KR101241744B1 - New chloride-containing allylating reagents and stereoselective ppeparation method of derivatives of vinyl chlorohydrins and vinyl oxiranes using the same - Google Patents

Abstract

The present invention relates to a stereoselective method for preparing vinyl chlorohydrin and vinyl oxirane using chlorine-containing allyltransfer reagents. This makes it possible to synthesize vinyl chlorohydrin and vinyloxirane of various substituents and to selectively obtain all possible stereoisomers. In addition, the present invention provides a novel method for synthesizing ponta epoxide which can be used as a synthetic intermediate of optically active natural products and pharmaceuticals with physiological activity.

Description

New Chlorine-Containing ALLYLATING REAGENTS AND STEREOSELECTIVE PPEPARATION METHOD OF DERIVATIVES OF VINYL CHLOROHYDRINS AND VINYL OXIRANES USING THE SAME}

The present invention relates to novel chlorine-containing allyltransfer reagents and to stereoselective preparation of vinylchlorohydrin and vinyloxirane using the same.

The present invention also relates to a method for producing pontica epoxide, which is a kind of vinyl oxirane derivative.

Homoallyl alcohol is relatively simple, but because it contains a hydroxyl group and an olefin group, since it is possible to synthesize a useful compound by functional group conversion has been applied and researched in various fields. Such homoallyl alcohol is obtained through the allyl addition reaction of aldehyde. In particular, the allyl addition reaction of the aldehyde is the most studied field in the chemical field together with the aldol reaction in the asymmetric synthesis field. Homoallyl alcohol produced through such a reaction has been widely used as a research object ranging from a relatively simple type of stereostereoselection reaction to a catalyst asymmetry reaction.

In the early 1980s, Hoffmann, Germany, proposed a new type of asymmetric synthesis method using a camphor derivative to synthesize an equivalent allylborane containing a chiral regulator and react with it to obtain an optically active product. Compounds obtained through this asymmetric synthesis method have made remarkable advances in terms of stereoselectivity and yield, and until recently, it has been proved to be an efficient methodology for constructing physiologically active natural products of very complex stereostructures.

Since then, many chemists have participated in this field of research to develop unique forms of improved methodologies. Despite these studies, only very simple allyl transfer reagents have been developed so far, and development of allyl transfer reagents containing functional groups is expected.

In this example, Org . Chem . ( Hu, S .; Jayaraman, S .; Oehlschlager, AC J. Org . Chem . 1996, 61 , 7513-7520) describe chloroallyl transfer reactions, but only one diastereomer is described. There is a problem in that the efficiency is poor in that it can be synthesized, the reaction conditions are made only under very strong base conditions, and other functional groups cannot be introduced, and the reaction yield and stereoselectivity are not ideal.

The present inventors came up with a new chlorine-containing allyl transfer reagent while envisioning an allyl transfer reaction that can be converted into various compounds, thereby completing the present invention.

It is an object of the present invention to provide novel chlorine-containing allyltransferases capable of selectively preparing both diastereomers and enantiomers, while improving the efficiency of reaction yields, stereoselectivity and the like and reacting under mild conditions.

Another object of the present invention is to provide a method for preparing optically active vinylchlorohydrin and vinyloxirane using the chlorine-containing allyltransferase of the present invention.

It is still another object of the present invention to provide a novel method for synthesizing ponticae epoxide (Ponticaepoxide), an optically active natural product having a physiological activity as a kind of vinyl oxirane derivative.

In order to achieve the above object, the present invention provides a chlorine-containing allyl transfer reagent obtained by reacting sulfyllide with chiral borane, which is very useful for asymmetric synthesis.

Specifically, the present invention provides

(i) chlorine-containing sulfur ylides selected from formulas 8-1 or 9-1, and

[Formula 8-1]

[Formula 9-1]

 (ii) a chiral borane selected from formula 13 or formula 13-1

[Chemical Formula 13]

[Formula 13-1]

It provides a chlorine-containing allyl transfer reagent obtained by reacting. In the compound of Formula 13 or Formula 13-1, the substituent Tol is 4-methylphenyl.

The chlorine-containing allyltransfer reagent of the present invention may be obtained, for example, by reacting a sulfide of Formula 8-1 with a chiral borane of Formula 13, or a sulfide of Formula 9-1 and a chiral of Formula 13 It can be obtained by reacting borane. The chlorine-containing allyltransfer reagent of the present invention is an intermediate which cannot be separated and can be represented by a structural formula as shown in Table 1 below.

The present invention is a method for preparing an anti-vinylchlorohydrin of Formula 15 or Formula 15-1 by reacting a chlorine-containing allyltransfer reagent of the present invention with an aldehyde of Formula 14 and syn-vinyl of Formula 16 or Formula 16-1 Further provided are methods for preparing chlorohydrin.

[Formula 14]

R-CHO

[Formula 15]

[Chemical Formula 16]

[Formula 15-1]

[Formula 16-1]

The present invention further provides a method of preparing a trans-vinyl oxirane of formula 17 by reacting an anti-vinylchlorohydrin of formula 15 prepared with a chlorine-containing allyltransferase of the present invention with a base.

[Chemical Formula 17]

The present invention further provides a method for preparing a trans-vinyl oxirane of formula (17-1) by reacting an anti-vinylchlorohydrin of formula (15-1) prepared with a chlorine-containing allyltransferase of the present invention with a base. .

[Formula 17-1]

The present invention further provides a process for preparing cis-vinyloxirane of formula (18) by reacting a syn-vinylchlorohydrin of formula (16) prepared using a chlorine-containing allyltransferase according to the present invention with a base.

 [Chemical Formula 18]

The present invention further provides a process for preparing cis vinyloxirane of formula (18-1) by reacting syn-vinylchlorohydrin of formula (16-1) prepared with a chlorine-containing allyltransferase according to the present invention with a base. .

[Formula 18-1]

In the above formulas, Tol is 4-methylphenyl, R is an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, an aralkyl group, an arkenyl group, or an aralkylyl group, preferably an alkyl group having 1 to 12 carbon atoms, Aralkyl groups in which an alkenyl group having 2 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, a cycloalkyl group having 3 to 12 carbon atoms, an aryl group having 6 to 12 carbon atoms, and an alkyl group having 1 to 12 carbon atoms is substituted with an aryl group having 6 to 12 carbon atoms , An alkenyl group in which an alkenyl group having 2 to 12 carbon atoms is substituted with an aryl group having 6 to 12 carbon atoms, or an aralkylyl group in which an alkynyl group having 2 to 12 carbon atoms is substituted with an aryl group having 6 to 12 carbon atoms, most preferably phenyl , Benzyl, cyclohexyl, phenylethenyl, phenylethynyl or phenylethyl.

The present invention further provides sulfonium ions of the formula (8) or formula (9) which are precursors of the sulfides of the present invention.

[Formula 8]

이고, Me는 메틸임)(Ts is

Me is methyl)

[Chemical Formula 9]

이고, Me는 메틸임)(Ts is

Me is methyl)

The present invention further provides a method for preparing ponticaepoxide using a chlorine-containing allyl transition reagent according to the present invention.

The present invention has the effect of providing high selective synthesis of all stereoisomers (diastereomers and enantiomers) by preparing vinylchlorohydrin and vinyloxirane using novel chlorine-containing allyltransfer reagents. Method using the chlorine-containing allyl transition reagent according to the present invention has the advantage that can be synthesized in a mild condition more stable production.

In addition, the present invention has the effect of providing a method for synthesizing ponta epoxide for the first time.

EMBODIMENT OF THE INVENTION Below, this invention is demonstrated in detail.

A. Sulfur Ilid  Precursor of Formula 8 or 9 Sulfonium  Preparation of ions

Sulfonium ions of the formula (8) or (9), which are the precursors of the sulfides according to the present invention, may be prepared according to Scheme 1 below.

[Reaction Scheme 1]

Synthesis of the compound of formula (1) (( E ) -chloroallyl alcohol) and the compound of formula (2) ((Z) -chloroallyl alcohol) can be carried out as it is reported in the literature or by improving the method.

The compound of formula 1 can be obtained, for example, by synthesizing epichlorohydrin from the reaction with butyllithium in the presence of tetramethylethylenediamine (TMEDA). This reaction produces the (E) -isomer and (Z) -isomer in a mixture of about 85:15. The resulting mixture and potassium tert-butoxide ( t- BuOK) were slowly heated to room temperature at 80 ° C. for at least 10 hours, followed by addition of water to terminate the reaction, followed by extraction with diethyl ether (Et ₂ O). can do. By using distillation as the extraction method, pure compound ( E ) -3-chloro-2-propen-1-ol of formula (1) can be obtained.

