CN102786454A - Bis[1-aryl(alkyl) substituted allyl]sulphane compound and synthetic method and application thereof - Google Patents
Bis[1-aryl(alkyl) substituted allyl]sulphane compound and synthetic method and application thereof Download PDFInfo
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- ACKJMDGEHFSKQZ-VXGBXAGGSA-N C=C[C@H](c1ccc[s]1)S[C@H](C=C)c1ccc[s]1 Chemical compound C=C[C@H](c1ccc[s]1)S[C@H](C=C)c1ccc[s]1 ACKJMDGEHFSKQZ-VXGBXAGGSA-N 0.000 description 1
- MDIIFXJFUPEKHP-UHFFFAOYSA-N CC(C=CC1C)S1(=O)=O Chemical compound CC(C=CC1C)S1(=O)=O MDIIFXJFUPEKHP-UHFFFAOYSA-N 0.000 description 1
- OFEVDDCTOVTZHT-UHFFFAOYSA-N CC(C=CC1I)S1(=O)=O Chemical compound CC(C=CC1I)S1(=O)=O OFEVDDCTOVTZHT-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention provides a bis[1-aryl(alkyl) substituted allyl]sulphane compound, a synthetic method and an application thereof; the compound is an optically pure compound with the following structural formula, wherein x is a chiral carbon atom, R1 is any one selected from C1-C16 alkyls, C4-C10 heterocyclic groups containing N, O or sulfur or C4-C10 ceteroary groups containing N, O or sulfur, or an aryl, and the aryl is a phenyl or a naphthyl. Compared with the prior art, the invention has the advantages of mild reaction conditions, simple operations, good reaction yield, and the like.
Description
Technical field
The present invention relates to catalyzer, relate in particular to a kind of two [1-virtue (alkane) basic substituted allyl] sulfane compounds and compound method thereof.
Background technology
The chirality organosulfur compound small molecules catalysis, pharmaceutical chemistry and complete synthesis in bringing into play important effect; The diallyl containing thioether is an important component part in the Bulbus Allii extract; In the last few years, related work had proved that it had the antitumor characteristic of various cancers [a) Wang, H.C.; Yang, J.H.; Hsieh, S.C.; Sheen.L.Y.J.Agric.Food Chem.2010,58,7096.b) Kim, M.J.; Kwak, J.H.; Baeka, S.H.et, al.Journal of Food Science and Nutrition, 2010,15,137.c) .Khan, A.; Shukla, Y.; Kalra, N.et, al.Mol.Med.2007,13,443.d) .Arora, A.; Kalra, N.; Shukla, Y.; Cancer Lett.2006,242,28.e) .Prasad, S.; Kalra, N.; Shukla, Y.Asian J.Androl.2006,8,719.f) .Haber-Mignard, D.; Suschetet, M.; Berges, R.; Astorg, P.; Siess, M.H.Nutr.Cancer.1996,25,61.g) .Wargovich, M.J.; Imada, O.; Stephens, L.C.Cancer Lett.1992,64,39.h) .Wargovich, M.J.; Woods, C.; Eng, V.W.Stephens, L.C.; Gray, K.Cancer Res.1988,48,6872.i) .Sparnins, V.L.; Barany, G.; Watterberg, L.W.Carcinogenesis.1988,9,131.].The known method for preparing the chirality sulfocompound comprises reaction of the asymmetric sulphur-unsaturated ketenes of this sulphur nucleophilic reagent of Micheal addition attack (aldehyde) and transition metal-catalyzed sulphur allylation reaction etc.Asymmetric sulphur-Micheal addition is the comparative maturity of development at present, and the chirality small molecules catalysis inductive method that its structure sulphur chiral centre mainly contains through the chirality prothetic group of chemical dose is induced, directly chiral reagent is participated in reaction and catalytic amount forms [a) K.Tomioka, A.Muraoka; And M.Kanai.J.Org.Chem.1995; 60,6188-6190.b) C.Palomo, M.Oiarbide; F.Dias; A.Ortiz, A.Linden.J.Am.Chem.Soc.2001,123,5602-5603.c) C.Palomo, M.Oiarbide, F.Dias, Lopez, R.; Linden, A.Angew.Chem., Int.Ed.2004,43,3307-3310.d) C.Palomo; M.Oiarbide et a1.J.Am.Chem.Soc.2006,128,15236.e) K.Nishide, M.Ozeki, H.Kunishige; Y.Shigeta, P.K.Patra, Y.Hagimoto, and M.Node.Angew.Chem.Int.Ed.2003; 42,4515-4517.e) M.Ozeki, K.Nishide, F.Teraoka and M.Node.Tetrahedron:Asymmetry.2004; 15,895-907.e) H.Hiemstra and H.Wynberg.J.Am.Chem.Soc.1981,103,417-430.f) P.McDaid; Y.Chen, and L.Deng.Angew.Chem.Int.Ed.2002,41,338-340.g) P.Ricci; A.Carlone, G.Bartoli, M.Bosco, L.Sambri; And P.Melchiorre.Adv.Synth.Catal.2008,350,49-53.h) K.Suzuki, A.Ikegawa; T.Mukaiyama.Bull.Chem.Soc.Jpn.1982,55,3277-3282.i) M.Marigo, T.Schulte; J.Franzen, and K.A.
