鎂粉促進“一鍋法”合成α,β-炔基酮類化合物

楊天宇, 黃丹鳳, 王克虎, 蘇瀛鵬, 胡雨來

(西北師范大學 化學化工學院，甘肅 蘭州 730070)

·研究論文·

鎂粉促進“一鍋法”合成α,β-炔基酮類化合物

楊天宇, 黃丹鳳, 王克虎, 蘇瀛鵬, 胡雨來*

(西北師范大學 化學化工學院，甘肅 蘭州 730070)

報道了鎂粉(4)促進下，以Weinreb 酰胺(1a～1j, 1l～1n, 1p～1r)、苯乙炔(2)和正丁基溴(3)為原料，“一鍋法”合成α,β-炔酮類化合物(5a～5j, 5l～5n, 5p～5r)的反應。結(jié)果表明：在最優(yōu)反應條件(THF為溶劑，3 1.1 mmol, 4 1.25 mmol,混拌2 h;加入2 0.75 mmol, 攪拌1 h;加入1 0.5 mmol,于室溫反應)下，5a～5j, 5l～5n, 5p～5r產(chǎn)率45%～86%，其結(jié)構(gòu)經(jīng)1H NMR和13C NMR確證。

一鍋法合成; 鎂粉促進; Weinreb酰胺; 苯乙炔;α,β-炔基酮

α,β-炔酮類化合物同時含有碳碳叁鍵和羰基兩種官能團，反應性質(zhì)活潑，是有機合成中重要的合成砌塊，廣泛用于雜環(huán)化合物的合成[1-5]。此外，許多天然產(chǎn)物、生物活性物種及有機中間體也含有炔酮結(jié)構(gòu)單元[6-14]。尋找簡單，便捷，高效的合成炔酮類化合物的方法成為化學家們關注的重點。

目前，合成該類化合物的方法主要有：(1)炔基化合物與醛發(fā)生加成氧化反應[15-18]；(2)末端炔與鹵化物通過Sonogashira羰基化反應[7,19-25]；(3)末端炔或炔基化合物與羧酸衍生物發(fā)生Sonogashira?；磻猍2,7,26-32]；(4)高價碘類炔基試劑與醛類化合物發(fā)生自由基形式的炔基化反應[33-34]；(5)α-酮酸的脫羧炔酮化反應[35]；(6)末端炔與鹵化物發(fā)生異腈插入反應[36]。

Weinreb酰胺(1)作為?；铣善鰤K廣泛應用于有機合成中[37-44]。1與金屬氫化物反應制得醛，與有機鋰或鎂試劑反應制得酮，金屬試劑過量也不會導致產(chǎn)物進一步反應。這一特點使1在含羰基化合物的合成中占有重要地位。本課題組報道了鎂粉(4)促進Weinreb酰胺和鹵代烴經(jīng)“一鍋法”合成酮類化合物的反應[45]，發(fā)現(xiàn)鎂粉促進的“一鍋法”反應可避免預先制備活潑鹵代烴的Grignard試劑。轉(zhuǎn)而通過鎂粉與鹵代烴的原位反應生成Grignard試劑，然后直接與其它反應物發(fā)生反應。

本文以Weinreb 酰胺(1a～1j, 1l～1n, 1p～1r)、苯乙炔(2)和正丁基溴(3)為原料，“一鍋法”合成α,β-炔酮類化合物(5a～5j, 5l～5n, 5p～5r, Scheme 1)，產(chǎn)率45%～86%，其結(jié)構(gòu)經(jīng)1H NMR和13C NMR確證。

Scheme 1

1 實驗部分

1.1 儀器與試劑

X-4B型顯微熔點儀(溫度未校正)；Varian Mercury 400 plus型核磁共振儀和Agilent DD2600型核磁共振儀(CDCl3為溶劑，TMS為內(nèi)標)。