Compounds of formula (2) are described, for example, in Urdaneta , NA; Salazar , J .; Herrera, JC; Lopez , SE Synthetic Communications , 2004, 34, 657 ] can be synthesized from ethyl propiolate using the method described.

The compound of Formula 1 or the compound of Formula 2 thus synthesized is placed in a container, and then a solvent is added. Thereafter, the compound of formula 3 (butyllithium) is added to the vessel at the reaction temperature, and then para-toluenesulfonyl chloride ( p- TsCl) is added at one time. The reaction temperature is generally -78 ° C to 0 ° C, preferably -78 ° C to -20 ° C, and the reaction is effective at low temperatures.

After reacting for 3 hours at the above temperature, it is purified by silica gel chromatography to synthesize a compound of Formula 5 [( E ) -3-chloroallyl-4-methylbenzenesulfonate]. The compound of Formula 5 thus obtained is reacted with tetrahydrothiophene of Formula 7 in a solvent to form a white salt, and the solvent is removed to remove the compound of Formula 8 [( E ) -1- (3-chloroallyl) -tetrahydro- 1-H-thiophenium-4-methylbenzenesulfonate] can be obtained. The solvent is preferably tetrahydrofuran.

In the same manner, the compound of formula 2 was used as a starting material to obtain a compound of formula 6 [(Z) -3-chloroallyl-4-methylbenzenesulfonate], and the compound of formula 9 was obtained from the compound of formula 6. You can get it.

B. Chlorine Allyl Transfer Reagent  And using it Vinylchlorohydrin  Stereoselective manufacturing

The present invention is to react the sulfur yilide and chiral borane to prepare a new chlorine-containing allyl transfer reagent, and reacted with the aldehyde to produce an optically active vinyl chlorohydrin. Specific reaction schemes can be identified through the following scheme 2.

[Reaction Scheme 2]

A compound of Formula 15-1 or a compound of Formula 16-1 may be prepared by the same method as in Scheme 2, except that the compound of Formula 11-1 and the chiralborane of Formula 13-1 are used.

[Formula 11-1]

B-1. Chlorine Allyl transfer reagent  Produce

The sulfonium ions of formula 8 or 9 can be obtained by reacting with methyllithium in a solvent. As for reaction temperature, -40 degreeC is preferable. The optical purity is high at this temperature.

The resulting sulfur illide is reacted with a chiral borane of Formula 13 to prepare a chlorine-containing allyltransfer reagent.

A chiral borane [(4R, 5R) -4,5-diphenyl-1,3-ditosyl-1,3,2-diazaboolidine] of formula 13 is a compound of formula 11 [(1R, 2R)- 1,2-diphenyl-N1, N2-ditosylethane-1,2-diamine] and 3 equivalents of the compound of formula 12 (borane, BH ₃ SMe ₂ ) can be obtained by high temperature and long reaction in a solvent. . Here, toluene is preferable, as for a solvent, 80 degreeC of reaction temperature is preferable, 20-24 hours are suitable for reaction time, and 24 hours are preferable. Thereafter, distillation under reduced pressure removes the volatiles and can be used immediately by dissolving in anhydrous solvent. It can be seen that the structural properties of the compound of formula 11 were very efficient for steric transition. The solvent is preferably tetrahydrofuran.

The sulfides prepared according to the invention are very unstable and must react with the chiral borane of the formula (13) in a short time, particularly preferably within 10 minutes.

B-2. Vinylchlorohydrin  Stereoselective manufacturing

The chlorine-containing allyltransfer reagent of the present invention may be reacted with an aldehyde of Formula 14 to prepare a compound of Formula 15 (anti-vinylchlorohydrin).

[Formula 14]

RCHO

In the above formula, R is an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, an aralkyl group, an arkenyl group, or an aralkyl group, preferably an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, Aralkyl groups in which an alkynyl group having 2 to 12 carbon atoms, a cycloalkyl group having 3 to 12 carbon atoms, an aryl group having 6 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms is substituted with an aryl group having 6 to 12 carbon atoms, and an alkenyl having 2 to 12 carbon atoms The group is an arkenyl group substituted with an aryl group having 6 to 12 carbon atoms, or an alkynyl group having 2 to 12 carbon atoms substituted with an aryl group having 6 to 12 carbon atoms, and most preferably phenyl, benzyl, cyclohexyl, or phenyl. Tenyl, phenylethynyl or phenylethyl.

As for the reaction temperature of the manufacturing method of vinylchlorohydrin which concerns on this invention, -78 degreeC is preferable.

When the same method is performed using the compound of Formula 9 as a starting material, the compound of Formula 16 (syn-vinylchlorohydrin) may be obtained with excellent selectivity.

The process of the present invention can synthesize vinylchlorohydrin starting from stable sulfonium ions through continuous operation in a single vessel. This reaction has the advantage of increasing the efficiency of the reaction by synthesizing the unstable compound (sulfur lead) in the air directly in the reaction vessel.

The partial stereoselectivity of the preparation process according to the invention produces more than 99% of the highly pure diastereomers in all reactions. In addition, the absolute stereoselectivity is also very high, NMR analysis of the product MTPA-ester and chiral high performance liquid chromatography (HPLC, Chiralcel AD-H) as a result of the 93 ~> 99% ee (Enantiomeric excess) characterized in that characterized do.

C. Vinyloxirane  Stereoselective manufacturing

The optically active vinylchlorohydrin obtained through the method described in A and B described above can be stereoselectively synthesized into optically active vinyloxirane under basic conditions. The vinyloxirane thus produced can be used not only as a major part of bioactive natural products but also as a substrate molecule of useful chemical transformation. The process of preparing vinyloxirane is described in detail through Scheme 3 below.

 Scheme 3

Compounds of formula 15 or 16 which are diastereomers can be synthesized with vinyl oxirane at basic conditions. It is preferable to use DBU (1,8-diazabicyclo [5,4,0] undes-7-ene) of formula (19) as the base.

The compound of formula 15 may be prepared as trans vinyloxirane of formula 17, and the compound of formula 16 may be prepared as cis vinyloxirane of formula 18. In Formulas 15 to 18, R is as defined in the aldehyde of Formula 14.

In the method for producing trans / cis vinyloxirane according to the present invention, the solvent may be appropriately selected by those skilled in the art, for example, dichloromethane, tetrahydrofuran, diethyl ether and the like. . In addition, although reaction temperature and reaction time are not specifically limited, It is suitable to carry out about 1-3 hours at room temperature.

Meanwhile, the compound of Formula 17-1 or the compound of Formula 18-1 may be prepared by the same method starting from the compound of Formula 15-1 or the compound of Formula 16-1, respectively.

D. Pontika Epoxide  Manufacturing method

Through Schemes 1 to 3, various optically active vinylchlorohydrins and vinyloxiranes were prepared using allyl transition reagents obtained by reacting sulfyllide and chiral borane.

Through the production method according to the present invention, it is possible to synthesize a polyacetylene-based physiologically active natural pontica epoxide. To date, no method of synthesizing ponticaepoxide has been reported (natural extraction and structural analysis, Mann, D .; Hartmann, R. J. Nat . Prod . 1992, 55, 29). Although this class of compounds shows various physiological activities, it is very important to find a synthetic route to them because of the limited amount available in nature.

The present invention provides for the first time a method for producing ponticaepoxide using a method for producing vinyloxirane using a chlorine-containing allyltransferase according to the present invention.

Specifically, the method for producing pontica epoxide according to the present invention,

(S1) reacting sulfonium ions of formula 8 with methyllithium to obtain chlorine-containing sulfides of formula 8-1;

[Formula 8]

이고, Me는 메틸임)(Ts is

Me is methyl)

[Formula 8-1]

(S2) reacting the chlorine-containing sulfide of Formula 8-1 with the chiral borane of Formula 13-1 to obtain an allyl transfer reagent;

[Formula 13-1]

Wherein Tol is 4-methylphenyl

(S3) reacting the allyl transfer reagent with an aldehyde of Formula 27 to generate vinylchlorohydrin of Formula 28; And

(27)

(28)

(S4) reacting the vinylchlorohydrin with DBU.

The aldehyde compound of formula 27 may be prepared according to a method known in the art, the solvent used in steps (S1) to (S3) is preferably tetrahydrofuran, and the reaction temperature of step (S1) is- The reaction temperature of 40 ° C., (S2) and (S3) is −78 ° C., and the solvent used in (S4) may be appropriately selected by one of ordinary skill in the art, and dichloromethane, tetra Hydrofuran, diethyl ether, etc. are mentioned, The reaction time and temperature are not specifically limited.