J.Am.Chem.Soc.2005,127,15710-15711.].And form the chirality sulphur compound through allylation reaction with metal catalytic; Because the sulphur nucleophilic reagent has great difficulty to the poisoning effect (metal being precipitated out or forming some non-tool catalytic activity forms makes reaction be difficult to carry out) of metal catalyst on synthetic from solution.In the previous research of this seminar, we have invented metal iridium catalytic is the allyl substitution reaction of nucleophilic reagent with virtue (alkane) basic sodium mercaptides, a) S.Zheng, N.Gao, W.Liu; D.Liu, X.Zhao, T.Cohen.Organic Letters 2010,12; 4454-4457.b) N.Gao, S.Zheng, W.Yang, X.Zhao.Organic Letters 2011; 13,1514-1516. and utilize more cheap inorganic sulphide has more Atom economy in reaction, also have more challenge.But, also do not have relevant report at present.
Summary of the invention
The object of the invention, for a kind of reaction conditions gentleness is provided, easy and simple to handle exactly, two [1-virtue (alkane) basic substituted allyl] sulfane compounds and compound method thereof that the productive rate of reaction is good.
In order to achieve the above object, the present invention has adopted following technical scheme: a kind of two [1-virtue (alkane) basic substituted allyl] sulfane compounds is characterized in that this compound is the optical pure compound with following structural formula
Wherein * is a chiral carbon atom, R
1Be selected from C arbitrarily
1-C
16Alkyl, C
4-C
10Heterocyclic radical that contains N, O or sulphur or C
4-C
10The heteroaryl that contains N, O or sulphur, aryl, said aryl is a phenyl or naphthyl.
The compound method of a kind of two [1-virtue (alkane) basic substituted allyl] sulfane compounds; It is characterized in that this method is in organic solvent, temperature of reaction is under-20 ℃-30 ℃; With allyl carbonate ester compound and sodium sulphite or sodium sulphite hydrate is raw material, with [Ir (COD) Cl]
2The iridium complex that generates with the part effect is as catalyzer, and reaction made two [fragrant (alkane) the basic substituted allyl of 1-] sulfane compounds in 36-48 hour under the effect of additive;
Reaction equation can be represented with following formula:
Wherein L is a chiral ligand, and Add. is various additive mentioned above and combination, and Sol. is an all kinds of SOLVENTS mentioned above, and LG is a leavings group, is methyl carbonate, ethyl-carbonate or the carbonic acid tert-butyl ester.
Said allyl carbonate ester cpds, sodium sulphite or sodium sulphite hydrate, [Ir (COD) Cl]
2, part, additive mol ratio be 1: 0.5-3: 0.01-0.5: 0.02-0.1: 0.05-5;
The structural formula of said allyl carbonate ester compound is:
Wherein: R
1Be selected from C arbitrarily
1-C
16Alkyl, C
4-C
10Heterocyclic radical that contains N, O or sulphur or C
4-C
10The heteroaryl that contains N, O or sulphur, aryl; L is a chiral ligand, and LG is a leavings group, is methyl carbonate, ethyl-carbonate or the carbonic acid tert-butyl ester;
The structural formula of said sodium sulphite or sodium sulphite hydrate is Na
2SxH
2O, wherein x=0 or 9;
Said part is the optically pure part with following structural formula:
Wherein: R
2Or R
3Be selected from C arbitrarily
3-C
16Naphthenic base, phenyl, naphthyl, C
1-C
4Substituted phenyl of alkoxyl group or C
1-C
4The substituted naphthyl of alkoxyl group;
Described additive is cesium carbonate, cesium fluoride, cesium chloride, lithium chloride, Silver monobromide or cesium hydroxide.
Said allyl carbonate ester cpds, sodium sulphite or sodium sulphite hydrate, [Ir (COD) Cl]
2, part, additive mol ratio be 1: 3: 0.02: 0.04: 3, said temperature of reaction was 5 ℃-25 ℃, and the reaction times is 36-48 hour.
Described organic solvent is toluene, methylene dichloride or THF.
Gained two [1-virtue (alkane) basic substituted allyl] sulfane compounds separates through the method for recrystallization, thin-layer chromatography, column chromatography or underpressure distillation.As use recrystallization method, the recommendation solvent is a Virahol, recommends solvent to can be Virahol-normal hexane mixed solvent.With the method for thin-layer chromatography, column chromatography, used developping agent is the mixed solvent of non-polar solvent and polar solvent.Recommend solvent to can be sherwood oil-methylene dichloride, petroleum ether-ethyl acetate, mixed solvents such as sherwood oil-ether, its volume ratio can be respectively: non-polar solvent: polar solvent=100-20: 1.For example: petrol ether/ethyl acetate=100-20/1, sherwood oil/methylene dichloride=100-20/1.
The application of a kind of two [1-virtue (alkane) basic substituted allyl] sulfane compounds; It is characterized in that; The sulfane compounds is used for the midbody of synthetic sulfur-bearing hybrid compounds, and potential chemotherapy and the antineoplastic chemicals of being used for said two [1-virtue (alkane) basic substituted allyls].
The application of a kind of two [1-virtue (alkane) basic substituted allyl] sulfane compounds is characterized in that, said two [1-virtue (alkane) basic substituted allyl] sulfane compounds is used to prepare the diallyl sulfone compound and closes the ring sulphones that ring forms.
Described ring sulphones is the optical purity
with following structure
Compared with prior art; The invention provides a kind of effectively with the chiral iridium complex compound as catalyzer, by the method for sodium sulphite or sodium sulphite hydrate and the high regioselectivity of allyl carbonate ester cpds, high enantioselectivity and high cis-selectivity synthetic two [1-virtue (alkane) basic substituted allyl] sulfane compounds; The method of preparation multiple two [1-virtue (alkane) basic substituted allyl] sulfane compounds is provided.This method is applicable to dissimilar allyl carbonate ester compounds, and reaction conditions is gentle, and is easy and simple to handle.The productive rate that reacts in addition is better (being generally 67%-99%) also, and the regioselectivity height (be generally 81: 19-＞99: 1), enantioselectivity high (being generally 97%-＞99%), cis-selectivity is high (to be generally 85: 15-99: 1).Synthetic of the present invention two [1-virtue (alkane) basic substituted allyl] sulfane compounds can also close ring through RCM and obtain encircling sulphones.
Embodiment
To help to understand the present invention through following embodiment, but not limit content of the present invention.
Embodiment 1～14:
The compound method of two [1-virtue (alkane) basic substituted allyl] sulfane compounds, this method is in organic solvent, temperature of reaction is under-20 ℃-30 ℃, is raw material with allyl carbonate ester compound and sodium sulphite or sodium sulphite hydrate, with [Ir (COD) Cl]
2The iridium complex that generates with the part effect is as catalyzer, and reaction made two [fragrant (alkane) the basic substituted allyl of 1-] sulfane compounds in 36-48 hour under the effect of additive; Reaction equation is following:
Wherein Additive refers to additive, and Solvent refers to solvent.
Wherein, additive, temperature and the solvent of the catalytic sodium sulphite allyl sulfide of iridium complex etherificate are different among each embodiment, and its reaction result is following:
Wherein DCM is a methylene dichloride, and THF is a THF.Toluene is a toluene.
Embodiment 15～19:
Different ligands is the reaction of the catalytic sodium sulphite allyl sulfide of iridium complex etherificate, and wherein the ligand structure formula is following:
Embodiment 20:
The reaction of the catalytic sodium sulphite allyl sulfide of iridium complex etherificate:
In the reaction tubes of an exsiccant argon shield, add successively [Ir (COD) Cl]
2(0.002mmol), chiral ligand (0.004mmol), Tri N-Propyl Amine (0.2mL) and THF (0.5mL), 50 ℃ of reactions 30 minutes down naturally cool under the room temperature rear pump or output pump and drain.In reaction tubes, add sodium sulphite hydrate (0.6mmol), cesium fluoride (0.6mmol), allyl carbonate (0.2mmol), DCM (2mL), stirring at room reaction more successively.After reaction finishes, after the removal of solvent under reduced pressure residue thin-layer chromatography obtain title product (sherwood oil/methylene dichloride=50/1, or petrol ether/ethyl acetate=50: 1, v/v).
The products therefrom i.e. character of this product is following:
P1: two [(R)-and 1-(4-p-methoxy-phenyl) allyl group] sulfane
Colourless liquid, 99% yield,＞99%ee, 98/2dr [chiral column Diacel CHIRALPAK AD-H (0.46cm x 25cm); Normal hexane/Virahol=98/2; Flow velocity=0.7mL/min; Detect wavelength=214nm; t
R=11.544 (meso), 14.450 (major) min].
[α]
D 20＝-142.0°(c?0.5，CHCl
3)，
1H?NMR(300MHz，CDCl
3)δ＝7.24(d，J＝8.4Hz，4H)，6.84(d，J＝8.8Hz，4H)，6.04(ddd，J＝16.8，10.2，8.7Hz，2H)，5.16(ddd，J＝10.2，1.5，0.6Hz，2H)，5.13(ddd，J＝16.8，1.2，0.9Hz，2H)4.27(d，J＝8.7Hz，1H)，3.77(s，6H)，
13C?NMR(75MHz，CDCl
3)δ＝158.7，138.2，132.0，128.9，115.5，113.9，55.2，51.7，
HRMS(EI)calcd?for?C
20H
22O
2S(M
+)：326.1341，Found：326.1345.IR(KBr)：v?
max(cm
-1)＝3902，3852，3751，3648，3629，2834，1866，1772，1538，1504，1456，1247，1174，1032，830，419。
P2: two [(R)-and 1-(3-p-methoxy-phenyl) allyl group] sulfane
Colourless liquid, 99% yield, 97%ee, 97/3dr [chiral column CHIRALCEL OJ-H (0.46cm x 25cm); Normal hexane/Virahol=80/20; Flow velocity=0.7mL/min; Detect wavelength=214nm; t
R=31.400 (major), 34.869 (meso), 56.381 (minor) min].
[α]
D 20＝-110.0°(c?0.7，CHCl
3)，
1H?NMR(300MHz，CDCl
3)δ7.23(t，J＝7.8Hz，2H)，6.91(d，J＝7.8Hz，2H)，6.87(s，2H)，6.79(d，J＝8.1Hz，2H)，6.05(ddd，J＝17.4，9.6，9.0Hz，2H)，5.18(d，J＝9.3Hz，2H)，5.16(d，J＝17.4Hz，2H)，4.29(d，J＝8.7Hz，2H)，3.79(s，6H)，
13C?NMR(75MHz，CDCl
3)δ＝159.7，141.5，137.9，129.5，120.2，115.9，113.3，112.9，55.1，52.5，
HRMS(EI)calcd?for?C
20H
22O
2S(M
+)：326.1341，Found：326.1344.IR(KBr)：v?
max(cm
-1)＝3851，3749，3645，3000，2967，2833，1595，1485，1264，1149，1047，919，764，693，455。
P3: two [(R)-and 1-p-methylphenyl allyl group] sulfane
Colourless liquid, 99% yield,＞99%ee, 96/4dr [chiral column CHIRALCEL OJ-H (0.46cm x15cm); Normal hexane/Virahol=97/3; Flow velocity=1.0mL/min; Detect wavelength=214nm; t
R=8.245 (major), 12.279 (minor), 14.984 (meso) min].
[α]
D 20＝-97.8°(c?0.3，CHCl
3)，
1H?NMR(300MHz，CDCl
3)δ＝7.21(d，J＝7.8Hz，4H)，7.12(d，J＝7.8Hz，4H)，6.05(ddd，J＝16.8，9.9，8.7Hz，2H)，5.15(d，J＝9.3Hz，2H)，5.13(d，J＝17.4Hz，2H)，4.28(d，J＝8.7Hz，2H)，2.32(s，6H)，
13C?NMR(75MHz，CDCl
3)δ＝138.2，137.0，136.9，129.3，127.8，115.7，52.2，20.9，
HRMS(EI)calcd?for?C
20H
22S(M
+)：294.1442，Found：294.1444.IR(KBr)：v?
max(cm
-1)＝2913，2847，1681，1509，1010，798，506，470。
P4: two [(R)-and 1-phenyl allyl group] sulfane
Colourless liquid, 99% yield, 96%ee, 95/5dr [chiral column CHIRALCEL OJ-H (0.46cm x 25cm); Normal hexane/Virahol=90/10; Flow velocity=0.7mL/min; Detect wavelength=214nm; t
R=28.335 (meso), 29.566 (minor), 30.970 (major) min].
[α]
D 20＝-130.4°(c?0.5，CHCl
3)，
1H?NMR(300MHz，CDCl
3)δ＝7.32-7.23(m，10H)，6.07(ddd，J＝17.1，9.6Hz，8.7，2H)，5.18(d，J＝9.6，2H)，5.15(d，J＝17.1，2H)，4.32(d，J＝8.4Hz，2H)，
13C?NMR(75MHz，CDCl
3)δ＝140.1，138.1，128.6，127.9，127.3，115.9，52.4，
HRMS(EI)calcd?for?C
18H
18S(M
+)：226.1129，Found：226.1128.IR(KBr)：v?
max(cm
-1)＝3903，3853，3750，3735，3675，3648，3628，3566，3028，1868，1770，1730，1679，1557，1505，1455，985，914，696，423，
P5: two [(R)-and 1-rubigan allyl group] sulfane
Colourless liquid, 80% yield,＞99%ee, 96/4dr [chiral column CHIRALPAK AD-H (0.46cm x25cm); Normal hexane/Virahol=98/2; Flow velocity=0.7mL/min; Detect wavelength=214nm; t
R=5.382 (meso), 5.662 (major) min].
[α]
D 20＝-166.8°(c?0.5，CHCl
3)，
1H?NMR(300MHz，CDCl
3)δ＝7.29(d，J＝8.4Hz，4H)，7.23(d，J＝8.4Hz，4H)，6.00(ddd，J＝17.1，9.9，8.4Hz，2H)，5.20(d，J＝10.5Hz，2H)，5.14(d，J＝17.1Hz，2H)，4.26(d，J＝8.4Hz，2H)，
13C?NMR(75MHz，CDCl
3)δ＝138.4，137.3，133.2，129.3，128.8，116.6，51.7，
HRMS(EI)calcdfor?C
18H
16SCl
2(M
+)：334.0350，Found：334.0349.IR(KBr)：v
max(cm
-1)＝3903，3869，3852，3837，3750，3735，3710，3689，3676，3648，3627，3565，3077，1718，1651，1557，1539，1505，1487，1455，1091，1013，920，820。
P6: two [(R)-1-to the bromophenyl allyl group] sulfane
Colourless liquid, 72% yield,＞99%ee, 97/3dr [chiral column Diacel CHIRALCEL AY-H (0.46cm x 25cm); Normal hexane/Virahol=99.5/0.5; Flow velocity=0.8mL/min; Detect wavelength=214nm; t
R=6.285 (meso), 7.103 (major) min].
[α]
D 20＝-117.6°(c?0.5，CHCl
3)，
1H?NMR(300MHz，CDCl
3)δ＝7.44(d，J＝8.4Hz，4H)，7.17(d，J＝8.4Hz，4H)，5.99(ddd，J＝16.8，9.9，8.7Hz，2H)，5.20(d，J＝9.9Hz，2H)，5.13(d，J＝16.8Hz，2H)，4.24(d，J＝8.4Hz，2H)，
13C?NMR(75MHz，CDCl
3)δ＝138.8，137.3，131.7，129.7，121.2，116.6，51.7，
HRMS(EI)calcd?for?C
18H
16S?
79Br
2(M
+)：421.9339，Found：421.9348.IR(KBr)：v?
max(cm
-1)＝3903，3852，3802，3751，3734，3676，3649，3628，3567，2925，2363，1870，1732，1717.89，1653，1560，1486，1455，1286，1071，1009，919，815，750，517，418。
P7: two [(R)-and 1-(3-trifluoromethyl) allyl group] sulfane
Colourless liquid, 67% yield,＞99%ee, 96/4dr [chiral column Diacel CHIRALCEL OJ-H (0.46cm x 15cm); Normal hexane/Virahol=99.8/0.2; Flow velocity=1.0mL/min; Detect wavelength=214nm; t
R=3.162 (meso), 3.631 (major) min].
[α]
D 20＝-113.8°(c?0.7，CHCl
3)。
1H?NMR(300MHz，CDCl
3)δ＝7.52(m，7.54-7.51，6H)，7.49-7.39(m，2H)，6.05(ddd，J＝17.1，9.9，8.7Hz，2H)，5.26(d，J＝9.9Hz，2H)，5.19(d，J＝17.1Hz，2H)，4.37(d，J＝8.7Hz，2H)。
13C?NMR(75MHz，CDCl
3)δ＝140.8，136.9，131.4，131.1(q，J＝30.0Hz)，129.2，124.8(q，J＝3.8Hz)，124.4(q，J＝3.8Hz)，124.0(q，J＝270.7Hz)，117.2，52.1。
19F?NMR(282MHz，CDCl
3)δ＝-62.60(s)。
HRMS(EI)calcd?for?C
20H
16F
6S(M
+)：402.0877，Found：402.0878.IR(KBr)：v?
max(cm
-1)＝3851，3733，3646，1714，1633，1555，1447，1332，1165，1125，1073，924，770，702，418。
P8: two [(R)-and 1-(2-thienyl) allyl group] sulfane
Colourless liquid, 99% yield,＞99%ee, 99/1dr [chiral column Diacel CHIRALCEL OJ-H (0.46cm x 15cm); Normal hexane/Virahol (0.1% triethylamine)=99/1; Flow velocity=1.0mL/min; Detect wavelength=214nm; t
R=13.363 (meso), 14.090 (major), 19.642 (minor) min].
[α]
D 20＝-63.6°(c?0.5，CHCl
3)。
1H?NMR(300MHz，CDCl
3)δ＝7.23(d，J＝5.1Hz，2H)，7.08-6.89(m，4H)，6.06(ddd，J＝16.8，9.9，8.7Hz，2H)，5.24(d，J＝9.0Hz，2H)，5.19(d，J＝15.9Hz，2H)，4.65(d，J＝8.7Hz，2H)。
13C?NMR(75MHz，CDCl
3)δ＝143.3，137.6，126.7，125.2，124.9，116.6，47.7。
HRMS(EI)calcd?for?C
14H
14S
3(M
+)：278.0258，Found：278.0260.IR(KBr)：v?
max(cm
-1)＝3903，3852，3819，3749，3735，3675，36483628，3566，3080，1869，1716，1653，1635，1558，1541，1506，1232，986，920，853，696。
P9: two [(S)-and penta-1-thiazolinyl-3-] sulfane
Colourless liquid; 84% yield; 98%ee; B/l=81/19,85/15dr, 98%ee. instrument: Agilent6890+CTC (automatic sampler) detector: FID chromatographic column: Rtx-13100 (30m*0.25mm*0.25um) temperature: 150 degree constant temperature 10min sample introduction temperature: 250 degree carrier gas: He flow velocity: 1.0mL/min splitting ratio: 100: 1.t
R=3.226 (major), 3.415 (minor, 4.103 (meso) min.
[α]
D 20＝-85.0°(c?0.1，CHCl
3)。
1H?NMR(400MHz，CDCl
3)δ＝5.57(dt，J＝16.8，10.0Hz，2H)，5.05(dd，J＝10.0，1.6Hz，2H)，4.94(ddd，J＝16.8，1.6Hz，0.4Hz?2H)，3.08-3.00(m，2H)，1.70-1.48(m，4H)，0.95(t，J＝7.6Hz，6H)。
Embodiment 21:
The conversion of chirality two [1-virtue (alkane) basic substituted allyl] sulfane compounds, equation is following:
Connect embodiment 20 operations, behind the reaction 48h, 0 ℃ of following one kettle way adds the adjacent chloroperoxybenzoic acid of 0.8mmol, stirs 2h, adds 10mL 10%Na
2S
2O
4Solution is the cancellation reaction in system, stirs 10 minutes, adds saturated NaHCO again
310mL, 20mL X 3 dichloromethane extractions, column chromatography obtains 6j.
In the reaction tubes (taking back the stream device) of an exsiccant argon shield, add the DCM solution of 6j, add Grubbs I reagent again, reflux state reaction down spends the night.The TLC detection reaction finishes, and chooses dichloromethane solution, and column chromatography obtains 7j.
P10: (S)-3-((S)-3-butene-2-sulfuryl)-1-butylene
One kettle way yield (from 3j) 51%, DL/Meso=89/11, b/1=87/13,99%ee. [chiral column Diacel CHIRALCEL IC (0.46cm x 25cm); Normal hexane/Virahol=90/10; Flow velocity=1.0mL/min; Detect wavelength=214nm; t
R=29.080 (major), 34.088 (minor) min].
[α]
D 20＝-118.3°(c?0.1，CHCl
3).
1H?NMR(400MHz，CDCl
3)δ＝5.86(ddd，J＝17.2，10.4，8.8Hz，2H)，5.41(d，J＝10.0Hz，2H)，5.34(d，J＝17.2Hz，2H)，3.88(dq，J＝8.8，7.2Hz，1H).
P11: (2S, 2S)-2,5-dimethyl--2,5-dihydro-thiophene 1,1-dioxide
86% yield, 94%ee as a colorless thick oil. [chiral column Diacel CHIRALPAK AD-H (0.46cmx25cm); Normal hexane/Virahol=90/10; Flow velocity=1.0mL/min; Detect wavelength=214nm; t
R=15.424 (minor), 17.364 (major) min].
[α]
D 20＝-128.2°(c?0.2，CHCl
3).
1H?NMR(400MHz，CDCl
3)δ＝5.95(s，1H)，3.73(q，J＝6.8Hz，1H)，1.44(d，J＝7.2Hz，3H)。
Embodiment 22
The compound method of a kind of two [1-virtue (alkane) basic substituted allyl] sulfane compounds, this method is in toluene, temperature of reaction is under-20 ℃, is raw material with allyl carbonate ester compound and sodium sulphite, with [Ir (COD) Cl]
2The iridium complex that generates with the part effect is as catalyzer, and reaction made two [fragrant (alkane) the basic substituted allyl of 1-] sulfane compounds in 36-48 hour under the effect of cesium carbonate; Said allyl carbonate ester cpds, sodium sulphite, [Ir (COD) Cl]
2, part, cesium carbonate mol ratio be 1: 3: 0.02: 0.04: 3.
Reaction equation can be represented with following formula:
Wherein L is a chiral ligand, and Add. is various additive mentioned above and combination, and Sol. is an all kinds of SOLVENTS mentioned above, and LG is a leavings group, is methyl carbonate.
The structural formula of said allyl carbonate ester compound is:
Wherein: R
1Be methyl; L is a chiral ligand, and LG is a leavings group, is methyl carbonate;
Said part is the optically pure part with following structural formula:
Wherein: R
2Be cyclohexyl, R
3Be cyclohexyl.
Gained two [1-virtue (alkane) basic substituted allyl] sulfane compounds separates through recrystallization method, and solvent adopts Virahol.
The sulfane compounds is used for the midbody of synthetic sulfur-bearing hybrid compounds, and potential chemotherapy and the antineoplastic chemicals of being used for said two [1-virtue (alkane) basic substituted allyls].
Embodiment 23
The compound method of a kind of two [1-virtue (alkane) basic substituted allyl] sulfane compounds, this method is in methylene dichloride, temperature of reaction is under 30 ℃, with allyl carbonate ester compound and Na
2S9H
2O is a raw material, with [Ir (COD) Cl]
2The iridium complex that generates with the part effect is as catalyzer, and reaction made two [fragrant (alkane) the basic substituted allyl of 1-] sulfane compounds in 48 hours under the effect of cesium chloride; Said allyl carbonate ester cpds, Na
2SH
2O, [Ir (COD) Cl]
2, part, cesium chloride mol ratio be 1: 3: 0.5: 0.1: 5.
Reaction equation can be represented with following formula:
Wherein L is a chiral ligand, and Add. is various additive mentioned above and combination, and Sol. is an all kinds of SOLVENTS mentioned above, and LG is a leavings group, is the carbonic acid tert-butyl ester.
The structural formula of said allyl carbonate ester compound is:
Wherein: R
1Be methyl; L is a chiral ligand, and LG is a leavings group, is the carbonic acid tert-butyl ester;
Said part is the optically pure part with following structural formula:
Wherein: R
2Be the substituted naphthyl of methoxyl group, R
3Be the substituted naphthyl of methoxyl group.
Gained two [1-virtue (alkane) basic substituted allyl] sulfane compounds separates through the method for thin-layer chromatography, column chromatography.Used developping agent is the mixed solvent of non-polar solvent and polar solvent: petroleum ether-ethyl acetate (volume ratio is 20/1).
Said two [1-virtue (alkane) basic substituted allyl] sulfane compounds is used to prepare the diallyl sulfone compound and closes the ring sulphones that ring forms.
Described ring sulphones is the optical purity
with following structure
Embodiment 24
The compound method of a kind of two [1-virtue (alkane) basic substituted allyl] sulfane compounds, this method is in THF, temperature of reaction is under 5 ℃, with allyl carbonate ester compound and Na
2S9H
2O is a raw material, with [Ir (COD) Cl]
2The iridium complex that generates with the part effect is as catalyzer, and reaction made two [fragrant (alkane) the basic substituted allyl of 1-] sulfane compounds in 36 hours under the effect of lithium chloride; Said allyl carbonate ester cpds, Na
2S9H
2O, [Ir (COD) Cl]
2, part, lithium chloride mol ratio be 1: 0.5: 0.01: 0.02: 0.05.
Reaction equation can be represented with following formula:
Wherein L is a chiral ligand, and Add. is various additive mentioned above and combination, and Sol. is an all kinds of SOLVENTS mentioned above, and LG is a leavings group, is ethyl-carbonate.
The structural formula of said allyl carbonate ester compound is:
Wherein: R
1Be C
10The heteroaryl of sulfur-bearing; L is a chiral ligand, and LG is a leavings group, is ethyl-carbonate;
Said part is the optically pure part with following structural formula:
Wherein: R
2Be methylbenzene, R
3Be methylbenzene.
Gained two [1-virtue (alkane) basic substituted allyl] sulfane compounds separates through the method for thin-layer chromatography, column chromatography.Used developping agent is the mixed solvent of non-polar solvent and polar solvent: sherwood oil-methylene dichloride (volume ratio is 100/1).
Embodiment 25
The compound method of a kind of two [1-virtue (alkane) basic substituted allyl] sulfane compounds, this method is in THF, temperature of reaction is under 25 ℃, with allyl carbonate ester compound and Na
2S9H
2O is a raw material, with [Ir (COD) Cl]
2The iridium complex that generates with the part effect is as catalyzer, and reaction made two [fragrant (alkane) the basic substituted allyl of 1-] sulfane compounds in 36 hours under the effect of cesium hydroxide; Said allyl carbonate ester cpds, Na
2S5H
2O, [Ir (COD) Cl]
2, part, cesium hydroxide mol ratio be 1: 1: 0.05: 0.08: 1.
Reaction equation can be represented with following formula:
Wherein L is a chiral ligand, and Add. is various additive mentioned above and combination, and Sol. is an all kinds of SOLVENTS mentioned above, and LG is a leavings group, is ethyl-carbonate.
The structural formula of said allyl carbonate ester compound is:
Wherein: R
1Be C
10The heterocyclic radical that contains N; L is a chiral ligand, and LG is a leavings group, is ethyl-carbonate;
Said part is the optically pure part with following structural formula:
Wherein: R
2Be C
4The substituted naphthyl of alkoxyl group, R
3Be C
4The substituted naphthyl of alkoxyl group.
Gained two [1-virtue (alkane) basic substituted allyl] sulfane compounds separates through the method for thin-layer chromatography, column chromatography.Used developping agent is the mixed solvent of non-polar solvent and polar solvent: sherwood oil-methylene dichloride (volume ratio is 50/1).
Claims (8)
1. two [1-virtue (alkane) basic substituted allyl] sulfane compounds is characterized in that this compound is the optical pure compound with following structural formula
2. the compound method of one kind as claimed in claim 1 pair [1-virtue (alkane) basic substituted allyl] sulfane compounds; It is characterized in that; This method is in organic solvent; Temperature of reaction is under-20 ℃-30 ℃, is raw material with allyl carbonate ester compound and sodium sulphite or sodium sulphite hydrate, with [Ir (COD) Cl]
2The iridium complex that generates with the part effect is as catalyzer, and reaction made two [fragrant (alkane) the basic substituted allyl of 1-] sulfane compounds in 36-48 hour under the effect of additive;
Said allyl carbonate ester cpds, sodium sulphite or sodium sulphite hydrate, [Ir (COD) Cl]
2, part, additive mol ratio be 1: 0.5-3: 0.01-0.5: 0.02-0.1: 0.05-5;
The structural formula of said allyl carbonate ester compound is:
Wherein: R
1Be selected from C arbitrarily
1-C
16Alkyl, C
4-C
10Heterocyclic radical that contains N, O or sulphur or C
4-C
10The heteroaryl that contains N, O or sulphur, aryl; L is a chiral ligand, and LG is a leavings group, is methyl carbonate, ethyl-carbonate or the carbonic acid tert-butyl ester;
The structural formula of said sodium sulphite or sodium sulphite hydrate is Na
2SxH
2O, wherein x=0 or 9;
Said part is the optically pure part with following structural formula:
Wherein: R
2Or R
3Be selected from C arbitrarily
3-C
16Naphthenic base, phenyl, naphthyl, C
1-C
4Substituted phenyl of alkoxyl group or C
1-C
4The substituted naphthyl of alkoxyl group;
Described additive is cesium carbonate, cesium fluoride, cesium chloride, lithium chloride, Silver monobromide or cesium hydroxide.
3. the compound method of two [1-virtue (alkane) basic substituted allyl] according to claim 2 sulfane compounds is characterized in that said allyl carbonate ester cpds, sodium sulphite or sodium sulphite hydrate, [Ir (COD) Cl]
2, part, additive mol ratio be 1: 3: 0.02: 0.04: 3, said temperature of reaction was 5 ℃-25 ℃, and the reaction times is 36-48 hour.
4. the compound method of two [1-virtue (alkane) basic substituted allyl] according to claim 2 sulfane compounds is characterized in that described organic solvent is toluene, methylene dichloride or THF.
5. the compound method of two [1-virtue (alkane) basic substituted allyl] according to claim 2 sulfane compounds; It is characterized in that gained two [1-virtue (alkane) basic substituted allyl] sulfane compounds separates through the method for recrystallization, thin-layer chromatography, column chromatography or underpressure distillation.
6. the application of two [1-virtue (alkane) basic substituted allyl] as claimed in claim 1 sulfane compounds; It is characterized in that; The sulfane compounds is used for the midbody of synthetic sulfur-bearing hybrid compounds, and potential chemotherapy and the antineoplastic chemicals of being used for said two [1-virtue (alkane) basic substituted allyls].
7. the application of two [1-virtue (alkane) basic substituted allyl] as claimed in claim 1 sulfane compounds; It is characterized in that, said two [1-virtue (alkane) basic substituted allyl] sulfane compounds is used to prepare the diallyl sulfone compound and closes the ring sulphones that ring forms.
8. the application of two [1-virtue (alkane) basic substituted allyl] according to claim 7 sulfane compounds; It is characterized in that described ring sulphones is the optical purity
with following structure
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