CN106608859B - Synthetic method of chiral 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide containing quaternary carbon - Google Patents

Synthetic method of chiral 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide containing quaternary carbon Download PDF

Info

Publication number
CN106608859B
CN106608859B CN201510688829.XA CN201510688829A CN106608859B CN 106608859 B CN106608859 B CN 106608859B CN 201510688829 A CN201510688829 A CN 201510688829A CN 106608859 B CN106608859 B CN 106608859B
Authority
CN
China
Prior art keywords
group
substituted
unsubstituted
compound
reaction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201510688829.XA
Other languages
Chinese (zh)
Other versions
CN106608859A (en
Inventor
徐明华
李翼
于月娜
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shanghai Institute of Materia Medica of CAS
Original Assignee
Shanghai Institute of Materia Medica of CAS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shanghai Institute of Materia Medica of CAS filed Critical Shanghai Institute of Materia Medica of CAS
Priority to CN201510688829.XA priority Critical patent/CN106608859B/en
Publication of CN106608859A publication Critical patent/CN106608859A/en
Application granted granted Critical
Publication of CN106608859B publication Critical patent/CN106608859B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/10—1,2,5-Thiadiazoles; Hydrogenated 1,2,5-thiadiazoles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/10—Preparation of carboxylic acid amides from compounds not provided for in groups C07C231/02 - C07C231/08
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/88—Nitrogen atoms, e.g. allantoin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/34—Other additions, e.g. Monsanto-type carbonylations, addition to 1,2-C=X or 1,2-C-X triplebonds, additions to 1,4-C=C-C=X or 1,4-C=-C-X triple bonds with X, e.g. O, S, NH/N
    • B01J2231/341—1,2-additions, e.g. aldol or Knoevenagel condensations
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/822—Rhodium

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention provides a synthesis method of chiral 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide containing quaternary carbon. Specifically, the complex formed by a monovalent rhodium metal compound and a chiral phosphorus alkene ligand is used for catalyzing an organic boron reagent to carry out asymmetric addition reaction on a 4-substituted-3 carbonyl-1, 2, 5-thiadiazole substrate and derivatives thereof, so as to obtain a corresponding compound containing a quaternary carbon chiral center. The method has high selectivity, and the product can be used for synthesizing a plurality of important chiral compounds such as alpha, alpha-diarylamino amide and the like through further functional group conversion, thereby having industrial production application prospect.