Hereinafter, the structure of the present invention will be described in more detail with reference to examples, but the scope of the present invention is not limited to the following examples.

Example  One: Sulfonium  Synthesis of Ions

Example  1-1: ( E ) -3- Chloroallyl -4- Methylbenzenesulfonate  synthesis

[Chemical Formula 5]

After drying 1 equivalent of ( E ) -3-chloroallyl-2-propene-1-ol in an oven, it was placed in a reaction vessel in a pure nitrogen gas atmosphere and anhydrous tetrahydrofuran (THF) was added thereto. One equivalent of butyl lithium was added to the reaction vessel in a pure nitrogen atmosphere dried at −78 ° C., and then 1.1 equivalent of paratoluenesulfonyl chloride was added at a time. The reaction was continued for 3 hours at the same temperature. After completion of the reaction by adding sodium chloride, the mixture was extracted with diethyl ether and dried over magnesium sulfate (MgSO ₄ ). The solvent was distilled under reduced pressure, and then purified by silica gel chromatography (SiO ₂ ) to synthesize a compound of Chemical Formula 5.

Yield: 74%

TLC, R f 0.4 (5: 1 Hexanes / EtOAc)

IR (film): 3068, 2953, 2887, 1639, 1598 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 2.45 (s, 3H), 4.52 (dt, J = 6.9, 1.2 Hz, 1H), 5.92 (dt, J = 13.5, 6.9 Hz, 1H), 6.30 (d, J = 13.5 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 21.8, 67.8, 12.5, 125.8, 128.0, 130.1, 133.1, 145.3

MS m / z (%) 246 (M +)

Example  1-2: ( Z ) -3- Chloroallyl -4- Of methylbenzenesulfonate  synthesis

[Formula 6]

The above compound was synthesized in the same manner as in Example 1-1 from (Z) -3-chloroallyl-2-propen-1-ol.

Yield: 67%

TLC, R f 0.4 (5: 1 Hexanes / EtOAc)

IR (film): 3090, 6055, 2926, 1633, 1597 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 2.45 (s, 3H), 4.74 (dd, J = 6.3, 1.5 Hz, 2H), 5.88 (dt, J = 7.5, 6.3 Hz, 1H), 6.21 (d, J = 7.5 Hz, 1H), 7.35 (d, J = 8.1 Hz, 2H), 7.8 0 (d, J = 8.1 Hz, 2H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 21.8, 65.1, 123.6, 124.6, 128.1, 130.0, 132.9, 145.2

MS m / z (%) 246 (M +)

Example  1-3: (E) -1- (3- Chloroallyl ) - Tetrahydro -1H- Thiophenium  4- Of methylbenzenesulfonate  synthesis

[Formula 8]

One equivalent of compound of formula 5 was added to a dried reaction vessel, followed by addition of anhydrous ether (Et ₂ O). Then 3 equivalents of compound of formula 7 were added under a dry nitrogen atmosphere. After reacting at room temperature (20 ° C.) for about 12 hours, a white salt was formed. The solvent was decanted and anhydrous ether was added thereto. The ether was removed again and dried under reduced pressure. As a result, very high purity (E) -1- (3-chloroal ¦´) -tetrahydro-1H-thiophenium 4-methylbenzenesulfonate was obtained.

Yield: 76%

IR (film): 3452, 3058, 2979, 29 50, 2236 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 1.93-2.35 (m, 4H), 2.33 (s, 3H), 3.47-3.53 (m, 2H), 3.63-3.72 (m, 2H), 4.42 (d, J = 8.1 Hz, 2H), 5.89 (dt, J = 13.2, 8.1 Hz, 1H), 6.77 (d, J = 13.2 Hz, 1H), 7.15 (d, J = 8.1 Hz, 2H), 7.67 (d, J = 8.1 Hz, 2H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 21.1, 28.7, 41.7, 42.3, 120.7, 125.4, 128.7, 129.8, 13 9.5, 143.5

Example  1-4: ( Z ) -1- (3- Chloroallyl ) - Tetrahydro -1H- Thiophenium  4- Of methylbenzenesulfonate  Synthesis of compounds

[Chemical Formula 9]

The above compound was synthesized in the same manner as in Example 1-3 from ( Z ) -1- (3-chloroallyl) -tetra hydro-1H-thiophenium 4-methylbenzenesulfonate (compound of Formula 6).

Yield: 75%

IR (film): 3461, 3300, 3195, 3050, 2983, 2948, 2235, 1625 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 2.06-2.36 (4H, m), 2.34 (s, 3H), 3.47-3.56 (m, 2H), 3.79-3.88 (m, 2H), 4.30 (d, J = 7.5 Hz, 2H), 6.19 (dt, J = 7.5, 7.5 Hz, 1H), 6.53 (d, 1H, J = 8.1 Hz, 1H), 7.15 (d, 2H, J = 8.1 Hz, 2H), 7.73 (d, 2H, J = 8.1 Hz, 2H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 21.2, 28.8, 38.0, 43.1, 120.0, 125.6, 128.3, 128.7, 139.4, 143.6

Example  2: Vinylchlorohydrin  Preparation of Derivatives

Example  2-1: (+)-(3S, 4R) -4- Chloro -One- Phenylhex Synthesis of -5-en-3-ol

Toluene was added to a flask with one equivalent of the compound of formula 11 (R, R) -bissulfonamide under a dry nitrogen atmosphere. To this was added 3 equivalents of the compound borane (BH ₃ · SMe ₂ ) of Formula 12, and then gradually increased the temperature to 80 ° C. After 20 hours, the compound chiral borane of Chemical Formula 13 was obtained by distillation under reduced pressure at 1 mmHg without air contact using Schlenk. This can be confirmed by NMR.

Anhydrous tetrahydrofuran (THF) was added thereto to dissolve and used for the next reaction. One equivalent of ( E ) -sulfonium ion of Chemical Formula 8 was dissolved in tetrahydrofuran (THF), and then the temperature was lowered to −40 ° C., and 1.1 equivalent of 1.0 M methyllithium (MeLi) was added to the vessel wall. After 10 minutes, chiral borane of formula 13 synthesized above was added. After reacting at -40 ° C for 2 hours, the temperature was gradually raised to 0 ° C. After 1 hour, the reaction mixture was lowered to -78 ° C, and then 1 equivalent of hydrocinnamaldehyde (R = PhCH ₂ CH ₂ ) of Formula 14 was added (+)-(3S, 4R) -4-chloro-1-phenyl-5 -Hexene-3-ol (R = PhCH ₂ CH ₂ ) was obtained.

Yield: 93%

[a] _D ²⁰ + 3.051 ° (c 1.56, CHCl ₃ )

TLC, R f 0.5 (3: 1 Hexanes / EtOAc); IR (film): 3431, 3025, 2924, 1602, 1453 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 1.77-1.85 (m, 2H), 2.15 (d, J = 4.5 Hz, 1H), 2.64-2.74 (m, 1H), 2.84-2.93 (m, 1H), 3.76-3.83 (m, 1H), 4.38 (dd, J = 3.9, 9.0 Hz, 1H), 5.25 (dd, J = 10.2, 1.0 Hz, 1H), 5.35 (dd, J = 17.5, 1.0 Hz, 1H) , 5.9 (ddd, J = 17.5, 10.2, 9.0 Hz, 1H), 7.19-7.29 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 32.2, 34.9, 68.0, 73.7, 120.0, 126.3, 128.7, 128.7, 134.0, 141.7

MS m / z (%) 210 (M +)

Example  2-2: (+)-(1S, 2R) -2- Chloro -One- Phenyl -3- Butene Synthesis of -1-ol

The above compound was obtained using the same method as Example 2-1 (wherein R = Ph of aldehyde).

Yield: 72%

[a] _D ²⁰ + 2.2 ° (c 0.2, CHCl ₃ )

TLC, R f 0.5 (3: 1 Hexanes / EtOAc)

IR (film): 3355, 2958, 2361, 1460, 1083 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 2.53 (d, J = 3.6 Hz, 1H), 4.58 (dd, J = 8.7, 4.2 Hz, 1H), 4.95 (dd, J = 4.2, 3.6 Hz, 1H) , 5.23 (d, J = 10.2 Hz, 1H), 5.25 (d J = 16.8 Hz, 1H,), 5.93 (ddd, J = 16.8, 10.2, 8.7 Hz, 1H), 7.28-7.37 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 67.6, 77.6, 120.3, 126.9, 128.5, 128.6, 133.5, 139.3

MS m / z (%) 182 (M +)

Example  2-3: (+)-(3S, 4R, E) -4- Chloro -One- Phenyl -1,5- Hexadiene Synthesis of 3-ol

The above compound was obtained using the same method as Example 2-1 (wherein R = PhCH = CH of aldehyde).

