CN106866574A - A kind of method of reduction amination synthesis of chiral sulfanilamide (SN) in palladium chtalyst asymmetric molecult - Google Patents
A kind of method of reduction amination synthesis of chiral sulfanilamide (SN) in palladium chtalyst asymmetric molecult Download PDFInfo
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Abstract
A kind of method of reduction amination synthesis of chiral sulfanilamide (SN) in palladium chtalyst asymmetric molecult, its catalyst system and catalyzing used is the chiral diphosphine complex of palladium.Corresponding chiral sulfonamide is obtained to ketoamine substrate reduction amination simple and easy to get, its enantiomeric excess can reach 99%.Present invention practicality easy to operate is easy, and raw material is simple and easy to get, and catalyst commercially available, reaction condition is gentle.Additionally, synthesizing chiral sulfonamide by asymmetric reduction amination, enantioselectivity is high, and yield is good, environmentally friendly.
Description
Technical field
A kind of homogeneous system height enantioselectivity the present invention relates to application palladium is catalyzed reduction amination synthesis of chiral sulfanilamide (SN)
Method.
Background technology
Chiral sulfonamide is the very important molecule of a class, and it is not only the important skeleton of many bioactive molecules, is also
Synthesize the important intermediate (bibliography one of many medicines：(a)Wells,G.J.；Tao,M.；Josef,K.A.；Bihovsky,
R.J.Med.Chem.2001,44,3488.(b)Cherney,R.J.；Mo,R.；Meyer,D.T.；Hardman,K.D.；Liu,
R.-Q.；Covington,M.B.；Qian,M.；Wasserman,Z.R.；Christ,D.D.；Trzaskos,J.M.；Newton,
R.C.；Decicco,C.P.J.Med.Chem.2004,47,2981.(c)Rolfe,A.；Young,K.；Hanson,
P.R.Eur.J.Org.Chem.2008,5254.).Although the method for many synthesis sulfanilamide (SN) has been developed at present, use
Be catalyzed asymmetric method come synthesis of chiral sulfanilamide (SN) example it is few in number.The method of early stage synthesis of chiral sulfanilamide (SN) is urged using ruthenium
Asymmetric hydrogenation of the agent to ring-type sulfimide.Afterwards, people have developed the transfer hydrogenation of a series of ruthenium or rhodium catalysis again
Method ring-type sulfimide hydrogenated carried out synthesis of chiral sulfanilamide (SN) (bibliography two：(a)Oppolzer,W.；Wills,
M.；Starkemann,C.；Bernardinelli,G.Tetrahedron Lett.1990,31,4117.(b)Ahn,K.H.；
Ham,C.；Kim,S.K.；Cho,C.W.J.Org.Chem.1997,62,7047.(c)Mao,J.M.；Baker,
D.C.Org.Lett.1999,1,841.(d)Chen,Y.-C.；Wu,T.-F.；Deng,J.-G.；Liu,H.；Cui,X.；Zhu,
J.；Jiang,Y.-Z.；Choi,M.C.K.；Chan,A.S.C.J.Org.Chem.2002,67,5301.).In the recent period, people send out again
The asymmetric hydrogenation for having opened up a series of ring-type sulfimide of homogeneous palladium chtalysts carrys out synthesis of chiral sulfanilamide (SN) (bibliography three：(a)
Yang,Q.；Shang,G.；Gao,W.-Z.；Deng,J.-G.；Zhang,X.-M.Angew.Chem.,Int.Ed.2006,45,
3832.(b)Wang,Y.-Q.；Lu,S.-M.；Zhou,Y.-G.J.Org.Chem.2007,72,3729.(c)Wang,Y.-Q.；
Yu,C.-B.；Wang,D.-W.；Wang,X.-B.；Zhou,Y.-G.Org.Lett.2008,10,2071.(d)Yu,C.-B.；
Wang,D.-W.；Zhou,Y.-G.J.Org.Chem.2009,74,5633.(e)Yu,C.-B.；Gao,K.；Wang,D.-S.；
Shi,L.；Zhou,Y.-G.Chem.Commun.2011,47,5052.(f)Song,B.；Yu,C.-B.；Huang,W.-X.；
Chen,M.-W.；Zhou,Y.-G.Org.Lett.2015,17,190.).In addition, people there have been developed several metal catalytics
Asymmetric cyclization strategies carry out synthesis of chiral sulfanilamide (SN) (bibliography four：(a)Zeng,W.；Chemler,
S.R.J.Am.Chem.Soc.2007,129,12948.(b)Miura,T.；Yamauchi,M.；Kosaka,A.；Murakami,
M.Angew.Chem.,Int.Ed.2010,49,4955.(c)Ichinose,M.；Suematsu,H.；Yasutomi,Y.；
Nishioka,Y.；Uchida,T.；Katsuki,T.Angew.Chem.,Int.Ed.2011,50,9884.).Although asymmetric
The strategy of hydrogenation and asymmetric cyclisation is the method for good synthesis of chiral sulfanilamide (SN), but after asymmetric hydrogenation needs are pre-synthesis
Troublesome cyclic imide is processed, the method for asymmetric cyclisation its regioselectivity height is according to resistance in suitable Substrate design.Therefore,
The new method of development carrys out synthesis of chiral sulfanilamide (SN) still has its necessity.
Asymmetric reduction amination is a kind of method (bibliography five of very easy synthesis of chiral amine：(a)Abdel-
Magid,A.F.；Carson,K.G.；Harris,B.D.；Maryanoff,C.A.；Shah,R.D.J.Org.Chem.1996,
61,3849.(b)Nugent,T.C.；El-Shazly,M.Adv.Synth.Catal.2010,352,753.(c)Wang,C.；
Villa-Marcos,B.；Xiao,J.Chem.Commun.2011,47,9773.(d)Wang,C.；Xiao,J.-L Top
Curr.Chem.2014,343,261.).Come in the past few decades, people have developed a series of transition metal-catalyzed, organic molecules
Catalysis, the method (bibliography six of the asymmetric reduction amination of living things catalysis：(a)Strotman,N.A.；Baxter,C.A.；
Brands,K.M.J.；Cleator,E.；Krska,S.W.；Reamer,R.A.；Wallace,D.J.；Wright,
T.J.J.Am.Chem.Soc.2011,133,8362.(b)Malkov,A.V.；S.；
P.Angew.Chem.,Int.Ed.2007,46,3722.(c)Desai,A.A.Angew,Chem.Int.Ed.2011,50,
1974.).Generally be used as nitrogen nucleophile when asymmetric reduction aminating reaction is carried out is simple alkyl or arylamine, and
Reductive amination process carried out as nitrogen nucleophile using sulfanilamide (SN) carry out synthesis of chiral sulfanilamide (SN) not to be reported also.We are devoted to always
The asymmetric method of development catalysis carrys out synthesis of chiral sulfanilamide (SN), therefore, it is contemplated that sulfanilamide (SN) can be used to enter as nitrogen nucleophile
Row asymmetric reduction amination carrys out synthesis of chiral sulfanilamide (SN).
The content of the invention
It is an object of the invention to provide a kind of homogeneous system height enantioselectivity catalysis reduction amination synthesis of application palladium
The method of chiral sulfonamide.Present invention practicality easy to operate, enantioselectivity is high, and yield is good, and reaction condition is gentle, environment-friendly
The advantages of.
To achieve the above object, technical scheme is as follows：
With the chiral diphosphine complex catalyst of palladium, sulfonic acid is additive to the present invention, to realize replacing ketone amine compound
Asymmetric reduction amination, reaction equation and condition are as follows：
In formula：
Temperature：50-80℃；
Solvent：Trifluoroethanol；
Time：15-24 hours；
Metal precursor：Trifluoracetic acid palladium
Chiral ligand：Biphosphine ligand；
Additive：Organic acid；
The preparation method of catalyst is：The metal precursor and chiral diphosphine ligand of palladium, room temperature is stirred in 1.0 milliliters of acetone
Mix 1 hour, be then concentrated in vacuo and remove acetone.
The R is the alkyl of C1-C10, phenyl and the phenyl ring containing substituted base, and substitution base is in F, Cl, Me, MeO
Plant substitution base or two kinds of substitution bases；
The additive is camphorsulfonic acid, p-methyl benzenesulfonic acid, tartaric acid, the one kind in benzoic acid；
The trifluoracetic acid palladium and biphosphine ligand are commercially available and unprocessed.
Reactions steps are：
Trifluoracetic acid palladium (3mol% of substrate consumption in formula 1) and chiral phosphine ligand (substrate in formula 1 are put into reaction bulb
The 3.3mol% of consumption), 1.0 milliliters of acetone are added after nitrogen displacement, it is stirred at room temperature 1 hour.Then it is concentrated in vacuo, adds under nitrogen
Enter 3.0 milliliters of trifluoroethanols, this solution is gone to and be placed with advance substitution substrate and organic acid compound (substrate consumption in formula 1
In reactor 100mol%), hydrogen 600psi is passed through, 50 DEG C are reacted 24 hours.Slow release hydrogen, after removing solvent directly
Column chromatography for separation obtains pure product.
The catalyst is the complex of trifluoracetic acid palladium and biphosphine ligand, and trifluoracetic acid palladium and biphosphine ligand are commercially available
And without any treatment.
The additive is organic acid compound, and reaction organic acid used is camphorsulfonic acid, p-methyl benzenesulfonic acid, winestone
Acid, benzoic acid.The mol ratio of organic acid usage amount and substitution ketone amine compound is 1 in reaction:1.
The reaction dissolvent is one or two the mixing in toluene, dichloromethane, trifluoroethanol, tetrahydrofuran.
The present invention has advantages below
1. reactivity and enantioselectivity are high, and reaction is complete, and generation product is single-minded so that energy convenient separation, can obtain
Enantiomeric excess sterling high.
2. the chiral sulfonamide of various substitution types can be obtained.
3. catalyst preparation is convenient, and operation is simple and practical.
4. reductive amination process mild condition.
5. the chiral sulfonamide for obtaining can further derivatization in the synthesis of natural products.
Specific embodiment
Below by embodiment in detail the present invention is described in detail, but the present invention is not limited to following embodiments.
Embodiment 1：The optimization of condition
Trifluoracetic acid palladium (3mol% of substrate consumption in formula 1) and chiral phosphine ligand (S, S)-f- are put into reaction bulb
Binaphane (3.3mol% of substrate consumption in formula 1), adds 1 milliliter of acetone after nitrogen displacement, be stirred at room temperature 1 hour.Then
Vacuum concentration, adds 3 milliliters of trifluoroethanols under nitrogen, this solution is gone to and is placed with substrate 1a (51.8 milligrams, 0.2 mmoles in advance
You) and the reactor of camphorsulfonic acid (100mol% of substrate consumption in formula 1) in, be passed through hydrogen 600psi, 50 DEG C to react 24 small
When.Slow release hydrogen, direct column chromatography for separation obtains pure product after removing solvent, and reaction equation and ligand structure are as follows：
Its yield is separation yield, and the enantiomeric excess of product is determined with Chiral liquid chromatography, refers to table 1.
The optimization of the asymmetric reduction aminating reaction condition of table 1.a
a Conditions:1a(0.2mmol),Pd(OCOCF3)2(3.0mol%), ligand (3.3mol%), acid
(100mol%), H2(600psi),solvent(3.0mL),50℃,24h.b Isolated yield.c Determined by
HPLC.
Embodiment 2：The amination of palladium chtalyst asymmetric reduction synthesizes various chiral sulfonamides 2
Trifluoracetic acid palladium (3mol% of substrate consumption in formula 1) and (S, S)-f-Binaphane are put into reaction bulb
(3.3mol% of substrate consumption in formula 1), adds 1 milliliter of acetone after nitrogen displacement, be stirred at room temperature 1 hour.Then it is concentrated in vacuo,
3 milliliters of trifluoroethanols are added under nitrogen, this solution is transferred to and is placed with substrate (0.2 mM) and the D-CSA (midsoles of formula 1 in advance
The 100mol% of thing consumption) reactor in, be passed through hydrogen to 600psi, at 50 DEG C react 15-24 hours, slow release hydrogen
Gas.Direct column chromatography for separation obtains pure product after removing solvent, and reaction equation is as follows：
Yield is separation yield, and the enantiomeric excess of product is determined with Chiral liquid chromatography, is shown in Table 2.
The palladium chtalyst asymmetric reduction amination of table 2. synthesizes various Chiral Amines 2a
a Conditions:1(0.2mmol),Pd(OCOCF3)2(3.0mol%), (S, S)-f-Binaphane
(3.3mol%),D- CSA (100mol%), H2(600psi),TFE(3.0mL),50℃,24h.b Isolated yield.c
Determined by HPLC.d 0.5mmol.
Embodiment 3：The amination of palladium chtalyst asymmetric reduction synthesizes various chiral sulfonamides 4
Trifluoracetic acid palladium (3mol% of substrate consumption in formula 1) and (S, S)-f-Binaphane are put into reaction bulb
(3.3mol% of substrate consumption in formula 1), adds 1 milliliter of acetone after nitrogen displacement, be stirred at room temperature 1 hour.Then it is concentrated in vacuo,
3 milliliters of trifluoroethanols are added under nitrogen, this solution is transferred to and is placed with substrate (0.2 mM) and the D-CSA (midsoles of formula 1 in advance
The 100mol% of thing consumption) reactor in, be passed through hydrogen to 600psi, at 50 DEG C react 15-24 hours, slow release hydrogen
Gas.Direct column chromatography for separation obtains pure product after removing solvent, and reaction equation is as follows：
Yield is separation yield, and the enantiomeric excess of product is determined with Chiral liquid chromatography, is shown in Table 3.
The palladium chtalyst asymmetric reduction amination of table 3. synthesizes various chiral sulfonamides 4a
a Conditions:3(0.2mmol),Pd(OCOCF3)2(3.0mol%), (S, S)-f-Binaphane
(3.3mol%),D- CSA (100mol%), H2(600psi),TFE(3.0mL),50℃,24h.b Isolated yield.c
Determined by HPLC.
Embodiment 4：The amination of palladium chtalyst asymmetric reduction synthesizes various chiral sulfonamides 6
Trifluoracetic acid palladium (3mol% of substrate consumption in formula 1) and (R, S are put into reaction bulbp,)-Cy-JosiPhos
(3.3mol% of substrate consumption in formula 1), adds 1 milliliter of acetone after nitrogen displacement, be stirred at room temperature 1 hour.Then it is concentrated in vacuo,
3 milliliters of trifluoroethanols are added under nitrogen, this solution is transferred to and is placed with substrate (0.2 mM) and the D-CSA (midsoles of formula 1 in advance
The 100mol% of thing consumption) reactor in, be passed through hydrogen to 200psi, at 80 DEG C react 15-24 hours, slow release hydrogen
Gas.Direct column chromatography for separation obtains pure product after removing solvent, and reaction equation is as follows：
Yield is separation yield, and the enantiomeric excess of product is determined with Chiral liquid chromatography, is shown in Table 4.
The palladium chtalyst asymmetric reduction amination of table 4. synthesizes various chiral sulfonamides 6a
a Conditions:5(0.2mmol),Pd(OCOCF3)2(3.0mol%), (R, Sp)-Cy-JosiPhos
(3.3mol%),D- CSA (100mol%), H2(200psi),TFE(3.0mL),80℃,24h.b Isolated yield.c
Determined by HPLC.
Embodiment 4：The amination of palladium chtalyst asymmetric reduction synthesizes various chiral sulfonamides 8
Trifluoracetic acid palladium (3mol% of substrate consumption in formula 1) and (R, S are put into reaction bulbp,)-tBu-JosiPhos
(3.3mol% of substrate consumption in formula 1), adds 1 milliliter of acetone after nitrogen displacement, be stirred at room temperature 1 hour.Then it is concentrated in vacuo,
3 milliliters of trifluoroethanols are added under nitrogen, this solution is transferred to and is placed with substrate (0.2 mM) and TsOHH in advance2O (formulas 1
The 100mol% of middle substrate consumption) reactor in, be passed through hydrogen to 600psi, at 80 DEG C react 15-24 hours, slow release
Hydrogen.Direct column chromatography for separation obtains pure product after removing solvent, and reaction equation is as follows：
Yield is separation yield, and the enantiomeric excess of product is determined with Chiral liquid chromatography, is shown in Table 5.
The palladium chtalyst asymmetric reduction amination of table 5. synthesizes various chiral sulfonamides 8a
a Conditions:7(0.2mmol),Pd(OCOCF3)2(3.0mol%), (R, Sp)-tBu-JosiPhos
(3.3mol%), TsOHH2O (100mol%), H2(200psi),TFE(3.0mL),80℃,24h.b Isolated
yield.c Determined by HPLC.d0.1mmol.e 60℃.
3-Phenyl-1,2-thiazolidine 1,1-dioxide(2a):95%yield, 97%ee (R), white
solid.1H NMR(400MHz,
30 DEG C, n-hexane/i-propanol=80/20, flow=0.8mL/min, retention time 24.8min and
33.5min(maj).
3-(4-fluorophenyl)-1,2-thiazolidine 1,1-dioxide(2b):95%yield, 95%ee
(R),white solid.1H
J=1.0Hz)；19F NMR(376MHz,CDCl3)δ-113.66.HPLC:Chiracel AD-H column,254nm,30℃,
N-hexane/i-propanol=85/15, flow=0.7mL/min, retention time 17.6min (maj) and
21.4min.
3-Methyl-1,2-thiazolidine 1,1-dioxide(2c):85%yield, colorless oil.1H
NMR(400MHz,CDCl3)
by the cinnamyl bromide.
N-Cinnamyl-3-methyl-1,2-thiazolidine 1,1-dioxide(2c’):To a solution
of 2a in THF was added
mixture was extracted with ether.The organic extracts were dried over Na2SO4
and concentrated.The residue was purified by column chromatography on silica
Gel (petroleum ether/EtOAc) to give colorless oil.90%ee (S)1H NMR(400 MHz,
CDCl3) δ 7.39-7.23 (m, 5H), 6.59 (d, J=15.9 Hz, 1H), 6.28-6.21 (m, 1H), 4.00-3.95 (m, 1H),
3.85-3.79(m,1H),3.55-3.49(m,1H),3.29-3.23(m,1H),3.09-3.01(m,1H),2.47-2.39(m,
1H), 2.04-1.94 (m, 1H), 1.28 (d, J=6.1 Hz, 3H)；13C NMR(100 MHz,CDCl3)δ136.4,134.1,
128.7,128.1,126.7,124.5,53.1,46.7,45.0,27.4,20.1.HPLC:Chiracel OJ-H column,
254 nm, 30 DEG C, n-hexane/i-propanol=70/30, flow=0.7mL/min, retention time 24.8
min(maj)and 34.2 min.
3-n-Butyl-1,2-thiazolidine 1,1-dioxide(2d):91%yield, colorless oil.1H
NMR(400 MHz,CDCl3)
13.9.Ee of this product was determined by the analysis of product derived by
the cinnamyl bromide.
N-Cinnamyl-3-n-butyl-1,2-thiazolidine 1,1-dioxide(2d’):It was
prepared in similar method of
(t, J=7.0 Hz, 3H)；13C NMR(100 MHz,CDCl3)δ136.4,134.1,128.7,128.0,126.6,124.5,
57.1,46.7,45.7,33.2,26.5,24.9,22.6,14.0.HPLC:Chiracel OJ-H column,254 nm,30
DEG C, the min (maj) of n-hexane/i-propanol=80/20, flow=0.7 mL/min, retention time 21.0
and 28.7 min.
3-n-Hexyl-1,2-thiazolidine 1,1-dioxide(2e):95%yield, colorless oil.1H
NMR(400 MHz,CDCl3)
22.5,14.0.Ee of this product was determined by the analysis of product
derived by the cinnamyl bromide.
N-Cinnamyl-3-n-hexyl-1,2-thiazolidine 1,1-dioxide(2e’):It was
prepared in similar method of 13C NMR(100 MHz,CDCl3)δ136.4,134.2,128.7,128.0,126.6,124.5,57.2,46.7,45.8,
33.6,31.7,29.2,24.9,24.3,22.6,14.1.HPLC:Chiracel OJ-H column,254 nm,30℃,n-
Hexane/i-propanol=80/20, flow=0.7 mL/min, retention time 15.3 min (maj) and
20.5 min.
3-benzyloxy-methyl-1,2-thiazolidine 1,1-dioxide(2f):81%yield, 82%ee
(R),colorless oil.1H
128.2,127.9,73.6,71.6,53.8,47.5,26.0.HPLC:Chiracel OD-H,215 nm,30℃,n-hexane/
The min. of i-propanol=80/20, flow=0.7 mL/min, retention time 25.8 min (maj) and 36.2
3-(2-Methylphenoxy)-methyl-1,2-thiazolidine 1,1-dioxide(2h):98%
Yield, 94%ee (R), colorless
Chiracel OD-H, 220 nm, 30 DEG C, n-hexane/i-propanol=70/30, flow=0.7 mL/min,
retention time 21.6 min(maj)and 27.8 min.
3-(4-Methylphenoxy)-methyl-1,2-thiazolidine 1,1-dioxide(2i):88%
Yield, 94%ee (R), white
131.1,130.2,114.6,69.8,53.3,47.4,25.9,20.6.HPLC:Chiracel OJ-H column,220 nm,
30 DEG C, the min (maj) of n-hexane/i-propanol=70/30, flow=0.7 mL/min, retention time 33.6
and 36.5 min.
3-[(Naphthalen-2-yloxy)methyl]-1,2-thiazolidine 1,1-dioxide(2j):96%
Yield, 94%ee (R), white
Nm, 30 DEG C, n-hexane/i-propanol=70/30, flow=0.8 mL/min, retention time 41.1min
(maj)and 44.6min.
3-Phenyl-1,2-benzisothiazoline 1,1-dioxide(4a):96%yield, 97%ee (S),
white solid.1H NMR(400
22.1 min(maj)and 24.6 min.
3-(2-Methylphenyl)-1,2-benzisothiazoline 1,1-dioxide(4b):98%yield,
94%ee (S), white solid.
time 13.9 min(maj)and 16.8 min.
3-(3-Methylphenyl)-1,2-benzisothiazoline 1,1-dioxide(4c):90%yield,
97%ee (S), white solid.
3-(4-Methylphenyl)-1,2-benzisothiazoline 1,1-dioxide(4d):92%yield,
83%ee (S), white solid.
time 22.1 min and 26.1 min(maj).
3-(4-Fluoro-phenyl)-1,2-benzisothiazoline 1,1-dioxide(4e):89%yield,
96%ee (S), white solid.
Chiracel OD-H column, 220 nm, 30 DEG C, n-hexane/i-propanol=70/30, flow=0.7 mL/min,
retention time 13.1 min(maj)and 20.4 min.
3-Methyl-1,2-benzisothiazoline 1,1-dioxide(4f):95%yield, 95%ee (S),
white solid.1H NMR(400
retention time 13.0 min(maj)and 16.7 min.
3-n-Butyl-1,2-benzisothiazoline 1,1-dioxide(4g):96%yield, 94%ee (S),
colorless oil.1H NMR(400MHz,CDCl3) δ 7.75 (d, J=7.8Hz, 1H), 7.62-7.59 (m,
1H), 7.52-7.50 (m, 1H), 7.38 (d, J=7.8Hz, 1H), 5.06 (br, 1H), 4.69 (dt, J=8.7,4.3Hz, 1H),
1.99-1.93 (m, 1H), 1.76-1.72 (m, 1H), 1.47-1.32 (m, 4H), 0.91 (t, J=6.9Hz, 3H)；13C NMR
(100MHz,CDCl3)δ140.8,135.7,133.2,129.3,124.2,121.4,58.0,35.6,27.9,22.5,
14.0.HPLC:Chiracel OD-H column, 220nm, 30 DEG C, n-hexane/i-propanol=80/20, flow=
0.7mL/min,retention time 11.1min(maj)and 20.1min.
3-i-Butyl-1,2-benzisothiazoline 1,1-dioxide(4h):98%yield, 96%ee (S),
white solid.1H NMR(400
Nm, 30 DEG C, n-hexane/i-propanol=80/20, flow=0.7mL/min, retention time 12.2min
(maj)and 25.9min.
3-Cyclohexyl-1,2-benzisothiazoline 1,1-dioxide(4i):96%yield, 90%ee
(S),white solid.1H NMR
HPLC:Chiracel OD-H column, 220nm, 30 DEG C, n-hexane/i-propanol=75/25, flow=0.7mL/
min,retention time 9.6min(maj)and 24.9min.
3-Cyclohexyl-1,2-benzisothiazoline 1,1-dioxide(6a):96%yield, 90%ee
(S),white solid.1H NMR
25.8.HPLC:Chiracel OD-H column, 220nm, 30 DEG C, n-hexane/i-propanol=75/25, flow=
0.7mL/min,retention time 9.6min(maj)and 24.9min.
Present invention application homogeneous palladium catalysts successfully realize the intramolecular asymmetric reduction amination to replacing ketone amine compound
Chiral sulfonamide is obtained, up to 98%, enantiomeric excess can reach 99% to its yield.The present invention is easy to operation, raw material and urges
Agent is simple and easy to get, and reaction condition is gentle.Additionally, synthesizing chiral sulfonamide by asymmetric reduction amination, enantioselectivity is high,
Yield is good, and reaction condition is gentle, environmentally friendly.
Claims (8)
1. in a kind of palladium chtalyst asymmetric molecult reduction amination synthesis of chiral sulfanilamide (SN) method, be palladium chtalyst asymmetric reduction amination
The method of synthesis of chiral sulfanilamide (SN), its catalyst system and catalyzing is the chiral diphosphine complex of palladium, and reaction equation and condition are as follows：
In formula：
Temperature：50-80℃；
Solvent：Organic solvent；
Time：15-24 hours；
Additive：Organic acid compound；
The R is alkyl, phenyl and the phenyl ring containing substituted base of C1-C10, and the substitution base on phenyl ring is in F, Cl, Me, MeO
One or two or more kinds substitution base, substitution base number is 1-3.
2. the method for claim 1, it is characterised in that：
Reactions steps are：Trifluoracetic acid palladium (3mol%_-5mol% of substrate consumption in formula 1) and chirality are put into reaction bulb
Phosphine ligands (3.3mol%-5.5mol% of substrate consumption in formula 1), add acetone after nitrogen displacement, be stirred at room temperature 1-3 hours；
Then vacuum concentration removes acetone, and trifluoroethanol is added under nitrogen, this solution is gone to and be placed with advance substitution substrate and organic acid
In the reactor of compound (10mol%-100mol% of substrate consumption in formula 1), hydrogen (200psi -800psi), 50 are passed through
Reacted 15-24 hours at DEG C -80 DEG C；Release hydrogen, direct column chromatography for separation obtains pure product after removing solvent.
3. the method for claim 1, it is characterised in that：The preparation method of catalyst is：The metal precursor and hand of palladium
Property biphosphine ligand be stirred at room temperature in acetone 1 hour, then vacuum concentration remove acetone；Metal precursor：Trifluoracetic acid palladium；It is chiral
Part：Biphosphine ligand (S, S)-f-binaphane；
The catalyst is the complex of trifluoracetic acid palladium and biphosphine ligand, and trifluoracetic acid palladium and biphosphine ligand are commercially available and nothing
Need any treatment.
4. method as claimed in claim 1 or 2, it is characterised in that：The additive is organic acid compound, and reaction is used
Organic acid is one or two or more kinds in camphorsulfonic acid, p-methyl benzenesulfonic acid, tartaric acid, benzoic acid.
5. method as claimed in claim 1 or 2, it is characterised in that：Organic acid usage amount and substitution ketoamine substrate in reaction
Mol ratio is 1:1, substrate substitution ketoamine substrate is 33/1-20/1 with the molar ratio of catalyst.
6. synthetic method as claimed in claim 1, it is characterised in that：Reaction organic solvent used is toluene, dichloromethane,
One or more mixing in trifluoroethanol, tetrahydrofuran.
