官能團化烯烴的氫甲?；磻芯考皯眠M展

劉　旭，劉仲能，顧松園

(1.中國石化綠色化工與工業催化國家重點實驗室，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

官能團化烯烴的氫甲?；磻芯考皯眠M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催化國家重點實驗室，上海 201208；2.中國石化上海石油化工研究院，上海 201208)

氫甲?；磻寻l展成為重要的工業均相催化反應之一，通過官能團化烯烴氫甲?；磻梢缘玫焦倌軋F化的醛類化合物，該類化合物大多是精細化學品或合成中間體，官能團化烯烴顯示出很多不一樣的特性。綜述近年來官能團化烯烴氫甲?；磻芯窟M展，介紹乙烯基芳烴、α-官能團化烯烴以及β-官能團化烯烴的氫甲?；磻皯?，并對官能團化烯烴氫甲?；磻M行展望。

精細化學工程;官能團化烯烴;氫甲?；?醛

氫甲?；磻侵赶N在催化劑作用下與CO/H2反應生成醛的過程，已發展成為迄今最重要的工業均相催化反應之一。據統計，全球通過氫甲?；a醛和醇的能力已達千萬噸規模[1]。通過官能團化烯烴氫甲?；磻梢缘玫焦倌軋F化的醛類化合物，而官能團化的醛大多是精細化學品或藥物、香精香料的合成中間體。與非官能團化烯烴相比，官能團的存在影響烯烴氫甲?；磻?，顯示出很多不一樣的特性[2]，這些特性是由于環狀金屬中間體的穩定性不同所致，同時影響反應的區域選擇性[3]。

本文綜述近年來官能團化烯烴氫甲?；磻芯窟M展，介紹乙烯基芳烴、α-官能團化烯烴以及β-官能團化烯烴的氫甲?；磻皯?，并對官能團化烯烴氫甲?；磻M行展望。

1　乙烯基芳烴

通常，烯基芳烴和烯基雜環類化合物[4-6]氫甲?；磻芍ф溔?，這是由于反應過程中形成了穩定的η3-丙烯基中間體[7]。在該類底物中，經常使用苯乙烯考察新的配體、催化劑和添加劑，并用于機理研究。使用四齒配體，有可能改變苯乙烯衍生物氫甲?；磻膮^域選擇性，對位取代基的電子效應在該反應中顯而易見(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]。當苯環上鄰位取代基的位阻較大時，也會傾向于生成支鏈醛。

美國安進公司報道了一種全合成鈣受體激動劑西那卡塞的方法[9]，由間三氟甲基苯乙烯出發，經氫甲?；磻瓦€原氨化反應得到藥物活性成分，氫氨甲基化反應可以不經分離中間體一步完成[10]。

Botteghi C等[11]研究發現，在烯基-1,1-二芳基化合物的氫甲?；磻?，Rh催化劑可以代替Co體系，與還原氨化反應結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-官能團化烯烴

文獻[14]報道了氯乙烯在Rh催化下的氫甲?；磻梢缘玫?-氯丙醛，由于化合物熱穩定性欠佳，采用反應條件比Co催化劑溫和的Rh催化劑，得到更好的結果。為了避免催化劑被HCl分解，體系中加入緩沖液或胺。反應區域選擇性較高，產物經氧化以及取代反應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，乙酸乙烯酯基本生成2-乙酰氧基丙醛[15]；使用雙膦配體時，主要得到支鏈產物[16]。體系內存在弱堿時，甲?；姿狨タ赊D化為β-乙酰氧基酮[17]；溫度較高且使用非改性Co催化劑時，可生成單乙?；Ｗo的丙二醇[18]。使用改性金屬/三齒膦配體在相對較低溫度下，區域選擇性會發生翻轉，并高選擇性生成乙酸-3-羥基丙酯(>99.9%)[19]，產物氫化后可生成1,3-丙二醇，單乙?；Ｗo的丙二醇可與對苯二甲酸聚合生成聚對苯二甲酸丙二醇酯。

在未改性Co催化劑的催化作用下，丙烯腈經氫甲?；磻傻玫溅?甲?；?，選擇性還原甲?；傻玫溅?羥基丁腈。使用Rh/P(OPh)3作為催化劑時，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?；磻俳浹趸?、鹵化和消除反應得到[21]。

丙烯酰胺同樣可以發生氫甲?；磻?，由于氨基的導向作用，反應主要發生在α-碳原子上，生成異構的醛[22]，在Rh催化反應中，單膦配體的反應效果優于雙膦配體[23]，丙烯酸酯的氫甲?；磻舶l生在α-位[24]。當α位有取代基的丙烯酸衍生物發生氫甲?；磻獣r，醛基依然在三級碳原子上生成[25]，生成的醛可轉化為α,α-取代的β氨基羧酸酯。