Yield: 62%

[a] _D ²⁰ + 5.71 ° (c 0.6, CHCl ₃ )

TLC, R f 0.5 (3: 1 Hexanes / EtOAc)

IR (film): 3399, 3027, 1649, 746 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 2.39 (d, J = 4.8 Hz, 1H), 4.49-4.56 (m, 2H), 5.32 (d, J = 10.2 Hz, 1H), 5.41 (d, J = 16.2 Hz, 1H), 5.98 (ddd, J = 16.2, 10.2, 8.4 Hz, 1H), 6.23 (dd, J = 16.2, 6.6 Hz, 1H), 6.70 (d, J = 16.2 Hz, 1H), 7.24- 7.39 (m, 5 H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 67.4, 75.6, 120.1, 126.6, 126.9, 128.4, 128.9, 133.8, 134.1, 136.4

MS m / z (%) 208 (M +)

Example  2-4: (+)-(3S, 4R) -4- Chloro -One- Phenyl -5- Hexen Synthesis of -1-yn-3-ol

The above compound was obtained in the same manner as in Example 2-1, except that R = PhC≡C of aldehyde.

Yield: 58%

[a] _D ² ° + 7.058 ° (c 1.2, CHCl ₃ )

TLC, R f 0.5 (3: 1 Hexanes / EtOAc)

IR (film): 3375, 3018, 2929, 2861, 2238 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 2.58 (d, J = 8.1 Hz, 1H), 4.61 (dd, J = 8.1, 3.4 Hz, 1H), 4.77 (dd, J = 8.1, 3.4 Hz, 1H) , 5.37 (d, J = 10.2 Hz, 1H), 5.49 (d, J = 17.1 Hz, 1H), 6.08 (ddd, J = 17.1, 10.2, 8.1 Hz, 1H), 7.31-7.47 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 66.5, 66.5, 85.4, 87.2, 120.3, 122.0, 128.5, 129.0, 132.0, 133.7

MS m / z (%) 206 (M +)

Example  2-5: (+)-(2S, 3R) -3- Chloro -One- Phenyl -4- Pentene Synthesis of 2-ol

The above compound was obtained using the same method as Example 2-1 (wherein R = PhCH _{2 of} aldehyde).

Yield: 67%

[a] _D ²⁰ + 13.20 ° (c 0.2, CHCl ₃ )

TLC, R f 0.5 (3: 1 Hexanes / EtOAc)

IR (film): 3431, 3062, 2923, 1602, 1280, 701 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 2.06 (s, 1H), 2.78-2.92 (m, 2H), 4.03-4.08 (m, 1H), 4.38 (dd, J = 9.0, 4.2 Hz, 1H), 5.36 (d, J = 9.9 Hz, 1H), 5.39 (d, J = 17.1 Hz, 1H), 6.04 (ddd, J = 17.2, 9.9, 9.0 Hz, 1H), 7.23-7.36 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ) δ = 39.6, 66.6, 75.6, 120.3, 126.9, 128.8, 129.6, 134.0, 137.5

MS m / z (%) 196 (M +)

Example  2-6: (+)-(1S, 2R) -2- Chloro -One- Cyclohexyl -3- Butene Synthesis of -1-ol

The above compound was obtained in the same manner as in Example 2-1, except that R = cyclohexyl of aldehyde.

Yield: 76%

[α] _D ²⁰ + 97.50 ° (c 0.2, CHCl ₃ )

TLC, R f 0.5 (3: 1 Hexanes / EtOAc)

IR (film): 3435, 2925, 2852, 1637, 1448, 1089 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 0.99-2.03 (m, 11H), 2.10 (d, J = 3.3 Hz, 1H), 3.48-3.53 (m, 1H), 4.55 (dd, J = 9.0, 3.9 Hz, 1H), 5.30 (d, J = 9.9 Hz, 1H), 5.36 (d, J = 17.1 Hz, 1H), 6.02 (ddd, J = 17.1, 9.9, 9.3 Hz, 1H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 25.9, 26.1, 26.5, 28.7, 29.1, 40.0, 65.9, 78.5, 119.8, 134.0

MS m / z (%) 188 (M +)

Example  2-7: (-)-(3S, 4S) -4- Chloro -One- Phenyl -5- Hexen Synthesis of 3-ol

The above compound is the same method as Example 2-1 except for using the compound (Z) -sulfonium ion of Formula 9 instead of (E) -sulfonium ion of Formula 8, except that R = PhCH ₂ CH _{2 of} aldehyde ) Was obtained.

Yield: 71%

[α] _D ²⁰ -8.80 ° (c 0.1, CHCl ₃ )

TLC, R f 0.5 (3: 1 Hexanes / EtOAc)

IR (film): 3573, 3055, 1601, 1264, 738 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 1.73-1.95 (m, 2H), 2.22 (d, J = 5.4 Hz, 1H), 2.66-3.00 (m, 2H), 3.63-3.71 (m, 1H), 4.38 (dd, J = 8.7, 6.0 Hz, 1H), 5.31 (d, J = 10.2 Hz, 1H), 5.36 (d, J = 16.8 Hz, 1H), 5.90 (ddd, J = 16.8, 10.2, 8.7 Hz , 1H), 7.15-7.18 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 32.0, 35.6, 69.3, 73.6, 119.54, 126.2, 128.7, 128.7, 135.2, 141.7

MS m / z (%) 210 (M +)

Example  2-8: (-)-(1S, 2S) -2- Chloro -One- Phenyl -3- Butene Synthesis of -1-ol

The above compound was obtained using the same method as in Example 2-7 (RCHO, R = Ph).

Yield: 64%

[α] _D ²⁰ -9.21 ° (c 0.6, CHCl ₃ )

TLC, R f 0.5 (3: 1 Hexanes / EtOAc)

IR (film): 3437, 3031, 2891, 1638, 1453 cm-1

¹ H NMR (300 MHz, CDCl 3): δ 2.82 (d, J = 3.6 Hz, 1H), 4.57 (dd, J = 8.1, 7.5 Hz, 1H), 4.95 (dd, J = 7.5, 3.6 Hz, 1H), 5.13 (d, J = 10.2 Hz, 1H), 5.21 (d, J = 16.8 Hz, 1H), 5.81 (ddd, J = 16.8, 10.2, 8.1 Hz, 1H), 7.26-7.37 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 66.6, 77.7, 119.7, 127.2, 128.6, 128.7, 134.4, 139.3

MS m / z (%) 182 (M +)

Example  2-9: (-)-(3S, 4S, E) -4- Chloro -One- Phenyl -1,5- Hexadiene Synthesis of 3-ol

The above compound was obtained using the same method as Example 2-7 (wherein R = PhCH = CH of aldehyde).

Yield: 50%

[α] _D ²⁰ -10.32 ° (c 0.2, CHCl ₃ )

TLC, R f 0.5 (3: 1 Hexanes / EtOAc)

IR (film): 3392, 3083, 2952, 2851, 1448 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 2.45 (d, J = 4.8 Hz, 1H), 4.38-4.47 (m, 2H), 5.30 (d, J = 10.2 Hz, 1H), 5.42 (d, J = 15.9 Hz, 1H), 5.98 (ddd, J = 15.9, 10.2, 8.1 Hz, 1H), 6.22 (dd, J = 15.9, 5.7 Hz, 1H), 6.72 (d, J = 15.9 Hz, 1H), 7.25- 7.42 (m, 5 H)

¹³ C NMR (75 MHz, CDCl ₃ ) δ 68.0, 75.4, 119.9, 126.9, 127.0, 128.3, 128.8, 133.3, 134.7, 136.4

MS m / z (%) 208 (M +)

Example  2-10: (-)-(3S, 4S) -4- Chloro -One- Phenyl -5- Hexen Synthesis of -1-yn-3-ol

The above compound was obtained in the same manner as in Example 2-7, except that R = PhC≡C of aldehyde.