石油醚(沸程60～90 ℃)和乙酸乙酯,工業(yè)級；1按文獻[46]方法合成；其余所用試劑均為分析純，THF使用前經(jīng)除水除氧處理。

1.2 5的合成通法

氬氣保護下，在干燥的兩口瓶中加入4 0.03 g(1.25 mmol)和THF 1 mL，于室溫攪拌10 min；滴加3 0.15 g(1.1 mmol)，滴畢，加熱至微沸(約2 min)，冷卻至室溫，攪拌2 h；緩慢滴加2 0.07 g(0.75 mmol)的THF(2 mL)溶液，滴畢，攪拌1 h；滴加1(0.5 mmol)，滴畢，于室溫反應至終點(TLC檢測)。加入飽和氯化銨溶液10 mL淬滅反應，用乙酸乙酯(3×10 mL)萃取，合并有機相，用無水硫酸鎂干燥，減壓蒸出乙酸乙酯，殘余物經(jīng)硅膠柱層析[洗脫劑：V(石油醚) ∶V(乙酸乙酯)=30 ∶1]純化得5。

1,3-二苯基-2-丙炔-1-酮(5a)[24]： 黃色液體，產(chǎn)率86%;1H NMRδ: 8.23～8.22(m, 2H), 7.69～7.68(m, 2H), 7.63(t,J=6.0 Hz, 1H), 7.53～7.47(m, 3H), 7.42(t,J=6.0 Hz, 2H);13C NMRδ: 178.0, 136.9, 134.1, 133.0, 130.8, 129.5, 128.6, 128.5, 120.1, 93.1, 86.9。

1-苯基-3-(4-甲苯基)-2-丙炔-1-酮(5b)： 淡黃色固體，產(chǎn)率82%, m.p.64～66 ℃(68～70 ℃[28]);1H NMRδ: 8.11(d,J=6.0 Hz, 2H), 7.66(d,J=6.0 Hz, 2H), 7.45(t,J=6.0 Hz, 1H), 7.39(t,J=9.0 Hz, 2H), 7.29(d,J=6.0 Hz, 2H), 2.41(s, 3H);13C NMRδ: 177.5, 145.1, 134.5, 132.9, 130.6, 129.5, 129.2, 128.5, 120.1, 92.5, 86.9, 21.7。

1-苯基-3-(3-甲苯基)-2-丙炔-1-酮(5c)[28]： 黃色液體，產(chǎn)率80%;1H NMRδ: 8.03(d,J=6.0 Hz, 1H), 7.99(s, 1H), 7.66(d,J=6.0 Hz, 2H), 7.45(t,J=6.0 Hz, 1H), 7.41～7.37(m, 4H), 2.42(s, 3H);13C NMRδ: 178.0, 138.3, 136.7, 134.8, 132.9, 130.6, 129.6, 128.5, 128.4, 126.9, 120.0, 92.7, 86.9, 21.2。

1-苯基-3-(2-甲苯基)-2-丙炔-1-酮(5d)[28]： 黃色液體，產(chǎn)率74%;1H NMRδ: 8.30(d,J=6.0 Hz, 1H), 7.65(d,J=12.0 Hz, 2H), 7.45(t,J=6.0 Hz, 2H), 7.40～7.34(m, 3H), 7.27(d,J=12.0 Hz, 1H), 2.67(s, 3H);13C NMRδ: 179.7, 140.4, 135.6, 133.1, 132.8, 132.1, 130.5, 128.6, 125.8, 120.3, 91.8, 88.3, 21.9。

1-苯基-3-(4-氯苯基)-2-丙炔-1-酮(5e)： 白色固體，產(chǎn)率71%, m.p.96～98 ℃(104～105 ℃[28]);1H NMRδ: 8.13(d,J=6.0 Hz, 2H), 7.66(d,J=6.0 Hz, 2H), 7.47～7.45(m, 3H), 7.41～7.39(m, 2H);13C NMRδ: 176.4, 140.6, 135.2, 133.0, 130.9, 130.7, 128.9, 128.6, 119.7, 93.5, 86.5。

