanoacetate (6-Cyano- Preparation of 2 - [(ethoxycarbonothionyl) sulfanyl] -5-oxo-6- (triphenyl-? ⁵ - phosphanylidene) hexyl cyanoacetate, 8f

S- [3- cyano-2-oxo-3- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) propyl] O - ethyl nodi thio carbonyl benzoate (1, 185.4 mg, 0.4 mmol ) and allyl cyano acetate ( 2f , 141.0 [mu] L, 3.0 eq.) In DCE (2 mL) was refluxed under argon gas for 15 min. To this reaction solution was added DLP (15.9 mg, 0.1 equivalent) periodically every hour while stirring under argon gas for 3 hours. The reaction solution was cooled to room temperature and the solvent was removed by rotary evaporation to remove the residue. The pure title compound ( 8f , 141.3 mg, 60%) was obtained by chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 40/1).

_{^{1 H NMR (CDCl 3, 400}} MHz) δ 1.43 (t, 3H, J = 7.1 Hz), 1.87-1.99 (m, 1H), 2.13-2.24 (m, 1H), 2.80-2.98 (m, 2H), 3.47 (s, 2H), 3.97-4.06 (m, 1H), 4.37 (dd, 2H, J 1 = 11.3 Hz, J ₂ = 5.9 Hz), 4.43 (qd, 2H, J ₁ = 11.3 Hz, J ₂ = 4.6 Hz), 4.66 (qd, 2H, J ₁ = 7.1 Hz, J ₂ = 1.5 Hz), 7.48-7.69 (m, 15H).

Further, the title compound ( 3f , 13.1 mg, 7%), in which the zetate functional group was removed as a by-product in the separation process, was obtained at the same time.

Example 8: Synthesis of 6-cyano-2 - [(ethoxycarbonothionyl) sulfanyl] -5-oxo-6- (triphenyl-λ ⁵ -phosphanylidene) hexylphenyl carbonate - [(ethoxycarbonothionyl) sulfanyl] -5-oxo-6- (triphenyl-? ⁵ - phosphanylidene) hexyl phenyl carbonate, 8g)

S- [3- cyano-2-oxo-3- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) propyl] O - ethyl nodi thio carbonyl benzoate (1, 185.4 mg, 0.4 mmol ) and allyl phenyl carbonate (2g , 195.1 [mu] L, 3.0 eq.) In DCE (2 mL) was refluxed under argon gas for 15 min. To this reaction solution was added DLP (15.9 mg, 0.1 equivalent) periodically every hour while stirring under argon gas for 3 hours. The reaction solution was cooled to room temperature and the solvent was removed by rotary evaporation to remove the residue. The pure title compound ( 8 g , 195.1 mg, 76%) was obtained by chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 40/1).

_{^{1 H NMR (CDCl 3, 400}} MHz) δ 1.41 (t, 3H, J = 7.1 Hz), 1.81-2.03 (m, 1H), 2.18-2.30 (m, 1H), 2.93 (t, 2H, J = 6.8 Hz), 4.02-4.12 (m, 1 H), 4.41 (dd, 2H, J ₁ = 11.0 Hz, J ₂ = 6.1 Hz), 4.46 (dd, 2H, J ₁ = 11.0 Hz, J ₂ = 4.6 Hz), 4.64 (qd, 2H, J ₁ = 7.1 Hz, J ₂ = 2.0 Hz), 7.12-7.38 (m, 5H), 7.46-7.68 (m, 15H).

Further, the title compound ( 3 g , 10.4 mg, 5%) in which the zetate functional group was removed as a by-product in the separation process was obtained at the same time.

Example 9: S - [1- benzyloxy-6-cyano-5-oxo-6- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) hexane-2-yl] O - ethyl nodi thio carbonyl benzoate (S - [1-Benzyloxy-6-cyano-5-oxo-6- (triphenyl-λ ⁵ -phosphanylidene) hexan-2-yl] O- ethyl carbonodithioate, 8h

S- [3- cyano-2-oxo-3- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) propyl] O - ethyl nodi thio carbonyl benzoate (1, 185.4 mg, 0.4 mmol ) and allyl benzyl ether (2h , 185.4 [mu] L, 3.0 eq.) In DCE (2 mL) was refluxed under argon gas for 15 min. To this reaction solution was added DLP (15.9 mg, 0.1 equivalent) periodically every hour while stirring under argon gas for 3 hours. The reaction solution was cooled to room temperature and the solvent was removed by rotary evaporation to remove the residue. The pure title compound ( 8h , 127.3 mg, 52%) was obtained by chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 40/1).