Description

Synthetic method of chiral 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide containing quaternary carbon
Technical Field
The invention belongs to the field of chemistry, and particularly relates to a method for constructing 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide containing quaternary carbon chiral centers by asymmetric 1, 2-addition reaction of an organic boron reagent catalyzed by monovalent rhodium metal on a 4-substituted-3-carbonyl-1, 2, 5-thiadiazole substrate and derivatives thereof.
Background
Sultams are a very important class of compounds which have very wide applications in organic chemistry, pharmaceutical chemistry and material science. Therefore, research on the synthesis of sultams has been the leading edge of the chemical research field. 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide which are important in sultams are paid attention to chemists and medicinal chemists due to unique pharmacodynamic and structural properties of the 1,2, 5-thiazolinone-1, 1-dioxide, so that the realization of efficient asymmetric synthesis of the 1,2, 5-thiazolinone-1, 1-dioxide and derivatives thereof is helpful for further promoting application research of the compounds in related fields.
At present, the methods for obtaining chiral 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide at home and abroad mainly depend on two modes of chiral resolution or chiral source synthesis, and the methods exist, for example: the method has the problems of low resolution efficiency, difficult acquisition of chiral sources, complex synthesis steps and the like, and has great limitation.
In recent years, the construction of functionalized chiral amine compounds by using transition metal catalyzed asymmetric addition strategy of organic boron reagent to imine is a research direction of attention of chemists. The strategy is used for efficient asymmetric synthesis of corresponding 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide, and no international success is reported at present. Hayashi et al attempted an asymmetric 1, 2-addition reaction of 4-methylbenzeneboronic acid ester to 4-phenyl-3-oxo-1, 2, 5-thiadiazole using rhodium/chiral diene complexes as catalysts, and only two products were constructed due to the unsatisfactory enantioselectivity of the reaction (Nishimura, t.; Ebe, y.; Fujimoto, h.; Hayashi, t.chem.commu.2013, 49,5504.). Therefore, the development of a new, efficient and practical catalytic system for catalyzing asymmetric 1, 2-addition of 4-substituted-3-carbonyl-1, 2, 5-thiadiazole substrate and derivatives thereof by organic boron reagent to realize the synthesis of 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide with high optical activity is still a problem to be solved urgently in the field.
Disclosure of Invention
The invention aims to provide a method for preparing 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide with high selectivity.
In a first aspect of the present invention, there is provided a process for preparing a compound containing a quaternary carbon chiral center represented by formula 3 and/or formula ent-3, the process comprising the steps of:
carrying out asymmetric addition reaction on an organic boron reagent shown in a formula 1 and a substrate shown in a formula 2 in an organic solvent in the presence of an additive and a complex catalyst formed by a monovalent rhodium metal compound and a chiral phosphorus alkene ligand to obtain a compound containing a quaternary carbon chiral center shown in a formula 3 and/or a formula ent-3:
Figure BDA0000826779940000021
in the formula (I), the compound is shown in the specification,
R1selected from the group consisting of: substituted or unsubstituted C6-30Aryl, substituted or unsubstituted C4-12Heteroaryl, wherein said substitution means that a hydrogen atom in the group is substituted with one or more (e.g., 1 to 5) substituents, and said heteroaryl contains a heteroatom which is oxygen or sulfur;
the substituents are selected from the following group: halogen, C1-6Alkyl radical, C1-6Haloalkyl, C1-6Alkoxy radical, C1-6Haloalkoxy, benzyloxy, unsubstituted or substituted C6-10Aryl, or a combination thereof; the halogen is F, Cl, Br or I;
R2is absent, or C1-6An alkyl group;
R3selected from the group consisting of: substituted or unsubstituted C6-30Aryl, substituted or unsubstituted C4-12Heteroaryl, wherein said substitution means that a hydrogen atom in the group is substituted with one or more (e.g., 1 to 5) substituents, and said heteroaryl contains a heteroatom which is oxygen or sulfur;
the substituents are selected from the following group: halogen, C1-6Alkyl radical, C1-6Haloalkyl, C1-6Alkoxy radical, C1-6Haloalkoxy, benzyloxy, unsubstituted or substituted C6-10Aryl, or a combination thereof; the halogen is F, Cl, Br or I;
R4is absent, or C1-3Linear or branched alkyl of (a);
[B]selected from the group consisting of: b (OR)2Or (BO)3Wherein R is H or C1-3Linear or branched alkyl of (a);
the dotted line represents a chemical bond or is absent.
In another preferred embodiment, the reaction formula is as follows:
Figure BDA0000826779940000022
wherein each group is as defined above.
In another preferred embodiment, the reaction formula is as follows:
Figure BDA0000826779940000023
wherein each group is as defined above.
In another preferred embodiment, R is1Is substituted or unsubstituted phenyl, naphthyl, or C4-12Heteroaryl, wherein the heteroatom is oxygen or sulfur.
In another preferred embodiment, R is2Is C1-6Linear or branched alkanes of (2)Radicals, for example, methyl.
In another preferred embodiment, R is3Is a substituted or unsubstituted phenyl group.
In another preferred embodiment, R is4Is C1-3Linear or branched alkyl of (2), for example, ethyl.
In another preferred embodiment, [ B ] is]Is B (OH)2。
In another preferred embodiment, the dosage of the monovalent rhodium metal catalyst is 1-30 mol% based on the dosage of the compound 4-substituted-3-oxo-1, 2, 5-thiadiazole substrate 2; and/or the dosage of the chiral phosphorus alkene ligand is 1-30 mol%.
In another preferred embodiment, the chiral phospholene ligand has the following structural formula (preferably, the formula I and formula II are each enantiomers):
Figure BDA0000826779940000031
in the formula (I), the compound is shown in the specification,
R6and R7Are linked to form a substituted or unsubstituted- (CH)2)n-wherein n is 3 or 4, or is linked to the carbon atom to which it is attached to form a substituted or unsubstituted phenyl group, wherein said substitution is one in which the hydrogen atom of the group is substituted with one or more (e.g. 1 to 5) substituents selected from the group consisting of: halogen, C unsubstituted or substituted by one or more halogens1-6Alkyl, or C unsubstituted or substituted by one or more halogen1-6An alkoxy group;
R8is H or substituted or unsubstituted C6-30Aryl, wherein said substitution is of a hydrogen atom on the group with one or more (e.g. 1-5) substituents selected from the group consisting of: halogen, C unsubstituted or substituted by one or more halogens1-6Alkyl, or C unsubstituted or substituted by one or more halogen1-6An alkoxy group;
R9is a group selected from the group consisting of: hydrogen and halogenElement, C unsubstituted or substituted by one or more halogens1-6Alkyl, or C unsubstituted or substituted by one or more halogen1-6An alkoxy group;
R5selected from the group consisting of: hydrogen, halogen, substituted or unsubstituted C1-6Alkyl, substituted or unsubstituted C1-6Alkoxy, substituted or unsubstituted phenyl, naphthyl, or other aryl, wherein substituted means that a hydrogen atom of a group is substituted with one or more (e.g., 1 to 5) substituents selected from the group consisting of: halogen, C unsubstituted or substituted by one or more halogens1-6Alkyl or C unsubstituted or substituted by one or more halogen1-6An alkoxy group.
In another preferred embodiment, R is6And R7Are linked to form a substituted or unsubstituted- (CH)2)n-, where n is 4.
In another preferred embodiment, R is8Is C6-30And (4) an aryl group.
In another preferred embodiment, R is9Is hydrogen, halogen, C1-6Alkyl or C1-6An alkoxy group.
In another preferred embodiment, R is5Is hydrogen, halogen, C1-6Alkyl, or substituted or unsubstituted phenyl.
In another preferred embodiment, the chiral phospholene ligand is selected from the group consisting of:
Figure BDA0000826779940000032
Figure BDA0000826779940000041
in another preferred embodiment, the monovalent rhodium metal compound is selected from the group consisting of: [ Rh (C)2H4)2Cl]2、[Rh(C2H4)2OH]2、[Rh(COE)2Cl]2、[Rh(COE)2OH]2Or a combination thereof.
In another preferred embodiment, the organoboron reagent of formula 1, [ B ] is]Is B (OR)2Or (BO)3Wherein R is H or C1-3Linear or branched alkyl of (a);
in another preferred embodiment, the method further has one or more characteristics selected from the group consisting of:
(1) the additive used in the reaction is an aqueous solution of salt with the concentration of 0.5 mol/L-5 mol/L, wherein the salt is selected from the following group: KF. KOH, K2CO3、Na2CO3、K3PO4、K2HPO4；
(2) The dosage of the reaction additive is 50mol percent to 500mol percent;
(3) the organic solvent used in the reaction is selected from the group consisting of: dichloromethane (CH)2Cl2) Toluene (Toluene), chloroform (CHCl)3) 1, 4-Dioxane (Dioxane), Tetrahydrofuran (THF), or a combination thereof;
(4) the reaction temperature is 0-100 ℃;
(5) the reaction time is 3-12 hours.
In a second aspect of the present invention, there is provided a compound of formula 3 or ent-3, said compound having the formula:
Figure BDA0000826779940000051
wherein R is1、R2、R3、R4Is as defined in the first aspect of the invention.
In another preferred embodiment, the ee value of said compound of formula 3 or ent-3 is 84% or more, preferably 90% or more, more preferably 95% or more.
In another preferred embodiment, R is1、R2、R3、R4The groups are the groups corresponding to the specific compounds in the examples.
In another preferred embodiment, the compound is the compound prepared in the examples.
In another preferred embodiment, the compound is selected from the group consisting of:
Figure BDA0000826779940000052
Figure BDA0000826779940000061
in a third aspect of the present invention, there is provided a use of a compound of formula 3 or ent-3 according to the second aspect of the present invention for:
Figure BDA0000826779940000071
(a) ring-opening the compound of formula 3 to remove the sulfonyl group, thereby forming an α, α -diarylaminoamide 4 with maintained optical activity;
Figure BDA0000826779940000072
(b) ring opening of the compound of formula 3 to form an α, α -diarylaminoamide 4, followed by cyclization to form a phenytoin analog 5, and two-step reaction of thionation and amination of compound 5 to form the compound of formula 7;
in the above formulae, R1，R2，R3The definition of (A) is as above.
In another preferred embodiment, said compound of formula 3 is a compound of formula 3aa, and said compound of formula 3aa is used for:
Figure BDA0000826779940000073
(a-1) treating the compound of formula 3aa with lithium aluminum hydride under reflux (preferably 70 ℃) in tetrahydrofuran solvent to obtain the corresponding optically active retained α, α -diarylamino acid amide 4 a.
In another preferred embodiment, the compound of formula 3 is a compound of formula 3ia, and the compound of formula 3ia is used for:
Figure BDA0000826779940000074
(b-1) treating the ia compound of formula 3 with lithium aluminum hydride to obtain a compound of formula 4 b; treating the compound of formula 4b with triphosgene to provide the corresponding phenytoin analog compound of formula 5 a; carrying out Lawson reaction on the compound shown in the formula 5a to obtain a thio product, namely a compound shown in a formula 6 a; the thio product compound shown as the formula 6a is subjected to two-step reaction of Suzuki coupling and ammoniation to prepare the BACE-1 inhibitor.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.
Detailed Description
The inventor of the invention has extensively and deeply studied, and found for the first time that the univalent rhodium/chiral phosphorus alkene complex is used as a catalyst to catalyze the asymmetric 1, 2-addition reaction of an organic boron reagent to a 4-substituted-3-carbonyl-1, 2, 5-thiadiazole substrate and a derivative thereof, so that 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide with high optical activity containing quaternary carbon chiral centers can be efficiently prepared. In addition, by selecting chiral phosphene ligands with different configurations, chiral 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide with opposite configurations can be obtained by the method. The present invention has been completed based on this finding.
Term(s) for
As used herein, the term "alkyl" refers to a straight or branched chain alkyl group, preferably C1-6In the present invention, the alkyl group also includes a group in which one or more H on the alkyl group is substituted with a substituent selected from the group consisting of: halogen, substituted or unsubstituted phenyl, C unsubstituted or substituted by one or more halogens1-6An alkyl group.It is understood that this term also includes C3-10Substituted or unsubstituted cycloalkyl.
