CN110551089A - Preparation method of (R) - (-) -massoialactone - Google Patents
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Abstract
The invention discloses a preparation method of (R) - (-) -massoialactone, which comprises the following steps of carrying out the following reaction on beta, gamma-unsaturated ester and n-hexanal in a solvent under the action of copper salt, alkali and a ligand to obtain the (R) - (-) -massoialactone, wherein the copper salt is Cu (CH 3 CN) 4 PF 6 or , the alkali is Barton' S Base, the tert-butoxide of alkali metal or , the ligand is (R, R) -Ph-BPE or (S) -DTBM-SEGPHOS, the invention can obtain the (R) - (-) -massoialactone with higher yield and ee value through one-step reaction, compared with other literature methods, the invention has the characteristics of simple route, easily obtained raw materials, mild conditions and the like, and has obvious advantages
Description
Technical Field
The invention relates to a preparation method of (R) - (-) -massolaactone.
Background
(R) - (-) -massoialactone was first isolated from the oil of Manchurian cinnamon in 1937 (Abe, S.J. chem.Soc. Jpn 1937,58,246), and its presence was later found in many other species (Toutai, R.; Ratovelomanna-Vidal, V.; Hassines, B.B.; Gen E.t, J. -P.tetrahedron: Asymmetry 2006,17, 3400). In addition to being a valuable fragrance, it has also been found to have some biological activity. Therefore, the synthesis of the compound is greatly researched, but most process routes are long and tedious. The most compact and efficient preparation is currently reported by the Ramachandran group to obtain (R) - (-) -malsoialactone (Ramachandran, p.v.; Reddy, m.v. R.; Brown, h.c. tetrahedron lett.2000,41,583) in 3 steps with 49% yield and 97% ee (Scheme 1), starting from the chiral substrate allylboronic acid ester 3 and the aldehyde 5, which are reacted first to give the alcohol 6, which is then reacted with the acid chloride to give the acid chloride 7, and finally the ring closure reaction for olefin metathesis is achieved with Grubbs' catalyst. The disadvantages are evident, first, the use of chiral substrates, not the catalytic approach to introduce chirality; secondly, the Grubbs catalyst is expensive, has low catalytic efficiency and needs a catalytic amount of 10 percent; thirdly, the steps are long.
therefore, the development of a simple, efficient and highly selective (R) - (-) -massosaalcanone preparation route is the focus of the current research.
Disclosure of Invention
the invention provides a method for preparing chiral (R) - (-) -massolaactone in order to overcome the defects of tedious and fussy preparation route steps, low yield and the like of the (R) - (-) -massolaactone in the prior art. The preparation method of the invention can react beta, gamma-unsaturated ester and n-hexanal under the action of commercially available copper salt, chiral phosphine ligand and alkali, and can obtain (R) - (-) -masssoialactone by one-step reaction with higher yield and higher ee value. Compared with other reported literature methods, the method has the characteristics of simple route, easily obtained raw materials, mild conditions, simple and convenient operation and the like, and has obvious advantages.
The invention provides a preparation method of (R) - (-) -massoialactone, which comprises the following steps: in a solvent, under the action of copper salt, alkali and a ligand, carrying out the reaction shown as the following on beta, gamma-unsaturated ester and hexanal to obtain (R) - (-) -masssoiactone; saidThe copper salt being Cu (CH)3CN)4PF6OrThe Base is Barton's Base, alkali metal tert-butoxide orThe ligand is (R, R) -Ph-BPE or (S) -DTBM-SEGPHOS;
R is substituted or unsubstituted C1-10an alkyl group; wherein, said substituted C1-10The substituents in the alkyl group are selected from one or more (preferably 1 to 3) of the following groups: substituted ethynyl, C6-14Aryl or substituted C2-C10An alkenyl group;
the substituent in the substituted ethynyl is C1-10Alkyl, substituted or unsubstituted C2-C10Alkenyl, substituted or unsubstituted C6-14Aryl, or 5-14 membered heteroaryl;
In R, the substituted C2-C10the substituent in the alkenyl group is C6-14an aryl group;
When the substituent in the substituted ethynyl group is substituted C2-C10When alkenyl, said substituted C2-C10the substituent in the alkenyl group is C6-14An aryl group;
When the substituent in the substituted ethynyl group is substituted C6-14Aryl, said substituted C6-14The substituents in the aryl group are independently selected from C1-4Alkyl radical, C1-4Alkoxy and C1-4One or more of haloalkyl;
when the substituent in the substituted ethynyl group is a 5-14 membered heteroaryl group, the heteroatom in the 5-14 membered heteroaryl group is one or more of N, O and S; the number of heteroatoms in the 5-14 membered heteroaryl is 1-4;
When the substituent is plural, the substituents may be the same or different.