_{^{1 H NMR (CDCl 3, 400}} MHz) δ 1.38 (t, 3H, J = 7.1 Hz), 1.91-2.03 (m, 1H), 2.18-2.33 (m, 1H), 2.87 (t, 2H, J = 7.3 Hz), 3.60 (dd, 2H, J ₁ = 10.0 Hz, J ₂ = 6.3 Hz), 3.72 (dd, 2H, J ₁ = 10.0 Hz, J ₂ = 4.4 Hz), 4.52 (s , 2H), 4.61 (qd, 2H, J 1 = 7.1 Hz, J ₂ = 1.5 Hz), 7.21-7.35 (m, 5H), 7.47-7.68 (m, 15H).

In addition, the title compound ( 3h , 11.8 mg, 6%), in which the zetate functional group was removed as a by-product during the separation, was obtained at the same time.

Preparation of - (phosphanylidene) dodecanenitrile, 3a 3 -Oxo-2- (triphenyl-λ 5) - 3- oxo-2- (triphenyl -λ ⁵ phosphazene-alkylpiperidinyl) dodecane nitrile: Example 10

Example 2 S obtained in [11-cyano-10-oxo-11 (triphenyl -λ ^{5-phosphazene-alkylpiperidinyl)} undecane-7-yl] O-ethyl nodi thio carbonyl benzoate (8a, 115.2 mg, 0.2 mmol) in 2 mL of ethanol was refluxed under argon gas for 15 min. To this reaction solution was added DLP (87.7 mg, 1.1 eq.) Periodically every hour while stirring under argon gas for 2 hours. The reaction solution was cooled to room temperature and the solvent was removed by rotary evaporation to remove the residue. Chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 40/1) afforded the title compound ( 3a , 79.3 mg, 87%).

_{^{1 H NMR (CDCl 3, 400}} MHz) δ 0.88 (t, 3H, J = 6.8 Hz), 1.17-1.39 (m, 12H), 1.58-1.72 (m, 2H), 2.68 (t, 2H, J = 7.6 Hz), 7.47-7.66 (m, 15H).

Preparation of - (phosphanylidene) dodecanenitrile, 3a 3 -Oxo-2- (triphenyl-λ 5) - 3- oxo-2- (triphenyl -λ ⁵ phosphazene-alkylpiperidinyl) dodecane nitrile: Example 11

Example 2 S obtained in [11-cyano-10-oxo-11 (triphenyl -λ ^{5-phosphazene-alkylpiperidinyl)} undecane-7-yl] O-ethyl nodi thio carbonyl benzoate (8a, 115.2 mg, 0.2 mmol) containing a 1,4-dioxane (1,4-dioxane) (2 mL ) in _{H 3 PO 2 (109.5 ㎕,} 5.0 eq., 50wt% in H ₂ O) solution and Et ₃ N ( 153.3 [mu] L, 5.5 eq.) Were added sequentially and refluxed under argon gas for 15 min. To this reaction solution, azobisisobutyronitrile (AIBN) (54.7 mg, 0.6 equivalent) was added and the mixture was refluxed with stirring for 1 hour and then cooled to room temperature. The reaction mixture was diluted with CH ₂ Cl ₂ (15 mL), washed with water (10 mL), and the lower organic layer was separated with a separatory funnel. The upper aqueous layer was washed twice with CH ₂ Cl ₂ Further extracted. The separated organic layers were combined and then treated with anhydrous magnesium sulfate (10 g), filtered, and the solvent was removed using a rotary evaporator. The resulting solid residue was purified by flash chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ the same title compound was prepared as in example 10 and separated by _{Cl 2 / EtOAc = 40/1) (} 3a, 80.2 mg, 88%) was obtained.

