李宗瑞, 鄧清海

(上海師范大學 生命與環(huán)境科學學院,上海 200234)

鐵催化烯基環(huán)丙烷類化合物的三氟甲基化反應

李宗瑞, 鄧清海

(上海師范大學 生命與環(huán)境科學學院,上海 200234)

對鐵催化的烯基環(huán)丙烷類化合物的自由基三氟甲基化反應進行了研究.以中等到良好的收率獲得了含三氟甲基的二氫萘衍生物.方法具有反應條件溫和,催化劑廉價易得,反應時間短等優(yōu)點.同時對反應機理進行了初步研究.

鐵催化; 三氟甲基化; 自由基反應; 二氫萘

0 前 言

由于三氟甲基(CF3)具有強吸電子性、親脂性和穩(wěn)定的C-F鍵等特性,將其引入到有機化合物中能夠顯著改變化合物的酸性、偶極距、極性、親脂性以及其化學和代謝穩(wěn)定性.因此含三氟甲基的化合物在醫(yī)藥、農藥和材料等領域得到廣泛應用[1].幾十年來,化學家發(fā)展了各種不同類型的向有機分子引入三氟甲基的反應[2],但這些方法存在反應條件苛刻,原料難得及選擇差等缺點.近幾年來,在金屬有機化學研究的推動下,三氟甲基化反應取得了重大突破[3-4].同時,對經典的通過三氟甲基自由基的反應開展了新的探索[5-6].

二氫萘類化合物在有機合成中是一類重要的主體框架,并且在很多具有生物活性的分子中代表一類重要骨架[7].近來,化學家發(fā)展了各種不同類型的方法合成此類化合物.但合成含有三氟甲基的二氫萘類化合物的方法報道較少.最近,本課題組報道了用FeCl2催化烯丙基環(huán)丙烷類化合物三氟甲基化合成含有三氟甲基的二氫萘類衍生物的方法[5].反應條件溫和,有較高的產率(最高達到96%),且底物普適性較好.本文作者在此基礎上進一步研究這一反應在一些芳雜環(huán)體系和特殊取代基體系的適用性,同時對反應機理進行了初步研究.

1 實驗部分

1.1 儀器和試劑

核磁共振采用300,400和600 MHz NMR型核磁共振儀測定;紅外光譜采用FI-IR紅外光譜儀(KBr壓片,4 000～400 cm-1)測定;X-單晶衍射采用Bruker SMART APEX II X-射線單晶衍射儀測定.

實驗所需藥品均為分析純.溶劑二氯甲烷用CaH2回流干燥除水,四氫呋喃用鈉和二苯甲酮回流干燥除水,柱層析用200～300目硅膠.

1.2 底物的合成

圖1 底物4的合成(反應條件:a) NaOH(1eq),MeOH,30 ℃,10 h;b) K2CO3(1eq),MW 130 ℃,15 min;c) I2(1eq),DBU(2eq),EtOH,35 ℃,4 h;d) CH3Ph3PBr(1.5eq),n-BuLi(1.5eq),THF,Ar,RT.,18 h)

1.2.1 查爾酮的制備[8]

取一茄形瓶,加入攪拌子,后將酮加入其中,再加入溶劑甲醇,放在冰浴下攪拌10 min,邊攪拌邊加入NaOH,再將醛緩慢滴加入其中,恢復室溫反應10 h后,向其中滴加稀鹽酸溶液,將反應體系的pH調至6～7,后過濾得到固體產物查爾酮1,產率70%～90%.

1.2.2 化合物2的制備[9]

取一個微波反應器專用的反應管(25 mL),將反式查爾酮1與丙二酸二甲酯以及碳酸鉀都加入反應管中,蓋上塞子放入微波反應器中,調微波反應器的參數(shù),時間為15 min,溫度為130 ℃.將所得的反應物用二氯甲烷稀釋,用二氯甲烷、乙醇重結晶(凍置),過濾得到固體化合物2,產率56%～75%.

1.2.3 化合物3的制備[10]

化合物2放入一個茄形瓶中,然后向其中加入乙醇作為溶劑,以及DBU和單質碘放入其中,將此混合物在35 ℃下攪拌4 h.待反應結束后,旋蒸除去大部分的乙醇,然后向其中60 mL的冷水,加完冷水后向其中緩慢加入Na2S2O3(邊加邊攪拌)直到棕色退去為止.用DCM萃取3次,合并有機相,無水硫酸鈉干燥,減壓蒸餾濃縮,柱層析純化,得到了化合物3,產率45%～75%.

1.2.4 化合物4的制備[4]

取一個干燥的舒?zhèn)惪藞A底燒瓶,向里面加入攪拌子和甲基三苯基溴化磷,通入氬氣,將反應瓶冰鹽浴,再加入重蒸的四氫呋喃和正丁基鋰,一起攪拌1 h后,再用少量四氫呋喃稀釋化合物3,然后用注射器將其加入反應瓶中,后溫度慢慢恢復至室溫反應18 h.反應結束后用飽和氯化銨淬滅,然后用乙酸乙酯萃取,硫酸鎂干燥除水,合并有機相,減壓濃縮蒸餾,柱層析純化,得到化合物4,產率為30%～65%.

1.3 鐵催化偶聯(lián)三氟甲基化反應的一般方法

圖2 鐵催化三氟甲基化

取一個干燥的舒?zhèn)惪斯?將底物4,Togni試劑,FeCl2加入反應管,沖入氬氣保護,加入干燥過的溶劑DCM,放入已經預先加熱到40 ℃的油浴中攪拌10～30 min,反應完成后用飽和K2CO3水溶液洗,DCM萃取3次,合并有機相,旋蒸除去溶劑后柱層析分離提純,得到目標產物5,產率17%～94%.

2 實驗結果與討論

2.1 三氟甲基化反應底物拓展

對不同類型的底物進行了三氟甲基化反應的研究(圖3).4a兩個苯基的底物能較好地進行反應,產率達到82%,4b,4c甲基在對位、間位的底物都能較好地進行反應,分別得到目標產物5b,5c且產率較高.但甲基在鄰位的底物4d反應不能發(fā)生,可能是鄰位有較大位阻的原因.帶有硝基強吸電子基團的底物也能較好地進行這個反應,但5e在摩爾分數(shù)為10%的氯化亞鐵催化下轉化率只有23%,催化劑用量增加到70%(摩爾分數(shù))后,產率達到76%,可能是因為底物或者產物對催化劑有一定的毒化作用.又對雜芳香環(huán)取代基的底物進行了研究,值得慶幸的是噻吩取代基的底物4g,4 h都能較好地進行這個反應,產率較為理想,但呋喃取代基不能較好地進行這個反應,反應體系比較復雜,可能是底物自身反應活性較高的原因.值得注意的是4k異丙基取代基的底物也可進行這個反應,且產率較高,4l底物雖然能進行這個反應,但產率只有17%.4m底物反應體系也比較復雜,未能得到目標產物.

圖3 底物拓展(反應條件:底物4(0.2 mmol),Togni試劑(0.26 mmol),FeCl2(0.01 mmol)DCM(2 mL);產率為分離收率.)

2.2 反應區(qū)域選擇性的確定

為了證明該反應有較好的區(qū)域選擇性,以圖3(5f)為參考進行分子結構研究,通過X-單晶衍射(圖4)分析可知環(huán)丙烷結構是在C3和C5之間斷裂.目前還不清楚有這么高的區(qū)域選擇性斷裂的原因,可能是FeCl2與兩個酯基相互作用促進了C3-C5鍵的斷裂.

2.3 反應機理研究

對三氟甲基化反應的機理進行了研究,設計的對照試驗如圖5所示,反應步驟:取一個干燥的舒?zhèn)惪斯?將底物4(0.2 mmol,1.0 equiv),Togni試劑(0.26 mmol,1.3 equiv),2,2,6,6-四甲基哌啶氧化物(TEMPO,0.26 mmol,1.3 equiv),FeCl2(0.02 mmol,0.1 equiv)加入反應管,沖入氬氣保護,加入干燥過的溶劑DCM,放入已經預先加熱到40 ℃的油浴中攪拌10 min,然后恢復至室溫后加入三氟甲基苯(0.26 mmol)作為內標,通過氟譜(圖6)分析未發(fā)現(xiàn)有目標產物5a生成,但得到TEMPO捕捉的化合物6(27%).由此表明反應很可能是自由基反應歷程.

圖4 5f X-單晶衍射圖

圖5 自由基淬滅反應

3 數(shù)據(jù)表征

3.1 底物數(shù)據(jù)表征

圖7 4a:無色油狀物;1H NMR (400 MHz,CDCl3) δ 7.55～7.53 (m,2H),7.33～7.21 (m,8H),5.60 (s,1H),5.20 (s,1H),3.59 (d,J=8.4 Hz,1H),3.54 (d,J=8.4 Hz,1H),3.38 (s,3H),3.35 (s,3H).13CNMR (100 MHz,CDCl3) δ 167.2,167.0,141.1,139.2,134.7,128.7,128.4,128.1,128.0,127.6,126.0,115.1,52.6,52.5,44.9,35.2,34.9.IR (KBr):vmax2 952,1 731,1 453,1 249,1 027 cm-1.

圖7 4b:無色油狀物;1H NMR (400 MHz,CDCl3) δ 7.46 (d,J=8.4 Hz,2H),7.32～7.24 (m,5H),7.15 (d,J=8.4 Hz,2H),5.63 (s,1H),5.23 (s,1H),3.67 (d,J=8.4 Hz,1H),3.60 (d,J=8.4 Hz,1H),3.47 (s,3H),3.45 (s,3H),2.35 (s,3H);13C NMR (100 MHz,CDCl3) δ 167.2,167.0,140.9,137.7,136.4,134.7,129.1,128.7,128.4,127.5,125.9,114.1,52.6,52.5,44.9,35.1,34.9,21.2;IR (KBr):vmax2 952,1 730,1 435,1 242,1 018 cm-1.

圖7 4c無色油狀物;1H NMR (400 MHz,CDCl3) δ 7.37 (d,J=7.6 Hz,2H),7.31～7.28 (m,5H),7.22 (d,J=8.0 Hz,1H),7.11 (d,J=8.0 Hz,1H),5.66 (s,1H),5.26 (s,1H),3.66 (d,J=8.4 Hz,1H),3.61 (d,J=8.4 Hz,1H),3.47 (s,3H),3.46 (s,3H),2.36 (s,3H);13C NMR (100 MHz,CDCl3) δ 167.2,167.0,141.2,139.3,137.8,134.7,128.72,128.69,128.4,128.3,127.6,126.7,123.2,114.9,52.6,52.5,45.0,35.2,35.0,21.6;IR (KBr):vmax2 951,1 729,1 435,1 249,1 121 cm-1.

圖3 4d無色油狀物;1H NMR (600 MHz,CDCl3) δ 7.30～7.23 (m,5H),7.22～7.11 (m,4H),5.46 (s,1H),5.23 (s,1H),3.61 (s,3H),3.57 (d,J=9.0 Hz,1H),3.52 (d,J=9.0 Hz,1H),3.40 (s,3H),2.41 (s,3H);13C NMR (150 MHz,CDCl3) δ 167.1,166.9,142.9,140.9,135.0,134.6,130.4,128.6,128.3,127.44,127.43,1 125.6,118.6,52.5,52.4,45.3,35.8,35.7,20.6.

圖6 自由基淬滅反應核磁圖

圖7 反應底物

圖7 4e黃色固體;m.p.:110～113 ℃;1H NMR (300 MHz,CDCl3) δ 8.22 (d,J=9.0 Hz,2H),7.74 (d,J=9.0 Hz,2H),7.32～7.28 (m,5H),5.86 (s,1H),5.51 (s,1H),3.68 (d,J=8.4 Hz,1H),3.59 (d,J=8.4 Hz,1H),3.50 (s,3H),3.46 (s,3H).

圖7 4f黃色固體;m.p.:100～102 ℃;1H NMR (400 MHz,CDCl3) δ 8.18 (d,J=8.8 Hz,2H),7.54 (d,J=6.8 Hz,2H),7.47 (d,J=8.8 Hz,2H),7.38～7.29 (m,3H),5.69 (s,1H),5.27 (s,1H),3.71 (d,J=8.4 Hz,1H),3.65 (d,J=8.4 Hz,1H),3.52 (s,3H),3.46 (s,3H);13C NMR (150 MHz,CDCl3) δ 166.7,166.4,147.4,142.4,140.6,138.9,129.7,128.5,128.2,126.0,123.7,115.4,53.0,52.8,45.5,35.2,34.5;IR (KBr):vmax2 923,1 729,1 436,1 294,1 143 cm-1.

圖7 4g黃色油狀物;1H NMR (400 MHz,CDCl3) δ 7.33～7.27 (m,5H),7.25 (dd,J=3.6,1.2 Hz,1H),7.18 (dd,J=5.2,1.2 Hz,1H),6.98 (dd,J=5.2,3.6 Hz,1H),5.62 (d,J=1.2 Hz,1H),5.16 (d,J=1.2 Hz,1H),3.68 (d,J=8.4 Hz,1H),3.61 (d,J=8.4 Hz,1H),3.53 (s,3H),3.48 (s,3H).

圖7 4 h黃色固體;m.p.:58～60 ℃;1H NMR (600 MHz,CDCl3) δ 7.55 (d,J=7.2 Hz,2H),7.35～7.33 (m,2H),7.30～7.27 (m,1H),7.20～7.19 (m,1H),6.94～6.93 (m,1H),5.68 (d,J=0.8 Hz,1H),5.29 (d,J=0.8 Hz,1H),3.60 (q,J=0.8 Hz,1H),3.58 (d,J=0.8 Hz,1H),3.58 (s,3H),3.43 (s,3H);13C NMR (150 MHz,CDCl3) δ 166.9,166.6,140.7,139.0,137.9,128.5,128.1,126.9,126.5,126.0,125.2,115.4,52.9,52.6,45.5,36.8,30.1;IR (KBr):vmax2 924,1 730,1 435,1 294,1 118 cm-1.

圖3 4i無色油狀物;1H NMR (600 MHz,CDCl3) δ 7.56 (d,J=7.2 Hz,2H),7.35～7.33 (m,3H),7.29 (d,J=7.2 Hz,1H),6.31 (q,J=1.8 Hz,1H),6.20 (q,J=3.6 Hz,1H),5.68 (s,1H),5.27 (s,1H),3.62 (s,3H),3.54 (s,2H),3.44 (s,3H).

圖3 4j黃色油狀物;1H NMR (400 MHz,CDCl3) δ 7.37 (d,J=1.2 Hz,1H),7.33～7.25 (m,5H),6.53 (d,J=3.2 Hz,1H),6.38 (q,J=1.6 Hz,1H),5.74 (s,1H),5.17 (s,1H),3.65 (d,J=8.4 Hz,1H),3.57 (s,3H),3.48 (d,J=8.4 Hz,1H),3.47 (s,3H).

圖7 4k無色油狀物;1H NMR (400 MHz,CDCl3) δ 7.50 (d,J=3.2 Hz,2H),7.33～7.25 (m,3H),5.56 (s,1H),5.12 (s,1H),3.81 (s,3H),3.35 (s,3H),2.89 (d,J=8.0 Hz,1H),2.16 (dd,J=10.4,8.0 Hz,1H),1.37～1.31 (m,1H),1.11 (d,J=6.4 Hz,3H),1.01 (d,J=6.4 Hz,3H);13C NMR (100 MHz,CDCl3) δ 168.9,167.5,141.9,139.5,128.3,127.8,126.0,114.5,52.7,52.3,42.6,39.1,36.7,28.2,22.4,21.5;IR (KBr):vmax2 956,1 728,1 436,1 293,1 152 cm-1.

圖7 4l無色油狀物;1H NMR (300 MHz,CDCl3) δ 7.50 (dd,J=8.7,1.2 Hz,2H),7.34～7.25 (m,3H),5.54 (s,1H),5.06 (s,1H),4.30～4.19 (m,2H),4.00～3.84 (m,2H),2.98 (q,J=9.0 Hz,1H),2.02 (dd,J=8.1,4.8 Hz,1H),1.58 (dd,J=5.7,4.8 Hz,1H),1.29 (q,J=7.2 Hz,3H),0.93 (q,J=7.2 Hz,3H);13C NMR (75 MHz,CDCl3) δ 169.9,166.6,141.3,139.8,128.2,127.8,126.1,113.9,61.7,61.3,37.2,31.7,18.3,14.1,13.8;IR (KBr):vmax3 057,2 982,1 724,1 317,1 026 cm-1.

圖3 4 m黃色油狀物;1H NMR (400 MHz,CDCl3) δ 7.37 (d,J=1.2 Hz,1H),7.33～7.25 (m,5H),6.53 (d,J=3.2 Hz,1H),6.38 (q,J=1.6 Hz,1H),5.74 (s,1H),5.17 (s,1H),3.65 (d,J=8.4 Hz,1H),3.57 (s,3H),3.48 (d,J=8.4 Hz,1H),3.47 (s,3H).

3.2 三氟甲基化產物數(shù)據(jù)表征

圖3 5a收率:82%;白色固體;m.p.:93～94 ℃;1H NMR (400 MHz,CDCl3):δ 7.55 (d,J=7.6 Hz,1H),7.38～7.35 (m,2H),7.33～7.31 (m,1H),7.20～7.15 (m,3H),7.01 (dd,J=8.0,1.6 Hz,2H) 6.26 (d,J=6.0 Hz,1H),4.56 (d,J=6.0 Hz,1H),3.66 (s,3H),3.48 (s,3H),3.41～3.32 (m,1H),3.28～3.17 (m,1H);13C NMR (100 MHz,CDCl3):δ 170.1,169.2,136.8,133.6,132.8,131.8,130.1,129.1,128.6,128.5,128.3,128.1,125.9 (q,J=276 Hz),124.8 (q,J=2.9 Hz),123.3,63.6,53.3,52.4,46.6,36.8 (q,J=29.8 Hz);19F NMR (376 MHz,CDCl3):δ-64.27 (t,J=10.2 Hz);IR (KBr):vmax2 954,1 736,1 647,1 384 cm-1.

圖3 5b收率:85%;白色固體;m.p.:156～158 ℃;1H NMR (400 MHz,CDCl3):δ 7.34 (s,1H),7.25～7.14 (m,5H),7.02～6.99 (m,2H),6.18 (d,J=6.0 Hz,1H),4.51 (d,J=6.0 Hz,1H),3.66 (s,3H),3.49 (s,3H),3.41～3.30 (m,1H),3.24～3,13 (m,1H),2.35 (s,3H);13C NMR (150 MHz,CDCl3):δ 170.1,169.3,138.1,137.1,132.5,132.4,130.1,129.7,129.2,129.1,128.4,127.9,125.9 (q,J=276 Hz),124.7 (q,J=2.7 Hz),123.2,63.6,53.2,52.3,46.7,36.8 (q,J=29.7 Hz),21.6;19F NMR (564 MHz,CDCl3):δ-63.29 (t,J=10.2 Hz);IR (KBr):vmax2 953,1 737,1 601,1 454,1 256,1 174,1 133,1 094 cm-1.

圖3 5c收率:93%;白色固體;m.p.:126～128 ℃;1H NMR (400 MHz,CDCl3):δ 7.44 (d,J=8.0 Hz,1H),7.20～7.12 (m,5H),7.02(d,J=6.4 Hz,2H),6.24 (d,J=6.0 Hz,1H),4.51 (d,J=6.0 Hz,1H),3.66 (s,3H),3.47 (s,3H),3.40～3.31 (m,1H),3.28～3,19 (m,1H),2.40 (s,3H);13C NMR (150 MHz,CDCl3):δ 170.2,169.4,138.3,137.0,133.5,132.6,131.7,129.1,129.0,128.5,128.0,126.8,126.0 (q,J=276 Hz),124.8 (q,J=2.8 Hz),124.1,63.3,53.3,52.3,46.6,36.8 (q,J=29.9 Hz),21.6;19F NMR (282 MHz,CDCl3):δ-64.66 (t,J=10.4 Hz);IR (KBr):vmax2 954,1 737,1 494,1 434,1 237,1 200,1 134,800 cm-1.

圖3 5e收率:76%;黃色固體;m.p.:158～160 ℃;1H NMR (600 MHz,CDCl3):δ 8.02 (d,J=9.0 Hz,2H),7.48 (d,J=7.8 Hz,1H),7.43～7.38 (m,2H),7.35 (t,J=7.2 Hz,1H),7.18 (d,J=9.0 Hz,2H),6.22 (d,J=6.0 Hz,1H),4.66 (d,J=6.0 Hz,1H),3.67 (s,3H),3.55 (s,3H),3.42～3.34 (m,1H),3.29～3,21 (m,1H);13C NMR (150 MHz,CDCl3):δ 168.9,168.2,147.3,138.7,137.9,135.1,131.5,128.9,128.8,128.6,127.5,125.6 (q,J=278 Hz),124.0,123.9 (q,J=3.0 Hz),123.89,63.1,53.8,52.9,46.4,37.0 (q,J=30.4 Hz),29.8;19F NMR (376 MHz,CDCl3):δ-63.45 (t,J=10.5 Hz).