The term "alkoxy" as used herein refers to C1-6In the present invention, the alkoxy group further includes a group in which one or more H of the alkyl group is substituted with a substituent selected from the group consisting of: halogen, substituted or unsubstituted phenyl, C unsubstituted or substituted by one or more halogens1-6An alkyl group.
As used herein, the term "aryl" or "Ar" refers to C6-30Representative examples of aryl groups of (a) are phenyl, naphthyl, anthryl, phenanthryl. In the present invention, the aryl group also includes a group in which one or more H on the aryl group is substituted by a substituent selected from the group consisting of: halogen, phenyl, C unsubstituted or substituted by one or more halogens1-6Alkyl, C unsubstituted or substituted by one or more halogens1-6An alkoxy group.
The term "heteroaryl" as used herein refers to C4-12Wherein the heteroatom is oxygen or sulfur, representative examples are furyl, thienyl, benzofuryl, benzothienyl. In the present invention, heteroaryl also includes a group in which one or more H on aryl is substituted by a substituent selected from the group consisting of: halogen, phenyl, C unsubstituted or substituted by one or more halogens1-6Alkyl, C unsubstituted or substituted by one or more halogens1-6An alkoxy group.
As used herein, the term "one or more" generally refers to 1-6, preferably 1-5, more preferably 1-3.
As used herein, the term "Ph" denotes phenyl.
As used herein, the term "RT" means room temperature, e.g., 10-40 ℃.
Preparation method
The synthesis method of the present invention can be represented by the following typical reaction formula:
Figure BDA0000826779940000081
the reaction substrate 1 is an organoboron reagent, wherein R1Is substituted or unsubstituted C6-30Aryl or C4-12Heteroaryl, wherein said substitution means having one or more (e.g. 1-5) substituents, the heteroatom being oxygen or sulfur, said substituents being selected from the group consisting of: halogen, C1-6Alkyl radical, C1-6Haloalkyl, C1-6Alkoxy radical, C1-6Haloalkoxy, benzyloxy, unsubstituted or substituted C6-10Aryl, or a combination thereof; the halogen is F, Cl, Br or I; [ B ]]Is B (OR)2Or (BO)3Wherein R is H or C1-3Linear or branched alkyl of (a);
the reaction substrate 2 is 4-substituted-3-oxo-1, 2, 5-thiadiazole, wherein R2Is absent, or C1-6Linear or branched alkyl of (a); r3Is substituted or unsubstituted C6-30Aryl or C4-12Heteroaryl, wherein said substitution means having one or more (e.g. 1-5) substituents, the heteroatom being oxygen or sulfur, said substituents being selected from the group consisting of: halogen, C1-6Alkyl radical, C1-6Haloalkyl, C1-6Alkoxy radical, C1-6Haloalkoxy, benzyloxy, unsubstituted or substituted C6-10Aryl, or a combination thereof; the halogen is F, Cl, Br or I; r4Is absent, or C1-3Linear or branched alkyl of (a); the dotted line represents a chemical bond or is absent.
[Rh(I)]Refers to monovalent rhodium metal catalysts, representative examples include (but are not limited to); [ Rh (C)2H4)2Cl]2、[Rh(C2H4)2OH]2、[Rh(COE)2Cl]2、[Rh(COE)2OH]2Or a combination thereof.
In the present invention, a representative chiral phospholene ligand has the following structural formula:
Figure BDA0000826779940000091
in the formula (I), the compound is shown in the specification,
R6and R7Are linked to form a substituted or unsubstituted- (CH)2)n-wherein n is 3 or 4, or is linked to the carbon atom to which it is attached to form a substituted or unsubstituted phenyl group, wherein said substitution is with one or more (e.g. 1-5) substituents selected from the group consisting of: halogen, C unsubstituted or substituted by one or more halogens1-6Alkyl or C unsubstituted or substituted by one or more halogen1-6An alkoxy group;
R8is a substituted or unsubstituted phenyl, naphthyl or other aryl group, wherein said substituted means having one or more (e.g., 1-5) substituents selected from the group consisting of: halogen, C unsubstituted or substituted by one or more halogens1-6Alkyl or C unsubstituted or substituted by one or more halogen1-6An alkoxy group;
R9is hydrogen, halogen, C unsubstituted or substituted by one or more halogens1-6Alkyl or C unsubstituted or substituted by one or more halogen1-6An alkoxy group;
R5is hydrogen, halogen, substituted or unsubstituted C1-6Alkyl, substituted or unsubstituted C1-6Alkoxy, substituted or unsubstituted phenyl, naphthyl, or other aryl, wherein substituted refers to having one or more (e.g., 1-5) substituents selected from the group consisting of: halogen, C unsubstituted or substituted by one or more halogens1-6Alkyl or C unsubstituted or substituted by one or more halogen1-6An alkoxy group.
In the present invention, the structural formula of a typical compound of the chiral phospholene ligand includes (but is not limited to):
Figure BDA0000826779940000101
in the invention, the additive can be KF, KOH or K with the concentration of 0.5mol/L to 5mol/L2CO3、Na2CO3、K3PO4、K2HPO4And the like aqueous solution;
in the invention, the dosage of the additive can be 50-500 mol%;
in the present invention, the organic solvent may be methylene Chloride (CH)2Cl2) Toluene (Toluene), chloroform (CHCl)3) 1, 4-Dioxane (Dioxane), Tetrahydrofuran (THF), or the like;
in the present invention, the reaction temperature is not particularly limited, and may be 0 to 100 ℃, preferably 10 to 60 ℃, and more preferably 25 to 40 ℃.
In the present invention, the reaction time is not particularly limited, and may be 3 to 12 hours, preferably 6 to 12 hours.
In a preferred embodiment of the present invention, a representative synthesis method can be described as follows:
the high optical purity 1,2, 5-thiazolinone-1, 1-dioxide containing quaternary carbon chirality and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide can be obtained by dissolving a monovalent rhodium catalyst, a chiral phosphoalkene ligand, an organic boron reagent and 4-substituted-3-oxo-1, 2, 5-thiadiazole in an organic solvent under the anaerobic condition, carrying out coordination reaction for 30 minutes at room temperature, then adding an additive and continuously reacting for 3-12 hours. In the reaction, the additive may be KF, KOH or K at a concentration of 0.5mol/L to 5mol/L2CO3、Na2CO3、K3PO4、K2HPO4Etc., preferably 2.5mol/L K3PO4An aqueous solution; the amount of the additive may be 50 to 500 mol%, preferably 100 mol%; the organic solvent may be dichloromethane (CH)2Cl2) Toluene (Toluene), chloroform (CHCl)3) 1, 4-Dioxane (Dioxane) or Tetrahydrofuran (THF), etc., preferably Toluene (tolumen); the monovalent rhodium metal catalyst may be [ Rh (C)2H4)2Cl]2、[Rh(C2H4)2OH]2、[Rh(COE)2Cl]2、[Rh(COE)2OH]2Or a combination thereof, preferably [ Rh (COE) ]2Cl]2(ii) a The dosage of the univalent rhodium metal catalyst is 1-30 mol%Preferably 3 mol%; the dosage of the chiral phospholene ligand is 1-30 mol%, preferably 3 mol%; the organic boron reagent 1 can be boric acid, boric acid ester, boric anhydride, potassium fluoborate, sodium tetraarylboron and the like, and boric acid is preferred; the molar ratio of the organoboron reagent 1 to the 4-substituted-3-oxo-1, 2, 5-thiadiazole 2 is (1-3): 1, preferably 2: 1; the reaction temperature is 25-60 ℃, preferably 25 ℃.
1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide containing quaternary carbon chiral center with high optical purity
By the method, 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide containing quaternary carbon chiral centers with high optical purity can be efficiently prepared.
In the present invention, some representative 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide containing quaternary carbon chiral centers are listed in tables 1 and 2.
1 equivalent (100 mol%) of K with a concentration of 2.5mol/L using toluene as solvent3PO4Aqueous solution as additive of monovalent rhodium [ Rh (COE)2Cl]2The compound formed by the chiral phospholene ligand (R) -4t is taken as a catalyst for example, the asymmetric 1, 2-addition reaction of the organic boric acid 1 to the 4-aryl-3-carbonyl-1, 2, 5-thiadiazole substrate 2a-d is catalyzed, the required reaction product can be efficiently prepared, the yield (yield) is good, the enantioselectivity (ee) is excellent, and the highest ee value can reach 98%.
TABLE 1 monovalent rhodium catalyzes the asymmetric 1, 2-addition reaction of organoboronic acids 1 to 4-aryl-3-carbonyl-1, 2, 5-thiadiazole 2a-d
Figure BDA0000826779940000111
Figure BDA0000826779940000112
Figure BDA0000826779940000121
The method can also be used for the development of the following substrates. Preferably, in the method, toluene is used as a solvent, 1 equivalent (100 mol%) of KF aqueous solution with the concentration of 1.5mol/L is used as an additive, and monovalent rhodium [ Rh (COE)2Cl]2The compound formed by the chiral phospholene ligand (R) -4t is taken as a catalyst for example, the asymmetric 1, 2-addition reaction of the organic boric acid 1 to the 4-aryl-3-ethoxy-1, 2, 5-thiadiazole substrate 2e-h is catalyzed, the required reaction product can be efficiently prepared, the yield (yield) is good, the enantioselectivity (ee) is excellent, and the highest ee value can reach 99%.
TABLE 2 univalent rhodium catalyzed asymmetric 1, 2-addition reaction of 1p 4-aryl-3-ethoxy-1, 2, 5-thiadiazole 2e-h organoborate
Figure BDA0000826779940000122
Figure BDA0000826779940000123
Figure BDA0000826779940000131
Application of 1,2, 5-thiazolinone-1, 1-dioxide containing quaternary carbon chiral center
The invention also provides the application of the 1,2, 5-thiazolinone-1, 1-dioxide containing quaternary carbon chiral center in the invention, in particular the application in preparing alpha, alpha-diaryl amino acid derivatives and active compounds with high optical purity.
In the present invention, one representative use is as follows:
Figure BDA0000826779940000132
in this application, the 1,2, 5-thiazolinone-1, 1-dioxide 3 containing a quaternary carbon chiral center of the present invention is subjected to ring opening to remove the sulfonyl group, thereby forming an optically active retained α, α -diarylamino amide 4.
Another representative use is as follows:
Figure BDA0000826779940000133
in this application, 1,2, 5-thiazolinone-1, 1-dioxide 3 containing a quaternary carbon chiral center in the present invention is subjected to ring opening to form α, α -diarylaminoamide 4, followed by cyclization to form phenytoin analog 5, and compound 5 is subjected to two steps of thioation and amination to form BACE-1 inhibitor 7, which is useful in the treatment of alzheimer's disease.
In the above formulae, R1，R2，R3The definition of (A) is as above.
In another preferred embodiment, representative uses are as follows:
Figure BDA0000826779940000134
the product obtained by carrying out asymmetric addition reaction on a 4-substituted-3-carbonyl-1, 2, 5-thiadiazole substrate by an organoboron reagent is treated by lithium aluminum hydride under the condition of reflux (70 ℃), and the corresponding alpha, alpha-diaryl amino acid amide with maintained optical activity is obtained.
In another preferred embodiment, representative uses are as follows:
Figure BDA0000826779940000141
the method comprises the steps of carrying out asymmetric addition reaction on a 4-substituted-3-carbonyl-1, 2, 5-thiadiazole substrate by an organic boron reagent to obtain a product, sequentially treating with lithium aluminum hydride and triphosgene to obtain a corresponding phenytoin analogue, carrying out a Lawson reaction to obtain a thio product, and finally carrying out two-step reaction of Suzuki coupling and ammoniation on the thio product to obtain a BACE-1 inhibitor developed by the Merck company, wherein the inhibitor can be used for treating Alzheimer's disease.
The main advantages of the invention include:
(1) the invention takes a complex formed by univalent rhodium metal and simple chiral phosphorus alkene ligand as a catalyst, and realizes the asymmetric 1, 2-addition reaction of cheap organic boron reagent to 4-substituted-3-carbonyl-1, 2, 5-thiadiazole substrate and derivatives thereof;
(2) the method can prepare various 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide containing quaternary carbon chiral centers, and further can be applied to synthesis of alpha, alpha-diaryl amino acid derivatives and active compounds with important structures and high optical purity;
(3) the method has good substrate universality, and can obtain better results for various different types of organic boron reagents, 4-substituted-3-carbonyl-1, 2, 5-thiadiazole substrates and derivatives thereof;
(4) the method has mild reaction conditions and simple and convenient operation;
(5) the reaction product of the invention has high stereoselectivity and industrial application prospect.
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out under conventional conditions or conditions recommended by the manufacturers. Unless otherwise indicated, percentages and parts are by weight.