Example 12: 3-oxo-7-phenyl-2- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) heptane nitrile (3-Oxo-7-phenyl -2- (triphenyl-λ 5 - phosphanylidene) heptaneniltrile, 3b )

S - [6-cyano-5-oxo-1-phenyl-6- (triphenyl- ⁵ -phosphonylidene) hexan-2-yl] O -ethylcarbodioate (obtained in Example 3 8b , 116.3 mg, 0.2 mmol) in 2 mL of ethanol was refluxed under argon gas for 15 min. To this reaction solution was added DLP (87.7 mg, 1.1 eq.) Periodically every hour while stirring under argon gas for 2 hours. The reaction solution was cooled to room temperature and the solvent was removed by rotary evaporation to remove the residue. Chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 40/1) afforded the title compound ( 3b , 73.8 mg, 80%).

_{^{1 H NMR (CDCl 3, 400}} MHz) δ 1.62-1.80 (m, 4H), 2.63 (t, 2H, J = 7.3 Hz), 2.73 (t, 2H, J = 7.1 Hz), 7.13-7.31 (m, 5H), 7.46-7.68 (m, 15H).

Example 13: 3-oxo-7-phenyl-2- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) heptane nitrile (3-Oxo-7-phenyl -2- (triphenyl-λ 5 - phosphanylidene) heptaneniltrile, 3b )

S - [6-cyano-5-oxo-1-phenyl-6- (triphenyl- ⁵ -phosphonylidene) hexan-2-yl] O -ethylcarbodioate (obtained in Example 3 8b, 116.3 mg, 0.2 mmol) containing a 1,4-dioxane (2 mL) solution of the _{H 3 PO 2 (109.5 ㎕,} 5.0 eq., 50wt% in H ₂ O) and Et ₃ N (153.3 ㎕, 5.5 Equivalent) was added sequentially, and the mixture was refluxed under argon gas for 15 minutes. AIBN (54.7 mg, 0.6 eq.) Was added to the reaction solution, and the mixture was refluxed with stirring for 1 hour and then cooled to room temperature. The reaction mixture was diluted with CH ₂ Cl ₂ (15 mL), washed with water (10 mL), and the lower organic layer was separated with a separatory funnel. The upper aqueous layer was washed twice with CH ₂ Cl ₂ Further extracted. The separated organic layers were combined and then treated with anhydrous magnesium sulfate (10 g), filtered, and the solvent was removed using a rotary evaporator. The resulting solid residue was purified by flash chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ separated by a Cl ₂ / EtOAc = 40/1) to give the title compound in example 12 the same as (3b, 75.7 mg, 82% ).

Example 14: 3-oxo-7- (2-oxo-cyclohexyl) -2- (triphenylmethyl -λ ⁵ - phosphazene-alkylpiperidinyl) heptane nitrile (3-Oxo-7- (2 -oxocyclohexyl) -2- ( triphenyl-λ ⁵ -phosphanylidene) heptaneniltrile, 3c)

Example 4 A S obtained in [6-cyano-5-oxo-1- (2-oxo-cyclohexyl) -6- (triphenyl -λ ^{5-phosphazene-alkylpiperidinyl)} hexane-2-yl] O - Ethyl Carbonodithioate ( 8c , 120.4 mg, 0.2 mmol) was refluxed under argon gas for 15 min. To this reaction solution was added DLP (87.7 mg, 1.1 eq.) Periodically every hour while stirring under argon gas for 2 hours. The reaction solution was cooled to room temperature and the solvent was removed by rotary evaporation to remove the residue. Chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 10/1) afforded the title compound ( 3c , 73.2 mg, 76%).

¹ H NMR (CDCl ₃ , 400 MHz)? 1.16-1.42 (m, 4H), 1.53-1.90 (m, 6H), 1.93-2.12 (m, 2H), 2.20-2.43 , 2H, J = 7.6Hz), 7.47-7.67 (m, 15H).

Example 15: 3-oxo-7- (2-oxo-cyclohexyl) -2- (triphenylmethyl -λ ⁵ - phosphazene-alkylpiperidinyl) heptane nitrile (3-Oxo-7- (2 -oxocyclohexyl) -2- ( triphenyl-λ ⁵ -phosphanylidene) heptaneniltrile, 3c)