3　β-官能團化烯烴

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的區域選擇性。烯丙醇的氫甲?；磻饕?-丁醇醛，該化合物可以合成1,4-丁二醇和四氫呋喃。除支鏈產物外，氫甲?；磻€可生成一些C3副產物，如正丙醇和丙醛[27]。最初反應使用未經改性的Rh催化劑，隨后單膦[28]或雙膦配體[29]逐漸應用于該反應。1-丁烯-3-醇的反應主要發生在γ位，得到α-羥基-β-甲基四氫呋喃，經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組成的催化劑對非環狀烯丙基醚氫甲?；磻?。Polo A等[32]使用二氫呋喃和二氫吡喃異構體研究了雜環化合物中氧原子的導向作用,通常，使用二氫呋喃反應條件較溫和，可先異構化為平面性更好的五元環，從而更好形成金屬絡合物。2H,5H-二氫呋喃易轉化為相應的2H,3H-異構體，與合成氣進行氫甲?；磻?。使用位阻較大的單膦配體時，主要生成2-甲?；臍溥秽?；使用PPh3作為配體時，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?，使用Rh-BIPHEPHOS催化劑可以得到更高的正異比,也應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?；磻膮^域選擇性,結果表明,使用Rh-PPh3作為催化劑時，僅得到中等的區域選擇性，但活性較高；使用Xantphos作為配體時，產物的正異比可達20∶1，但反應速率較低。使用水溶性Rh-TPPTS得到的效果最好，4-乙酰氨基丙烯可轉化為N-乙?；?5-甲氧基色胺(褪黑素),是一種可以調節睡眠周期的天然產物。

官能團化烯丙胺在Rh的催化作用下可發生氫甲?；磻猍36-37],區域選擇性較高，產物可作為合成β內酰胺的中間體，用于合成抗生素。對于N-烯丙基-鄰苯二甲酰亞胺，Rh-BIPHEPHOS作為催化劑時，目標產物收率可達95%，產物正異比可達18∶1[38]。

Lambers-Verstappen M M H等[39]研究了烯丙腈的氫甲?；磻?，正異比可達77∶23。使用手性雙膦配體時，更易得到支鏈的醛，并且對映選擇性非常好[40]。Lazzaroni R等[41]由光學純的α-氨基酸高對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，然后在未經修飾的Rh催化劑作用下經氫甲?；磻玫秸龢嫷娜?，再經關環脫水反應得到稠雜環化合物。

烯丙基芳基的高區域選擇性氫甲?；磻痍P注，因為單萜類丁香酚、黃樟素、甲基胡椒酚和其異構體可得到相應的醛，在香精香料和藥物領域應用廣泛,如黃樟素在2位選擇性氫甲?；磻梢缘玫较懔闲卵筌岳蛉42]。Da Silva等[43]研究發現,NAPHOS作為配體可得到較高的區域選擇性，dppp作為配體時主要得到支鏈醛。單膦配體與Rh組成的催化劑在丁香酚的氫甲?；磻?，區域選擇性最高可達84%[44]。

4　結語與展望

經過多年發展，官能團化烯烴的氫甲?；磻〉昧孙@著進步，開發了多種配體和金屬絡合物，表現出較高的活性和區域選擇性，成功應用于天然產物類藥物的合成。但存在烯基砜和亞砜類化合物的氫甲?；磻芯坎粔蛏钊?、反應區域選擇性不易控制、配體及催化劑制備限制了在大規模合成中的應用、底物類型不夠豐富和催化劑通用性欠佳等缺點。在官能團化烯烴的氫甲?；磻?，新配體和催化劑開發仍具有挑戰性，具有廣闊的應用前景。

[1]Naqvi S.Oxo Alcohols[C]//Process Economics Program Report 21E,Menlo Park,CA:SRI Consulting,2010.

[2]Reinius H K,Krause A O I.Hydroformylation of functional alkenes with heterodonor phosphine rhodium catalysts:substrate or ligand directed regioselectivity?[J].Catalysis Letters,2000,70(3):149-154.

[3]Fremy G,Monflier E,Carpentier J F,et al.An unusual enhancement of catalytic activity in biphasic catalysis:the rhodium catalyzed hydroformylation of acrylic esters[J].Journal of Molecular Catalysis A:Chemical,1998,129(1):35-40.

[4]Settambolo R,Pucci S,Bertozzi S,et al.Remarkable α-regioselectivity in the rhodium-catalyzed hydroformylation of 2-vinylpyridine[J].Journal of Organometallic Chemistry,1995,489(1/2):50-51.