Example 1
Synthesis of compound 3 aa:
under the protection of argon, 4-phenyl-3-carbonyl-1, 2, 5-thiadiazole substrate 2a (0.25mmol,100 mol%), 4-methylphenylboronic acid 1a (0.5mmol,200 mol%), [ Rh (COE)2Cl]2(0.0075mmol,1.5 mol%), phospholene ligand (R) -4t (0.0075mmol,3 mol%) was put into a reaction flask, toluene (1mL) was added, the reaction was stirred at room temperature for 30min, and 2.5mol/L of K was added to the system3PO4Aqueous (0.1mL) and the reaction was continued. After TLC monitoring reaction completion, spin-dryThe reaction was chromatographed on silica gel to give product 3aa as a white solid in 99% yield and 96% ee.
Figure BDA0000826779940000151
1H NMR(300MHz,CDCl3)δ7.47–7.40(m,2H),7.37–7.31(m,3H),7.28(d,J＝8.3Hz,2H),7.14(d,J＝8.4Hz,2H),5.40(s,1H),3.11(s,3H),2.33(s,3H)；13C NMR(125MHz,CDCl3)δ168.8,139.3,138.2,135.4,129.6,129.2,128.8,127.7,127.6,75.4,26.2,21.2；HRMS(ESI)for C16H15O3N2S[M-H]-calcd 315.0809,found 315.0816.
Example 2
Synthesis of Compound 3 ba:
the same experiment as in example 1 was conducted except that 4-methylphenylboronic acid 1a used in example 1 was changed to 4-chlorophenylboronic acid 1 b. Product 3ba was obtained as a white solid, 95% yield, 96% ee.
Figure BDA0000826779940000152
1H NMR(300MHz,CDCl3)δ7.47(d,J＝2.0Hz,1H),7.45(d,J＝2.0Hz,1H),7.41–7.28(m,7H),5.40(s,1H),3.15(s,3H)；13C NMR(125MHz,CDCl3)δ168.4,138.3,136.2,135.5,129.6,129.23,129.17,129.1,127.6,75.0,26.4；HRMS(ESI)for C15H12O3N2SCl[M-H]-calcd 335.0263,found 335.0267.
Example 3
Synthesis of Compound 3 ca:
the same experiment as in example 1 was carried out except that 4-methylphenylboronic acid 1a used in example 1 was changed to 4-methoxyphenylboronic acid 1 c. Product 3ca was obtained as a white solid in 99% yield and 92% ee.
Figure BDA0000826779940000153
1H NMR(300MHz,CDCl3)δ7.46(dd,J＝6.3,3.3Hz,2H),7.36(dd,J＝6.1,2.8Hz,4H),7.31(s,1H),6.86(d,J＝8.9Hz,2H),5.30(s,1H),3.78(s,3H),3.15(s,3H)；13C NMR(125MHz,CDCl3)δ169.0,160.2,138.3,130.3,129.2,129.1,128.9,127.7,114.3,75.3,55.5,26.3；HRMS(ESI)for C16H15O4N2S[M-H]-calcd 331.0758,found 331.0762.
Example 4
Synthesis of Compound 3 ca':
the phospholene ligand (R) -4t used in example 3 was replaced by (S) -4t and the rest of the experimental work was the same as in example 3. Product 3 ca' was obtained as a white solid in 99% yield, 92% ee.
Figure BDA0000826779940000161
1H NMR(300MHz,CDCl3)δ7.45(dd,J＝6.3,3.3Hz,2H),7.35(dd,J＝6.1,2.8Hz,4H),7.29(s,1H),6.85(d,J＝8.9Hz,2H),5.32(s,1H),3.77(s,3H),3.14(s,3H)；13C NMR(125MHz,CDCl3)δ169.1,160.3,138.4,130.3,129.2,129.0,128.9,127.8,114.3,75.4,55.5,26.4；HRMS(ESI)for C16H15O4N2S[M-H]-calcd 331.0758,found 331.0762.
Example 5
Synthesis of Compound 3 da:
the same experiment as in example 1 was conducted except that 4-methylphenylboronic acid 1a used in example 1 was changed to 4-fluorophenylboronic acid 1 d. Product 3da was obtained as a white solid in 94% yield and 94% ee.
Figure BDA0000826779940000162
1H NMR(300MHz,CDCl3)δ7.54–7.46(m,2H),7.39(s,5H),7.13–7.00(m,2H),5.46(s,1H),3.17(s,3H)；13C NMR(125MHz,CDCl3)δ168.6,163.1(d,1JCF＝248.8Hz),138.4,133.7,129.8(d,3JCF＝8.4Hz),129.5,129.1,127.6,115.8(d,2JCF＝21.3Hz),75.0,26.3；HRMS(ESI)for C15H12O3N2FS[M-H]-calcd 319.0558,found 319.0560.
Example 6
Synthesis of compound 3 ea:
the same experiment as in example 1 was carried out except that 4-methylphenylboronic acid 1a used in example 1 was changed to 4-bromobenzylboronic acid 1 e. Product 3ea was obtained as a white solid in 96% yield in 96% ee.
Figure BDA0000826779940000163
1H NMR(300MHz,CDCl3)δ7.52(d,J＝2.0Hz,1H),7.49(d,J＝2.1Hz,1H),7.42(d,J＝2.0Hz,1H),7.40–7.29(m,6H),5.34(s,1H),3.16(s,3H)；13C NMR(125MHz,CDCl3)δ168.3,138.3,136.7,132.0,129.7,129.5,129.3,127.6,123.8,75.1,26.4；HRMS(ESI)for C15H12O3N2BrS[M-H]-calcd 378.9757,found 378.9766.
Example 7
Synthesis of compound 3 ea':
the phospholene ligand (R) -4t used in example 6 was replaced by (S) -4t and the rest of the experimental work was the same as in example 6. Product 3 ea' was obtained as a white solid in 96% yield, 96% ee.
Figure BDA0000826779940000171
1H NMR(300MHz,CDCl3)δ7.53(d,J＝2.0Hz,1H),7.50(d,J＝2.1Hz,1H),7.41(d,J＝2.0Hz,1H),7.40–7.27(m,6H),5.33(s,1H),3.15(s,3H)；13C NMR(125MHz,CDCl3)δ168.3,138.5,136.7,132.1,123.0,129.5,129.3,127.5,123.7,75.2,26.4；HRMS(ESI)for C15H12O3N2BrS[M-H]-calcd 378.9757,found 378.9766.
Example 8
Synthesis of compound 3 fa:
the same experiment as in example 1 was conducted except that 4-methylphenylboronic acid 1a used in example 1 was changed to 4-phenylphenylboronic acid 1 f. Product 3fa was obtained as a white solid in 96% yield in 96% ee.
Figure BDA0000826779940000172
1H NMR(300MHz,CDCl3)δ7.54(dd,J＝12.0,5.7Hz,5H),7.50–7.40(m,4H),7.40–7.24(M,5H),5.42(s,1H),3.14(s,3H)；13C NMR(100MHz,CDCl3)δ168.7,142.1,140.0,138.2,137.0,129.4,129.0,128.97,128.1,127.9,127.7,127.6,127.2,75.4,26.3；HRMS(ESI)for C21H17O3N2S[M-H]-calcd 377.0965,found 377.0973.
Example 9
Synthesis of compound 3 fa':
the phospholene ligand (R) -4t used in example 8 was replaced by (S) -4t and the rest of the experimental work was the same as in example 8. The product 3 fa' was obtained as a white solid in 96% yield, 96% ee.
Figure BDA0000826779940000173
1H NMR(300MHz,CDCl3)δ7.55(dd,J＝12.0,5.7Hz,5H),7.51–7.41(m,4H),7.41–7.23(M,5H),5.43(s,1H),3.15(s,3H)；13C NMR(100MHz,CDCl3)δ168.8,142.1,140.2,138.1,137.1,129.4,129.2,128.9,128.1,127.9,127.7,127.5,127.4,75.4,26.3；HRMS(ESI)for C21H17O3N2S[M-H]-calcd 377.0965,found 377.0973.
Example 10
Synthesis of compound 3 ga:
the same experiment as in example 1 was conducted except that 4-methylphenylboronic acid 1a used in example 1 was changed to 3-fluorophenylboronic acid 1 g. Product 3ga was obtained as a white solid, 91% yield, 95% ee.
Figure BDA0000826779940000181
1H NMR(300MHz,CDCl3)δ7.45–7.30(m,7H),7.29–7.20(m,1H),7.12–7.00(m,1H),5.39(s,1H),3.17(s,3H)；13C NMR(125MHz,CDCl3)δ168.2,162.8(d,1JCF＝246.3Hz),140.1(d,3JCF＝7.2Hz),138.2,130.5(d,3JCF＝8.2Hz),129.6,129.2,127.6,123.4(d,4JCF＝2.9Hz),116.4(d,2JCF＝20.0Hz),115.2(d,2JCF＝23.8Hz),75.0,26.4；HRMS(ESI)for C15H12O3N2FS[M-H]-calcd 319.0558,found 319.0562.
Example 11
Synthesis of compound 3 ga':
the phospholene ligand (R) -4t used in example 10 was replaced by (S) -4t and the rest of the experimental work was the same as in example 10. Product 3 ga' was obtained as a white solid in 90% yield, -95% ee.
Figure BDA0000826779940000182
1H NMR(300MHz,CDCl3)δ7.45–7.32(m,7H),7.30–7.21(m,1H),7.12–7.01(m,1H),5.40(s,1H),3.16(s,3H)；13C NMR(125MHz,CDCl3)δ168.3,162.9(d,1JCF＝246.3Hz),140.0(d,3JCF＝7.2Hz),138.3,130.6(d,3JCF＝8.2Hz),130.0,129.2,127.6,123.5(d,4JCF＝2.9Hz),116.5(d,2JCF＝20.0Hz),115.2(d,2JCF＝23.8Hz),75.1,26.4；HRMS(ESI)for C15H12O3N2FS[M-H]-calcd 319.0558,found 319.0562.
Example 12
Synthesis of compound 3 ha:
the same experiment as in example 1 was carried out except that the 4-methylphenylboronic acid 1a used in example 1 was changed to 3-methylphenylboronic acid 1 h. Product 3ha was obtained as a white solid in 96% yield and 94% ee.
Figure BDA0000826779940000183
1H NMR(300MHz,CDCl3)δ7.54–7.43(m,2H),7.40–7.33(m,3H),7.27–7.13(m,4H),5.17(s,1H),3.17(s,3H),2.33(s,3H)；13C NMR(100MHz,CDCl3)δ168.7,138.9,138.3,138.1,130.2,129.3,128.9,128.1,127.7,124.8,75.6,26.3,21.6；HRMS(ESI)for C16H15O3N2S[M-H]-calcd 315.0809,found 315.0817.
Example 13
Synthesis of compound 3 ha':
the phospholene ligand (R) -4t used in example 12 was replaced by (S) -4t and the rest of the experimental work was the same as in example 12. Product 3 ha' was obtained as a white solid in 97% yield, 94% ee.
Figure BDA0000826779940000191
1H NMR(300MHz,CDCl3)δ7.55–7.43(m,2H),7.41–7.32(m,3H),7.28–7.13(m,4H),5.20(s,1H),3.16(s,3H),2.34(s,3H)；13C NMR(100MHz,CDCl3)δ168.8,139.0,138.4,138.0,130.1,129.4,128.9,128.1,127.8,124.8,75.7,26.2,21.5；HRMS(ESI)for C16H15O3N2S[M-H]-calcd 315.0809,found 315.0817.
Example 14
Synthesis of compound 3 ia:
example 1 was followed by replacing 4-methylbenzeneboronic acid 1a used in example 1 with 3-bromobenzeneboronic acid 1 i. Product 3ia was obtained as a white solid in 98% yield and 93% ee.
Figure BDA0000826779940000192
1H NMR(300MHz,CDCl3)δ7.70(s,1H),7.51(t,J＝8.4Hz,2H),7.44–7.32(m,5H),7.26(t,J＝8.0Hz,1H),5.21(s,1H),3.19(s,3H)；13C NMR(125MHz,CDCl3)δ168.1,139.9,138.2,132.5,130.7,130.4,129.7,129.3,127.6,126.4,123.1,74.9,26.5；HRMS(ESI)for C15H13O3N2BrSNa[M+Na]+calcd 402.9722,found 402.9729.
Example 15
Synthesis of compound 3 ja:
the same experiment as in example 1 was conducted except that 4-methylphenylboronic acid 1a used in example 1 was changed to 2-naphthylphenylboronic acid 1 j. Product 3ja was obtained as a white solid in 98% yield and 94% ee.
Figure BDA0000826779940000193
1H NMR(300MHz,CDCl3)8.03(d,J＝1.8Hz,1H),7.85–7.74(m,3H),7.55–7.47(m,2H),7.47–7.39(m,3H),7.35(dt,J＝4.9,2.6Hz,3H),5.44(s,1H),3.13(s,3H)；13C NMR(125MHz,CDCl3)δ168.6,138.2,135.2,133.3,132.8,129.4,129.04,129.01,128.7,127.8,127.7,127.3,127.1,126.9,124.8,75.7,26.3；HRMS(ESI)for C19H15O3N2S[M-H]-calcd 351.0809,found 351.0814.
Example 16
Synthesis of Compound 3 ka:
the same experiment as in example 1 was conducted except that 4-methylphenylboronic acid 1a used in example 1 was changed to 1-naphthylphenylboronic acid 1 k. Product 3ka was obtained as a white solid in 93% yield and 84% ee.
Figure BDA0000826779940000201
1H NMR(300MHz,CDCl3)δ7.90(d,J＝8.0Hz,1H),7.85(d,J＝8.0Hz,1H),7.78(d,J＝7.0Hz,1H),7.66–7.46(m,4H),7.44–7.21(m,5H),5.60(s,1H),3.13(s,3H)；13C NMR(125MHz,CDCl3)δ167.7,138.5,135.3,133.4,131.1,129.6,129.0,128.9,127.0,126.8,126.2,125.3,125.0,76.6,26.3；HRMS HRMS(ESI)for C19H15O3N2S[M-H]-calcd 351.0809,found 351.0811.
Example 17
Synthesis of compound 3 la:
the same experiment as in example 1 was conducted except that the 4-methylphenylboronic acid 1a used in example 1 was changed to 2-methylphenylboronic acid 1 l. Product 3la was obtained as a white solid in 90% yield and 85% ee.
Figure BDA0000826779940000202
1H NMR(300MHz,CDCl3)δ7.54(dd,J＝6.3,2.6Hz,2H),7.42–7.30(m,3H),7.27(d,J＝7.6Hz,2H),7.17(t,J＝6.7Hz,2H),5.43(s,1H),3.10(s,3H),2.00(s,3H)；13C NMR(100MHz,CDCl3)δ168.3,137.6,137.1,136.8,133.3,129.8,128.82,128.78,128.7,127.3,126.4,76.2,26.2,21.0；HRMS(ESI)for C16H15O3N2S[M-H]-calcd 315.0809,found 315.0815.
Example 18
Synthesis of compound 3 ma:
the same experiment as in example 1 was carried out except that the 4-methylphenylboronic acid 1a used in example 1 was changed to 3-thiopheneboronic acid 1 m. Product 3ma was obtained as a white solid in 45% yield and 98% ee.
Figure BDA0000826779940000203
1H NMR(300MHz,CDCl3)δ7.71–7.57(m,2H),7.40–7.27(m,4H),6.29(d,J＝3.1Hz,1H),6.21(d,J＝3.3Hz,1H),5.53(s,1H),3.09(s,3H)；13C NMR(125MHz,CDCl3)δ167.8,141.4,137.9,129.8,129.1,128.2,127.8,127.4,127.1,72.7,26.5；HRMS(ESI)for C13H11O3N2S2[M-H]-calcd 307.0217,found 307.0222.
Example 19
Synthesis of compound 3 na:
the same experiment as in example 1 was carried out except that 4-methylphenylboronic acid 1a used in example 1 was changed to 3-furanboronic acid 1 n. Product 3na was obtained as a white solid in 72% yield and 98% ee.
Figure BDA0000826779940000211
1H NMR(300MHz,CDCl3)δ7.71–7.57(m,2H),7.40–7.27(m,4H),6.29(d,J＝3.1Hz,1H),6.21(d,J＝3.3Hz,1H),5.53(s,1H),3.09(s,3H)；13C NMR(125MHz,CDCl3)δ166.2,149.5,144.4,134.5,129.6,128.8,127.1,112.5,111.1,70.9,26.3；HRMS(ESI)for C13H11O4N2S[M-H]-calcd 291.0445,found 291.0451.
Example 20
Synthesis of compound 3 ob:
under the protection of argon, 4- (4-methylphenyl) -3-carbonyl-1, 2, 5-thiadiazole substrate 2b (0.25mmol,100 mol%), phenylboronic acid 1o (0.5mmol,200 mol%), [ Rh (COE)2Cl]2(0.0075mmol,1.5 mol%), phospholene ligand (R) -4t (0.0075mmol,3 mol%) was put into a reaction flask, toluene (1mL) was added, the reaction was stirred at room temperature for 30min, and 2.5mol/L of K was added to the system3PO4Aqueous (0.1mL) and the reaction was continued. After completion of the TLC monitoring reaction, the reaction solution was dried by spinning and separated by silica gel column chromatography to give the product 3ob as a white solid in 96% yield and 94% ee.
Figure BDA0000826779940000212
1H NMR(300MHz,CDCl3)δ7.53–7.44(m,2H),7.41–7.35(m,3H),7.32(d,J＝8.3Hz,2H),7.18(d,J＝8.0Hz,2H),5.06(s,1H),3.19(s,3H),2.35(s,3H)；13C NMR(125MHz,CDCl3)δ168.9,139.5,138.2,135.5,129.8,129.3,129.0,127.7,127.6,75.6,26.4,21.3；HRMS(ESI)for C16H17N2O3S[M+H]+calcd 317.0954,found 317.0959.
Example 21
Synthesis of compound 3 bb:
under the protection of argon, 4- (4-methylphenyl) -3-carbonyl-1, 2, 5-thiadiazole substrate 2b (0.25mmol,100 mol%)4-Chlorobenzeneboronic acid 1b (0.5mmol,200 mol%), [ Rh (COE)2Cl]2(0.0075mmol,1.5 mol%), phospholene ligand (R) -4t (0.0075mmol,3 mol%) was put into a reaction flask, toluene (1mL) was added, the reaction was stirred at room temperature for 30min, and 2.5mol/L of K was added to the system3PO4Aqueous (0.1mL) and the reaction was continued. After completion of the reaction monitored by TLC, the reaction was spun dry and isolated by silica gel column chromatography to give product 3bb as a white solid in 95% yield and 95% ee.
Figure BDA0000826779940000213
1H NMR(300MHz,CDCl3)δ7.51(d,J＝8.8Hz,2H),7.39–7.32(m,2H),7.19(d,J＝3.3Hz,4H),5.06(s,1H),3.19(s,3H),2.35(s,3H)；13C NMR(125MHz,CDCl3)δ168.6,139.9,136.2,135.6,135.5,130.0,129.2,129.1,127.5,75.0,26.5,21.3；HRMS(ESI)for C16H16O3N2ClS[M+H]+calcd 351.0565,found 351.0558.