Example 4 A S obtained in [6-cyano-5-oxo-1- (2-oxo-cyclohexyl) -6- (triphenyl -λ ^{5-phosphazene-alkylpiperidinyl)} hexane-2-yl] O - Ethyl Carbonodithioate (8c, 120.4 mg, 0.2 mmol ) containing a 1,4-dioxane (2 mL) solution of the _{H 3 PO 2 (109.5 ㎕,} 5.0 eq., 50wt% in H ₂ O) and Et ₃ N (153.3 ㎕, 5.5 eq.) Were added sequentially and refluxed under argon gas for 15 min. AIBN (54.7 mg, 0.6 eq.) Was added to the reaction solution, and the mixture was refluxed with stirring for 1 hour and then cooled to room temperature. The reaction mixture was diluted with CH ₂ Cl ₂ (15 mL), washed with water (10 mL), and the lower organic layer was separated with a separatory funnel. The upper aqueous layer was washed twice with CH ₂ Cl ₂ Further extracted. The separated organic layers were combined and then treated with anhydrous magnesium sulfate (10 g), filtered, and the solvent was removed using a rotary evaporator. The resulting solid residue was purified by flash chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 10/1) to obtain the title compound ( 3c , 77.1 mg, 80%) identical to that of Example 14.

Example 16: 6-cyano-5-oxo-6- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) hexyl acetate (6-Cyano-5-oxo -6- (triphenyl-λ 5 - phosphanylidene) hexyl acetate , 3d)

(Ethoxycarbonothionyl) sulfanyl] -5-oxo-6- (triphenyl-? ⁵ -phosphanilidene) hexyl acetate obtained in Example 5 ( 8d , 112.7 mg , 0.2 mmol) in 2 mL of ethanol was refluxed under argon gas for 15 min. To this reaction solution was added DLP (87.7 mg, 1.1 eq.) Periodically every hour while stirring under argon gas for 2 hours. The reaction solution was cooled to room temperature and the solvent was removed by rotary evaporation to remove the residue. Chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 5/1) afforded the title compound ( 3d , 62.1 mg, 70%).

_{^{1 H NMR (CDCl 3, 400}} MHz) δ 1.63-1.78 (m, 4H), 2.04 (s, 3H), 2.73 (t, 2H, J = 7.1 Hz), 4.07 (t, 2H, J = 6.1 Hz) , 7.49-7.67 (m, 15H).

Example 17: 6-cyano-5-oxo-6- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) hexyl acetate (6-Cyano-5-oxo -6- (triphenyl-λ 5 - phosphanylidene) hexyl acetate , 3d)

(Ethoxycarbonothionyl) sulfanyl] -5-oxo-6- (triphenyl-? ⁵ -phosphanilidene) hexyl acetate obtained in Example 5 ( 8d , 112.7 mg H ₂ PO ₂ (109.5 μL, 5.0 eq., 50 wt% in H ₂ O) and Et ₃ N (153.3 μL, 5.5 eq.) Were sequentially added to a 1,4-dioxane solution (2 mL) And refluxed under argon gas for 15 minutes. AIBN (54.7 mg, 0.6 eq.) Was added to the reaction solution, and the mixture was refluxed with stirring for 1 hour and then cooled to room temperature. The reaction mixture was diluted with CH ₂ Cl ₂ (15 mL), washed with water (10 mL), and the lower organic layer was separated with a separatory funnel. The upper aqueous layer was washed twice with CH ₂ Cl ₂ Further extracted. The sum of all of the separated organic layer over anhydrous magnesium sulfate (10 g) and processing the resultant filtered and the solvent was removed with a rotary evaporator under reduced pressure the solid residue was purified by flash chromatography (silica gel with: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAC = 5/1), the title compound ( 3d , 71.9 mg, 81%) was obtained.

Preparation of - (phosphanylidene) octanedinitrile, 3e 3 -Oxo-2- (triphenyl-λ 5) - 3- oxo-2- (triphenyl -λ ⁵ phosphazene-alkylpiperidinyl) octane dinitrile: Example 18

Exemplary S obtained in Examples 6 - [1,6-dicyano-5-oxo-6- (triphenyl -λ ^{5-phosphazene-alkylpiperidinyl)} hexane-2-yl] O-ethyl nodi thio carbonyl benzoate (8e, 106.1 mg, 0.2 mmol) in 2 mL of ethanol was refluxed under argon gas for 15 min. To this reaction solution was added DLP (87.7 mg, 1.1 eq.) Periodically every hour while stirring under argon gas for 2 hours. The reaction solution was cooled to room temperature and the solvent was removed by rotary evaporation to remove the residue. Chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EOAc = 10/1) afforded the title compound ( 3e , 58.3 mg, 71%).