[5]Botteghi C,Marchetti M,Paganelli S,et al.Study on the regioselectivity in the rhodium-catalyzed hydroformylation of vinyl-pyridine derivatives[J].Journal of Molecular Catalysis A:Chemical,1997,118:173-179.

[6]Lazzaroni R,Settambolo R,Caiazzo A,et al.Rhodium-catalyzed hydroformylation of 4-vinylpyridine:4-ethylpyridine formation via an unusual cleavage of the Rh-C bond by the enolic form of the oxo product[J].Organometallics,2002,21:2454-2459.

[7]Del Rio I,Pamies O,Van Leeuwen P W N M,et al.Mechanistic study of the hydroformylation of styrene catalyzed by the rhodium/BDPP system[J].Journal of Organometallic Chemistry,2000,608:115-121.

[8]Yu S,Chie Y M,Guan Z H,et al.Highly regioselective hydroformylation of styrene and its derivatives catalyzed by Rh complex with tetraphosphorus ligands[J].Organic Letters,2009,11(1):241-244.

[9]Thiel O,Bernard C,Larsen R,et al.Methods of synthesizing cinacalcet and salts thereof:WO,2009002427[P].2008-12-31.

[10]Fogg D E,Dos Santos E N.Tandem catalysis:a taxonomy and illustrative review[J].Coordination Chemistry Reviews,2004,248(21/24):2365-2379.

[11]Botteghi C,Marchetti M,Paganelli S,et al.Rhodium catalyzed hydroformylation of 1,1-bis(p-fluorophenyl)allyl or propargyl alcohol:a key step in the synthesis of fluspirilen and Penfluridol[J].Tetrahedron,2001,57:1631-1637.

[12]Botteghi C,Corrias T,Marchetti M,et al.A new efficient route to tolterodine[J].Organic Process Research & Development,2002,6(4):379-383.

[13]Botteghi C,Cazzaloto L,Marchetti M,et al.New synthetic route to pharmacologically active 1-(N,N-dialkylamino)-3,3-diarylpropanes via rhodium-catalyzed hydroformylation of 1,1-diarylethenes[J].Journal of Organic Chemistry,1995,60:6612-6615.

[14]Ono H,Kasuga T,Kiyono S,et al.Production process of 2-chloropropionaldehyde:EP,0260944[P].1988-03-23.

[15]Drent E.Process for preparation of branched aldehydes:GB,2217318[P].1989-10-25.

[16]K?ckritz A,Bischoff S,Kant M,et al.Asymmetric hydroformylation and hydrogenation catalyzed by chiral rhodium and ruthenium complexes of phosphorylated 2,2’-bis(diphenyl-phosphino)-1,1’-binaphthyls[J].Journal of Molecular Catalysis A:Chemical,2001,174(1/2):119-126.

[17]Siegel H,Himmele W.Synthesis of intermediates by rhodium-catalyzed hydroformylation[J].Angewandte Chemie International Edition,1980,19(3):178-183.

[18]Fell B,Barl M.Hydroformylierung von vinylacetat zu propandiolderivaten[J].Journal of Molecular Catalysis,1977,2:301-306.

[19]Chen X.Methods for preparing ester of 1,3-propylene glycol and 1,3-propylene glycol:WO,2011075905[P].2011-06-30.

[20]Kurkov V P.Preparation of 2-cyanoaldehydes by rhodium-catalyzed hydroformylation:US,4344896[P].1982-08-17.

[21]Botteghi C,Lando C,Matteoli U,et al.Studies on the preparation of 2-(trifluoromethyl)acrylic acid and its esters from 3,3,3-trifluoropropene via hydrocarbonylation reactions[J].Journal of Fluorine Chemistry,1997,83(1):67-71.

[22]Consiglio G,Kollar L,Kolliker R.Cyclometallated compounds Ⅵ.Cyclopalladation of 2-phenylpyrimidines with pendant pyrazole donors[J].Journal of Organometallic Chemistry,1990,395(3):375-381.

[23]Garcia L,Claver C,Dieguez M,et al.A highly selective synthesis of 3-hydroxy-2-methylpropionamide involving a one-pot tandem hydroformylation-hydrogenation sequence[J].Chemical Communications,2006,2:191-193.

[24]Saidi O,Liu S,Xiao J.Effects of ligands on the rhodium-catalyzed hydroformylation of acrylate[J].Journal of Molecular Catalysis A:Chemical,2009,305(1/2):130-134.

[25]Reetz M T,Li X.The influence of mixtures of monodentate achiral ligands on the regioselectivity of transition-metal-catalyzed hydroformylation[J].Angewandte Chemie International Edition,2005,44(19):2962-2964.

