鈀催化C-H鍵活化實現(xiàn)偶氮苯與醇的氧化交叉偶聯(lián)反應(yīng)-碩士答辯

1、復(fù)旦大學(xué)鈀催化鈀催化C-H鍵活化實現(xiàn)偶氮苯鍵活化實現(xiàn)偶氮苯與醇的氧化交叉偶聯(lián)反應(yīng)與醇的氧化交叉偶聯(lián)反應(yīng)作者姓名唐*學(xué)科專業(yè)應(yīng)用化學(xué)指導(dǎo)教師林*副教授答辯日期2015年6月1日2主要內(nèi)容主要內(nèi)容研究背景研究背景2 偶氮苯與醇的反應(yīng)研究偶氮苯與醇的反應(yīng)研究3結(jié)結(jié) 論論3C-H鍵活化（雜）芳環(huán)的直接 C-H 酰基化反應(yīng)N, O, S第一章第一章 研究背景研究背景4DGR+ArCHOPd(OAc)2 (10 mol %)xylene, air, 120 or 130 DGROArDG= 2-Py, -C(O)(2-Py), -O(2-Py)+Pd(PhCN)2Cl2Ag2O, K2S2O8Dioxan

2、e/AcOH/DMSO 120 NROOHOHNORGe, H., et al. Org. Lett. , 2010, 12(15): 3464-3467.Cheng, et al. J., Org. Lett. , 2009, 11(14): 3120-3123. 1.1 過渡金屬催化過渡金屬催化N原子導(dǎo)向的?；磻?yīng)原子導(dǎo)向的?；磻?yīng)5+PdCl2(5 mol%)TBHP (3 equiv)PhCl, 140 NR1R2OHNR1R2OLi, C.-J., et al. Org. Lett. , 2011, 13(7): 1614-1617. DGHR1+HHHR210% Pd(OAc)

3、2tBuOOH (2 equiv)120DGR1OR2R1=H, OMe, BrR2=H, Me, OMe, ClDG=NNONOMe2-Py-O(2-Py)-C=N-OMePatel, B. K., et al. Org. Lett. , 2012, 14(20): 5294-5297.6NR2R1+HOR3OPd(OAc)2, TFAA100,16hNR2R1R3OFu, H., et al. Adv. Synth. Catal. 2013, 355:529-536HNOMe+HR2OCp*RhCl22 ( 0.05 equiv)AgSbF6 ( 0.2 equiv)Ag2CO3 ( 2.

4、5 equiv)CH2Cl2 ( 0.2 M)85 , 24hR1NOMeR1R2OLi, Y.C., et al. Adv. Synth. Catal. 2012, 354: 2916-2920.7Tan, Z., et al. Chem. Commun., 2013, 49(15): 1560-1562.HXNOMeR+OHPd(OAc)2( 5 mol%)TBHP( 3 equiv)XNOMeROAcOH( 3 equiv)DCE( 0.3 M),80Kim, I.S., et al. Eur. J. Org. Chem. 2013, 66566665.NHOR2R1+OOHO10% P

5、d(OAc)2(NH4)2S2O8diglyme,N2NHOR2R1O8HNMeOMe+Pd(OAc)2 ( 0.05 equiv)TBHP ( 6 equiv)AcOH ( 3 equiv)DCE, 80 , 6hNMeOMeArOClArOArClKim, I.S., et al. J. Org. Chem. 2014, 79:275 284.NNR1R2+OHOOPd(OAc)2 ( 10 mol%)K2S2O8 ( 2.0 equiv)dioxane/AcOH/DMSO=7:2:180，10 hNNR1R2OWang,G.-W., et al. J. Org. Chem. 2013,

6、78:10414- 10420.9NNRHR+OR1HPd(OAc)2TBHPNNRROR1Zn-NH4ClNNRR1RWang, L., et al. Org. Lett. 2013, 15(3):620-623.NN+CH3Pd(OAc)2 (10 mol%)TBHP (12 equiv)PhCF3, 80, 30hNNOZeng, W., et al. Org. Lett. , 2013, 15(21):54445447.10HNOH+ROOHO10 mol % Pd(TFA)22 equiv (NH4)2S2O8diglyme, rtNHOROGe, H., et al. J. Am.

7、 Chem. Soc. 2010, 132(34): 11898-11899.NHR1OR2+OHPd(OAc)2(10 mol %)TBHP (4 equiv）TfOH (0.5 equiv)AcOH/DMA90 , 5hNHR1OR2OWang, X., et al. Adv. Synth. Catal. , 2011, 353 (18): 3373-3379.1.2 過渡金屬催化過渡金屬催化O原子導(dǎo)向的?；磻?yīng)原子導(dǎo)向的酰基化反應(yīng)11NHR2OR1+H5 mol % Pd(TFA)2TBHP, toluene90 , 24hNHR2OR1OOR3R3Kwong, F. Y., et a

8、l. Org. Lett. , 2011, 13(12): 3258-3261.HNO+R1R2Pd(OAc)2 (5 mol %)TBHP (4 equiv)DMSO,100, 20hNHR1OOR2Sun, P.P., et al. J. Org. Chem. 2012, 77: 11339-11344.12COOHHR1+R2OOHOPd(TFA)2 ( 10 %)Ag2CO3( 3.0 equiv)DME, 150 COOHR1OR2OHOHR1+R2OOR2ORh(cod)Cl2(1.5 mol%)Cs2CO3, mesitylene16h, 145OHOR1OR2Ge, H.B.,

9、 et al. Org. Lett. . 2013, 15(12):29302933.J. Gooen, L., et al. Angew. Chem. Int. Ed. 2013, 52:6704 -6708.13OCONMe2HClR1+OHOOR2Pd(OAc)2, (NH4)2S2O8TfOH, DCE, r.t., 20 hOClR1OR2OMe2NKim, I.S., et al. Adv. Synth. Catal. 2013, 355:667-672.141.3 過渡金屬催化過渡金屬催化S原子導(dǎo)向的?；磻?yīng)原子導(dǎo)向的?；磻?yīng)SRHR2+OHOOPd(OAc)2 (5 mol

10、%)Ag2CO3(2.0 equiv)DMA, 120SRR2OR1R1Kuang, C.X., et al. Eur. J. Org. Chem. 2014, 2576-2583.15本課題的設(shè)計與提出CH2OHNNOxidantPdNNOH16第二章第二章 偶氮苯與醇的反應(yīng)研究偶氮苯與醇的反應(yīng)研究表2-1催化劑對反應(yīng)的影響NNHCH2OHPd catalyst (10 mol%)TBHP (4.0 equiv),DCE Ar, 110,30hNNO1a2a3-1aEntryCatalystYield(%)b1PdCl2372Pd(TFA)2343PdCl2(MeCN)2354PdCl2(P

11、Ph3)2trace5Pd(OAc)2406-02. 1 反應(yīng)條件優(yōu)化反應(yīng)條件優(yōu)化17表2-2氧化劑對反應(yīng)的影響NNHCH2OHPd(OAc)2 (10 mol%)Oxidant (4.0 equiv),DCE Ar, 110,30hNNO1a2a3-1aEntryOxidantYield(%)b1TBHP402DDQtrace3MnO2trace4Na2S2O8trace5O2trace6PhI(OAc)2trace18表2-3溶劑對反應(yīng)的影響EntrySovlentTempretureYield(%)b1CH2ClCH2Cl110402DMSO110trace3DMF110NR4CHCl2

12、CHCl2110475CH3NO2110286chlorobenzene110110687trifluorotoluene1105881,4-dioxane110NR19EntrySovlentTempretureYield(%)b9CH3CN802310CH3COOC2H58035 11CH2Cl27042 續(xù)上表20表2-4溫度對反應(yīng)的影響NNHCH2OHPd(OAc)2(10 mol %) Ar,Chlorobenzene, TBHP(4.0 equiv),temp 30 hNNO1a2a3-1aEntryTemperatureTimeYield(%)b112530h49211030h6

13、838030h8146030h6821表2-5時間對反應(yīng)的影響NNHCH2OHPd(OAc)2(10 mol %) Ar,Chlorobenzene, TBHP(4.0 equiv),80 timeNNO1a2a3-1aEntryTemperatureTimeYield(%)b18030h8128048h6338024h5822表2-6 物料比對反應(yīng)的影響NNHCH2OHPd(OAc)2(10 mol %) Ar,Chlorobenzene, TBHP(x equiv),80 30 hNNO1a2a3-1aEntry1a2aTBHPYield111663%211481%311363%41123

14、3%5 1 2 4 63%61 1.5 4 68%23表2-7醇類底物的拓展NNPd(OAc)2 (10 mol %)TBHP (4.0 equiv)NNRO1a23HR CH2OHPhCl, 80 oC, 30 h+NNO3-1a: 81%NNO3-1b: 56%MeNNO3-1c: 48%NNO3-1d: 43%HOMeMeOOMeNNO3-1h: 59%BrNNO3-1e: 0%NNO3-1g: 67%ClNNO3-1f: 71%OHF2.2 底物的拓展底物的拓展 24NNO3-1j: 83%NNO3-1k: 80%NNO3-1i: 80%NO2CF3NN3-1l: 27%O2NOSNN

15、O3-1n: 28%NNO3-1o: 26%NNO3-1m: 33%25表2-8偶氮苯類底物的拓展NNPd(OAc)2 (10 mol %)TBHP (4.0 equiv)NNPhO12a3HCH2OHPhCl, 80 oC, 30 hR1+R1R2R2NNO3-2a: 60%NNO3-2b: 66%NNO3-2c: 27%MeMeMeMeMeMeNNO3-2d: 68%NNO3-2e: 42%NNO3-2f: 51%MeOOMeFFClCl26NNO3-2g: 48%NNO3-2h: 80%NNO3-2i: 37%BrBrEtO2CCO2EtHMeONNO3-2j: 27%NNO3-2k:

16、32%NNO3-2l: 25%MeMeOMeOMeMeONNNNO3-2o: 0%NNO3-2m: 37%NNO3-2n: 20%CO2EtEtO2C272.3 機理的研究機理的研究CH2OHPd(OAc)2 (10 mol%)TBHP (4.0 equiv)PhCl (2 mL), 80 oC, 12 hCHO2a2abNNCH2OHNNO1a2a3a-1HPd(OAc)2 (10 mol%)TBHP (4 equiv)TEMPO (1.0 equiv)PhCl (2 mL), 80 oC, 30 hnot observed(58% GC yield)a)c)NNNNO1a2ab3a-1HP

17、d(OAc)2 (10 mol%)TBHP (4 equiv)PhCl (2 mL), 80 oC, 30 hb)HO75% yield28Pd(OAc)2NNNNPdOAcR-CH2OHORNNPd(IV)RONNOR1aABCDETBHPRCHOtBuOtBuOH.F圖2-1鈀催化偶氮苯與苯甲醇的酰基化反應(yīng)機理292.4 應(yīng)用應(yīng)用-偶氮基偶氮基芴酮芴酮類化合物類化合物4的合成反應(yīng)的合成反應(yīng)NNNNONN+Pd(OAc)2(10 mol%)TBHP (4.0 equiv)PhCl, 80 oC, 30 h60% yieldPd(PPh3)4 ( 10 mol%)DavePhos (10 mo

18、l%)KOAc (2.0 equiv)1a2p3-2p4HOBrBrOK2CO3 (2.0 equiv)DMA, 110 oC, 24 h35% yield301.利用偶氮化合物中N=N雙鍵作為導(dǎo)向基團，以偶氮苯和苯甲醇做為反應(yīng)底物，研究了在Pd(OAc)2/PhCl體系下實現(xiàn)偶氮苯鄰位?；磻?yīng)的可能性，從而構(gòu)建C-C鍵。通過一系列的條件篩選后，得到了最優(yōu)反應(yīng)條件，即在氬氣保護下，偶氮苯(1a) (0.15 mmol)，苯甲醇(2a) (0.15 mmol)，醋酸鈀(10 mol %)，TBHP(4 equiv)溶于溶劑PhCl中 (2.0 mL)中，在80反應(yīng)30h，能以25%-83%的收率得到?；a(chǎn)物，并合成了30種?；a(chǎn)物。2.通過機理研究控制實驗，我們提出了一個可能的機理：首先Pd(OAc)2與偶氮苯通過sp2C-H活化得到五元環(huán)鈀中間體，苯甲醇在TBHP的作用下，自由基引發(fā)得到苯甲?；杂苫c五元環(huán)鈀中間體進行自由基氧化加成，得到新環(huán)鈀中間體。最后，新環(huán)鈀中間體