_{^{1 H NMR (CDCl 3, 400}} MHz) δ 1.63-1.87 (m, 4H), 2.33 (t, 2H, J = 7.1 Hz), 2.74 (t, 2H, J = 7.1 Hz), 7.48-7.72 (m, 15H).

Preparation of - (phosphanylidene) octanedinitrile, 3e 3 -Oxo-2- (triphenyl-λ 5) - 3- oxo-2- (triphenyl -λ ⁵ phosphazene-alkylpiperidinyl) octane dinitrile: Example 19

Exemplary S obtained in Examples 6 - [1,6-dicyano-5-oxo-6- (triphenyl -λ ^{5-phosphazene-alkylpiperidinyl)} hexane-2-yl] O-ethyl nodi thio carbonyl benzoate (8e, 106.1 mg, the 1, 4-dioxane (2 mL) in _{H 3 PO 2 (109.5 ㎕,} 5.0 eq., 50wt% in H ₂ O) and Et ₃ N (153.3 ㎕, 5.5 equivalents of a solution containing 0.2 mmol)) Was added sequentially and refluxed under argon gas for 15 minutes. AIBN (54.7 mg, 0.6 eq.) Was added to the reaction solution, and the mixture was refluxed with stirring for 1 hour and then cooled to room temperature. The reaction mixture was diluted with CH ₂ Cl ₂ (15 mL), washed with water (10 mL), and the lower organic layer was separated with a separatory funnel. The upper aqueous layer was washed twice with CH ₂ Cl ₂ Further extracted. The separated organic layers were combined and then treated with anhydrous magnesium sulfate (10 g), filtered, and the solvent was removed using a rotary evaporator. The resulting solid residue was purified by flash chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ the same title compound was prepared as in example 18 and separated by _{Cl 2 / EtOAC = 5/1) (} 3e, 63.2 mg, 77%) was obtained.

Example 20: 6-cyano-5-oxo-6- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) hexyl cyanoacetate (6-Cyano-5-oxo -6- (triphenyl-λ 5 - phosphanylidene) hexyl cyanoacetate, 3f)

(6-cyano-2 - [(ethoxycarbonothionyl) sulfanyl] -5-oxo-6- (triphenyl- ⁵ -phosphanylidene) hexyl cyanoacetate obtained in Example 7 ( 8f , 117.7 mg, 0.2 mmol) was refluxed under argon gas for 15 min. To this reaction solution was added DLP (87.7 mg, 1.1 eq.) Periodically every hour while stirring under argon gas for 2 hours. The reaction solution was cooled to room temperature and the solvent was removed by rotary evaporation to remove the residue. Chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAc = 5/1) afforded the title compound ( 3f , 68.4 mg, 73%).

_{^{1 H NMR (CDCl 3, 400}} MHz) δ 1.67-1.81 (m, 4H), 2.73 (t, 2H, J = 6.8 Hz), 3.46 (s, 2H), 4.22 (t, 2H, J = 5.9 Hz) , 7.48-7.69 (m, 15H).

Example 21: 6-cyano-5-oxo-6- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) hexyl cyanoacetate (6-Cyano-5-oxo -6- (triphenyl-λ 5 - phosphanylidene) hexyl cyanoacetate, 3f)

(6-cyano-2 - [(ethoxycarbonothionyl) sulfanyl] -5-oxo-6- (triphenyl- ⁵ -phosphanylidene) hexyl cyanoacetate obtained in Example 7 (8f, 117.7 mg, 0.2 mmol ) containing a 1,4-dioxane (2 mL) solution of the _{H 3 PO 2 (109.5 ㎕,} 5.0 eq., 50wt% in H ₂ O) and Et ₃ N (153.3 ㎕, 5.5 eq.) Were added sequentially and refluxed under argon gas for 15 min. AIBN (54.7 mg, 0.6 eq.) Was added to the reaction solution, and the mixture was refluxed with stirring for 1 hour and then cooled to room temperature. The reaction mixture was diluted with CH ₂ Cl ₂ (15 mL), washed with water (10 mL), and the lower organic layer was separated with a separatory funnel. The upper aqueous layer was washed twice with CH ₂ Cl ₂ Further extracted. The separated organic layers were combined and then treated with anhydrous magnesium sulfate (10 g), filtered, and the solvent was removed using a rotary evaporator. The resulting solid residue was purified by flash chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ the same title compound was prepared as in example 20 and separated by _{Cl 2 / EtOAC = 5/1) (} 3f, 71.2 mg, 76%) was obtained.