Example 22
Synthesis of Compound 3 db:
under the protection of argon, 4- (4-methylphenyl) -3-carbonyl-1, 2, 5-thiadiazole substrate 2b (0.25mmol,100 mol%), 4-fluorobenzeneboronic acid 1d (0.5mmol,200 mol%), [ Rh (COE)2Cl]2(0.0075mmol,1.5 mol%), phospholene ligand (R) -4t (0.0075mmol,3 mol%) was put into a reaction flask, toluene (1mL) was added, the reaction was stirred at room temperature for 30min, and 2.5mol/L of K was added to the system3PO4Aqueous (0.1mL) and the reaction was continued. After completion of the reaction monitored by TLC, the reaction was spun dry and isolated by silica gel column chromatography to give the product 3db as a white solid in 94% yield and 94% ee.
Figure BDA0000826779940000221
1H NMR(300MHz,CDCl3)δ7.53(dd,J＝8.7,5.2Hz,2H),7.24(d,J＝8.3Hz,2H),7.18(d,J＝8.2Hz,2H),7.07(t,J＝8.6Hz,2H),5.06(s,1H),3.19(s,3H),2.36(s,3H)；13C NMR(125MHz,CDCl3)δ168.8,163.2(d,1JCF＝248.8Hz),139.8,135.7,133.7,130.0,129.8(d,3JCF＝8.8Hz),127.5,115.9(d,2JCF＝22.5Hz),115.8,75.1,26.4,21.3；HRMS(ESI)for C16H16O3N2FS[M+H]+calcd 335.0860,found 335.0856.
Example 23
Synthesis of Compound 3 oc:
under the protection of argon, 4- (4-chlorophenyl) -3-carbonyl-1, 2, 5-thiadiazole substrate 2c (0.25mmol,100 mol%), phenylboronic acid 1o (0.5mmol,200 mol%), [ Rh (COE)2Cl]2(0.0075mmol,1.5 mol%), phospholene ligand (R) -4t (0.0075mmol,3 mol%) was put into a reaction flask, toluene (1mL) was added, the reaction was stirred at room temperature for 30min, and 2.5mol/L of K was added to the system3PO4Aqueous (0.1mL) and the reaction was continued. After completion of the TLC monitoring reaction, the reaction solution was spun dry and the product 3oc was isolated by silica gel column chromatography as a white solid in 98% yield and 96% ee.
Figure BDA0000826779940000222
1H NMR(300MHz,CDCl3)δ7.49(d,J＝8.7Hz,2H),7.44–7.30(m,7H),5.13(s,1H),3.19(s,3H)；13C NMR(125MHz,CDCl3)δ168.4,138.4,136.2,135.6,129.7,129.3,129.2,129.1,127.6,75.1,26.5；HRMS(ESI)for C15H14O3N2ClS[M+H]+calcd 337.0408,found 337.0404.
Example 24
Synthesis of compound 3 ac:
under the protection of argon, 4- (4-chlorophenyl) -3-carbonyl-1, 2, 5-thiadiazole substrate 2c (0.25mmol,100 mol%), 4-methylphenylboronic acid 1a (0.5mmol,200 mol%), [ Rh (COE)2Cl]2(0.0075mmol,1.5 mol%), phospholene ligand (R) -4t (0.0075mmol,3 mol%) was put into a reaction flask, toluene (1mL) was added, the reaction was stirred at room temperature for 30min, and 2.5mol/L of K was added to the system3PO4Aqueous solution (0.1mL), followed byAnd (5) continuing the reaction. After completion of the reaction monitored by TLC, the reaction was dried by spinning and isolated by silica gel column chromatography to give product 3ac as a white solid in 98% yield and 96% ee.
Figure BDA0000826779940000231
1H NMR(300MHz,CDCl3)δ7.51(d,J＝8.8Hz,2H),7.39–7.33(m,2H),7.20(d,J＝3.3Hz,4H),5.07(s,1H),3.19(s,3H),2.36(s,3H)；13C NMR(100MHz,CDCl3)δ168.6,139.9,136.2,135.6,135.5,130.0,129.2,129.1,127.5,75.0,26.5,21.3；HRMS(ESI)for C16H16O3N2ClS[M+H]+calcd 351.0565,found 351.0561.
Example 25
Synthesis of Compound 3 od:
under the protection of argon, 4- (4-fluorophenyl) -3-carbonyl-1, 2, 5-thiadiazole substrate 2d (0.25mmol,100 mol%), phenylboronic acid 1o (0.5mmol,200 mol%), [ Rh (COE)2Cl]2(0.0075mmol,1.5 mol%), phospholene ligand (R) -4t (0.0075mmol,3 mol%) was put into a reaction flask, toluene (1mL) was added, the reaction was stirred at room temperature for 30min, and 2.5mol/L of K was added to the system3PO4Aqueous (0.1mL) and the reaction was continued. After completion of the TLC monitoring reaction, the reaction was spun off and the product was isolated by silica gel column chromatography as a white solid in 94% yield and 97% ee.
Figure BDA0000826779940000232
1H NMR(300MHz,CDCl3)δ7.51(dd,J＝9.1,5.1Hz,2H),7.38(s,5H),7.07(t,J＝8.7Hz,2H),5.11(s,1H),3.20(s,3H)；13C NMR(125MHz,CDCl3)δ168.6,163.2(d,1JCF＝248.8Hz),138.5,133.7,129.8(d,3JCF＝8.4Hz),129.7,129.3,127.6,116.0(d,2JCF＝21.3Hz),75.1,26.5；HRMS(ESI)for C15H14O3N2FS[M+H]+calcd 321.0704,found 321.0706.
Example 26
Synthesis of compound 3 bd:
under the protection of argon, 4- (4-fluorophenyl) -3-carbonyl-1, 2, 5-thiadiazole substrate 2d (0.25mmol,100 mol%), 4-chlorobenzeneboronic acid 1b (0.5mmol,200 mol%), [ Rh (COE)2Cl]2(0.0075mmol,1.5 mol%), phospholene ligand (R) -4t (0.0075mmol,3 mol%) was put into a reaction flask, toluene (1mL) was added, the reaction was stirred at room temperature for 30min, and 2.5mol/L of K was added to the system3PO4Aqueous (0.1mL) and the reaction was continued. After completion of the reaction monitored by TLC, the reaction solution was spun dry and separated by silica gel column chromatography to give the product 3bd as a white solid in 95% yield and 96% ee.
Figure BDA0000826779940000241
1H NMR(300MHz,CDCl3)δ7.48–7.32(m,6H),7.08(t,J＝8.6Hz,2H),5.12(s,1H),3.20(s,3H)；13C NMR(125MHz,CDCl3)δ168.3,163.3(d,1JCF＝250.0Hz),136.4,135.9,133.8,129.8(d,3JCF＝8.5Hz),129.3,129.1,116.3(d,2JCF＝21.3Hz),74.5,26.5；HRMS(ESI)for C15H12O3N2ClFSNa[M+Na]+calcd 377.0133,found 377.0141.
Example 27
Synthesis of compound 3 ad:
under the protection of argon, 4- (4-fluorophenyl) -3-carbonyl-1, 2, 5-thiadiazole substrate 2d (0.25mmol,100 mol%), 4-methylphenylboronic acid 1a (0.5mmol,200 mol%), [ Rh (COE)2Cl]2(0.0075mmol,1.5 mol%), phospholene ligand (R) -4t (0.0075mmol,3 mol%) was put into a reaction flask, toluene (1mL) was added, the reaction was stirred at room temperature for 30min, and 2.5mol/L of K was added to the system3PO4Aqueous (0.1mL) and the reaction was continued. After completion of the reaction monitored by TLC, the reaction was spun off and the product 3ad was isolated by silica gel column chromatography as a white solid in 95% yield and 96% ee.
Figure BDA0000826779940000242
1H NMR(300MHz,CDCl3)δ7.58–7.46(m,2H),7.24(d,J＝8.2Hz,2H),7.18(d,J＝8.4Hz,2H),7.12–6.99(m,2H),5.05(s,1H),3.19(q,J＝1.1Hz,3H),2.35(s,3H)；13C NMR(125MHz,CDCl3)δ168.8,163.2(d,1JCF＝247.5Hz),139.8,135.7,133.7,130.0,129.8(d,3JCF＝8.8Hz),127.5,115.9(d,2JCF＝21.3Hz),115.8,75.1,26.4,21.3；HRMS(ESI)for C16H16O3N2FS[M+H]+calcd 335.0860,found 335.0858.
Example 28
Synthesis of compound 3 ae:
under the protection of argon, 4-phenyl-3-ethoxy-1, 2, 5-thiadiazole substrate 2e (0.25mmol,100 mol%), 4-methylphenylboronic acid 1a (0.5mmol,200 mol%), [ Rh (COE)2Cl]2(0.0075mmol,1.5 mol%), and 4t (0.0075mmol,3 mol%) of phospholene ligand (R) -4 were put into a reaction flask, toluene (1mL) was added, and after stirring the reaction at room temperature for 30min, 1.5mol/L aqueous KF solution (0.167mL) was added to the system to continue the reaction. After completion of the TLC monitoring reaction, the reaction was spun dry and the product 3ae was isolated by silica gel column chromatography as a white solid in 95% yield and 99% ee.
Figure BDA0000826779940000243
1H NMR(300MHz,CDCl3)δ7.40(dt,J＝4.6,1.9Hz,5H),7.25(d,J＝5.9Hz,2H),7.18(d,J＝8.1Hz,2H),4.87(s,1H),4.51(q,J＝7.1Hz,2H),2.37(s,3H),1.37(t,J＝7.1Hz,3H)；13C NMR(100MHz,CDCl3)δ177.3,139.4,138.2,135.4,129.7,129.3,128.9,127.9,127.8,70.1,21.3,13.9；HRMS(ESI)for C17H18O3N2NaS[M+Na]+calcd 353.0936,found 353.0927.
Example 29
Synthesis of compound 3 ae':
the phospholene ligand (R) -4t used in example 28 was replaced by (S) -4t and the rest of the experiment was performed as in example 28. The product 3 ae' was obtained as a white solid in 95% yield, -98% ee.
Figure BDA0000826779940000251
1H NMR(300MHz,CDCl3)δ7.41(dt,J＝4.6,1.9Hz,5H),7.24(d,J＝5.9Hz,2H),7.20(d,J＝8.1Hz,2H),4.88(s,1H),4.50(q,J＝7.1Hz,2H),2.38(s,3H),1.37(t,J＝7.1Hz,3H)；13C NMR(100MHz,CDCl3)δ177.4,139.4,138.3,135.3,129.8,129.4,129.0,127.9,127.9,70.2,21.4,13.9；HRMS(ESI)for C17H18O3N2NaS[M+Na]+calcd 353.0936,found 353.0927.
Example 30
Synthesis of Compound 3 be:
the same experiment as in example 28 was conducted except that 4-methylphenylboronic acid 1a used in example 28 was changed to 4-chlorophenylboronic acid 1 b. Product 3be was obtained as a white solid in 95% yield and 98% ee.
Figure BDA0000826779940000252
1H NMR(300MHz,CDCl3)δ7.52–7.32(m,7H),7.32–7.24(m,2H),5.14(s,1H),4.51(qd,J＝7.0,3.3Hz,2H),1.37(t,J＝7.1Hz,3H).13C NMR(100MHz,CDCl3)δ176.6,138.3,136.2,135.5,129.7,129.5,129.3,129.1,127.7,70.4,13.9；HRMS(ESI)for C16H15O3N2NaSCl[M+Na]+calcd 373.0390,found 373.0400.
Example 31
Synthesis of compound 3 be':
the phospholene ligand (R) -4t used in example 30 was replaced by (S) -4t and the rest of the experiment was performed as in example 30. Product 3 be' was obtained as a white solid in 95% yield, -98% ee.
Figure BDA0000826779940000253
1H NMR(300MHz,CDCl3)δ7.53–7.32(m,7H),7.31–7.24(m,2H),5.15(s,1H),4.50(qd,J＝7.0,3.3Hz,2H),1.37(t,J＝7.1Hz,3H).13C NMR(100MHz,CDCl3)δ176.8,138.4,136.3,135.6,129.6,129.5,129.3,129.1,127.8,70.5,13.9；HRMS(ESI)for C16H15O3N2NaSCl[M+Na]+calcd 373.0390,found 373.0400.
Example 32
Synthesis of Compound 3 ce:
the same experiment as in example 28 was conducted except that 4-methylphenylboronic acid 1a used in example 28 was changed to 4-methoxyphenylboronic acid 1 c. Product 3ce was obtained as a white solid in 97% yield and 98% ee.
Figure BDA0000826779940000261
1H NMR(300MHz,CDCl3)δ7.39(t,J＝3.4Hz,5H),7.29(d,J＝8.8Hz,2H),6.88(d,J＝8.8Hz,2H),5.03(s,1H),4.50(q,J＝7.1Hz,2H),3.81(s,3H),1.36(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ177.4,160.3,138.4,130.2,129.30,129.25,129.0,127.9,114.3,70.1,55.5,13.9；HRMS(ESI)for C17H18O4N2NaS[M+Na]+calcd 369.0885,found 369.0888.
Example 33
Synthesis of compound 3 ce':
the phospholene ligand (R) -4t used in example 32 was replaced by (S) -4t and the rest of the experimental work was the same as in example 32. Product 3 ce' was obtained as a white solid in 98% yield, -98% ee.
Figure BDA0000826779940000262
1H NMR(300MHz,CDCl3)δ7.40(t,J＝3.4Hz,5H),7.30(d,J＝8.8Hz,2H),6.87(d,J＝8.8Hz,2H),5.05(s,1H),4.51(q,J＝7.1Hz,2H),3.81(s,3H),1.37(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ177.5,160.3,138.4,130.3,129.3,129.2,129.0,128.0,114.3,70.2,55.6,13.9；HRMS(ESI)for C17H18O4N2NaS[M+Na]+calcd 369.0885,found 369.0888.
Example 34
Synthesis of Compound 3 ge:
the same experiment as in example 28 was conducted except that 4-methylphenylboronic acid 1a used in example 28 was changed to 3-fluorophenylboronic acid 1 g. Product 3ge was obtained as a white solid in 93% yield and 94% ee.
Figure BDA0000826779940000263
1H NMR(300MHz,CDCl3)δ7.47–7.35(m,4H),7.35–7.26(m,3H),7.18(d,J＝10.0Hz,1H),7.10(t,J＝8.1Hz,1H),4.95(s,1H),4.53(qd,J＝7.1,2.1Hz,2H),1.39(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ176.5,162.8(d,1JCF＝246.0Hz),140.2(d,3JCF＝7.2Hz),138.2,130.5(d,3J＝8.2Hz),129.7,129.3,127.7,123.7(d,4J＝2.9Hz),116.4(d,2JCF＝21.0Hz),115.5(d,2JCF＝24.0Hz),70.4,13.9；HRMS(ESI)for C16H15O3N2NaSF[M+Na]+calcd 357.0685,found 357.0687.
Example 35
Synthesis of compound 3 ge':
the phospholene ligand (R) -4t used in example 34 was replaced by (S) -4t and the rest of the experiment was performed as in example 34. Product 3 ge' was obtained as a white solid in 95% yield, 94% ee.
Figure BDA0000826779940000271
1H NMR(300MHz,CDCl3)δ7.46–7.36(m,4H),7.37–7.25(m,3H),7.20(d,J＝10.0Hz,1H),7.11(t,J＝8.1Hz,1H),4.97(s,1H),4.53(qd,J＝7.1,2.1Hz,2H),1.39(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ176.6,162.8(d,1JCF＝246.0Hz),140.3(d,3JCF＝7.2Hz),138.2,130.6(d,3J＝8.2Hz),129.7,129.43,127.8,123.7(d,4J＝2.9Hz),116.5(d,2JCF＝21.0Hz),115.5(d,2JCF＝24.0Hz),70.5,13.9；HRMS(ESI)for C16H15O3N2NaSF[M+Na]+calcd 357.0685,found 357.0687.
Example 36
Synthesis of compound 3 he:
the same experiment as in example 28 was carried out except that 4-methylphenylboronic acid 1a used in example 28 was changed to 3-methylphenylboronic acid 1 h. Product 3he was obtained as a white solid in 92% yield and 98% ee.
Figure BDA0000826779940000272
1H NMR(300MHz,CDCl3)δ7.40(dd,J＝10.7,5.0Hz,5H),7.26(dd,J＝9.0,5.9Hz,1H),7.16(dd,J＝16.0,9.2Hz,3H),4.88(s,1H),4.51(q,J＝7.1Hz,2H),2.34(s,3H),1.37(t,J＝7.1Hz,3H)；13C NMR(125MHz,CDCl3)δ177.2,139.0,138.3,138.1,130.1,129.3,128.9,128.3,127.9,125.0,70.1,21.7,13.9；HRMS(ESI)for C17H18O3N2NaS[M+Na]+calcd 353.0936,found 353.0927.
Example 37
Synthesis of compound 3 je:
the same experiment as in example 28 was conducted except that 4-methylphenylboronic acid 1a used in example 28 was changed to 2-naphthylboronic acid 1 j. Product 3je was obtained as a white solid in 72% yield and 96% ee.
Figure BDA0000826779940000281
1H NMR(300MHz,CDCl3)δ8.00(s,1H),7.84(d,J＝8.4Hz,3H),7.54(dd,J＝9.1,5.3Hz,2H),7.45–7.32(m,6H),5.01(s,1H),4.54(q,J＝7.1Hz,2H),1.38(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ177.1,138.3,135.2,133.4,132.9,129.5,129.1,128.9,128.8,127.9,127.7,127.6,127.4,127.0,125.1,70.3,13.9；HRMS(ESI)for C20H18O3N2NaS[M+Na]+calcd 389.0936,found 389.0938.
Example 38
Synthesis of compound 3 me:
the same experiment as in example 28 was carried out except that 4-methylphenylboronic acid 1a used in example 28 was changed to 3-thiopheneboronic acid 1 m. Product 3me was obtained as a white solid in 87% yield and 98% ee.
Figure BDA0000826779940000282
1H NMR(300MHz,CDCl3)δ7.50–7.44(m,1H),7.44–7.30(m,6H),6.99(dd,J＝5.0,0.9Hz,1H),5.01(s,1H),4.51(q,J＝7.1Hz,2H),1.38(t,J＝7.1Hz,3H)；13C NMR(125MHz,CDCl3)δ176.7,138.5,138.1,129.6,129.2,127.4,127.3,126.8,125.7,74.9,70.2,13.9；HRMS(ESI)for C14H14O3N2NaS2[M+Na]+calcd 345.0344,found 345.0338.
Example 39
Synthesis of compound 3 ne:
the same experiment as in example 28 was conducted except that 4-methylphenylboronic acid 1a used in example 28 was changed to 3-furanboronic acid 1 n. Product 3ne was obtained as a white solid in 50% yield and 84% ee.
Figure BDA0000826779940000283
1H NMR(300MHz,CDCl3)δ7.58–7.59(m,1H),7.47–7.48(m,1H),7.41-7.43(m,5H),6.36-6.37(m,1H),4.99(s,1H),4.47-4.57(m,2H),1.39(t,J＝7.2Hz,3H)；13C NMR(125MHz,CDCl3)δ176.7,144.4,142.4,137.4,129.7,129.3,127.1,124.0,109.7,72.1,70.2,13.9.
Example 40
Synthesis of Compound 3 pe:
example 28 was followed by replacing 4-methylbenzeneboronic acid 1a used in example 28 with 2-benzofuranboronic acid 1 p. Product 3pe was obtained as a white solid in 80% yield and 89% ee.
Figure BDA0000826779940000291
1H NMR(300MHz,CDCl3)δ7.79(s,1H),7.48–7.55(m,3H),7.35-7.43(m,3H),7.31(t,J＝6.9Hz,1H),7.14-7.22(m,2H),5.12(s,1H),4.47-4.55(m,2H),1.33(t,J＝7.5Hz,3H)；13C NMR(125MHz,CDCl3)δ176.5,156.3,145.5,136.1,129.8,129.3,127.3,125.4,124.8,123.4,121.2,118.9,112.2,72.3,70.4,13.9.
EXAMPLE 41
Synthesis of compound 3 cf:
under the protection of argon, 4- (4-methyl) -3-ethoxy-1, 2, 5-thiadiazole substrate 2f (0.25mmol,100 mol%), 4-methoxyphenylboronic acid 1c (0.5mmol,200 mol%), [ Rh (COE)2Cl]2(0.0075mmol,1.5 mol%), and 4t (0.0075mmol,3 mol%) of phospholene ligand (R) -4 were put into a reaction flask, toluene (1mL) was added, and after stirring the reaction at room temperature for 30min, 1.5mol/L aqueous KF solution (0.167mL) was added to the system to continue the reaction. After completion of the reaction monitored by TLC, the reaction solution was spun dry and separated by silica gel column chromatography to give the product 3cf as a white solid in 93% yield and 98% ee.
Figure BDA0000826779940000292
1H NMR(300MHz,CDCl3)δ7.39–7.23(m,4H),7.18(d,J＝8.1Hz,2H),6.88(d,J＝8.9Hz,2H),4.98(s,1H),4.49(q,J＝7.1Hz,2H),3.80(s,3H),2.36(s,3H),1.36(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ177.6,160.2,139.4,135.6,130.2,129.7,129.3,127.7,114.2,70.0,55.5,21.2,13.9；HRMS(ESI)for C18H20O4N2NaS[M+Na]+calcd 383.1041,found 383.1050.
Example 42
Synthesis of compound 3 df:
under the protection of argon, 4- (4-methyl) -3-ethoxy-1, 2, 5-thiadiazole is subjected to reactionSubstrate 2f (0.25mmol,100 mol%), 4-fluorobenzeneboronic acid 1d (0.5mmol,200 mol%), [ Rh (COE)2Cl]2(0.0075mmol,1.5 mol%), and 4t (0.0075mmol,3 mol%) of phospholene ligand (R) -4 were put into a reaction flask, toluene (1mL) was added, and after stirring the reaction at room temperature for 30min, 1.5mol/L aqueous KF solution (0.167mL) was added to the system to continue the reaction. After completion of the reaction monitored by TLC, the reaction was spun off and the product was isolated by silica gel column chromatography to give 3df as a white solid in 92% yield and 96% ee.
Figure BDA0000826779940000293
1H NMR(300MHz,CDCl3)δ7.45–7.50(m,2H),7.15-7.21(m,4H),7.04-7.10(m,2H),4.89(s,1H),4.47-4.55(m,2H),2.37(s,3H),1.37(t,J＝7.5Hz,3H)；13C NMR(150MHz,CDCl3)δ177.1,163.2(J＝247.5Hz),139.7,135.6,133.6(J＝2.5Hz),130.1,129.9(J＝10Hz),127.6,115.8(J＝21.25Hz),70.2,21.2,13.9.
Example 43
Synthesis of compound 3 og:
under the protection of argon, 2g (0.25mmol,100 mol%) of 4- (4-chloro) -3-ethoxy-1, 2, 5-thiadiazole substrate, 1o (0.5mmol,200 mol%) of phenylboronic acid, [ Rh (COE) ]2Cl]2(0.0075mmol,1.5 mol%), and 4t (0.0075mmol,3 mol%) of phospholene ligand (R) -4 were put into a reaction flask, toluene (1mL) was added, and after stirring the reaction at room temperature for 30min, 1.5mol/L aqueous KF solution (0.167mL) was added to the system to continue the reaction. After completion of the reaction monitored by TLC, the reaction was spun off and the product isolated by silica gel column chromatography to give 3og as a white solid in 98% yield and 94% ee.
Figure BDA0000826779940000301
1H NMR(300MHz,CDCl3)δ7.27–7.31(m,2H),7.35-7.45(m,7H),4.94(s,1H),4.47-4.58(m,2H),1.38(t,J＝7.2Hz,3H)；13C NMR(150MHz,CDCl3)δ176.7,138.3,136.3,135.5,129.7,129.5,129.3,129.1,127.7,77.0,70.4,13.9.
Example 44
Synthesis of compound 3 cg:
under the protection of argon, 2g (0.25mmol,100 mol%) of 4- (4-chloro) -3-ethoxy-1, 2, 5-thiadiazole substrate, 1c (0.5mmol,200 mol%) of 4-methoxyphenylboronic acid, [ Rh (COE) ]2Cl]2(0.0075mmol,1.5 mol%), and 4t (0.0075mmol,3 mol%) of phospholene ligand (R) -4 were put into a reaction flask, toluene (1mL) was added, and after stirring the reaction at room temperature for 30min, 1.5mol/L aqueous KF solution (0.167mL) was added to the system to continue the reaction. After completion of the reaction monitored by TLC, the reaction was spun off and the product was isolated by silica gel column chromatography as a white solid in 94% yield and 98% ee.
Figure BDA0000826779940000302
1H NMR(300MHz,CDCl3)δ7.44(d,J＝8.8Hz,2H),7.36(d,J＝8.8Hz,2H),7.19(d,J＝8.9Hz,2H),6.89(d,J＝8.9Hz,2H),5.05(s,1H),4.51(pd,J＝7.5,3.3Hz,2H),3.82(s,3H),1.37(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ176.9,160.4,136.4,135.4,130.3,129.5,129.1,129.0,114.6,70.3,55.6,13.9；HRMS(ESI)for C17H17O4N2NaSCl[M+Na]+calcd 403.0495,found 403.0496.
Example 45
Synthesis of compound 3 dg:
under the protection of argon, 2g (0.25mmol,100 mol%) of 4- (4-chloro) -3-ethoxy-1, 2, 5-thiadiazole substrate, 1d (0.5mmol,200 mol%) of 4-fluorobenzeneboronic acid, [ Rh (COE) ]2Cl]2(0.0075mmol,1.5 mol%), and 4t (0.0075mmol,3 mol%) of phospholene ligand (R) -4 were put into a reaction flask, toluene (1mL) was added, and after stirring the reaction at room temperature for 30min, 1.5mol/L aqueous KF solution (0.167mL) was added to the system to continue the reaction. After completion of the TLC monitoring reaction, the reaction was spun off and the product was isolated by silica gel column chromatography as a white solid in 95% yield and 98% ee.
Figure BDA0000826779940000311
1H NMR(300MHz,CDCl3)δ7.46–7.21(m,6H),7.08(t,J＝8.6Hz,2H),5.28(s,1H),4.52(q,J＝7.1Hz,2H),1.38(t,J＝7.1Hz,3H)；13C NMR(125MHz,CDCl3)δ176.4,163.3(d,1JCF＝248.8Hz),136.4,135.8,133.8,129.9(d,3J＝8.5Hz),129.3(d,4J＝1.8Hz),116.2(d,2JCF＝21.3Hz),70.5,13.9；HRMS(ESI)for C16H14O3N2NaSClF[M+Na]+calcd 391.0295,found 391.0292.
Example 46
Synthesis of Compound 3 ch:
under the protection of argon, 4- (3-chloro) -3-ethoxy-1, 2, 5-thiadiazole substrate was reacted for 2h (0.25mmol,100 mol%), 4-methoxyphenylboronic acid 1c (0.5mmol,200 mol%), [ Rh (COE)2Cl]2(0.0075mmol,1.5 mol%), and 4t (0.0075mmol,3 mol%) of phospholene ligand (R) -4 were put into a reaction flask, toluene (1mL) was added, and after stirring the reaction at room temperature for 30min, 1.5mol/L aqueous KF solution (0.167mL) was added to the system to continue the reaction. After completion of the TLC monitoring reaction, the reaction was spun off and the product 3ch was isolated by silica gel column chromatography as a white solid in 96% yield and 97% ee.
Figure BDA0000826779940000312
1H NMR(300MHz,CDCl3)δ7.58–7.29(m,4H),7.20(d,J＝8.5Hz,2H),6.89(d,J＝8.5Hz,2H),5.05(s,1H),4.52(dt,J＝6.3,4.8Hz,2H),3.82(s,3H),1.38(t,J＝7.0Hz,3H)；13C NMR(150MHz,CDCl3)δ176.7,160.5,139.9,134.9,130.1,129.5,129.1,128.3,126.2,114.6,70.4,55.6,13.9；HRMS(ESI)for C17H17O4N2NaSCl[M+Na]+calcd 403.0495,found 403.0496.
Example 47
Synthesis of compound 3 dh:
under the protection of argon, 4- (3-chloro) -3-ethoxy-1, 2, 5-thiadiazole substrate was reacted for 2h (0.25mmol,100 mol%), 4-fluorobenzeneboronic acid 1d (0.5mmol,200 mol%), [ Rh (COE)2Cl]2(0.0075mmol,1.5 mol%), and 4t (0.0075mmol,3 mol%) of phospholene ligand (R) -4 were put into a reaction flask, toluene (1mL) was added, and after stirring the reaction at room temperature for 30min, 1.5mol/L aqueous KF solution (0.167mL) was added to the system to continue the reaction. After completion of the reaction monitored by TLC, the reaction solution was dried by spinning and separated by silica gel column chromatography to give the product 3dh as a white solid in 98% yield and 97% ee.
Figure BDA0000826779940000321
1H NMR(300MHz,CDCl3)δ7.48–7.27(m,6H),7.09(t,J＝8.6Hz,2H),4.94(s,1H),4.54(q,J＝7.1Hz,2H),1.39(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ176.2,163.3(d,1JCF＝249.0Hz),139.9,135.2,133.6(d,4J＝3.1Hz),130.4,129.9(d,3J＝6.6Hz),128.1,126.0,116.3(d,2JCF＝21.0Hz),70.6,13.9；HRMS(ESI)for C16H14O3N2NaSClF[M+Na]+calcd 391.0295,found 391.0301.
Example 48
Synthesis of compound 4 a:
lithium aluminum hydride (0.4mmol,200 mol%) and tetrahydrofuran (2mL) were added to a reaction flask under an argon blanket, placed at 0 deg.C, and compound 3aa (0.2mmol,100 mol%) was added to the system, which was then heated to reflux (70 deg.C) for three hours. After TLC monitoring reaction was complete, the reaction flask was placed in an ice bath and quenched with water, 10% sodium hydroxide solution in sequence, the aqueous layer was extracted three times with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was removed under pressure and the product 4a was isolated by silica gel column chromatography as a white solid in 88% yield and 96% ee.
Figure BDA0000826779940000322
1H NMR(300MHz,CDCl3)δ7.36(d,J＝7.9Hz,2H),7.34–7.17(m,5H),7.12(d,J＝8.0Hz,2H),2.84(d,J＝4.9Hz,3H),2.33(s,3H),2.16(s,2H)；13C NMR(100MHz,CDCl3)174.5,145.5,142.3,137.3,129.1,128.4,127.6,127.5,127.4,68.0,26.7,21.2；HRMS(ESI)for C16H19ON2[M+H]+calcd 255.1492,found 255.1490.
Example 49
Synthesis of compound 4 b:
the same experiment as in example 48 was carried out except that the compound 3aa used in example 48 was changed to the compound 3 ia. Product 4b was obtained as a white solid in 86% yield.
Figure BDA0000826779940000323
1H NMR(300MHz,CDCl3)δ7.56(s,1H),7.42(d,J＝7.7Hz,1H),7.38–7.27(m,6H),7.19(t,J＝7.8Hz,1H),2.85(d,J＝4.9Hz,3H),2.04(s,3H)；13C NMR(125MHz,CDCl3)δ173.7,147.6,144.5,130.7,130.6,130.0,128.6,127.8,127.5,126.7,122.6,67.9,26.7；HRMS(ESI)for C15H16ON2Br[M+H]+calcd 319.0441,found 319.0436.
Example 50
Synthesis of compound 5 a:
compound 4b (0.2mmol,100 mol%) was dissolved in tetrahydrofuran (2mL) under nitrogen, placed at 0 deg.C, and triphosgene (0.2mmol,100 mol%) and triethylamine (1.0mmol,500 mol%) were added slowly in that order, and the reaction was allowed to warm to room temperature for 12 hours. After TLC monitoring reaction was complete, ice water was added to the reaction system to quench the reaction, the aqueous layer was extracted three times with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, solvent was removed under pressure, and product 5a was isolated by silica gel column chromatography as a white solid in 71% yield.
Figure BDA0000826779940000331
1H NMR(300MHz,CDCl3)δ7.57(d,J＝1.4Hz,1H),7.49(d,J＝7.8Hz,1H),7.44–7.30(m,6H),7.23(d,J＝7.8Hz,1H),6.70(s,1H),3.10(s,3H)；13C NMR(125MHz,CDCl3)δ173.0,156.7,141.3,138.7,132.0,130.5,130.0,129.2,129.0,126.8,125.9,123.1,69.9,25.3；HRMS(ESI)for C16H14O2N2Br[M+H]+calcd 345.0233,found 345.0229.
Example 51
Synthesis of compound 6 a:
compound 5a (0.2mmol,100 mol%) and Lawesson's reagent (0.4mmol,200 mol%) were dissolved in toluene (5mL) under nitrogen and heated at reflux (110 ℃ C.) for 12 hours. After TLC monitoring the reaction was complete, the solvent was removed under reduced pressure and the product 6a was isolated by silica gel column chromatography as a white solid in 95% yield and 93% ee.
Figure BDA0000826779940000332
1H NMR(300MHz,CDCl3)δ8.25(s,1H),7.59–7.45(m,2H),7.42–7.34(M,3H),7.33–7.20(m,4H),3.33(s,3H)；13C NMR(125MHz,CDCl3)δ183.0,173.1,140.0,137.5,132.3,130.6,130.0,129.4,126.9,125.8,123.2,71.9,28.3；HRMS(ESI)for C16H14ON2BrS[M+H]+calcd 361.0005found 360.9999.
Example 52
Synthesis of compound 7 a:
compound 6a (0.2mmol,100 mol%), 3-methoxyphenylboronic acid (0.3mmol,150 mol%) and tetrakistriphenylphosphine palladium (0.02mmol,10 mol%) were dissolved in toluene (5mL) and ethanol (1mL) under nitrogen, followed by addition of 2mol/L aqueous sodium carbonate (0.2mL,200 mol%) and heating (80 ℃) for 5 hours. After TLC monitoring of the reaction completion, the reaction was quenched by addition of water, the aqueous layer was extracted three times with ethyl acetate (3X 20mL), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure and the product 7a was isolated by silica gel column chromatography as a white solid in 92% yield and 93% ee.
Figure BDA0000826779940000341
1H NMR(300MHz,CDCl3)δ8.08-8.13(m,1H),7.53-7.58(m,2H),7.29-7.46(m,7H),7.08(d,J＝7.5Hz,1H),7.03(s,1H),6.88(d,J＝8.1Hz,1H),5.30(s,1H),3.83(s,3H),3.34(s,3H)；HRMS(ESI)for C23H21O2N2S[M+H]+calcd 389.1324found 389.1329.
Example 53
Synthesis of BACE-1 inhibitors:
compound 7a (0.2mmol,100 mol%) was dissolved in methanol (2mL) under nitrogen, and tert-butyl peroxy-alcohol (1mL) and aqueous ammonia (1mL) were added in this order, and the mixture was heated (50 ℃ C.) to react for 12 hours. After TLC monitoring reaction was complete, water was added to quench the reaction, the aqueous layer was extracted three times with dichloromethane (3X 20mL), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure, and silica gel column chromatography gave the product BACE-1 inhibitor as a white solid in 81% yield.
Figure BDA0000826779940000342
1H NMR(300MHz,CDCl3)δ7.70(s,1H),7.44-7.49(m,4H),7.29-7.40(m,5H),7.13(d,J＝8.1Hz,1H),7.08(s,1H),6.87(d,J＝8.1Hz,1H),3.83(s,3H),3.60(s,2H),3.11(s,3H)；HRMS(ESI)for C23H22O2N3[M+H]+calcd 372.1712found 372.1709.
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims (7)