[26]Zhang X,Cao B,Yu S,et al.Rhodium-catalyzed asymmetric hydroformylation of N-allylamides:highly enantioselective approach to β2-amino aldehydes[J].Angewandte Chemie International Edition,2010,49:4047-4050.

[27]White D F,Boogaerts I,Cole-Hamilton D J.Hydroformylation process:WO,2011084268[P].2011-07-14.

[28]Dureanleau R G,Knifton J F.Process for separation of product resulting from hydroformylation:US,4678857[P].1987-07-07.

[29]White D F,Boogaerts I,Cole-Hamilton J.Hydroformylation process:US,7790932[P].2010-09-07.

[30]Kilroy T G,O Sullivan T P,Guiry P J.Synthesis of dihydrofurans substituted in the 2-position[J].European Journal of Organic Chemistry,2005,2005(23):4929-4949.

[31]Ruiz N,Polo A,Castillon S,et al.Hydroformylation of allyl ethers.A study of the regioselectivity using rhodium catalysts[J].Journal of Molecular Catalysis A:Chemical,1999,137(1/3):93-100.

[32]Polo A,Claver C,Castillon S,et al.Regioselective hydroformylation of cyclic vinyl and allyl ethers with rhodium catalysts.Crucial influence of the size of the phosphorus cocatalyst[J].Organometallics,1992,11(11):3525-3533.

[33]Briggs J R,Klosin J,Whiteker G T.Synthesis of biologically active amines via rhodium-bisphosphite-catalyzed hydroaminomethylation[J].Organic Letters,2005,7(22):4795-4798.

[34]Whiteker G.Synthesis of fexofenadine via rhodium-catalyzed hydroaminomethylation[J].Topics in Catalysis,2010,53(15):1025-1030.

[35]Verspui G,Elbertse G,Sheldon F A,et al.Selective hydroformylation of N-allylacetamidein an inverted aqueous two-phase catalytic system,enabling a shortsynthesis of melatonin[J].Chemical Communications,2000,28(10):1363-1364.

[36]Dekeukeleire S,Dhooghe M,Muller C,et al.Rhodium-catalysed hydroformylation of N-(2-propenyl)-β-lactams as a key step in the synthesis of functionalised N-[4-(2-oxoazetidin-1-yl)but-1-enyl]acetamides[J].New Journal of Chemistry,2010,34:1079-1083.

[37]Cesarotti E,Rimoldi I.Stereoselective synthesis of 1-methylcarbapenem precursors:studies on the diastereoselective hydroformylation of 4-vinyl β-lactam with aminophosphonite-phosphinite and aminophosphine-phosphite rhodium(Ⅰ) complexes[J].Tetrahedron:Asymmetry,2004,15:3841-3845.

[38]Cuny G D,Buchwald S L.Practical,high-yield,regioselective,rhodium-catalyzed hydroformylation of functionalized alpha-olefins[J].Journal of the American Chemical Society,1993,115:2066-2068.

[39]Lambers-Verstappen M M H,De Vries J G.Rhodium-catalysed asymmetric hydroformylation of unsaturated nitriles[J].Advanced Synthesis & Catalysis,2003,345:478-482.

[40]Cobley C C,Gardner K,Klosin J,et al.Synthesis and application of a new bisphosphite ligand collection for asymmetric hydroformylation of allyl cyanide[J].Journal of Organic Chemistry,2004,69:4031-4040.

[41]Lazzaroni R,Settambolo R.Synthesis of indolizidines from optically pure α-amino acids via stereocontrolled rhodium-catalyzed hydroformylation of N-allylpyrroles[J].Chirality,2011,23(9):730-735.

[42]Alhaffar M,Suleiman R,El Ali B.Rhodium-catalyzed one-pot hydroformylation-cyclization of allylbenzene derivatives:simple and efficient route to 5,6-dihydronaphthalenes[J].Catalysis Communications,2010,11(8):778-782.

[43]Da Silva A C,De Oliveira K C B,Gusevskaya E V,et al.Rhodium-catalyzed hydroformylation of allylbenzenes and propenylbenzenes:effect of phosphine and diphosphine ligands on chemo-and regioselectivity[J].Journal of Molecular Catalysis A:Chemical,2002,179:133-141.

[44]Alhaffar M,Suleiman R,Hussain S M S,et al.Ultranox626 as a selective ligand in rhodium-catalyzed hydroformylation-acetalization of allylbenzene derivatives[J].Reaction Kinetics,Mechanisms and Catalysis,2011,104(2):323-336.

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基金項目：中國石化基金(414088)資助項目

劉旭，1983年生，男，河南省鄭州市人，博士，工程師，研究方向為均相催化。

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