Example 22: 6-cyano-5-oxo-6- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl), hexyl phenyl carbonate (6-Cyano-5-oxo -6- (triphenyl-λ 5 - phosphanylidene) hexyl phenyl carbonate, 3g)

Sulfanyl] -5-oxo-6- (triphenyl-? ⁵ -phosphanylidene) hexylphenyl carbonate ( 8 g , 128.3 mol) obtained in Example 8 mg, 0.2 mmol) was refluxed under argon gas for 15 min. To this reaction solution was added DLP (87.7 mg, 1.1 eq.) Periodically every hour while stirring under argon gas for 2 hours. The reaction solution was cooled to room temperature and the solvent was removed by rotary evaporation to remove the residue. The title compound ( 3 g , 59.5 mg, 57%) was obtained by chromatography (silica gel: Merck 70-230, mobile phase: Hexane / EtOAc = 2/3).

_{^{1 H NMR (CDCl 3, 400}} MHz) δ 1.73-1.87 (m, 4H), 2.77 (t, 2H, J = 6.6 Hz), 4.26 (t, 2H, J = 6.1 Hz), 7.14-7.41 (m, 5H), 7.48-7.68 (m, 15H).

Example 23 6-Cyano-5-oxo-6- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl), hexyl phenyl carbonate (6-Cyano-5-oxo -6- (triphenyl-λ 5 - phosphanylidene) hexyl phenyl carbonate, 3g)

Sulfanyl] -5-oxo-6- (triphenyl-? ⁵ -phosphanylidene) hexylphenyl carbonate ( 8 g , 128.3 mol) obtained in Example 8 H ₃ PO ₂ (109.5 μL, 5.0 eq., 50 wt% in H ₂ O) and Et ₃ N (153.3 μL, 5.5 eq.) were added to a solution of 1,4-dioxane Was added sequentially and refluxed under argon gas for 15 min. AIBN (54.7 mg, 0.6 eq.) Was added to the reaction solution, and the mixture was refluxed with stirring for 1 hour and then cooled to room temperature. The reaction mixture was diluted with CH ₂ Cl ₂ (15 mL), washed with water (10 mL), and the lower organic layer was separated with a separatory funnel. The upper aqueous layer was washed twice with CH ₂ Cl ₂ Further extracted. The separated organic layers were combined and then treated with anhydrous magnesium sulfate (10 g), filtered, and the solvent was removed using a rotary evaporator. The resulting solid residue was purified by flash chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ the same title compound was separated by a Cl ₂ / EtOAC = 5/1) as in example 22 (3g, 75.2 mg, 72 %) was obtained.

Example 24: 7-Benzyloxy-3-oxo-2- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) heptane nitrile (7-Benzyloxy-3-oxo -2- (triphenyl-λ 5 - phosphanylidene) heptanenitrile, 3h)

S - [1-benzyloxy-6-cyano-5-oxo-6- (triphenyl-? ⁵ -phosphanylidene) hexan-2-yl] O -ethylcarbododioate obtained in Example 9 ( 8h , 122.4 mg, 0.2 mmol) was refluxed under argon gas for 15 min. To this reaction solution was added DLP (87.7 mg, 1.1 eq.) Periodically every hour while stirring under argon gas for 2 hours. The reaction solution was cooled to room temperature and the solvent was removed by rotary evaporation to remove the residue. Purification by chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / Et ₂ O = 20/1) afforded the title compound ( 3h , 41.3 mg, 42%).

_{^{1 H NMR (CDCl 3, 400}} MHz) δ 1.62-1.80 (m, 4H), 2.72 (t, 2H, J = 7.3 Hz), 3.49 (t, 2H, J = 6.6 Hz), 4.49 (s, 2H) , 7.23-7.37 (m, 5H), 7.47-7.67 (m, 15H).

