劉　旭，劉仲能，顧松園

(1.中國石化綠色化工與工業(yè)催化國家重點(diǎn)實(shí)驗(yàn)室，上海 201208；2.中國石化上海石油化工研究院，上海 201208)

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綜述與展望

官能團(tuán)化烯烴的氫甲?；磻?yīng)研究及應(yīng)用進(jìn)展

劉旭1,2*，劉仲能1,2，顧松園1,2

(1.中國石化綠色化工與工業(yè)催化國家重點(diǎn)實(shí)驗(yàn)室，上海 201208；2.中國石化上海石油化工研究院，上海 201208)

氫甲?；磻?yīng)已發(fā)展成為重要的工業(yè)均相催化反應(yīng)之一，通過官能團(tuán)化烯烴氫甲?；磻?yīng)可以得到官能團(tuán)化的醛類化合物，該類化合物大多是精細(xì)化學(xué)品或合成中間體，官能團(tuán)化烯烴顯示出很多不一樣的特性。綜述近年來官能團(tuán)化烯烴氫甲?；磻?yīng)研究進(jìn)展，介紹乙烯基芳烴、α-官能團(tuán)化烯烴以及β-官能團(tuán)化烯烴的氫甲?；磻?yīng)及應(yīng)用，并對(duì)官能團(tuán)化烯烴氫甲?；磻?yīng)進(jìn)行展望。

精細(xì)化學(xué)工程;官能團(tuán)化烯烴;氫甲?；?醛

氫甲?；磻?yīng)是指烯烴在催化劑作用下與CO/H2反應(yīng)生成醛的過程，已發(fā)展成為迄今最重要的工業(yè)均相催化反應(yīng)之一。據(jù)統(tǒng)計(jì)，全球通過氫甲?；a(chǎn)醛和醇的能力已達(dá)千萬噸規(guī)模[1]。通過官能團(tuán)化烯烴氫甲酰化反應(yīng)可以得到官能團(tuán)化的醛類化合物，而官能團(tuán)化的醛大多是精細(xì)化學(xué)品或藥物、香精香料的合成中間體。與非官能團(tuán)化烯烴相比，官能團(tuán)的存在影響烯烴氫甲酰化反應(yīng)，顯示出很多不一樣的特性[2]，這些特性是由于環(huán)狀金屬中間體的穩(wěn)定性不同所致，同時(shí)影響反應(yīng)的區(qū)域選擇性[3]。

本文綜述近年來官能團(tuán)化烯烴氫甲?；磻?yīng)研究進(jìn)展，介紹乙烯基芳烴、α-官能團(tuán)化烯烴以及β-官能團(tuán)化烯烴的氫甲?；磻?yīng)及應(yīng)用，并對(duì)官能團(tuán)化烯烴氫甲?；磻?yīng)進(jìn)行展望。

1　乙烯基芳烴

通常，烯基芳烴和烯基雜環(huán)類化合物[4-6]氫甲?；磻?yīng)生成支鏈醛，這是由于反應(yīng)過程中形成了穩(wěn)定的η3-丙烯基中間體[7]。在該類底物中，經(jīng)常使用苯乙烯考察新的配體、催化劑和添加劑，并用于機(jī)理研究。使用四齒配體，有可能改變苯乙烯衍生物氫甲?；磻?yīng)的區(qū)域選擇性，對(duì)位取代基的電子效應(yīng)在該反應(yīng)中顯而易見(l/b：p-氟-苯乙烯，14.2；p-甲基-苯乙烯，19.4；苯乙烯，21.2；p-甲氧基-苯乙烯，26.0)[8]。當(dāng)苯環(huán)上鄰位取代基的位阻較大時(shí)，也會(huì)傾向于生成支鏈醛。

美國安進(jìn)公司報(bào)道了一種全合成鈣受體激動(dòng)劑西那卡塞的方法[9]，由間三氟甲基苯乙烯出發(fā)，經(jīng)氫甲?；磻?yīng)和還原氨化反應(yīng)得到藥物活性成分，氫氨甲基化反應(yīng)可以不經(jīng)分離中間體一步完成[10]。

Botteghi C等[11]研究發(fā)現(xiàn)，在烯基-1,1-二芳基化合物的氫甲?；磻?yīng)中，Rh催化劑可以代替Co體系，與還原氨化反應(yīng)結(jié)合可以合成抗精神病藥物氟斯必靈和五氟利多以及泌尿系統(tǒng)藥物托特羅定[12]，也可用于合成芬哌丙烷[13]，治療腸胃功能紊亂。

2　α-官能團(tuán)化烯烴

文獻(xiàn)[14]報(bào)道了氯乙烯在Rh催化下的氫甲?；磻?yīng)可以得到2-氯丙醛，由于化合物熱穩(wěn)定性欠佳，采用反應(yīng)條件比Co催化劑溫和的Rh催化劑，得到更好的結(jié)果。為了避免催化劑被HCl分解，體系中加入緩沖液或胺。反應(yīng)區(qū)域選擇性較高，產(chǎn)物經(jīng)氧化以及取代反應(yīng)可以生成消旋的乳酸。

作為烯基酯類底物，使用P(OPh)3作為配體時(shí)，乙酸乙烯酯基本生成2-乙酰氧基丙醛[15]；使用雙膦配體時(shí)，主要得到支鏈產(chǎn)物[16]。體系內(nèi)存在弱堿時(shí)，甲?；姿狨タ赊D(zhuǎn)化為β-乙酰氧基酮[17]；溫度較高且使用非改性Co催化劑時(shí)，可生成單乙?；Ｗo(hù)的丙二醇[18]。使用改性金屬/三齒膦配體在相對(duì)較低溫度下，區(qū)域選擇性會(huì)發(fā)生翻轉(zhuǎn)，并高選擇性生成乙酸-3-羥基丙酯(>99.9%)[19]，產(chǎn)物氫化后可生成1,3-丙二醇，單乙?；Ｗo(hù)的丙二醇可與對(duì)苯二甲酸聚合生成聚對(duì)苯二甲酸丙二醇酯。

在未改性Co催化劑的催化作用下，丙烯腈經(jīng)氫甲?；磻?yīng)可得到β-甲?；妫x擇性還原甲?；傻玫溅?羥基丁腈。使用Rh/P(OPh)3作為催化劑時(shí)，主要得到α-甲?；‰?，是合成聚甲基丙烯酸甲酯的起始原料[20]。作為共聚單體的2-三氟甲基丙烯酸，可以由3,3,3-三氟丙烯通過Rh催化的氫甲酰化反應(yīng)再經(jīng)氧化、鹵化和消除反應(yīng)得到[21]。

丙烯酰胺同樣可以發(fā)生氫甲?；磻?yīng)，由于氨基的導(dǎo)向作用，反應(yīng)主要發(fā)生在α-碳原子上，生成異構(gòu)的醛[22]，在Rh催化反應(yīng)中，單膦配體的反應(yīng)效果優(yōu)于雙膦配體[23]，丙烯酸酯的氫甲?；磻?yīng)也發(fā)生在α-位[24]。當(dāng)α位有取代基的丙烯酸衍生物發(fā)生氫甲酰化反應(yīng)時(shí)，醛基依然在三級(jí)碳原子上生成[25]，生成的醛可轉(zhuǎn)化為α,α-取代的β氨基羧酸酯。

3　β-官能團(tuán)化烯烴

Zhang X等[26]使用膦-亞磷酰胺配體與Rh的催化體系，考察了該類底物反應(yīng)的區(qū)域選擇性。烯丙醇的氫甲?；磻?yīng)主要生成4-丁醇醛，該化合物可以合成1,4-丁二醇和四氫呋喃。除支鏈產(chǎn)物外，氫甲?；磻?yīng)還可生成一些C3副產(chǎn)物，如正丙醇和丙醛[27]。最初反應(yīng)使用未經(jīng)改性的Rh催化劑，隨后單膦[28]或雙膦配體[29]逐漸應(yīng)用于該反應(yīng)。1-丁烯-3-醇的反應(yīng)主要發(fā)生在γ位，得到α-羥基-β-甲基四氫呋喃，經(jīng)脫水可以制備取代的二氫呋喃[30]。

Ruiz N等[31]研究了單膦配體與Rh組成的催化劑對(duì)非環(huán)狀烯丙基醚氫甲?；磻?yīng)。Polo A等[32]使用二氫呋喃和二氫吡喃異構(gòu)體研究了雜環(huán)化合物中氧原子的導(dǎo)向作用,通常，使用二氫呋喃反應(yīng)條件較溫和，可先異構(gòu)化為平面性更好的五元環(huán)，從而更好形成金屬絡(luò)合物。2H,5H-二氫呋喃易轉(zhuǎn)化為相應(yīng)的2H,3H-異構(gòu)體，與合成氣進(jìn)行氫甲酰化反應(yīng)。使用位阻較大的單膦配體時(shí)，主要生成2-甲?；臍溥秽皇褂肞Ph3作為配體時(shí)，主要生成3-甲?；臍溥秽?二氫吡喃也有類似的特性。

Briggs J R等[33]研究了支鏈烯丙基硅和烯丙醇類化合物的氫甲?；磻?yīng)，使用Rh-BIPHEPHOS催化劑可以得到更高的正異比,也應(yīng)用于抗心律失衡藥物伊布利特和抗組胺劑非索非那定[34]的全合成。

Verspui G等[35]研究了N-乙?；┍吩谒蛢上囿w系中氫甲酰化反應(yīng)的區(qū)域選擇性,結(jié)果表明,使用Rh-PPh3作為催化劑時(shí)，僅得到中等的區(qū)域選擇性，但活性較高；使用Xantphos作為配體時(shí)，產(chǎn)物的正異比可達(dá)20∶1，但反應(yīng)速率較低。使用水溶性Rh-TPPTS得到的效果最好，4-乙酰氨基丙烯可轉(zhuǎn)化為N-乙酰基-5-甲氧基色胺(褪黑素),是一種可以調(diào)節(jié)睡眠周期的天然產(chǎn)物。

官能團(tuán)化烯丙胺在Rh的催化作用下可發(fā)生氫甲?；磻?yīng)[36-37],區(qū)域選擇性較高，產(chǎn)物可作為合成β內(nèi)酰胺的中間體，用于合成抗生素。對(duì)于N-烯丙基-鄰苯二甲酰亞胺，Rh-BIPHEPHOS作為催化劑時(shí)，目標(biāo)產(chǎn)物收率可達(dá)95%，產(chǎn)物正異比可達(dá)18∶1[38]。

Lambers-Verstappen M M H等[39]研究了烯丙腈的氫甲?；磻?yīng)，正異比可達(dá)77∶23。使用手性雙膦配體時(shí)，更易得到支鏈的醛，并且對(duì)映選擇性非常好[40]。Lazzaroni R等[41]由光學(xué)純的α-氨基酸高對(duì)映選擇性合成手性吲哚里西啶類化合物,先合成手性N-乙烯基吡咯，然后在未經(jīng)修飾的Rh催化劑作用下經(jīng)氫甲?；磻?yīng)得到正構(gòu)的醛，再經(jīng)關(guān)環(huán)脫水反應(yīng)得到稠雜環(huán)化合物。

烯丙基芳基的高區(qū)域選擇性氫甲酰化反應(yīng)引起關(guān)注，因?yàn)閱屋祁惗∠惴?、黃樟素、甲基胡椒酚和其異構(gòu)體可得到相應(yīng)的醛，在香精香料和藥物領(lǐng)域應(yīng)用廣泛,如黃樟素在2位選擇性氫甲酰化反應(yīng)可以得到香料新洋茉莉醛[42]。Da Silva等[43]研究發(fā)現(xiàn),NAPHOS作為配體可得到較高的區(qū)域選擇性，dppp作為配體時(shí)主要得到支鏈醛。單膦配體與Rh組成的催化劑在丁香酚的氫甲?；磻?yīng)中，區(qū)域選擇性最高可達(dá)84%[44]。

4　結(jié)語與展望

經(jīng)過多年發(fā)展，官能團(tuán)化烯烴的氫甲?；磻?yīng)取得了顯著進(jìn)步，開發(fā)了多種配體和金屬絡(luò)合物，表現(xiàn)出較高的活性和區(qū)域選擇性，成功應(yīng)用于天然產(chǎn)物類藥物的合成。但存在烯基砜和亞砜類化合物的氫甲?；磻?yīng)研究不夠深入、反應(yīng)區(qū)域選擇性不易控制、配體及催化劑制備限制了在大規(guī)模合成中的應(yīng)用、底物類型不夠豐富和催化劑通用性欠佳等缺點(diǎn)。在官能團(tuán)化烯烴的氫甲?；磻?yīng)中，新配體和催化劑開發(fā)仍具有挑戰(zhàn)性，具有廣闊的應(yīng)用前景。

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Research and application advance in hydroformylation of functionalized olefins

LiuXu1,2*,LiuZhongneng1,2,GuSongyuan1,2

(1.Sinopec State Key Laboratory of Green Chemical Engineering and Industrial Catalysis, Shanghai 201208, China; 2.Sinopec Shanghai Research Institute of Petrochemical Technology, Shanghai 201208, China)

Hydroformylation is one of the most important homogeneous catalytic processes in industry.Hydroformylation of functionalized olefins provides the routes to obtaining aldehydes with one or more additional functional groups.Such functionalized aldehydes can be sold as final products or used as intermediates in the synthesis of fine chemicals,pharmaceuticals and fragrances.The hydroformylation showed distinct differences compared to the reaction with unfunctionalized alkenes.In this paper, the progress in hydroformylation of functionalized olefins and its application were introduced,including vinyl arenes,α-functionalized olefins and β-functionalized olefins.The development prospects of hydroformylation of functionalized olefins was put forward．

fine chemical engineering; functionalized olefins; hydroformylation; aldehyde

TQ426.94;O643.36Document code: AArticle ID: 1008-1143(2016)08-0001-06

2016-04-14基金項(xiàng)目：中國石化基金(414088)資助項(xiàng)目

劉旭，1983年生，男，河南省鄭州市人，博士，工程師，研究方向?yàn)榫啻呋?/p>

劉旭。

10.3969/j.issn.1008-1143.2016.08.001

TQ426.94;O643.36

A

1008-1143(2016)08-0001-06

doi:10.3969/j.issn.1008-1143.2016.08.001