1. A method for preparing a compound containing a quaternary carbon chiral center represented by formula 3 and/or formula ent-3, comprising the steps of:
carrying out asymmetric addition reaction on an organic boron reagent shown in a formula 1 and a substrate shown in a formula 2 in an organic solvent in the presence of an additive and a complex catalyst formed by a monovalent rhodium metal compound and a chiral phosphorus alkene ligand to obtain a compound containing a quaternary carbon chiral center shown in a formula 3 and/or a formula ent-3:
Figure 992713DEST_PATH_IMAGE001
in the formula (I), the compound is shown in the specification,
R1selected from the group consisting of: substituted or unsubstituted C6-30Aryl, substituted or unsubstituted C4-12Heteroaryl, wherein said substitution means that a hydrogen atom on the group is substituted with one or more substituents, and said heteroaryl contains a heteroatom that is oxygen or sulfur;
the substituents are selected from the following group: halogen, C1-6Alkyl radical, C1-6Haloalkyl, C1-6Alkoxy radical, C1-6Haloalkoxy, benzyloxy, unsubstituted or substituted C6-10Aryl, or a combination thereof; the halogen is F, Cl, Br or I;
R2is absent, or C1-6An alkyl group;
R3selected from the group consisting of: substituted or unsubstituted C6-30Aryl, substituted or unsubstituted C4-12Heteroaryl, wherein said substitution means that a hydrogen atom on the group is substituted with one or more substituents, and said heteroaryl contains a heteroatom that is oxygen or sulfur;
the substituents are selected from the following group: halogen, C1-6Alkyl radical, C1-6Haloalkyl, C1-6Alkoxy radical, C1-6Haloalkoxy, benzyloxy, unsubstituted or substituted C6-10Aryl, or a combination thereof; the halogen is F, Cl, Br or I;
R4is absent, or C1-3Linear or branched alkyl of (a);
[B]selected from the group consisting of: b (OR)2Or (BO)3Wherein R is H or C1-3Linear or branched alkyl of (a);
the dotted line represents a chemical bond or is absent;
and the chiral phospholene ligand has the following structural formula, wherein the formula I and the formula II are enantiomers of each other:
Figure 412193DEST_PATH_IMAGE002
in the formula (I), the compound is shown in the specification,
R6and R7Are linked to form a substituted or unsubstituted- (CH)2)n-wherein n is 4 or is linked to the carbon atom to which it is attached to form a substituted or unsubstituted phenyl group, wherein said substitution is such that the hydrogen atom of the group is substituted with one or more substituents selected from the group consisting of: halogen, C unsubstituted or substituted by one or more halogens1-6An alkyl group;
R8is substituted or unsubstituted phenyl or naphthyl, wherein the substitution is that hydrogen atoms on the group are substituted by one or more substituents selected from the group consisting of: halogen, C unsubstituted or substituted by one or more halogens1-6Alkyl, or C unsubstituted or substituted by one or more halogen1-6An alkoxy group;
R9is a group selected from the group consisting of: hydrogen;
R5selected from the group consisting of: hydrogen, substituted or unsubstituted C1-6Alkyl, substituted or unsubstituted phenyl, wherein said substitution means that a hydrogen atom on the group is substituted with one or more substituents selected from the group consisting of: halogen, C unsubstituted or substituted by one or more halogens1-6An alkyl group;
or the ligand has a structural formula selected from the group consisting of:
Figure 560277DEST_PATH_IMAGE003
2. the method of claim 1, wherein the monovalent rhodium metal catalyst is present in an amount of 1 to 30 mole percent, based on the amount of compound 4-substituted-3-oxo-1, 2, 5-thiadiazole substrate 2; and/or the dosage of the chiral phosphorus alkene ligand is 1-30 mol%.
3. The method of claim 1, wherein the chiral phospholene ligand has the following formula:
Figure 506237DEST_PATH_IMAGE004
in the formula (I), the compound is shown in the specification,
R6and R7Are linked to form a substituted or unsubstituted- (CH)2)n-wherein n is 4 or is linked to the carbon atom to which it is attached to form a substituted or unsubstituted phenyl group, wherein said substitution is such that the hydrogen atom of the group is substituted with one or more substituents selected from the group consisting of: halogen, C unsubstituted or substituted by one or more halogens1-6An alkyl group;
R8is substituted or unsubstituted phenyl or naphthyl, wherein the substitution is that hydrogen atoms on the group are substituted by one or more substituents selected from the group consisting of: halogen, C unsubstituted or substituted by one or more halogens1-6Alkyl, or C unsubstituted or substituted by one or more halogen1-6An alkoxy group;
R9is a group selected from the group consisting of: hydrogen;
R5is H.
4. The method of claim 1, wherein the chiral phospholene ligand is selected from the group consisting of:
Figure 652047DEST_PATH_IMAGE005
Figure 683457DEST_PATH_IMAGE006
。
5. the method of claim 1, wherein said monovalent rhodium metal compound is selected from the group consisting of: [ Rh (C)2H4)2Cl]2、[Rh(C2H4)2OH]2、[Rh(COE)2Cl]2、[Rh(COE)2OH]2Or a combination thereof.
6. The method of claim 1, wherein the method further comprises one or more characteristics selected from the group consisting of:
(1) the additive used in the reaction is an aqueous solution of salt with the concentration of 0.5 mol/L-5 mol/L, wherein the salt is selected from the following group: KF. KOH, K2CO3、Na2CO3、K3PO4、K2HPO4；
(2) The dosage of the reaction additive is 50mol percent to 500mol percent;
(3) the organic solvent used in the reaction is selected from the group consisting of: dichloromethane (CH)2Cl2) Toluene (Toluene), chloroform (CHCl)3) 1, 4-Dioxane (Dioxane), Tetrahydrofuran (THF), or a combination thereof;
(4) the reaction temperature is 0-100 deg.CoC；
(5) The reaction time is 3-12 hours.
7. A process for preparing a compound of formula 7, comprising the steps of:
Figure 369653DEST_PATH_IMAGE007
ring opening of the compound of formula 3 to form an α, α -diarylaminoamide 4, followed by cyclization to form a phenytoin analog 5, and two-step reaction of thionation and amination of compound 5 to form the compound of formula 7;
in the above formulae, R1，R2，R3Is as defined in claim 1.
CN201510688829.XA 2015-10-21 2015-10-21 Synthetic method of chiral 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide containing quaternary carbon Active CN106608859B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510688829.XA CN106608859B (en) 2015-10-21 2015-10-21 Synthetic method of chiral 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide containing quaternary carbon