Yield: 51%

[α] _D ²⁰ -2.337 ° (c 0.95, CHCl ₃ )

TLC, R f 0.5 (3: 1 Hexanes / EtOAc)

IR (film): 3381, 3062, 2924, 2236 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 2.50 (S, 1H), 4.53 (dd, J = 8.4, 5.4 Hz, 1H), 4.72 (d, J = 5.4 Hz, 1H), 5.38 (d, J = 10.2 Hz, 1H), 5.49 (d, J = 17.1 Hz, 1H), 6.08 (ddd, J = 17.1, 10.2, 8.4 Hz, 1H), 7.31-7.47 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 66.0, 66.7, 85.8, 87.2, 120.6, 122.1, 128.5, 129.1, 132.0, 134.0

MS m / z (%) 206 (M +)

Example  2-11: (-)-(2S, 3S) -3- Chloro -One- Phenyl -4- Pentene Synthesis of 2-ol

The above compound was obtained using the same method as Example 2-7 (wherein R = PhCH _{2 of} aldehyde).

Yield: 51%

[α] _D ²⁰ -5.565 ° (c 0.575, CHCl ₃ )

TLC, R f 0.5 (3: 1 Hexanes / EtOAc)

IR (film): 3419, 3027, 2923, 1603, 700 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 2.13 (d, J = 6.0 Hz, 1H), 2.77-3.00 (m, 2H), 3.89-3.97 (m, 1H), 4.36 (dd, J = 8.4, 18.4 Hz, 1H), 5.29 (d, J = 10.2 Hz, 1H), 5.37 (d, J = 17.1 Hz, 1H), 6.01 (ddd, J = 17.1, 10.2, 8.4 Hz, 1H), 7.18-7.35 (m , 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 40.4, 67.3, 75.3, 119.4, 126.9, 128.8, 129.6, 135.4, 137.5

MS m / z (%) 196 (M +)

Example  2-12: (-)-(1S, 2S) -2- Chloro -One- Cyclohexyl -3- Butene Synthesis of -1-ol

The above compound was obtained in the same manner as in Example 2-7, except that R = cyclohexyl of aldehyde.

Yield: 67%

[α] _D ²⁰ -50.89 ° (c 0.705, CHCl ₃ )

TLC, R f 0.5 (3: 1 Hexanes / EtOAc)

IR (film): 3406, 3083, 2926, 1449 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 1.06-1.85 (m, 11H), 1.97 (d, J = 6.6 Hz, 1H), 3.35-3.40 (m, 1H), 4.55 (dd, J = 9,1 , 5.1 Hz, 1H), 5.25 (d, J = 10.2 Hz, 1H), 5.38 (d, J = 16.8 Hz, 1H), 6.00 (ddd, J = 16.8, 10.2, 8.7 Hz, 1H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 26.1, 26.3, 26.4, 27.3, 29.8, 40.8, 67.2, 78.5, 118.7, 135.9

MS m / z (%) 188 (M +)

Example  3: vinyl Oxirane  Synthesis of derivatives

Example  3-1: (-)-(2S, 3S) -2- Phenyl -3- Vinyloxirane  synthesis

One equivalent of the anti-vinylchlorohydrin derivative (R = Ph) obtained in Example 2-2 was placed in a dried flask and dichloromethane was added thereto. After adding 3 equivalents of DBU at room temperature and reacting at room temperature (20 ° C.) for 2 hours, water was added to terminate the reaction. After extraction with dichloromethane it was dried over magnesium sulfate (MgSO ₄ ). The solvent was distilled under reduced pressure and purified by silica gel chromatography to obtain (-)-(2S, 3S) -2-phenyl-3-vinyloxirane, a vinyloxirane derivative, in pure form.

Yield: 75%

[α] _D ²⁰ -43.0 ° (c 0.2, CHCl ₃ )

TLC, R f 0.5 (5: 1 Hexanes / EtOAc)

IR (film): 3087, 3033., 2924, 2851, 1639, 1606, 1495, 1458, 1440 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 3.36 (d, J = 7.2 Hz, 1H), 3.76 (S, 1H), 5.33 (d, J = 10.2 Hz, 1H), 5.43 (d, J = 17.4 Hz , 1H), 5.71 (ddd, J = 17.4, 10.2, 7.2 Hz, 1H), 7.37-7.24 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 60.4, 63.2, 119.8, 125.7, 128.4, 128.7, 135.3, 137.2

MS m / z (%) 146 (M +)

Example  3-2: (-)-(2S, 3S, E) -2- Styryl -3- Vinyloxirane  synthesis

The above compound was obtained in the same manner as in Example 3-1, using the anti-vinylchlorohydrin derivative obtained in Example 2-3 as a starting material.

Yield: 70%

[α] _D ²⁰ -5.065 ° (c 1.23, CHCl ₃ )

TLC, R f 0.5 (5: 1 Hexanes / EtOAc)

IR (film): 3025, 2989, 1682, 1642, 1494, 1450 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 3.38 (d, J = 7.5 Hz, 1H) 3.43 (d, J = 7.5 Hz, 1H), 5.33 (d, J = 9.9 Hz, 1H), 5.52 (d, J = 16.5 Hz, 1H), 5.66 (ddd, J = 16.5, 9.9, 7.5 Hz, 1H), 5.95 (dd, J = 16.5, 7.5 Hz, 1H), 6.79 (d, J = 16.5 Hz, 1H), 7.40-7.24 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 60.7, 61.0, 119.7, 126.2, 126.3, 128.3, 128.8, 135.2, 136.3, 138.4

MS m / z (%) 172 (M +)

Example  3-3: (-)-(2S, 3S) -2- ( Phenylethynyl ) -3- Vinyloxirane  synthesis

The above compound was obtained in the same manner as in Example 3-1, using the anti-vinylchlorohydrin derivative obtained in Example 2-4 as a starting material.

Yield: 62%

(α) _D ²⁰ -21.61 ° (c 0.67, CHCl ₃ )

TLC, R f 0.5 (5: 1 Hexanes / EtOAc)

IR (film): 3053, 2985, 2304 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 3.48 (d, J = 2.1 Hz, 1H), 3.60-3.63 (m, 1H), 5.36-5.40 (m, 1H), 5.58-5.62 (m, 2H), 7.29-7.47 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 47.7, 60.6, 84.2, 85.1, 120.9, 122.0, 128.4, 128.9, 132.0, 134.0

MS m / z (%) 170 (M +)

Example  3-4: (-)-(2S, 3S) -2- Phenethyl -3- Vinyloxirane  synthesis

The above compound was obtained in the same manner as in Example 3-1 using the anti-vinylchlorohydrin derivative obtained in Example 2-1 as a starting material.

Yield: 80%

[α] _D ²⁰ -22.79 ° (c 2.355, CHCl ₃ )

TLC, R f 0.5 (5: 1 Hexanes / EtOAc)

IR (film): 3055, 3027, 2959, 2925, 2854, 1601, 1454, 1263 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 1.85-1.93 (m, 2H), 2.68-2.80 (m, 2H), 2.82-2.88 (m, 1H), 3.05 (d, J = 7.5 Hz, 1H) , 5.23 (d, J = 9.9 Hz, 1H), 5.39 (d, J = 17.1 Hz, 1H), 5.54 (ddd, J = 17.1, 9.9, 7.5 Hz, 1H), 7.31-7.18 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 32.2, 33.8, 58.9, 59.7, 119.1, 126.1, 128.4, 128.5, 135.7, 141.2

MS m / z (%) 174 (M +)

Example  3-5: (+)-(2S, 3S) -2-benzyl-3- Vinyloxirane  synthesis

The above compound was obtained in the same manner as in Example 3-1, using the anti-vinylchlorohydrin derivative obtained in Example 2-5 as a starting material.

Yield: 75%

[α] _D ²⁰ + 2.60 ° (c 0.2, CHCl ₃ )

TLC, R f 0.5 (5: 1 Hexanes / EtOAc)

IR (film): 3027, 2981, 2916, 1642, 1604, 1496, 1453, 1403 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 2.86-2.98 (m, 2H), 306-3.11 (m, 1H), 3.19 (d, J = 7.2 Hz, 1H), 5.28 (m, 1H), 5.47 ( d, J = 17.1 Hz, 1H), 5.53-5.65 (m, 1H), 7.24-7.35 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 38.3, 58.7, 60.4, 119.4, 126.8, 128.6, 129.1, 135.4, 137.1

MS m / z (%) 160 (M +)

Example  3-6: (-)-(2S, 3S) -2- Cyclohexyl -3- Vinyloxirane  synthesis

The above compound was obtained in the same manner as in Example 3-1 using the anti-vinylchlorohydrin derivative obtained in Example 2-6 as a starting material.