1-苯基-3-(3-氯苯基)-2-丙炔-1-酮(5f)： 白色固體，產(chǎn)率67%, m.p.93～95 ℃(86～90 ℃[16]);1H NMRδ: 8.15(s, 1H), 8.09(d,J=12.0 Hz, 1H), 7.67(d,J=12.0 Hz, 2H), 7.58(d,J=6.0 Hz, 1H), 7.49～7.40(m, 4H);13C NMRδ: 176.3, 138.3, 134.8, 133.9, 133.1, 131.0, 130.0, 129.2, 128.7, 127.6, 119.7, 93.9, 86.4。

1-苯基-3-(2-氯苯基)-2-丙炔-1-酮(5g)[47]： 橘紅色液體，產(chǎn)率45%;1H NMRδ: 8.09(d,J=6.0 Hz, 1H), 7.65(d,J=6.0 Hz, 2H), 7.48～7.47(m, 3H), 7.42～7.39(m, 3H);13C NMRδ: 176.7, 135.8, 133.5, 133.3, 133.1, 132.5, 131.5, 130.9, 128.7, 126.8, 120.0, 93.9, 88.3。

1-苯基-3-(4-甲氧基苯基)-2-丙炔-1-酮(5h)： 白色固體，產(chǎn)率82%, m.p.93～95 ℃(98～99 ℃[28]);1H NMRδ: 8.18(d,J=6.0 Hz, 2H), 7.65(d,J=6.0 Hz, 2H), 7.44(t,J=9.0 Hz, 1H), 7.39(t,J=9.0 Hz, 2H), 6.97(d,J=6.0 Hz, 2H), 3.85(s, 3H);13C NMRδ: 176.4, 164.3, 132.7, 131.7, 130.4, 130.1, 128.5, 120.1, 113.7, 92.1, 86.8, 55.4。

1-苯基-3-(4-氟苯基)-2-丙炔-1-酮(5i)： 白色固體，產(chǎn)率73%, m.p.48～50 ℃(47～49 ℃[29]);1H NMRδ: 8.24～8.22(m, 2H), 7.66(d,J=12.0 Hz, 2H), 7.47(t,J=9.0 Hz, 1H), 7.41(t,J=6.0 Hz, 2H), 7.17(t,J=9.0 Hz, 2H);13C NMRδ: 176.2, 166.3(d,JC-F=255.0 Hz), 133.3(d,JC-F=3.0 Hz), 133.0, 132.1(d,JC-F=10.5 Hz), 130.8, 128.6, 119.8, 115.7 (d,JC-F=22.5 Hz), 93.2, 86.5;19F NMRδ: -63.54。

1-苯基-3-(4-三氟甲基苯基)-2-丙炔-1-酮(5j)： 淡黃色固體，產(chǎn)率68%, m.p.65～67 ℃(70～73 ℃[28]);1H NMRδ: 8.30(d,J=6.0 Hz, 2H), 7.76(d,J=6.0 Hz, 2H), 7.68(d,J=6.0 Hz, 2H), 7.49～7.47(m, 1H), 7.41(t,J=9.0 Hz, 2H);13C NMRδ: 176.5, 139.3, 135.0 (q,JC-F=31.5 Hz), 133.1, 131.1, 129.6, 128.7, 125.5(q,J=4.5 Hz), 123.5(q,JC-F=271.5 Hz), 119.5, 94.3, 86.5;19F NMRδ: -63.53。

1-苯基-3-(3,5-二氯苯基)-2-丙炔-1-酮(5l)： 黃色固體，產(chǎn)率55%, m.p.80～82 ℃;1H NMRδ: 8.02～8.01(m, 2H), 7.68(d,J=6.0 Hz, 2H), 7.56～7.55(m, 1H), 7.52～7.49(m, 1H), 7.43(t,J=6.0 Hz, 2H);13C NMRδ: 174.9, 139.1, 135.6, 133.5, 133.2, 131.2, 128.7, 127.6, 119.3, 94.7, 86.1; HR-MS(ESI)m/z: Calcd for C15H8OCl2{[M+H]+}275.002 5, found 275.002 2。