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510688829.XA CN106608859B (en) 2015-10-21 2015-10-21 Synthetic method of chiral 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide containing quaternary carbon

Publications (2)

Publication Number Publication Date
CN106608859A CN106608859A (en) 2017-05-03
CN106608859B true CN106608859B (en) 2021-11-19

Family

ID=58611324

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510688829.XA Active CN106608859B (en) 2015-10-21 2015-10-21 Synthetic method of chiral 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide containing quaternary carbon

Country Status (1)

Country Link
CN (1) CN106608859B (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1347412A (en) * 1999-04-22 2002-05-01 拜尔公司 O-aryl dithiazole dioxides
CN101003533A (en) * 2007-01-12 2007-07-25 南开大学 Derivative of thiadiazoles containing cyclo oxdiazole, synthetic method, and biological activity
WO2011162514A2 (en) * 2010-06-21 2011-12-29 한국화학연구원 Method for preparing [1,2,3]-oxathiazolidine-2,2-dioxide or [1,2,5]-thiadiazolidine-1,1-dioxide derivatives
CN104744514A (en) * 2013-12-27 2015-07-01 中国科学院上海药物研究所 Chiral phosphorus alkene ligand, synthesis method and application thereof in asymmetric reaction

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1347412A (en) * 1999-04-22 2002-05-01 拜尔公司 O-aryl dithiazole dioxides
CN101003533A (en) * 2007-01-12 2007-07-25 南开大学 Derivative of thiadiazoles containing cyclo oxdiazole, synthetic method, and biological activity
WO2011162514A2 (en) * 2010-06-21 2011-12-29 한국화학연구원 Method for preparing [1,2,3]-oxathiazolidine-2,2-dioxide or [1,2,5]-thiadiazolidine-1,1-dioxide derivatives
CN104744514A (en) * 2013-12-27 2015-07-01 中国科学院上海药物研究所 Chiral phosphorus alkene ligand, synthesis method and application thereof in asymmetric reaction

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
An improved procedure for the synthesis of 4,4-disubstituted 3-oxo-1,2,5-thiadiazolidine 1,1-dioxides;Zejun Xiao等;《Journal of Heterocyclic Chemistry》;20000831;第37卷;第774页scheme2 和table2 *
Asymmetric synthesis of gem-diaryl substituted cyclic sulfamidates and sulfamides by rhodium-catalyzed arylation of cyclic ketimines;Takahiro Nishimura等;《Chem. Commun.》;20130425;第49卷;第5505页右栏第3段、第5505页右栏化合物3jm和3km、第5506页scheme2 *
Highly enantioselective synthesis of cyclic sulfamidates and sulfamides via rhodium-catalyzed transfer hydrogenation;Sun Ah Lee等;《Chem. Commun.》;20101217;第47卷;第2373页右栏scheme1 *
Rhodium-Catalyzed Highly Enantioselective Arylation of Cyclic Diketimines: Efficient Synthesis of Chiral Tetrasubstituted 1,2,5-Thiadiazoline 1,1-Dioxides;Hui Wang等;《Org. Lett.》;20140716;第16卷;第3962-3965页 *
Takahiro Nishimura等.Asymmetric synthesis of gem-diaryl substituted cyclic sulfamidates and sulfamides by rhodium-catalyzed arylation of cyclic ketimines.《Chem. Commun.》.2013,第49卷第5504—5506页. *
手性膦烯配体在铑催化的芳基硼酸对β-芳基-α,β-不饱和磺酸酯不对称共轭加成反应中的应用;于月娜等;《化学学报》;20140626;第72卷;第815-819页 *

Also Published As

Publication number Publication date
CN106608859A (en) 2017-05-03

Similar Documents

Publication Publication Date Title
CN108409747B (en) Synthetic method of 2-aminoquinoline dihydrofuran compound
Kurihara et al. An N‐Linked Bidentate Phosphoramidite Ligand (N‐Me‐BIPAM) for Rhodium‐Catalyzed Asymmetric Addition of Arylboronic Acids to N‐Sulfonylarylaldimines
CN114920775B (en) Axial chiral bisindole catalyst and synthetic method and application thereof
TWI422430B (en) New ruthenium complexes as catalysts for metathesis reactions
WO2021139499A1 (en) Preparation method for and application of chiral spirocyclic phosphine-nitrogen-phosphine tridentate ligand and iridium catalyst thereof
WO2007073698A1 (en) 2,2',6,6'-tetraoxazoline ligands with a biphenyl backbone and their preparation methods
CN107286202B (en) Chiral Ugi's amine, derivatives thereof, and synthesis method and application of optical isomers
CN111848322B (en) Axial chiral oxindole-substituted styrene compound and resolution method and application thereof
CN106608859B (en) Synthetic method of chiral 1,2, 5-thiazolinone-1, 1-dioxide and 2, 3-dihydro-1, 2, 5-thiadiazole-1, 1-dioxide containing quaternary carbon
CN111620896A (en) Preparation method of tetra-coordinated N, N-chelated diaryl borate compound with 8-aminoquinoline derivative as bidentate ligand
CN112920173A (en) Chiral chroman compound and synthesis method thereof
CN114874126B (en) Synthetic method of 3-bromoindole compound
CN104817583A (en) Carbon-bridged diacylamino rare earth amide and preparation thereof, and application of carbon-bridged diacylamino rare earth amide in catalysis of amidation of aldehyde and amine
CN114349686B (en) 1, 4-dihydropyridine chiral hybrid hydrogenation reagent, preparation method and application thereof
US8729303B2 (en) 2,2′,6,6′-tetrasubstituted aminophosphine ligand and its synthesis method
CN112209947A (en) Chiral indoxazinone compound and synthesis method thereof
CN113004248A (en) Method for synthesizing carbazole compound by catalyzing hydrocarbon amination reaction with cobalt
WO2017193288A1 (en) Synthesis of phosphine ligands bearing tunable linkage: methods of their use in catalysis
EP3303296A1 (en) Benzo[h]quinoline ligands and complexes thereof
CN108341757B (en) Chiral amino acid ester compound and preparation method and application thereof
CN114605273B (en) Method for synthesizing arylaminophenol compound by palladium-catalyzed CO-participated 1, 4-eneyne aromatization reaction
CN115057848B (en) Axis chiral isopyranone-indole derivative and synthesis method thereof
CN114634407B (en) Method for stereospecifically synthesizing 2-enal, 2-enone compound and deuterated compound thereof
CN114591369B (en) Phosphoramidite ligand and preparation method and application thereof
CN109796372B (en) Method for preparing polysubstituted alkenyl amidine

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant