江銀枝,周 俊

(浙江理工大學(xué)化學(xué)系,浙江杭州310018)

查爾酮參與的不對(duì)稱Michael加成反應(yīng)研究進(jìn)展

江銀枝＊,周 俊

(浙江理工大學(xué)化學(xué)系,浙江杭州310018)

綜述了近十年來(lái),金雞納堿、硫脲、手性離子液體、季銨鹽、脯氨酸和葡萄糖類衍生物等有機(jī)小分子在催化查爾酮的不對(duì)稱Michael加成反應(yīng)中的應(yīng)用.有機(jī)小分子催化的機(jī)理大部分都是通過(guò)氫鍵、離子鍵等與底物相互作用而使其有較好的對(duì)映選擇性.

有機(jī)小分子;查爾酮;不對(duì)稱Michael加成

查爾酮是黃酮類化合物的一種,具有抗炎癥、殺菌、除草等功效,因此對(duì)查爾酮的研究成為醫(yī)藥、食品等領(lǐng)域的一個(gè)重要課題.大多數(shù)藥物都具有手性,且構(gòu)型的不同可能表現(xiàn)出不同的藥理活性,故對(duì)手性的控制意義顯得尤為突出.近年來(lái),不對(duì)稱催化已經(jīng)成為合成手性分子的一個(gè)重要手段.發(fā)展得較早的是手性配體與稀土或過(guò)渡金屬聯(lián)合催化,但是由于金屬離子的引入使得后處理時(shí)殘余的金屬不容易除去,不利于在制藥領(lǐng)域的工業(yè)化生產(chǎn).

有機(jī)小分子催化因其不含金屬、非常穩(wěn)定、價(jià)廉易得、無(wú)毒性、易于回收等,在近幾十年來(lái)越來(lái)越受到人們的關(guān)注,并取得了迅猛的發(fā)展.有機(jī)小分子通過(guò)與親核或親電試劑形成氫鍵、離子鍵或共價(jià)鍵,起到催化劑和手性試劑的作用[1].Michael加成是有機(jī)合成中構(gòu)建C-C鍵的重要反應(yīng)之一,因此一直是有機(jī)合成化學(xué)家感興趣的研究課題[2].本文作者就近十年來(lái)查爾酮參與的不對(duì)稱Michael加成反應(yīng)中使用的有機(jī)小分子催化劑進(jìn)行了綜述.

1 有機(jī)小分子催化劑研究進(jìn)展

1.1 金雞納堿

1981年,Wynberg等首次將天然的金雞納堿應(yīng)用于Michael加成[3](Scheme 1).自從Corey等[4]成功地將金雞納堿用于不對(duì)稱雙羥基化反應(yīng)以來(lái),其在不對(duì)稱合成中的應(yīng)用越來(lái)越受到重視.

2006年,Li等[5]分別以金雞納堿化合物1、2、3催化查爾酮與硫代酸的Michael加成反應(yīng),產(chǎn)率>91%,但e e值幾乎為零.2007年,Gu等[6]利用金雞納堿化合物4催化α-氰基乙酸乙酯與查爾酮的Michael加成反應(yīng),產(chǎn)率為78%,e e值為72%.2008年,Deng等[7]分別將金雞納堿化合物5、6、7應(yīng)用于丙二氰與查爾酮的不對(duì)稱Michael加成中,發(fā)現(xiàn)化合物5在DCM和TFA中催化的產(chǎn)率為93%,e e值為95%,發(fā)現(xiàn)化合物5可以作為雙功能催化劑.2009年Xie等[8]也報(bào)道了類似的反應(yīng).

Wang等[9]分別以金雞納堿化合物2、7催化2(5H)-呋喃酮與查爾酮的不對(duì)稱Michael加成反應(yīng),e e值分別為60%和68%.Wang等[10]首次以苯并三唑?yàn)橛H核試劑對(duì)查爾酮進(jìn)行不對(duì)稱Michael加成,考察了查爾酮上不同取代基對(duì)產(chǎn)率和e e值的影響.

此外,Scettri等[11]首次在無(wú)溶劑條件下利用化合物1、2、3、7、8、9催化苯胺與查爾酮的不對(duì)稱Michael加成,但e e值普遍不高.

1.2 手性硫脲

2005年,Tibor等[12-13]分別以化合物 10、11催化硝基甲烷與查爾酮的不對(duì)稱 Michael加成反應(yīng)(Scheme 2),發(fā)現(xiàn)化合物10a、10b、11a手性誘導(dǎo)效果較好,e e值為89%～98%.

2006年,Wang等[14]研究了10a、12、13催化硫代酸與查爾酮的不對(duì)稱加成,e e值為33%～65%.2007年,Gu等[6]使用了三種硫脲化合物10b、14、15催化α-氰基乙酸乙酯與查爾酮的不對(duì)稱Michael加成反應(yīng).

Biddle等[15]利用硫脲化合物10a、12、16催化查爾酮合成了手性黃酮(Scheme 3).e e高達(dá)92%.

最近,匈牙利學(xué)者Pham等[16]使用10a、10b催化氰甲基亞磷酸二乙酯與查爾酮的不對(duì)稱共軛加成時(shí),發(fā)現(xiàn)在含氧原子的溶劑中,由于氧的存在阻礙了過(guò)渡態(tài)中氫鍵的形成,從而導(dǎo)致使用此類溶劑時(shí)產(chǎn)物的e e值很低.2010年,Wang等[9]考察了化合物17a、17b、17c、17d催化2(5H)-呋喃酮對(duì)查爾酮的不對(duì)稱 Michael加成反應(yīng),發(fā)現(xiàn)17b由于三氟甲基的引入使得胺基的酸性和形成氫鍵的能力加強(qiáng),其產(chǎn)物e e值為77%,但產(chǎn)率低;同時(shí)發(fā)現(xiàn)LiOAc和γ-丁烯羥酸內(nèi)酯的加入,使得產(chǎn)率達(dá)到92%,且e e值不變.

1.3 手性離子液體

2005年,Wang等[17]利用手性離子液體18、19、20、21、22、23催化丙二酸二乙酯與查爾酮的不對(duì)稱Michael加成反應(yīng)(Scheme 4).發(fā)現(xiàn)21的催化活性較22高,產(chǎn)率≥90%,e e為10%～25%.

Wang等[18]使用離子液體24催化查爾酮與環(huán)己酮的不對(duì)稱Michael加成反應(yīng),發(fā)現(xiàn)通過(guò)改變?nèi)軇?產(chǎn)物構(gòu)型可發(fā)生翻轉(zhuǎn).

1.4 季銨鹽

2000年,Corey等[19]使用25有效地催化了苯乙酮和查爾酮的不對(duì)稱加成反應(yīng)(Scheme 5).

Ooi等[20]與Dere等[21]使用化合物26、27催化丙二酸二乙酯與查爾酮的Michael加成反應(yīng),發(fā)現(xiàn)產(chǎn)率高達(dá)94%～99%.化合物26的產(chǎn)物手性選擇性較好,e e值可達(dá)85%～94%.2006年,Cho等[22]研究了化合物28、29催化的丙二酸二酯與查爾酮的不對(duì)稱Michael加成反應(yīng),發(fā)現(xiàn)28a的產(chǎn)物手性選擇性較好,e e為45%～70%.

1.5 脯氨酸

Wang等[23]和Xu等[24]研究了化合物30、31、32催化環(huán)酮與查爾酮的不對(duì)稱加成,發(fā)現(xiàn)e e值為73%～100%.

2007年,Kumar等[25]使用L-脯氨酸催化了硫醇(酚)與查爾酮的不對(duì)稱Michael加成,產(chǎn)率為80%～98%,但e e值 ≤39%.

除了上述五類化合物作為查爾酮參與的Michael不對(duì)稱加成催化劑外,Suresh與 Torke等[26-29]研究了葡萄糖類化合物催化硝基烷烴與查爾酮的不對(duì)稱Michael加成反應(yīng).產(chǎn)率為90%～100%,e e值為58%～65%.Allingham等[30]使用化合物33催化2-硝基丙烷對(duì)查爾酮的不對(duì)稱Michael加成(Scheme 6),產(chǎn)率為70%,e e值為23%.

2 總結(jié)與展望

由于查爾酮在醫(yī)藥領(lǐng)域的應(yīng)用,對(duì)其手性衍生物的研究具有重要的意義.其參與的不對(duì)稱Michael加成反應(yīng)是通過(guò)引入C-C鍵、C-N鍵及C-O鍵合成新的手性化合物或雜環(huán)化合物的重要方法,這其中有機(jī)小分子催化劑的研究顯得十分重要.

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Organo-catalyzed Enantioselective Michael Addition to Chalcone

J IANG Yin-zhi＊,ZHOU Jun

(Chemistry Department,Zhejiang Sci-Tech University,Hangzhou310018,Zhejiang,China)

Organo-catalyzed asymmetric Michaael addition to chalcone in this decade has been reviewed.The mechanism of the catalysis interaction with the substance may usually be through the hydrogen bond or ionic bond.

organo-catalyst;chalcone;enantioselective Michael addition

O 622.4

A

1008-1011(2010)06-0100-05

2010-07-06.

國(guó)家自然科學(xué)基金資助項(xiàng)目(20901067);浙江省自然科學(xué)基金資助項(xiàng)目(Y4080342).

江銀枝(1973-),女,副教授,博士,研究領(lǐng)域:有機(jī)化學(xué)、配位化學(xué),藥物化學(xué).E-mail:jiangyinzhi2003@yahoo.com.cn.