Yield: 70%

[α] _D ²⁰ -8.7 ° (c 0.2, CHCl ₃ )

TLC, R f 0.5 (5: 1 Hexanes / EtOAc)

IR (film): 3086, 2924, 2852, 1643, 1451, 1404 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 0.82-1.88 (m, 11H), 2.63 (d, J = 6.6 Hz, 1H), 3.16 (d, J = 7.2 Hz, 1H), 5.23 (d, J = 10.2 Hz, 1H), 5.43 (d, J = 17.4 Hz, 1H), 5.58 (ddd, J = 17.4, 10.2, 7.2 Hz, 1H)

¹³ C NMR (75 MHz, CDCl 3): δ 25.6, 25.8, 26.4, 29.04, 29.6, 40.2, 57.6, 64.8, 118.8, 136.2

MS m / z (%) 152 (M +)

Example  3-7: (-)-(2S, 3R) -2- Phenyl -3- Vinyloxirane  synthesis

The above compound was obtained in the same manner as in Example 3-1, except that 1 equivalent of the cis chlorohydrin derivative obtained in Example 2-8 was added.

Yield: 61%

[α] _D ²⁰ -10.57 ° (c 0.615, CHCl ₃ )

TLC, R f 0.5 (5: 1 Hexanes / EtOAc)

IR (film): 3086, 3031, 2957, 2924, 2853, 1496, 1453, 1441 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 3.68 (dd, J = 7.8, 4.2 Hz, 1H), 4.26 (d, J = 4.2 Hz, 1H), 5.28 (dd, J = 10.2, 1.8 Hz, 1H) , 5.40 (ddd, J = 16.8, 10.2, 7.8 Hz, 1H), 5.56 (dd, J = 16.8, 1.8 Hz, 1H), 7.37-7.30 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 59.1, 60.0, 122.3, 126.6, 127.9, 128.3, 132.2, 135.3

MS m / z (%) 146 (M +)

Example  3-8: (+)-(2S, 3R, E) -2- Styryl -3- Vinyloxirane  synthesis

The above compound was obtained in the same manner as in Example 3-7 except that 1 equivalent of the cis chlorohydrin derivative obtained in Example 2-9 was added.

Yield: 63%

[α] _D ^{2 0} + 3.6 ° (c 0.2, CHCl ₃ )

TLC, R f 0.5 (5: 1 Hexanes / EtOAc)

IR (film): 3027, 2954, 2853, 1640, 1494, 1450 cm ^-1

¹ H NMR (300MHz, CDCl ₃ ): δ 3.59-3.63 (m, 1H), 3.75 (d, J = 7.2, 4.5 Hz, 1H), 5.41 (dd, J = 10.5, 0.9 Hz, 1H), 5.57 ( dd, J = 15.9, 0.9 Hz, 1H), 5.81 (ddd, J = 15.9, 10.5, 7.2 Hz, 1H), 6.06 (dd, J = 15.9, 7.8 Hz, 1H), 6.83 (d, J = 15.9 Hz , 1H), 7.27-7.41 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 59.2, 59.6, 121.2, 123.5, 126.7, 128.3, 128.8, 132.5, 135.9, 136.3

MS m / z (%) 172 (M +)

Example  3-9: (-)-(2S, 3R) -2- ( Phenylethynyl ) -3- Vinyloxirane  synthesis

The above compound was obtained in the same manner as in Example 3-7 except that 1 equivalent of the cis chlorohydrin derivative obtained in Example 2-10 was added.

Yield: 60%

[α] _D ²⁰ -24.58 ° (c 0.45, CHCl ₃ )

TLC, R f 0.5 (5: 1 Hexanes / EtOAc)

IR (film): 3056, 2956, 2924, 2853, 2225 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 3.59 (dd, J = 8.1, 4.0 Hz, 1H), 3.83 (d, J = 4.0 Hz, 1H), 5.5 (dd, J = 10.5, 1.2 Hz, 1H) , 5.65 (dd, J = 17.4, 1.2 Hz, 1H), 5.89 (ddd, J = 17.4, 10.5, 8.1 Hz, 1H), 7.27-7.48 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 47.0, 58.7, 83.8, 85.8, 122.0, 122.4, 128.4, 128.9, 132.0, 132.9

MS m / z (%) 170 (M +)

Example  3-10: (-)-(2S, 3R) -2- ( Phenylethynyl ) -3- Vinyloxirane  synthesis

The above compound was obtained in the same manner as in Example 3-7, except that 1 equivalent of the cis chlorohydrin derivative obtained in Example 2-7 was added.

Yield: 75%

[α] _D ²⁰ -24.99 ° (c 1.005, CHCl ₃ )

TLC, R f 0.5 (5: 1 Hexanes / EtOAc)

IR (film): 3026, 2955, 2924, 2856, 1495, 1453 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 1.75-1.98 (m, 2H), 2.68-2.88 (m, 2H), 3.11-3.17 (m, 1H), 3.43 (dd, J = 7.2, 4.5 Hz, 1H ), 5.34 (dd, J = 10.5, 1.5 Hz, 1H), 5.46 (dd, J = 17.1, 1.5 Hz, 1H), 5.68 (ddd, J = 17.1, 10.5, 7.2 Hz, 1H), 7.32-7.18 ( m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 29.8, 32.7, 57.5, 58.4, 120.7, 126.3, 128.6, 128.6, 132.4, 141.4

MS m / z (%) 174 (M +)

Example  3-11: (+)-(2S, 3R) -2-benzyl-3- Vinyloxirane  synthesis

The above compound was obtained in the same manner as in Example 3-7 except that 1 equivalent of the cis chlorohydrin derivative obtained in Example 2-11 was added.

Yield: 71.2%

[a] _D ² ° + 4.522 ° (c 0.92, CHCl ₃ )

TLC, R f 0.5 (5: 1 Hexanes / EtOAc)

IR (film): 3086, 3063, 3028, 2922, 2853, 1640, 1496, 1456, 1405 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 2.77-2.99 (m, 2H), 3.29-3.35 (m, 1H), 3.52 (dd, J = 6.9, 4.2 Hz, 1H), 5.45 (d, J = 10.5 Hz, 1H), 5.56 (d, J = 16.5 Hz, 1H), 5.89 (ddd, J = 16.5, 10.5, 6.9 Hz, 1H), 7.35-7.24 (m, 5H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 34.3, 57.6, 59.3, 121.4, 126.9, 128.8, 129.1, 132.5, 137.7

MS m / z (%) 160 (M +)

Example  3-12: (-)-(2S, 3R) -2- Cyclohexyl -3- Vinyloxirane  synthesis

The above compound was obtained in the same manner as in Example 3-7 except that 1 equivalent of the cis chlorohydrin derivative obtained in Example 2-12 was added.

Yield: 65%

[α] _D ²⁰ -3.7 ° (c 0.2, CHCl ₃ )

TLC, R f 0.5 (5: 1 Hexanes / EtOAc)

IR (film): 3086, 2926, 2851, 1638, 1449, 1413 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 0.86-1.99 (m, 11H), 2.77-2.81 (m, 1H), 3.41 (dd, J = 7.5, 4.5 Hz, 1H), 5.35 (dd, J = 10.2 , 1.8 Hz, 1H), 5.49 (dd, J = 17.4, 1.8 Hz, 1H), 5.72 (ddd, J = 17.4, 10.2, 7.5 Hz, 1H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 24.3, 24.4, 25.1, 27.4, 29.6,35.5, 56.2, 62.2, 119.5, 131.7

MS m / z (%) 152 (M +)

Example  4: Of Ponticaepoxide  synthesis

Ponticaepoxide was prepared according to Scheme 4 below.

[Reaction Scheme 4]

Example  4-1 :( E ) - Deca Preparation of 2-ene-4,6,8-trin-1-ol

(25)

1 equivalent of the synthesized triene tin compound (tributyl (hepta-1,3,5-triyl) stannan) of the compound of formula 20 was added to a dry flask, and then 10 mol% of the palladium catalyst of formula 22 (PdCl ₂ (PPh ₃ ) ₂ ), 0.3 equivalent of CuI of the formula (23) was added. Tetrahydrofuran (THF) was added as a reaction organic solvent. 1 equivalent of (E) -3- (iodoallyloxy) trimethylsilane, a compound of Formula 21 diluted in tetrahydrofuran (THF), was added and allowed to react at room temperature for 2 hours.