In the present invention, said C6-14Aryl is preferably phenyl, naphthyl, anthryl or phenanthryl. The naphthyl group is preferably
In the substituent of said substituted ethynyl group, when said C is6-14The substituent in the aryl group being C1-4When alkyl, said C1-4The alkyl group is preferably a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a tert-butyl group or an isobutyl group.
In the substituent of said substituted ethynyl group, when said C is6-14The substituent in the aryl group being C1-4at alkoxy, said C1-4the alkoxy group is preferably methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy or isobutoxy.
In the substituent of said substituted ethynyl group, when said C is6-14The substituent in the aryl group being C1-4When halogenated with alkyl, said "C1-4haloalkyl "is preferably C1-2more preferably trifluoromethyl.
among the substituents of the substituted ethynyl group, when the substituent of the substituted ethynyl group is C1-10When alkyl, said C1-10Alkyl is preferably C1-5alkyl radicals, e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl or
among the substituents of the substituted ethynyl group, the "5-14-membered heteroaryl group" of the substituted or unsubstituted 5-14-membered heteroaryl group is preferably a 5-or 6-membered heteroaryl group, more preferably a thienyl group, for example,
In R, said substituted C1-10In the alkyl radicalThe substituents of (a) are preferably selected from one or more of the following groups: phenyl, phenyl-substituted ethenyl, substituted phenyl, substituted ethynyl, C1-4An alkyl-substituted ethynyl group, a vinyl-substituted ethynyl group, a naphthyl-substituted ethynyl group, or a thienyl-substituted ethynyl group; the substituent in the substituted phenyl group is preferably trifluoromethyl or methoxy.
Preferably, R is any one of the following structures:
The solvent may be a conventional solvent in the art for performing such a reaction, and is preferably one or more of an ether solvent, a halogenated hydrocarbon solvent, an aromatic solvent and a naphthenic solvent. The ether solvent is preferably tetrahydrofuran, for example, anhydrous tetrahydrofuran. The halogenated hydrocarbon solvent is preferably dichloromethane. The aromatic solvent is preferably toluene. The naphthenic solvent is preferably cyclohexane. The solvent may be used in an amount conventional in the art for carrying out such a reaction, preferably in a volume molar ratio to n-hexanal of 1 to 25L/mol, more preferably 5 to 10L/mol, for example 5.0L/mol.
The copper salt is preferablyThe copper salt may be used in an amount conventional in the art for carrying out such a reaction, preferably in a molar ratio of 0.01 to 0.3, more preferably 0.02 to 0.1, e.g., 0.05, to n-hexanal.
the tert-butoxide of the alkali metal can be lithium tert-butoxide, sodium tert-butoxide or potassium tert-butoxide. The base is preferablyThe base may be used in an amount conventional in the art for carrying out such a reaction, preferably in a molar ratio to n-hexanal of 0.01 to 0.3, more preferably 0.02 to 0.1, e.g. 0.05.
SaidThe reaction may be carried out using a copper salt or a base. Therefore, when present, during the reactionIn this case, no additional alkali may be added.
the ligand is preferably (R, R) -Ph-BPE. The ligand may be used in an amount conventional in the art for carrying out such reactions, preferably in a molar ratio to n-hexanal of 0.01 to 0.3, more preferably 0.02 to 0.1, e.g. 0.05.
The molar ratio of the beta, gamma-unsaturated ester and the hexanal can be the conventional ratio for carrying out such reaction in the field, and is preferably 0.1-10, more preferably 1.0-3.0, for example, 1.5.
the reaction is preferably carried out under anhydrous conditions.
In a preferred embodiment of the invention, said copper salt is preferably Cu (CH)3CN)4PF6Preferably, the Base is Barton' S Base, the ligand is (S) -DTBM-SEGPHOS, and R is preferably of any one of the following structures:
In a preferred embodiment of the invention, said copper salt is preferably Cu (CH)3CN)4PF6Preferably, the Base is Barton's Base, the ligand is (R, R) -Ph-BPE, and R is preferably of any of the following structures:
In a preferred embodiment of the present invention, said copper salt is preferablythe base is preferablyThe ligand is preferably (R, R) -Ph-BPE, and R is preferably
A preferred process for the preparation of (R) - (-) -massoialactone comprises the following steps: mixing the copper salt, the alkali, the ligand and the solvent, mixing with beta, gamma-unsaturated ester and n-hexanal, and carrying out the reaction to obtain the (R) - (-) -masssoialactone. Preferably, the copper salt, the base and the ligand are mixed under anhydrous conditions, then the solvent is added, and then the beta, gamma-unsaturated ester and the n-hexanal are sequentially added.
the reaction temperature is the conventional temperature for such reaction, and is preferably room temperature to 50 ℃, and more preferably room temperature.
the progress of the reaction can be monitored by monitoring methods conventional in the art (e.g., TLC, HPLC or NMR), typically at the end of the reaction when the n-hexanal disappears. The reaction time is preferably 10 to 16 hours, for example, 12 hours.
After the reaction is finished, the method also can comprise the operation of post-treatment. The work-up procedure is a conventional work-up procedure for such reactions, preferably comprising the steps of: and mixing an activating agent, the reaction liquid after the reaction and acid anhydride or acyl chloride.
the acid anhydride may be any acid anhydride conventional in the art, and is preferably oneRaAnd RbEach independently is C1-4Alkyl, more preferably acetic anhydride. The acid chloride may be any acid chloride conventionally used in the art, and is preferably selected from the group consisting ofRcIs C1-4Alkyl, M is halogen, more preferably acetyl chloride. The acid anhydride or acid chloride may be used in an amount conventional in the art for carrying out such reactions, preferably on a molar basis with n-hexanalThe ratio is 1.0 to 2.0, for example, 1.1.
The activator may be conventional in the art, preferably pyridine and/or DMAP, more preferably DMAP. The activating agent can be used in an amount which is conventional in the art for carrying out such reactions, and preferably has a molar ratio to n-hexanal of 0.01 to 0.1, for example, 0.01.
in the post-treatment, the mixing may be further completed, and the stirring temperature is preferably room temperature. The stirring time is preferably 1 to 5 hours, for example, 2 hours.
The stirring operation can further comprise a purification operation. The operation is preferably to spin dry the solvent under vacuum and purify the solvent by silica gel column chromatography. The silica gel column chromatography method and conditions can adopt the conventional methods and conditions of the operation in the field.
The invention also provides a preparation method of the compound (S) - (+) -masssoialcactone, which comprises the following steps: in a solvent, under the action of copper salt, alkali and a ligand, carrying out the reaction shown as the following on beta, gamma-unsaturated ester and n-hexanal to obtain (S) - (+) -masssoialactone; the copper salt and the alkali are the same as those described above; the ligand is (S, S) -Ph-BPE or (R) -DTBM-SEGPHOS; the conditions other than the ligand in the process for the reaction are the same as those in the process for the preparation of (R) - (-) -massolactone;
r is as defined above.
the above preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention without departing from the common general knowledge in the art.
the reagents and starting materials used in the present invention are commercially available (see methods for the preparation of beta, gamma-unsaturated esters, see Jean, M.; Van de Weghe, P.tetrahedron Lett.2011,52,3509-3513, preparation of compound 11, page 7 of support information).
In the invention, the room temperature is 0-35 ℃, preferably 10-30 ℃; .
In the present invention, the Barton's Base is 2-tert-butyl-1, 1,3, 3-tetramethylguanidine (CAS: 29166-72-1); the TMG is tetramethylguanidine (CAS: 80-70-6); the (R, R) -Ph-BPE is (-) -1, 2-bis ((2R,5R) -2, 5-diphenylphosphino) ethane (CAS: 528565-79-9).
The positive progress effects of the invention are as follows: the (R) - (-) -massoialactone can be obtained by one-step reaction with higher yield and ee value, and compared with other reported literature methods, the method has the characteristics of simple route, easily obtained raw materials, mild conditions, simple and convenient operation and the like, and has obvious advantages.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.