3-苯基-1-(2-萘基)-2-丙炔-1-酮(5m)： 白色固體，產(chǎn)率77%, m.p.82～84 ℃(81～83 ℃[29]);1H NMRδ: 8.71(s, 1H), 8.17(d,J=12.0 Hz, 1H), 7.95(d,J=12.0 Hz, 1H), 7.85～7.81(m, 2H), 7.68(t,J=6.0 Hz, 2H), 7.57～7.50(m, 2H), 7.45～7.37(m, 3H);13C NMRδ: 177.6, 135.9, 134.2, 132.9, 132.4, 132.2, 130.6, 129.7, 128.8, 128.5, 128.3, 127.7, 126.8, 123.7, 120.0, 92.9, 87.0。

3-苯基-1-(1-萘基)-2-丙炔-1-酮(5n)： 淡黃色固體，產(chǎn)率64%, m.p.85～87 ℃( 92～94 ℃[28]);1H NMRδ: 9.25(d,J=6.0 Hz, 1H), 8.63 (d,J=12.0 Hz, 1H), 8.05(d,J=6.0 Hz, 1H), 7.88(d,J=12.0 Hz, 1H), 7.66(d,J=9.0 Hz, 3H), 7.57～7.53(m, 2H), 745～7.37(m, 3H);13C NMRδ: 179.6, 135.0, 134.5, 133.8, 132.8, 130.6, 130.5, 128.9, 128.6, 128.5, 126.7, 126.0, 124.4, 120.2, 91.6, 88.4。

1,4-二苯基-3-丁炔-2-酮(5p)[22]： 黃色液體，產(chǎn)率53%;1H NMRδ: 7.45(d,J=6.0 Hz, 2H), 7.42(d,J=6.0 Hz, 1H), 7.37(t,J=9.0 Hz, 2H), 7.34(s, 1H), 7.33～7.29(m, 4H), 3.92(s, 2H);13C NMRδ: 185.2, 133.2, 133.1, 130.8, 129.8, 128.7, 128.5, 127.4, 119.8, 92.9, 87.7, 52.1。

1,5-二苯基-1-戊烯-4-炔-3-酮(5q)[17]： 黃色液體，產(chǎn)率49%;1H NMRδ: 7.91(d,J=16.2 Hz, 1H), 7.65(d,J=7.2 Hz, 2H), 7.59(t,J=3.9 Hz, 2H), 7.47～7.35(m, 6H), 6.86(d,J=16.2 Hz, 1H);13C NMRδ: 178.1, 148.2, 134.0, 132.8, 131.1, 130.5, 129.0, 128.6, 128.6, 128.5, 120.1, 91.5, 86.6。

1-苯基-4-己烯-1-炔-3-酮(5r)[29]： 黃色液體，產(chǎn)率48%;1H NMRδ: 7.60(d,J=8.4 Hz, 2H), 7.45(t,J=7.8 Hz, 1H), 7.39(t,J=7.8 Hz, 2H), 7.32～7.26(m, 1H), 6.26(d,J=15.6 Hz, 1H), 2.03(d,J=6.6 Hz, 3H);13C NMRδ: 178.3, 149.4, 134.0, 132.8, 130.5, 128.6, 120.2, 91.0, 86.2, 18.4。

2 結(jié)果與討論

2.1 5a的合成條件優(yōu)化

以5a的合成(Scheme 2)為例，研究了物料比r[n(1a) ∶n(2) ∶n(3) ∶n(4)]和反應溶劑對5a產(chǎn)率的影響，結(jié)果見表1。

Scheme 2表1 反應條件篩選和優(yōu)化aTable 1 Optimization of the synthesis conditions for 5a

Entryr溶劑產(chǎn)率/%11∶1∶1.3∶1.5THF3521∶1∶1.5∶1.8THF4331∶1.1∶1.5∶1.8THF6241∶1.5∶1.5∶1.8THF6751∶1.5∶2∶2.3THF7661∶1.5∶2.2∶2.5THF8671∶1.5∶2.5∶2.8THF848b1∶1.5∶2.2∶2.5THF569c1∶1.5∶2.2∶2.5THF010d1∶1.5∶2.2∶2.5THF70111∶1.5∶2.2∶2.5Et2O74121∶1.5∶2.2∶2.51,4-dioxane0

a反應條件同1.2；b氬氣氛下，2, 3和4于室溫攪拌1 h;加入1a 0.5 mmol；c氬氣氛下，在THF中滴加3 7～8滴，滴畢，加入4，反應10 min;緩慢加入剩余的3, 2和1a 0.5 mmol；d氬氣氛下，先加入3和4，于室溫攪拌1 h，緩慢加入2和1a 0.5 mmol的混合溶液。