The reaction solvent was evaporated and filtered under reduced pressure. The product thus obtained was placed in a reaction vessel, methanol was added as a reaction solvent, and 5 equivalents of potassium carbonate (K ₂ CO ₃ ) of Chemical Formula 24 was added at 0 ° C. Then, the reaction was terminated by adding water, followed by extraction with ether (Et ₂ O) and drying with sodium sulfate (Na ₂ SO ₄ ). And purified by column chromatography.

Yield: 62%

TLC, R f 0.37 (2: 1 Hexanes / EtOAc)

IR (film) 3053, 2985, 2357, 2305, 2223 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 1.61 (s, 1H), 1.98 (s, 3H), 4.25 (s, 2H), 5.80 (d, J = 15.9 Hz, 1H), 6.46 (dt, J = 4.5, 15.9 Hz, 1H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 4.8, 59.0, 62.8, 64.9, 67.2, 73.6, 75.2, 78.3, 108.4, 146.9

MS m / z (%) 144 (M +)

Example  4-2: (E)- Deca 2-en-4,6,8- Trinal  Produce

(27)

1 equivalent of ( E ) -deca-2-ene-4,6,8-tri-1-ol and 15 equivalents of activated MnO ₂ of formula 26 were added to a reaction vessel, followed by reaction. Dichloromethane was added as a solvent. After reacting for 3 hours at room temperature, the compound was filtered and then distilled under reduced pressure. Finally purified by silica gel chromatography to obtain the aldehyde compound of formula 26.

Yield: 97%

TLC, R f 0.43 (5: 1 Hexanes / EtOAc)

IR (film): 3062, 3053, 3027, 2916, 2851, 2825, 2220, 2168, 1734, 1718 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 2.04 (s, 3H), 6.59 (m, 2H), 9.58 (m, 1H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 4.8, 57.7, 64.6, 70.8, 73.8, 82.4, 88.3, 130.3, 142.2, 192.6

MS m / z (%) 142 (M +)

Example  4-3: (+)-( E ) -3- Chlorotrideca -1,5- Diene Preparation of -7,9,11-Trin-4-ol

(28)

The above compound was obtained by the same method as Example 2-7 except for using (S, S) -chiral borane of Chemical Formula 13-1.

Yield: 97%

TLC, R f 0.43 (5: 1 Hexanes / EtOAc)

IR (film): 3062, 3053, 3027, 2916, 2851, 2825, 2220, 2168, 1734, 1718 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 2.04 (s, 3H), 6.59 (m, 2H), 9.58 (m, 1H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 4.8, 57.7, 64.6, 70.8, 73.8, 82.4, 88.3, 130.3, 142.2, 192.6

MS m / z (%) 142 (M +)

Example  4-4: (-)-(E) -2- (nona-1-ene-3,5,7- Trinyl ) -3- Vinyloxirane  Produce

[Formula 29]

The above compound was obtained by the same method as in Example 3-1.

Yield: 75%

(α) _D ²⁰ -48.29 ° (c 0.14, CHCl ₃ )

TLC, R f 0.57 (5: 1 Hexanes / EtOAc)

IR (film): 2978, 2911, 2355, 2343, 2221 cm ^-1

¹ H NMR (300 MHz, CDCl ₃ ): δ 1.99 (s, 3H), 3.18-3.23 (m, 2H), 5.33 (dd, J = 2.1, 9.3 Hz, 1H), 5.49 (dd, J = 2.1, 15.9 Hz, 1H), 5.59 (ddd, J = 6.6, 9.3, 15.9 Hz, 1H), 5.87 (d, J = 15.9 Hz, 1H), 6.12 (dd, J = 6.6, 15.9 Hz, 1H)

¹³ C NMR (75 MHz, CDCl ₃ ): δ 4.8, 29.8, 58.8, 59.1, 61.3, 64.9, 68.1, 72.8, 78.8, 111.7, 120.3, 134.2, 144.0

MS m / z (%) 182 (M +)

Claims (30)

(S1) reacting a chlorine-containing sulfur ylide of Formula 8-1 with a chiral borane of Formula 13 to obtain an allyl transfer reagent;
[Formula 8-1]

[Chemical Formula 13]

Wherein Tol is 4-methylphenyl
(S2) reacting the allyl transition reagent with an aldehyde of Formula 14 to obtain an anti-vinylchlorohydrin of Formula 15; And
[Chemical Formula 14]
R-CHO
[Chemical Formula 15]

(Wherein R is an alkyl, alkenyl group, alkynyl group, cycloalkyl, aryl, aralkyl group, arkenyl group, or aralkylyl group)
(S3) reacting the anti-vinylchlorohydrin with a base to produce a trans-vinyloxirane derivative of Formula 17
[Chemical Formula 17]

Wherein R is an alkyl, alkenyl group, alkynyl group, cycloalkyl, aryl, aralkyl group, arkenyl group, or aralkylyl group)
Method for producing a trans-vinyl oxirane containing. (S1) reacting a chlorine-containing sulfide of Formula 8-1 with a chiral borane of Formula 13-1 to obtain an allyl transfer reagent;
[Formula 8-1]

[Formula 13-1]

Wherein Tol is 4-methylphenyl
(S2) reacting the allyl transfer reagent with an aldehyde of Formula 14 to obtain an anti-vinylchlorohydrin of Formula 15-1; And
[Chemical Formula 14]
R-CHO
[Formula 15-1]

Wherein R is an alkyl, alkenyl group, alkynyl group, cycloalkyl, aryl, aralkyl group, arkenyl group, or aralkylyl group)
(S3) reacting the anti-vinylchlorohydrin with a base to produce a trans-vinyloxirane derivative of Formula 17-1
[Formula 17-1]

Wherein R is an alkyl, alkenyl group, alkynyl group, cycloalkyl, aryl, aralkyl group, arkenyl group, or aralkylyl group)
Method for producing a trans-vinyl oxirane containing. The method according to claim 1 or 2,
R is phenyl, benzyl, cyclohexyl, phenylethenyl, phenylethynyl or phenylethyl. The method according to claim 1 or 2,
The base used in step (S3) is DBU (1,8- diazabicyclo [5,4,0] undes-7-ene) The method for producing trans-vinyl oxirane, characterized in that. The method according to claim 1 or 2,
The reaction of each step is carried out in a solvent, the solvent of step (S1) and (S2) is tetrahydrofuran, and the solvent of step (S3) is dichloromethane. The method according to claim 1 or 2, before step (S1),
(a) providing a chlorine containing sulfonium ion of Formula 8; And
[Chemical Formula 8]

(b) reacting the chlorine-containing sulfonium ions with methyllithium to provide a chlorine-containing sulfide of formula 8-1
[Formula 8-1]

Method for producing a trans-vinyl oxirane characterized in that it further comprises. According to claim 6, wherein step (a),
(a1) reacting a compound of Formula 1, butyllithium and a compound of Formula 4 to obtain a compound of Formula 5; And
[Formula 1]

[Chemical Formula 4]

Wherein Me is methyl
[Chemical Formula 5]

(Ts is

Me is methyl)
(a2) reacting the compound of Formula 5 with tetrahydrothiophene to provide a chlorine-containing sulfonium ion of Formula 8
[Chemical Formula 8]

(Ts is

Me is methyl)
Method for producing a trans-vinyl oxirane characterized in that it further comprises. (S1) reacting a chlorine-containing sulfide of Formula 9-1 with a chiral borane of Formula 13 to obtain an allyl transfer reagent;
[Formula 9-1]

[Chemical Formula 13]

Wherein Tol is 4-methylphenyl
(S2) reacting the allyl transfer reagent with an aldehyde of Formula 14 to obtain syn-vinylchlorohydrin of Formula 16;
[Chemical Formula 14]
R-CHO
[Chemical Formula 16]

Wherein R is an alkyl, alkenyl group, alkynyl group, cycloalkyl, aryl, aralkyl group, arkenyl group, or aralkylyl group)
(S3) reacting the syn-vinylchlorohydrin with a base to produce a cis-vinyloxirane derivative of Formula 18
[Chemical Formula 18]

Wherein R is an alkyl, alkenyl group, alkynyl group, cycloalkyl, aryl, aralkyl group, arkenyl group, or aralkylyl group)
Method for producing cis-vinyl oxirane comprising a. (S1) reacting a chlorine-containing sulfide of Formula 9-1 with a chiral borane of Formula 13-1 to obtain an allyl transfer reagent;
[Formula 9-1]

[Formula 13-1]

Wherein Tol is 4-methylphenyl
(S2) reacting the allyl transition reagent with an aldehyde of Formula 14 to obtain syn-vinylchlorohydrin of Formula 16-1;
[Chemical Formula 14]
R-CHO
[Formula 16-1]