圖3 5f收率:94%;黃色固體;m.p.:158～160 ℃;1H NMR (600 MHz,CDCl3):δ 8.02 (d,J=9.0 Hz,2H),7.48 (d,J=7.8 Hz,1H),7.43～7.38 (m,2H),7.35 (t,J=7.2 Hz,1H),7.18 (d,J=9.0 Hz,2H),6.22 (d,J=6.0 Hz,1H),4.66 (d,J=6.0 Hz,1H),3.67 (s,3H),3.55 (s,3H),3.42～3.34 (m,1H),3.29～3,21 (m,1H);13C NMR (100 MHz,CDCl3):δ 169.7,169.0,147.6,144.8,132.4,132.0,131.4,130.8,129.8,129.1,129.0,126.5 (q,J=2.7 Hz),125.8 (q,J=276 Hz),123.64,123.63,63.5,53.5,52.7,46.1,36.8 (q,J=29.9 Hz);19F NMR (282 MHz,CDCl3):δ-63.27 (t,J=9.0 Hz);IR (KBr):vmax2 955,1 737,1 522,1 491,1 349,1 256,1 182,1 135 cm-1.

圖3 5g收率:65%;黃色固體;m.p.:87～90 ℃;1H NMR (400 MHz,CDCl3):δ 7.25～7.22 (m,2H),7.21～7.17 (m,3H),7.07～7.05 (m,2H),6.01 (d,J=6.0 Hz,1H),4.59 (d,J=6.0 Hz,1H),3.68 (s,3H),3.42 (s,3H),3.23～3.10 (m,2H);19F NMR (282 MHz,CDCl3):δ-64.9 (t,J=10.4 Hz).

圖3 5h收率:90%;白色固體;m.p.:87～89 ℃;1H NMR (600 MHz,CDCl3):δ 7.57 (d,J=7.8 Hz,1H),7.41～7.32 (m,3H),7.07 (d,J=5.4 Hz,1H),6.83～6.82 (m,1H),6.75 (d,J=3.0 Hz,1H),6.32 (d,J=6.0 Hz,1H),4.87 (d,J=6.0 Hz,1H),3.66 (s,3H),3.64 (s,3H),3.39～3.31 (m,1H),3.24～3.16 (m,1H);13C NMR (150 MHz,CDCl3):δ 169.7,168.9,139.4,133.6,132.6,131.3,130.0,128.7,128.4,127.1,126.5,125.8 (q,J=276 Hz),125.7,125.0 (q,J=2.7 Hz),123.1,64.0,53.3,52.7,41.8,36.7 (q,J=29.7 Hz);19F NMR (564 MHz,CDCl3):δ-64.23(t,J=10.2 Hz);IR (KBr):vmax2 954,1 737,1 434,1 255,1 182,1 133,1 109,1 028 cm-1.

圖3 5k收率:90%;無色油狀;1H NMR (600 MHz,CDCl3):δ 7.42～7.40 (m,1H),7.12～7.09 (m,2H),7.05 (d,J=7.8 Hz,1H),5.93 (d,J=6.0 Hz,1H),3.64 (s,3H),3.42 (s,3H),3.14 (dd,J=6.0,4.2 Hz,1H),3.11～3.02 (m,2H),1.62～1.64 (m,1H),0.81 (d,J=6.6 Hz,3H),0.33 (d,J=6.6 Hz,3H);13C NMR (150 MHz,CDCl3):δ 170.4,170.0,133.0,131.5,131.2,130.3,128.2,127.8,126.6 (q,J=2.7 Hz),126.0 (q,J=276 Hz),123.0,62.3,53.1,52.6,44.6,36.9 (q,J=29.7 Hz),31.4,21.6,16.8;19F NMR (564 MHz,CDCl3):δ-64.70(q,J=10.7 Hz);IR (KBr):vmax2 959,1 736,1 435,1 256,1 225,1 189,1 134,1 104 cm-1.