由表1可以看出，Entry 1～7為r對5a產(chǎn)率的影響，隨著2, 3和4的用量增大，產(chǎn)率逐漸升高，當r=1 ∶1.5 ∶2.2 ∶2.5時，產(chǎn)率最高(86%)。 Entry 7～10為加料順序?qū)Ψ磻挠绊懀葘?, 3和4混合，于室溫攪拌反應1 h后再加入1a，產(chǎn)率僅56%。將少量3和4加入體系中引發(fā)反應，然后加入剩余的3, 2和1a，反應不能發(fā)生。將3和4先于室溫攪拌反應1 h；然后緩慢加入2和1a，產(chǎn)率也較低(70%)。最后，我們研究了反應溶劑對產(chǎn)率的影響(Entry 6, 11, 12),乙醚為溶劑，反應能夠發(fā)生，但產(chǎn)率較低(74%)；1,4-二氧六環(huán)為溶劑，反應不能進行。

綜上所述，合成5a的最佳條件為：THF為溶劑，3 1.1 mmol, 4 1.25 mmol,混拌2 h;加入2 0.75 mmol, 攪拌1 h;加入1a 0.5 mmol,于室溫反應。

2.2 反應普適性

在最優(yōu)反應條件下，我們換用其他Weinreb酰胺進行反應(Scheme 3)，研究該合成方法的普適性，結(jié)果見表2。

Scheme 3表2 鎂粉促進Weinreb酰胺和苯乙炔的 “一鍋法”反應研究aTable 2 Study on the “one-pot” reaction of Weinreb amines with phenylacetylene promoted by magnesium

EntryR產(chǎn)物產(chǎn)率/%1C6H55a8624-MeC6H45b8233-MeC6H45c8042-MeC6H45d7454-ClC6H45e7163-ClC6H45f6772-ClC6H45g4584-MeOC6H45h8294-FC6H45i73104-CF3C6H45j68112,6-(MeO)2C6H35k0123,5-Cl2C6H35l55132-naphthalenyl5m77141-naphthalenyl5n64153-pyridinyl5onr16C6H5CH25p5317C6H5CH=CH5q4918CH3CH=CH5r4819t-butyl5s020adamantyl5t0

a反應條件同表1中加料方式c。

由表2可見，在鎂粉促進下，大多數(shù)芳香族Weinreb酰胺都能和苯乙炔，正丁基溴發(fā)生“一鍋法”反應得到α,β-炔酮類化合物(Entry 1～10, 12～14)。 Weinreb酰胺苯環(huán)上的取代基對產(chǎn)率有較大影響，苯環(huán)上連有供電子基，產(chǎn)率比吸電子基高,但當苯環(huán)上連有兩個取代基時，情況有所不同。如2,6-二甲氧基芳香Weinreb酰胺不能發(fā)生反應(Entry 11)， 3,5-二氯芳香Weinreb酰胺可以反應，產(chǎn)率55%(Entry 12)。此外，取代基在苯環(huán)上的位置對反應也有影響，無論取代基是吸電子基還是供電子基，取代基位于苯環(huán)對位的Weinreb酰胺的產(chǎn)率均高于取代基在鄰位和間位的(Entry 2～4和Entry 5～7)。當Weinreb酰胺的取代基為萘環(huán)時，反應可以進行(Entry 13～14)，但是雜環(huán)Weinreb酰胺不能發(fā)生反應(Entry 15)。對于側(cè)鏈有苯環(huán)的Weinreb酰胺, 如取代基是芐基，肉桂基和巴豆基時，反應可以進行，但產(chǎn)率降低(Entry 16～18)?？臻g位阻較大(叔丁基和金剛烷基)的脂肪族Weinreb酰胺作底物,沒有合成預計的目標產(chǎn)物(Entry 19～20)。