Example 25: 7-Benzyloxy-3-oxo-2- (triphenyl -λ ⁵ - phosphazene-alkylpiperidinyl) heptane nitrile (7-Benzyloxy-3-oxo -2- (triphenyl-λ 5 - phosphanylidene) heptanenitrile, 3h)

S - [1-benzyloxy-6-cyano-5-oxo-6- (triphenyl-? ⁵ -phosphanylidene) hexan-2-yl] O -ethylcarbododioate obtained in Example 9 (8h, 122.4 mg, 0.2 mmol ) containing a 1,4-dioxane (2 mL) solution of the _{H 3 PO 2 (109.5 ㎕,} 5.0 eq., 50wt% in H ₂ O) and Et ₃ N (153.3 ㎕, 5.5 eq.) Were added sequentially and refluxed under argon gas for 15 min. AIBN (54.7 mg, 0.6 eq.) Was added to the reaction solution, and the mixture was refluxed with stirring for 1 hour and then cooled to room temperature. The reaction mixture was diluted with CH ₂ Cl ₂ (15 mL), washed with water (10 mL), and the lower organic layer was separated with a separatory funnel. The upper aqueous layer was washed twice with CH ₂ Cl ₂ Further extracted. The separated organic layers were combined and then treated with anhydrous magnesium sulfate (10 g), filtered, and the solvent was removed using a rotary evaporator. The resulting solid residue was purified by flash chromatography (silica gel: Merck 70-230, mobile phase: CH ₂ Cl ₂ / EtOAC = 5/1) to obtain the title compound ( 3h , 66.9 mg, 68%) as in Example 24.

Claims (10)

(i) reacting an S- [3-cyano-2-oxo-3- (triphenyl-? ⁵ -phosphanylidene) propyl] O- ethylcarbodioate with an olefin compound represented by the following formula An addition reaction to obtain a valerate adduct of the formula (8); And
(ii) a step of subjecting a side-chain adduct of the following formula (8) to a radical reduction reaction to prepare an? -keto (cyanomethylene) triphenylphosphorine compound of the following formula
[Chemical Formula 1]

(2)

[Chemical Formula 8]

(3)

In this formula,
Xa is -SC (= S) OEt,
R is a C ₁ -C ₆ alkyl group, a C ₃ -C ₁₀ cycloalkanonyl group, an aryl group, a -OCOR ₁ , a cyano or an aryloxy group,
R ₁ is a C ₁ -C ₆ alkyl group or an aryloxy group which is unsubstituted or substituted by cyano. The method according to claim 1,
R is a C ₁ -C ₆ alkyl group, a C ₃ -C ₁₀ cycloalkanonyl group, phenyl, -OCOR ₁ , cyano or benzyloxy,
R ₁ is cyano substituted or are C ₁ alkyl group, or a phenoxy admitted process for producing a -C ₆ unsubstituted. The method according to claim 1,
R is n -pentyl, cyclohexanonyl, phenyl, -OCOR < _{1 &} gt ;, cyano or benzyloxy,
Wherein R < ₁ > is methyl, cyanomethyl or phenoxy. The process according to claim 1, wherein the addition reaction is carried out using a radical initiator. 5. The process according to claim 4, wherein the radical initiator is dilauryl peroxide. The process according to claim 1, wherein the radical reduction reaction is carried out in the presence of dilauryl peroxide. The process according to claim 1, wherein the radical reduction reaction is carried out in the presence of hypophosphorous acid (H ₃ PO ₂ ), triethylamine (Et ₃ N) and azobisisobutyronitrile (AIBN). S - [3-cyano-2-oxo-3- (triphenyl-? ⁵ -phosphanylidene) propyl] O -ethylcarbonodithioate of the following formula 1:
[Chemical Formula 1]

(a) to the formula (4) (triphenyl Fora alkylpiperidinyl) acetonitrile and ethyl chloride to the formula (5) to condensation reaction of 4-chloro-3-oxo-2-chloride of formula (6) (triphenyl -λ ⁵ - Phosphanylidene) butanenitrile; And
(b) reacting 4-chloro-3-oxo-2- (triphenyl-? ⁵ -phosphanylidene) butanenitrile of formula 6 with potassium O- Method for producing S- [3-cyano-2-oxo-3- (triphenyl-? ⁵ -phosphanylidene) propyl] O -ethylcarbodioate of formula
[Chemical Formula 4]

[Chemical Formula 5]

[Chemical Formula 6]

(7)

[Chemical Formula 1]

The method of claim 9, wherein the condensation reaction the N, O - bis (trimethylsilyl) acetamide: prepared is performed by using the (N, O -Bis (trimethylsilyl) acetamide BSA).