圖3 5l收率:17%;無色油狀;1H NMR (400 MHz,CDCl3):δ 7.36～7.33 (m,1H),7.29 (d,J=7.6 Hz,2H),7.19 (d,J=7.6 Hz,1H),6.11 (t,J=4.4 Hz,1H),4.29～4.16 (m,4H),3.23 (q,J=10.4 Hz,2H),3.03 (d,J=4.4 Hz,2H),1.23 (t,J=7.2 Hz,6H);13C NMR (100 MHz,CDCl3):δ 170.9,133.0,132.9,129.0,128.3,128.0,127.41,127.34 (q,J=2.9 Hz),125.8 (q,J=276 Hz),123.4,62.1,59.3,36.8 (q,J=29.7 Hz),30.8,14.1;19F NMR (376 MHz,CDCl3):δ-64.68 (t,J=10.5 Hz);IR (KBr):vmax1 927,1 726,1 628,1 285,1 183 cm-1.

4 結 論

研究了鐵催化的烯基環(huán)丙烷類化合物的三氟甲基化反應.以商用便宜的FeCl2為催化劑,Togni試劑為三氟甲基化試劑,高區(qū)域選擇性地獲得了一系列三氟甲基取代的二氫萘衍生物.初步的機理研究表明反應為自由基反應歷程.

[1] Wang J,Sánchez-Roselló M,Acea J L,et al.Fluorine in pharmaceutical industry:Fluorine-containing drugs introduced to the market in the last decade (2001～2011) [J].Chemical Reviews,2014,114(4):2432-2506.

[2] Ma J A,Cahard D.Update 1 of:Asymmetric fluorination,trifluoromethylation,and perfluoroalkylation reactions [J].Chemical Reviews,2008,108(9):PR1-PR43.

[3] Wang F,Zhu N,Chen P,et al.Copper-catalyzed trifluoromethylazidation of alkynes:Efficient access to CF3-substituted azirines and aziridines [J].Angewandte Chemie International Edition,2015,54(32):9356-9360.

[4] Tomashenko O A,GrushinV V.Aromatic trifluoromethylation with metal complexes [J].Chemical Reviews,2011,111(8):4475-4521.

[5] Zong R L,Xing X B,Qing H D,et al.Iron-catalyzed trifluoromethylation of vinylcyclopropanes:facile synthesis of CF3-containing dihydronaphthalene derivatives [J].Organic Chemistry Frontiers,2016,3(8):934-938.

[6] Zhu Z Z,Chen Kai,Yu L Z,et al.Copper(I)-catalyzed intramolecular trifluoromethylation of methylenecyclopropanes [J].Organic Letters,2015,17(24):5994-5997.

[7] Pape A R,Kaliappan K P,Kündig E P.Transition-metal-mediated dearomatization reactions [J].Chemical Reviews,2000,100(8):2917-2940.

[8] George R F,Fouad M A,Gomaa I E O.Synthesis and cytotoxic activities of some pyrazoline derivatives bearing phenyl pyridazine core as new apoptosis inducers [J].European Journal of Medicinal Chemistry,2016,112:48-59.

[9] Yang G S,Sun Y X,Shen Y.Cis-2,3-disubstituted cyclopropane 1,1-diesters in[3+2]annulations with aldehydes:highly diastereoselective construction of densely substituted tetrahydrofurans [J].Journal of Organic Chemistry,2013,78(11):5393-5400.

[10] Miao C B,Zhang M,Tian Z Y.Base-controlled selective conversion of michael adducts of malonates with enones in the presence of iodine [J].Journal of Organic Chemistry,2011,76(23):9809-9816.

(責任編輯：包震宇,郁 慧)

Iron(II)-catalyzed trifluoromethylation of vinylcyclopropanes

LI Zongrui, DENG Qinghai

(College of Life and Environmental Sciences,Shanghai Normal University,Shanghai 200234,China)

An efficient iron(II)-catalyzed trifluoromethylation of vinylcyclopropanes was developed.A series of CF3-containing dihydronaphthalene derivatives were prepared with a moderate to high yield.This method offers several advantages in terms of its mild condition,readily available and cheap catalyst,as well as short reaction time.Furthermore,the reaction mechanism was investigated preliminarily.

iron(II)-catalyzed; trifluoromethylation; radical reaction; dihydronaphthalene

2016-09-22

國家自然科學基金(21402119);上海高校特聘教授 (東方學者) 崗位計劃資助;上海市青年科技啟明星計劃(16QA1403100).

鄧清海,中國上海市徐匯區(qū)桂林路100號,上海師范大學生命與環(huán)境科學學院,郵編:200234,E-mail:qinghaideng@shnu.edu.cn

O 625.15

A

1000-5137(2016)06-0655-08