報道了一種鎂粉促進“一鍋法”合成α,β-炔基酮類化合物的方法。該方法具有操作簡便、條件溫和和反應時間短等優(yōu)點，為α,β-炔基酮類化合物的合成提供了一定參考。

[2] Shankar R, Chakravarti B, Singh U S,etal. Synthesis and biological evaluation of 3,4,6-triaryl-2-pyranones as a potential new class of anti-breast cancer agents[J].Bioorg Med Chem,2009,17:3847-3856.

[3] Fuchs F C, Eller G A, Holzer W. Heterocyclic analogs of thioflavones:Synthesis and NMR spectroscopic investigations[J].Molecules,2009,14:3814-3832.

[4] Forsyth C J, Xu J, Nguyen S T,etal. Antibodies with broad specificity to azaspiracids by use of synthetic haptens[J].J Am Chem Soc,2006,128:15114-15116.

[5] Marco C J, Opazo E. Synthesis of enantiomerically pure,highly functionalized,medium-sized carbocycles from carbohydrates:Formal total synthesis of (+)-Calystegine B2[J].J Org Chem,2002,67:3705-3717.

[6] Jiang H, Pan X, Huang L,etal. Synthesis of 4H-cyclopenta[c]furans via cooperative PdCl2-FeCl2catalyzed cascade cyclization reaction involving a novel acyl rearrangement process[J].Chem Commun,2012,48:4698-4700.

[7] Kirkham J D, Edeson S J, Stokes S,etal. Synthesis of ynone trifluoroborates toward functionalized pyrazoles[J].Org Lett,2012,14:5354-5357.

[8] Bannwarth P, Valleix A, Grée D,etal. Flexible synthesis of pyrimidines with chiral monofluorinated and difluoromethyl side chains[J].J Org Chem,2009,74:4646-4649.

[9] Liu H L, Jiang H F, Zhang M,etal. One-pot three-component synthesis of pyrazoles through a tandem coupling-cyclocondensation sequence[J].Tetrahedron Lett,2008,49:3805-3809.

[10] Arcadi A, Aschi M, Marinelli F,etal. Pd-catalyzed regioselective hydroarylation ofα-(2-aminoaryl)-α,β-ynones with organoboron derivatives as a tool for the synthesis of quinolines:Experimental evidence and quantum-chemical calculations[J].Tetrahedron,2008,64:5354-5361.

[11] Lee K Y, Lee M J, Kim J N. Facile synthesis ofα,β-acetylenic ketones and 2,5-disubstituted furans:Consecutive activation of triple and double bond with ZnBr2toward the synthesis of furan ring[J].Tetrahedron,2005,61:8705-8710.

[12] Karpov A S, Merkul E, Rominger F,etal. Concise syntheses of meridianins by carbonylative alkynylation and a four component pyrimidine synthesis[J].Angew Chem Int Ed,2005,44:6951-6956.

[13] Kel’in A V, Sromek A W, Gevorgyan V. A novel Cu-sssisted cycloisomerization of alkynyl imines:Efficient synthesis of pyrroles and pyrrole-containing heterocycles[J].J Am Chem Soc,2001,123:2074-2075.

[14] Arcadi A, Marinelli F, Rossi E. Synthesis of functionalised quinolines through tandem addition/annulation reactions ofβ-(2-aminophenyl)-α,β-ynones[J].Tetrahedron,1999,55:13233-13250.

[15] Yuan J W, Wang J, Zhang G H,etal. Bimetallic zinc complex-active species in coupling of terminal alkynes with aldehydes via nucleophilic addition/oppenauer oxidation[J].Chem Commun,2015,576-581.

[16] Ogiwara Y, Kubota M, Kurogi K,etal. Oxidative coupling of terminal alkynes with aldehydes leading to alkynyl ketones by using indium(III) bromide[J].Chem Eur J,2015,21:18598-18600.

[17] Heffernan S J, Tellam J P, Queru M E,etal. Double gold-catalysed annulation of indoles by enynones[J].Adv Synth Catal,2013,355:1149-1159.

[18] Pu L. Asymmetric alkynylzinc additions to aldehydes and ketones[J].Tetrahedron,2003,59:9873-9886.

[19] Chavan S P, Varadwaj G B B, Parida K,etal. Palladium anchored on amine-functionalized K10 as an efficient, heterogeneous and reusable catalyst for carbonylative Sonogashira reaction[J].Applied Cata A:General,2015,506:237-245.

[20] Zhao H, Cheng M Z, Zhang J T,etal. Recyclable and reusable PdCl2(PPh3)2/PEG-2000/H2O system for the carbonylative Sonogashira coupling reaction of aryl iodides with alkynes[J].Green Chem,2014,16:2515-2522.

[21] Neumann K T, Laursen S R, Lindhardt A T,etal. Palladium-catalyzed carbonylative sonogashira coupling of aryl bromides using near stoichiometric carbon monoxide[J].Org Lett,2014,16:2216-2219.

[22] Feng X J, Song J L, Liu H S,etal. Palladium-catalyzed carbonylative coupling of (chloromethyl)arenes with terminal arylalkynes to produce 1,4-diaryl-3-butyn-2-ones[J].RSC Advances,2013,3:18985-18991.

[23] Wang Y, Liu J H, Xia C G. Cross-linked polymer supported palladium catalyzed carbonylative Sonogashira coupling reaction in water[J].Tetrahedron Lett,2011,52:1587-1591.

[24] Wu X F, Neumann H, Beller M. A general and convenient palladium-catalyzed carbonylative Sonogashira coupling of aryl bromides[J].Chem Eur J,2010,16:12104-12107.

[25] Ahmed M S M, Mori A. Carbonylative Sonogashira coupling of terminal alkynes with aqueous ammonia[J].Org Lett,2003,5:3057-3060.

[26] Sun W J, Wang Y, Wu X,etal. Palladium-,ligand-,and solvent-free synthesis of ynones by the coupling of acyl chlorides and terminal alkynes in the presence of a reusable copper nanoparticle catalyst[J].Green Chem,2013,15:2356-2361.

[27] Boersch C, Merkul E, Müller T J J. Catalytic syntheses ofN-heterocyclic ynones and ynediones byinsituactivation of carboxylic acids with oxalyl chloride[J].Angew Chem Int Ed,2011,50:10448-10452.

[28] Park A, Park K, Kim Y,etal. Pd-catalyzed carbonylative reactions of aryl iodides and alkynyl carboxylic acids via decarboxylative couplings[J].Org Lett,2011,13:944-947.

[29] Santra S, Dhara K, Ranjan P,etal. A supported palladium nanocatalyst for copper free acyl sonogashira reactions:One-pot multicomponent synthesis ofN-containing heterocycles[J].Green Chem,2011,11:3238-3247.

[30] D’Souza D M, Müller T J J. Catalytic alkynone generation by Sonogashira reaction and its application in three-component pyrimidine synthesis[J].J Nat Protoc,2008,3:1660-1665.

[31] Karpov A S, Müller T J J. New entry to a three-component pyrimidine synthesis by TMS-ynones via Sonogashira coupling[J].Org Lett,2003,5:3451-3454.

[32] Karpov A S, Muller T J J. Straight forward novel one-pot enaminone and pyrimidine syntheses by coupling-addition-cyclocondensation sequences[J].Synthesis,2003,35:2815-2826.

[33] Lei A W, Wu Y X, Tang H Y,etal. Rh(III)- or Ir(III)-catalyzed ynone synthesis from aldehydes via chelation-assisted C—H bond activation[J].Chem Commun, 2015,7871-7875.

[34] Zhang R Y, Xi L Y, Zhang L,etal. Metal-free synthesis of ynones via direct C—H alkynylation of aldehydes with ethynylbenziodoxolones[J].Tetrahedron,2015,71:6176-6173

[35] Huang H C, Zhang G J , Chen Y Y. Dual hypervalent iodine(III) reagents and photoredox catalysis enable decarboxylative ynonylation under mild conditions[J].Angew Chem Int Ed,2015,54:7872-7876.

[36] Tang T, Fei X D, Ge Z Y,etal. Palladium-catalyzed carbonylative Sonogashira coupling of aryl bromides via tert-butyl isocyanide insertion[J].J Org Chem,2013,78:3170 - 3175.

[37] 趙蔚，劉偉. Weinreb 酰胺在有機合成中的應用進展[J].有機化學,2015,35:55-69．

[38] Singh J, Satyamurthi N, Aidhen I S. The growing synthetic utility of Weinreb’s amide[J].J Prakt Chem/Chem-Ztg,2000,342:340-354.

[39] Sibi M P. Chemistry ofN-methoxy-N-methylsmides:Applications in synthesis a review[J].Org Prep Proced Int,1993,25:15-40.

[40] Pérez M, Pozo C D, Reyes F,etal. Total synthesis of natural myriaporones[J].Angew Chem Int Ed, 2004,43:1724-1727.

[41] Lygo B, Bhatias M, Cooke J W B,etal. Synthesis of (±)-solanapyrones A and B[J].Tetrahedron Lett,2003,44:2529-2532.

[42] Dias L C, Sousa M A D. Synthetic studies directed toward the total synthesis of dolabriferol[J].Tetrahedron Lett,2003,44:5625-5628.

[43] Shimizu T, Kusada J, Ishiyama H,etal. Efficient synthesis of the 6,6-spiroacetal of spirofungin A[J].Tetrahedron Lett,2003,44:4965-4968.

[44] Taillier C, Bellosta V, Meyer C,etal. Synthesis ofω-hydroxy ketones fromω-benzyloxy weinreb amides by using a chemoselective nucleophilic addition/Birch reduction process[J].Org Lett,2004,6:2145-2147.

[45] 王鳳嬌，陸愛玲，黃丹鳳，等. 鎂粉促進 Weinreb 酰胺和鹵代烴的“一鍋法”制備酮類反應研究[J].有機化學,2015,35:1046-1051.

[46] Niu T, Wang K H, Huang D,etal. One-pot transition-metal-free synthesis of Weinreb amides directly from carboxylic acids[J].Synthesis,2014,46:320-330.

[47] Maeda Y, Kakiuchi N, Matsumura S,etal. Oxovanadium complex-catalyzed aerobic oxidation of propargylic alcohols[J].J Org Chem,2002,67:6718-6724.

“One-Pot” Synthesis ofα,β-Alkynones Promoted by Magnesium Powder

YANG Tian-yu, HUANG Dan-feng, WANG Ke-hu, SU Ying-peng, HU Yu-lai*

(College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, China)

“One-pot” synthesis ofα,β-alkynones(5a～5j, 5l～5n, 5p～5r) from Weinreb amides(1a～1j, 1l～1n, 1p～1r) and phenylacetylene(2) promoted by magnesium powder(4) in the presence ofn-butyl bromide(3) was reported. The results indicated that under the optimum reaction conditions(THF as solvent, 3 1.1 mmol, 4 1.25 mmol, stirring for 2 h; then add 2 0.75 mmol, stirring for 1 h; add 1 0.5 mmol, reaction at rt), the yield of 5a～5j, 5l～5n, 5p～5r were 45%～86%. The structures were confirmed by1H NMR and13C NMR.

one-pot synthesis; magnesium powder promotion; Weinreb amide; phenylacetylene;α,β-alkynone

2016-10-21;

2017-01-05

國家自然科學基金資助項目(21262031, 21462037)

楊天宇(1990-)，男，回族，遼寧沈陽人，碩士研究生，主要從事有機合成的研究。 E-mail: maxli101@sina.com

胡雨來，教授，博士生導師, E-mail: huyl@nwnu.edu.cn

O622.4

A

10.15952/j.cnki.cjsc.1005-1511.2017.02.16264