Wherein R is an alkyl, alkenyl group, alkynyl group, cycloalkyl, aryl, aralkyl group, arkenyl group, or aralkylyl group)
(S3) reacting the syn-vinylchlorohydrin with a base to generate a cis-vinyloxirane derivative of Formula 18-1
[Formula 18-1]

Wherein R is an alkyl, alkenyl group, alkynyl group, cycloalkyl, aryl, aralkyl group, arkenyl group, or aralkylyl group)
Method for producing cis-vinyl oxirane comprising a. 10. The method according to claim 8 or 9,
R is phenyl, benzyl, cyclohexyl, phenylethenyl, phenylethynyl or phenylethyl. 10. The method according to claim 8 or 9,
A process for producing cis-vinyl oxirane, characterized in that the base used in step (S3) is 1,8-diazabicyclo [5,4,0] undes-7-ene (DBU). 10. The method according to claim 8 or 9,
The reaction of each step is carried out in a solvent, the solvent of step (S1) and (S2) is tetrahydrofuran, and the solvent of step (S3) is dichloromethane. The method according to claim 8 or 9, before step (S1),
(a) providing a chlorine containing sulfonium ion of Formula 9; And
[Chemical Formula 9]

(Ts is

Me is methyl)
(b) reacting the chlorine-containing sulfonium ions with methyllithium to provide a chlorine-containing sulfide of formula 9-1
[Formula 9-1]

Method for producing cis-vinyl oxirane further comprising. The method of claim 13, wherein step (a) comprises:
(a1) reacting a compound of Formula 2, butyllithium and a compound of Formula 4 to obtain a compound of Formula 6; And
(2)

[Chemical Formula 4]

Wherein Me is methyl
[Chemical Formula 6]

(Ts is

Me is methyl)
(a2) reacting the compound of Formula 6 with tetrahydrothiophene to provide a chlorine-containing sulfonium ion of Formula 9
[Chemical Formula 9]

(Ts is

Me is methyl)
Method for producing cis-vinyl oxirane further comprising. (i) chlorine-containing sulfides selected from formulas 8-1 or 9-1; And
[Formula 8-1]

[Formula 9-1]

(ii) a chiral borane selected from formula 13 or formula 13-1
[Chemical Formula 13]

[Formula 13-1]

Wherein Tol is 4-methylphenyl
Allyl transfer reagent obtained by reacting. As a method for producing pontica epoxide having the following structural formula,

Wherein Me is methyl
(S1) reacting sulfonium ions of formula 8 with methyllithium to obtain chlorine-containing sulfides of formula 8-1;
[Chemical Formula 8]

(Ts is

Me is methyl)
[Formula 8-1]

(S2) reacting the chlorine-containing sulfide of Formula 8-1 with the chiral borane of Formula 13-1 to obtain an allyl transfer reagent;
[Formula 13-1]

Wherein Tol is 4-methylphenyl
(S3) reacting the allyl transfer reagent with an aldehyde of Formula 27 to generate vinylchlorohydrin of Formula 28; And
[Formula 27]

[Formula 28]

(S4) reacting the vinylchlorohydrin with DBU
Method for producing a ponta epoxide comprising a. A compound of formula
[Chemical Formula 8]

(Ts is

Me is methyl) A compound of formula (9)
[Chemical Formula 9]

(Ts is

Me is methyl) (S1) reacting a chlorine-containing sulfide of Formula 8-1 with a chiral borane of Formula 13 to obtain an allyl transfer reagent;
[Formula 8-1]

[Chemical Formula 13]

Wherein Tol is 4-methylphenyl
(S2) reacting the allyl transition reagent with an aldehyde of Formula 14
[Chemical Formula 14]
R-CHO
Method for producing an anti-vinylchlorohydrin of the formula (15) comprising a.
[Chemical Formula 15]

Wherein R is an alkyl, alkenyl group, alkynyl group, cycloalkyl, aryl, aralkyl group, arkenyl group, or aralkylyl group) (S1) reacting a chlorine-containing sulfide of Formula 8-1 with a chiral borane of Formula 13-1 to obtain an allyl transfer reagent;
[Formula 8-1]

[Formula 13-1]

Wherein Tol is 4-methylphenyl
(S2) reacting the allyl transition reagent with an aldehyde of Formula 14
[Chemical Formula 14]
R-CHO
Method for producing an anti-vinylchlorohydrin of formula 15-1 containing
[Formula 15-1]

Wherein R is an alkyl, alkenyl group, alkynyl group, cycloalkyl, aryl, aralkyl group, arkenyl group, or aralkylyl group) 21. The method according to claim 19 or 20,
R is phenyl, benzyl, cyclohexyl, phenylethenyl, phenylethynyl or phenylethyl. A process for producing anti-vinylchlorohydrin. 21. The method according to claim 19 or 20,
The reaction of each step is carried out in a solvent, the solvent of step (S1) and (S2) is a method for producing anti-vinylchlorohydrin, characterized in that tetrahydrofuran. The method according to claim 19 or 20, before step (S1),
(a) providing a chlorine containing sulfonium ion of Formula 8; And
[Chemical Formula 8]

(Ts is

Me is methyl)
(b) reacting the chlorine-containing sulfonium ions with methyllithium to provide a chlorine-containing sulfide of formula 8-1
[Formula 8-1]

Method for producing an anti-vinyl chlorohydrin further comprising. The method of claim 23, wherein step (a) comprises:
(a1) reacting a compound of Formula 1, butyllithium and a compound of Formula 4 to obtain a compound of Formula 5; And
[Formula 1]

[Chemical Formula 4]

Wherein Me is methyl
[Chemical Formula 5]

(Ts is

Me is methyl)
(a2) reacting the compound of Formula 5 with tetrahydrothiophene to provide a chlorine-containing sulfonium ion of Formula 8
[Chemical Formula 8]

(Ts is

Me is methyl)
Method for producing an anti-vinyl chlorohydrin further comprising. (S1) reacting a chlorine-containing sulfide of Formula 9-1 with a chiral borane of Formula 13 to obtain an allyl transfer reagent;
[Formula 9-1]

[Chemical Formula 13]

Wherein Tol is 4-methylphenyl
(S2) reacting the allyl transfer reagent with an aldehyde of Formula 14;
[Chemical Formula 14]
R-CHO
Method of producing a syn-vinylchlorohydrin of the formula (16) comprising a.
[Chemical Formula 16]

Wherein R is an alkyl, alkenyl group, alkynyl group, cycloalkyl, aryl, aralkyl group, arkenyl group, or aralkylyl group) (S1) reacting a chlorine-containing sulfide of Formula 9-1 with a chiral borane of Formula 13-1 to obtain an allyl transfer reagent;
[Formula 9-1]

[Formula 13-1]

Wherein Tol is 4-methylphenyl
(S2) reacting the allyl transition reagent with an aldehyde of Formula 14
[Chemical Formula 14]
R-CHO
Method of producing syn-vinylchlorohydrin of the formula (16-1) comprising a.
[Formula 16-1]

Wherein R is an alkyl, alkenyl group, alkynyl group, cycloalkyl, aryl, aralkyl group, arkenyl group, or aralkylyl group) 27. The method of claim 25 or 26,
R is phenyl, benzyl, cyclohexyl, phenylethenyl, phenylethynyl or phenylethyl. The process for producing syn-vinylchlorohydrin. 27. The method of claim 25 or 26,
The reaction of each step is carried out in a solvent, the solvent of step (S1) and (S2) is a method for producing syn-vinylchlorohydrin, characterized in that tetrahydrofuran. The method of claim 25 or 26, wherein, prior to step (S1),
(a) providing a chlorine containing sulfonium ion of Formula 9; And
[Chemical Formula 9]

(Ts is

Me is methyl)
(b) reacting the chlorine-containing sulfonium ions with methyllithium to provide a chlorine-containing sulfide of formula 9-1
[Formula 9-1]

Method of producing a syn-vinyl chlorohydrin further comprises. The method of claim 29, wherein the step (a),
(a1) reacting a compound of Formula 2, butyllithium and a compound of Formula 4 to obtain a compound of Formula 6; And
(2)

[Chemical Formula 4]

Wherein Me is methyl
[Chemical Formula 6]

(Ts is

Me is methyl)
(a2) reacting the compound of Formula 6 with tetrahydrothiophene to provide a chlorine-containing sulfonium ion of Formula 9
[Chemical Formula 9]

(Ts is

Me is methyl)
Method of producing a syn-vinyl chlorohydrin further comprises.