7. the synthetic method as described in claim 1,2 or 6, it is characterised in that：When it is 0.2mmol to replace substrate consumption, have
The consumption of machine solvent is 3.0 milliliters.
8. method as claimed in claim 1 or 2, it is characterised in that：The reaction equation is that ketoamine substrate reduction amination is obtained
Corresponding chiral sulfonamide compound, acid additives are sulfonic acid, and solvent is trifluoroethanol, when temperature is 50 DEG C to 80 DEG C, hydrogen
Atmospheric pressure is 200psi-800psi, and different substrates have respective optimal ligand.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110790694A (en) * | 2018-08-03 | 2020-02-14 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral indoline by using indole generated in situ by asymmetric hydrogenation under catalysis of palladium |
| CN111320590A (en) * | 2018-12-13 | 2020-06-23 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral seven-element cyclic sulfonamide |
| CN112574014A (en) * | 2019-09-29 | 2021-03-30 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral beta-hydroxy ketone by palladium-catalyzed asymmetric reduction |
| CN115819389A (en) * | 2021-09-16 | 2023-03-21 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral flavonoid derivative through dynamic kinetic resolution |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101260085A (en) * | 2007-03-07 | 2008-09-10 | 中国科学院大连化学物理研究所 | Catalytic asymmetric hydrogenation synthesis method for chiral gamma-sultam |
| CN101423504A (en) * | 2007-10-31 | 2009-05-06 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral sultam containing hetero atom unsymmetrical hydrogenation using Pd as catalyst |
| CN102030721A (en) * | 2009-09-29 | 2011-04-27 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral benzosultam via palladium-catalytic asymmetric hydrogenation |
-
2015
- 2015-12-12 CN CN201510924853.9A patent/CN106866574B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101260085A (en) * | 2007-03-07 | 2008-09-10 | 中国科学院大连化学物理研究所 | Catalytic asymmetric hydrogenation synthesis method for chiral gamma-sultam |
| CN101423504A (en) * | 2007-10-31 | 2009-05-06 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral sultam containing hetero atom unsymmetrical hydrogenation using Pd as catalyst |
| CN102030721A (en) * | 2009-09-29 | 2011-04-27 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral benzosultam via palladium-catalytic asymmetric hydrogenation |
Non-Patent Citations (3)
| Title |
|---|
| CHANG-BIN YU ET AL: "Enantioselective Pd-catalyzed hydrogenation of enesulfonamides", 《CHEMCOMM》 * |
| CHANG-BIN YU ET AL: "Highly Enantioselective Synthesis of Sultams via Pd-Catalyzed Hydrogenation", 《JOURNAL OF ORGANIC CHEMISTRY》 * |
| 余长斌: "钯催化不对称氢化合成手性磺胺化合物研究", 《豆丁》 * |
Cited By (8)
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| CN110790694A (en) * | 2018-08-03 | 2020-02-14 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral indoline by using indole generated in situ by asymmetric hydrogenation under catalysis of palladium |
| CN110790694B (en) * | 2018-08-03 | 2021-04-23 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral indoline by using indole generated in situ by asymmetric hydrogenation under catalysis of palladium |
| CN111320590A (en) * | 2018-12-13 | 2020-06-23 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral seven-element cyclic sulfonamide |
| CN111320590B (en) * | 2018-12-13 | 2022-08-12 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral seven-element cyclic sulfonamide |
| CN112574014A (en) * | 2019-09-29 | 2021-03-30 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral beta-hydroxy ketone by palladium-catalyzed asymmetric reduction |
| CN112574014B (en) * | 2019-09-29 | 2022-03-11 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral beta-hydroxy ketone by palladium-catalyzed asymmetric reduction |
| CN115819389A (en) * | 2021-09-16 | 2023-03-21 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral flavonoid derivative through dynamic kinetic resolution |
| CN115819389B (en) * | 2021-09-16 | 2024-04-12 | 中国科学院大连化学物理研究所 | Method for synthesizing chiral flavonoid derivative through dynamic kinetic resolution |
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