In the following examples, the specific operating temperature is not limited, but it is understood that the operation is carried out at room temperature (0 to 35 ℃ C.).
rt is room temperature.
example 1 substrate screening
In the following substrate screening, the copper salt used was Cu (CH)3CN)4PF6(CAS: 64443-05-6); the ligand is (S) -DTBM-SEGPHOS](CAS: 210169-40-7); the Base used was Barton's Base (CAS: 29166-72-1). The results of the substrate structure screening were as follows (the values are in turn the hydrogen nuclear magnetic yield and the ee value):
Drying a 10mL reaction tube and a stirrer, putting the reaction tube and the stirrer into a glove box, and weighing Cu (CH) in sequence3CN)4PF6(3.7mg, 0.01mmol) and (S) -DTBM-SEGPHOS (11.8mg,0.01mmol), the glove box was taken out with a rubber stopper sealed, and dry THF (2.0mL) was added via syringe and stirred at room temperature for 15 minutes. Hexanal (21.0mg,0.2mmol) and the corresponding β, γ -unsaturated ester (0.3mmol) were added sequentially with a micro-syringe followed by Barton's Base (2 μ L,0.01mmol) and reacted at room temperature for 12 hours. Drying the solvent under vacuum, adding internal standard nitromethane 0.4mmol, adding 2mL deuterated chloroform, and mixingAnd synthesizing a uniform hydrogen spectrum to determine the nuclear magnetic yield. The ee value was determined by HPLC.
Example 2 reaction temperature and screening of substrates
In the following substrate screening, the copper salt used was Cu (CH)3CN)4PF6(CAS: 64443-05-6); the ligand used was (R, R) -Ph-BPE (CAS: 528565-79-9); the Base used was Barton's Base (CAS: 29166-72-1). The results of the substrate structure screening were as follows:
EXAMPLE 3 screening of base and copper salts
The substrate structure was immobilized, and the ligand used was (R, R) -Ph-BPE (CAS: 528565-79-9).
EXAMPLE 4 screening of the amount of catalyst used
A10 mL reaction tube and a stirrer were dried, placed in a glove box, weighed sequentially into mesitylcopper (I) (3.6mg, 0.02mmol) and (R, R) -Ph-BPE (10.1mg,0.02mmol), the rubber stopper was sealed, removed from the glove box, and anhydrous THF (2.0mL) was added via a syringe, followed by stirring at room temperature for 15 minutes. Hexanal (40.1mg,0.4mmol) and the beta, gamma-unsaturated ester but-2-yn-1-yl but-3-enoate (82.9mg,0.6 mmol) were added sequentially with a micro-syringemmol), and reacted at room temperature for 12 hours. Acetic anhydride (CAS number 108-24-7,45mg,0.44mmol) and DMAP (CAS number 112-58-7,5mg,0.004mmol) were added with a micro-syringe under nitrogen protection and reacted at room temperature for 2 hours. The solvent was dried under vacuum and subjected to 300-400 mesh silica gel column chromatography (petroleum ether: ethyl acetate: 7: 1) to give the desired product (R) - (-) -massoialactone (45.8mg, 68%) as a colorless liquid.1H NMR(400MHz,CDCl3)δ6.92-6.87(m,1H),6.02(d,J＝9.8Hz,1H),4.46-4.39(m,1H),2.41-2.27(m,2H),1.86-1.75(m,1H),1.69-1.60(m,1H),1.58-1.47(m,1H),1.46-1.38(m,1H)1.32(s,4H),0.90(t,J＝6.6Hz,3H)ppm.13C NMR(100MHz,CDCl3)δ164.53,145.07,121.25,77.94,34.72,31.42,29.28,24.38,22.40,13.88ppm.Optical rotation：[α]D 27＝-76.938(c＝1.035,CHCl3,90％ee).HPLC：DAICEL CHIRALPAK IE,hexane/i-PrOH＝47/3,flow rate：0.5mL/min,λ＝207nm,tR(major)＝52.1min,tR(minor)＝50.8min,ee＝90％.
It can be seen that the catalytic amount of ten percent and the catalytic amount of five percent are consistent in effect, preferably the catalytic amount is low and more economical.
EXAMPLE 5 preparation of (S) - (+) -masssoialactone
Drying a 10mL reaction tube and a stirrer, putting the reaction tube and the stirrer into a glove box, and weighing Cu (CH) in sequence3CN)4PF6(3.7mg, 0.01mmol) and (R) -DTBM-SEGPHOS (11.8mg,0.01mmol), the glove box was taken out with a rubber stopper sealed, and dry THF (2.0mL) was added via syringe and stirred at room temperature for 15 minutes. N-hexanal (21.0mg,0.2mmol) and beta, gamma-unsaturated ester but-2-yn-1-ylbut-3 are added in turn by a micro-injectorEnoate (41.5mg,0.3mmol) and Barton's Base (2. mu.L, 0.01mmol), at room temperature for 12 hours. And (3) drying the solvent in vacuum, adding 0.4mmol of internal standard nitromethane, adding 2mL of deuterated chloroform, uniformly mixing, performing hydrogen spectrum analysis to determine that the nuclear magnetic yield is 90%, and determining the ee value (-) 72% by HPLC.
a10 mL reaction tube and a stirrer were dried, placed in a glove box, weighed sequentially into mesitylcopper (I) (1.8mg, 0.01mmol) and (S, S) -Ph-BPE (5.1mg,0.01mmol), the rubber stopper was sealed, taken out of the glove box, and anhydrous THF (2.0mL) was added via a syringe and stirred at room temperature for 15 minutes. Hexanal (21.0mg,0.2mmol) and beta, gamma-unsaturated ester but-2-yn-1-yl but-3-enoate (41.5mg,0.3mmol) were added in sequence by a micro syringe and reacted at room temperature for 12 hours. And (3) drying the solvent in vacuum, adding 0.4mmol of internal standard nitromethane, adding 2mL of deuterated chloroform, uniformly mixing, performing hydrogen spectrum analysis to determine the nuclear magnetic yield of 76%, and determining the ee value (-) 90% by HPLC.
Claims (10)
1. a process for the preparation of (R) - (-) -massoialactone comprising the steps of: in a solvent, under the action of copper salt, alkali and a ligand, carrying out the reaction shown as the following on beta, gamma-unsaturated ester and hexanal to obtain (R) - (-) -masssoiactone;
The copper salt is Cu (CH)3CN)4PF6OrThe Base is Barton's Base, alkali metal tert-butoxide orthe ligand is (R, R) -Ph-BPE or (S) -DTBM-SEGPHOS;
R is substituted or unsubstituted C1-10An alkyl group; wherein, said substituted C1-10The substituents in the alkyl group are selected from one or more of the following groups: substituted ethynyl, C6-14Aryl or substituted C2-C10An alkenyl group;
The substituent in the substituted ethynyl is C1-10Alkyl, substituted or unsubstituted C2-C10alkenyl, substituted or unsubstituted C6-14Aryl, or 5-14 membered heteroaryl;
Said substituted C2-C10the substituent in the alkenyl group is C6-14an aryl group;
When the substituent in the substituted ethynyl group is substituted C2-C10When alkenyl, said substituted C2-C10The substituent in the alkenyl group is C6-14An aryl group;
when the substituent in the substituted ethynyl group is substituted C6-14Aryl, said substituted C6-14The substituents in the aryl group are independently selected from C1-4Alkyl radical, C1-4Alkoxy and C1-4One or more of haloalkyl;
When the substituent in the substituted ethynyl group is a 5-14 membered heteroaryl group, the heteroatom in the 5-14 membered heteroaryl group is one or more of N, O and S; the number of heteroatoms in the 5-14 membered heteroaryl is 1-4;
When the substituent is plural, the substituents may be the same or different.
2. The method according to claim 1, wherein the reaction mixture,
Said C6-14Aryl is phenyl, naphthyl, anthryl or phenanthryl; the naphthyl group is preferably
And/or, said substituted ethynyl groupIn the substituents, when said C6-14The substituent in the aryl group being C1-4when alkyl, said C1-4Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl or isobutyl;
And/or, in the substituent of said substituted ethynyl, when said C is6-14The substituent in the aryl group being C1-4At alkoxy, said C1-4Alkoxy is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy or isobutoxy;
And/or, in the substituent of said substituted ethynyl, when said C is6-14The substituent in the aryl group being C1-4When halogenated alkyl, said C1-4Haloalkyl being C1-2Haloalkyl of (a), preferably trifluoromethyl;
and/or, in the substituent of the substituted ethynyl, when the substituent of the substituted ethynyl is C1-10When alkyl, said C1-10Alkyl is C1-5Alkyl radicals, e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl or
And/or, in the substituent of said substituted ethynyl group, the "5-14 membered heteroaryl" of said 5-14 membered heteroaryl group is a 5 or 6 membered heteroaryl group, preferably a thienyl group, for example,
3. The method of claim 1, wherein in R, said substituted C1-10The substituents in the alkyl group are selected from one or more of the following groups: phenyl, phenyl-substituted ethenyl, substituted phenyl, substituted ethynyl, C1-4An alkyl-substituted ethynyl group, a vinyl-substituted ethynyl group, a naphthyl-substituted ethynyl group, or a thienyl-substituted ethynyl group; the substituents of said substituted phenylpreferably trifluoromethyl or methoxy.
4. The method of claim 3, wherein R is of any one of the following structures:
5. The method according to claim 1, wherein the reaction mixture,
The solvent is one or more of an ether solvent, a halogenated hydrocarbon solvent, an aromatic solvent and a naphthenic solvent;
And/or the volume molar ratio of the solvent to the n-hexanal is 1-25L/mol;
And/or, the copper salt is
And/or the molar ratio of the copper salt to the hexanal is 0.01-0.3;
And/or the tert-butoxide of the alkali metal is lithium tert-butoxide, sodium tert-butoxide or potassium tert-butoxide;
And/or, the base
and/or the molar ratio of the alkali to the n-hexanal is 0.01-0.3;
And/or, the ligand is (R, R) -Ph-BPE;
And/or the molar ratio of the ligand to the hexanal is 0.01-0.3;
and/or the molar ratio of the beta, gamma-unsaturated ester to the n-hexanal is 0.1-10;
And/or the reaction temperature is between room temperature and 50 ℃.
6. the method according to claim 5,
the ether solvent is tetrahydrofuran;
And/or the halogenated hydrocarbon solvent is dichloromethane;
And/or the aromatic solvent is toluene;
and/or the naphthenic solvent is cyclohexane;
And/or the volume molar ratio of the solvent to the n-hexanal is 5-10L/mol;
And/or, the copper salt is
And/or the molar ratio of the copper salt to the hexanal is 0.02-0.1;
and/or the molar ratio of the alkali to the n-hexanal is 0.02-0.1;
And/or the molar ratio of the ligand to the n-hexanal is 0.02-0.1;
And/or the molar ratio of the beta, gamma-unsaturated ester to the n-hexanal is 1.0-3.0;
And/or, the reaction is carried out under anhydrous conditions;
and/or the reaction temperature is room temperature.
7. The method according to claim 6,
The copper salt is Cu (CH)3CN)4PF6the Base is Barton' S Base, the ligand is (S) -DTBM-SEGPHOS, and R is any one of the following structures:
And/or, the copper salt is Cu (CH)3CN)4PF6The Base is Barton's Base, the ligand is (R, R) -Ph-BPE, and R is any one of the following structures:
And/or, the copper salt isThe base isThe ligand is (R, R) -Ph-BPE, and R is
8. The method of any one of claims 1 to 7, comprising the steps of: mixing the copper salt, the alkali, the ligand and the solvent, mixing with beta, gamma-unsaturated ester and n-hexanal, and carrying out the reaction to obtain the (R) - (-) -masssoialactone.
9. the process according to any one of claims 1 to 7, wherein the reaction further comprises a post-treatment operation after the completion of the reaction; the post-treatment comprises the following steps: mixing an activating agent, the reaction liquid after the reaction and acid anhydride or acyl chloride; the acid anhydride is preferably acetic anhydride; the acyl chloride is preferably acetyl chloride; the mole ratio of the acid anhydride or the acyl chloride to the n-hexanal is preferably 1.0-2.0; the activating agent is preferably pyridine and/or DMAP, more preferably DMAP; the preferable molar ratio of the activating agent to the hexanal is 0.01-0.1; in the post-treatment, the mixing operation is further carried out after the mixing is finished, and the stirring temperature is preferably room temperature; the stirring time is preferably 1-5 hours.
10. A process for the preparation of the compound (S) - (+) -masssoialactone comprising the steps of: in a solvent, under the action of copper salt, alkali and a ligand, carrying out the reaction shown as the following on beta, gamma-unsaturated ester and n-hexanal to obtain (S) - (+) -masssoialactone; the copper salt and the base are as defined in any one of claims 1 to 7; the ligand is (S, S) -Ph-BPE or (R) -DTBM-SEGPHOS; the conditions other than the ligand in the process for the reaction are the same as those in the process for the preparation of (R) - (-) -massolactone described in any one of claims 1 to 9;
r is as defined in any one of claims 1 to 4.
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| CN103113308A (en) * | 2013-01-25 | 2013-05-22 | 浙江大学 | Method for preparing dihydropyrimidinone derivative |
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| CN101058569A (en) * | 2007-05-28 | 2007-10-24 | 华东师范大学 | Method of preparing 3,6-dialkyl-5,6-dihydro-4-hydroxy-2H-pyran-2-one |
| WO2012027573A2 (en) * | 2010-08-25 | 2012-03-01 | University Of Massachusetts | Biodegradable shape memory polymer |
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