不对称有机催化反应文献综述.pdf

4 亲核催化反应 手性膦亲核催化反应 手性膦 手性胺手性胺 氮杂环卡宾 氮杂环卡宾 MBH 环化反应 环化反应 4 定义定义 反应类型反应类型 1 MBH反应 背景 机理 典型例子反应 背景 机理 典型例子 2 异构化反应异构化反应 3 环化反应环化反应 Ynoate Allenoate ketene 4 动力学拆分动力学拆分 Reviews Basavaiah D Chem Rev 2003 103 811 Lamaty F Chem Rev 2009 109 1 Basavaiah D Chem Rev 2010 110 5447 Taylor J E Chem Soc Rev 2012 41 2109 Wei Y Shi M Acc Chem Res 2010 43 1005 Fu G C Acc Chem Res 2004 33 542 Vedejs E Jure M Angew Chem Int Ed 2005 44 3974 亲核催化反应亲核催化反应 定义定义 5 Principle reaction rate is enhanced by a nucleophilic compound that forms a low energy intermediate Of course the nucleophile does not end up in the reaction product Criteria for a nucleophilic catalyst 1 The catalyst Nu has to react faster with the substrate R X than the nucleophilic particle Y 2 The intermediate R Nu has to react faster with Y than the starting material R X This means that the catalyst has to be both a very effective nucleophile and a good leaving group Or to say the latter in other words the intermediate complex has to be very susceptible to nucleophilic attack Catalysis by a Lewis base involving formation of a Lewis adduct as a reaction intermediate IUPAC 亲核催化反应亲核催化反应 定义定义 Example Both reaction steps are faster than the direct interaction of the p nitrophenyl acetate with water Furthermore imidazole is recovered unchanged after the reaction so imidazole is a real nucleophilic catalyst 7 亲核催化反应亲核催化反应 Nucleophilic Catalysts N Nucleophilic Cat P Nucleophilic Cat C Nucleophilic Cat Others 8 亲核催化反应亲核催化反应 Morita Baylis Hillman Reaction 8 Morita K Suzuki Z Hirose H Bull Chem Soc Jpn 1968 41 2815 Classic Mechanism Hoffmann 1983 The Morita Baylis Hillman reaction is the reaction of electron deficient alkenes with aldehydes catalyzed by nucleophilic amines or phosphines 亲核催化反应亲核催化反应 Morita Baylis Hillman Reaction 9 Aggarwal and Lloyd Jones concluded that proton transfer is rate limiting in the initial stage of the reaction but becomes increasingly efficient at higher conversion causing the aldol type coupling to become rate limiting and making the reaction autocatalytic Aggarwal V K Fulford S Y Lloyd Jones G C Angew Chem Int Ed 2005 44 1706 亲核催化反应亲核催化反应 Morita Baylis Hillman Reaction BINOL TADDOL Thiourea Proline isocupreidine ICD Chiral Phosphine Catalyst System 11 亲核催化反应亲核催化反应 Morita Baylis Hillman Reaction BINOL Schaus S E JACS 03 125 12094 2 mol catalyst 0 5 equiv PEt3 Two important keys to enantioselectivity 1 saturation of the BINOL derivative 2 substitution at the 3 3 positions entry catalyst yieldb eec 1 5 2 1 74 32 3 2a 73 48 4 2b 73 79 5 2c 69 86 6 2d 9 31 7 2e 70 88 8 2f 84 86 9 3 43 3 10 4 15 3 aliphatic aldehydes give better results than conjugated aldehydes Activation of the electrophile 12 亲核催化反应亲核催化反应 Morita Baylis Hillman Reaction Thiourea 12 From enone substrate to simple acrylate derivatives Jacobsen E N ASC 2005 347 1701 Thiourea 20 mol DABCO 20 mol 77 88 ee for aryl aldehyde with good yield Wang W et al Org Lett 2005 7 4293 Shi M Org Lett 2008 10 1043 Up to 94 ee 80 yield for alkyl aldehyde 25 49 yield 87 99 ee 亲核催化反应亲核催化反应 Morita Baylis Hillman Reaction Proline Substrate MVK arylaldehydes 13 Shi M Jiang J K Li C Q Tetrahedron Lett 2002 43 127 Miller S J Acc Chem Res 2004 37 601 Tang C et al Tetrahedron Lett 2006 47 5717 Utsumi N Zhang H Tanaka F Barbas III F C Angew Chem Int Ed 2007 46 1878 Shi 2002 Time 24h yield 90 ee 5 10 Miller 2004 up to 81 ee Chiral tertiary amine proline co catalyzed up to 83 ee up to 84 ee Intramolecular Reaction 亲核催化反应亲核催化反应 Morita Baylis Hillman Reaction Proline Intramolecular MBH reaction 14 Sarshar S et al Tetrahedron Lett 2005 46 8899 Barrett A G M Cook A S Kamimura A Chem Comm 1998 2533 Early Work 亲核催化反应亲核催化反应 Morita Baylis Hillman Reaction ICD 16 16 IsocuIsocu Isocupreidine ICD the first highly efficient catalyst for enantioselective MBH reactions for enantioselective MBH reactions S Hatakeyama et al J Am Chem Soc 1999 121 10219 亲核催化反应亲核催化反应 Morita Baylis Hillman Reaction ICD 亲核催化反应亲核催化反应 Morita Baylis Hillman Reaction Binol Based Bifunctional Catalysts H Sasai et al J Am Chem Soc 2005 127 3680 Tetrahedron Asymmetry 2006 17 578 18 亲核催化反应亲核催化反应 Morita Baylis Hillman Reaction Phosphine 18 Atmospheric Pressure Long reaction time Low yield and ee Hayase T Shibata T Soai K Wakatsuki Y Chem Commun 1998 1271 First Chiral Phosphine MBH Reaction 亲核催化反应亲核催化反应 Morita Baylis Hillman Reaction Phosphine 19 Shi M Chen L H Li C Q J Am Chem Soc 2005 127 3790 R 2 2 disubstituted 1 1 binapthyl 亲核催化反应亲核催化反应 Alkyne to 1 3 Diene Isomerization 20 Trost B M Kazmaier U J Am Chem Soc 1992 114 7933 Guo C Lu X J Chem Soc Perkin Trans 1 1993 1921 亲核催化反应亲核催化反应 Alkyne to 1 3 Diene Isomerization 21 Reactivity order ketone ester amide Catalytic acetic acid and higher temps necessary for esters and amides PBu3 was faster but considerable oligomerization No reaction was observed with tertiary amines Trost B M Kazmaier U J Am Chem Soc 1992 114 7933 Isomerization Reactivity 亲核催化反应亲核催化反应 Alkyne to 1 3 Diene Isomerization Trost B M Li C J J Am Chem Soc 1994 116 3167 23 亲核催化反应亲核催化反应 Alkyne to 1 3 Diene Isomerization 23 Chen Z Zhu G Jiang Q Xiao D Cao P Zhang X J Org Chem 1998 63 5631 亲核催化反应亲核催化反应 3 2 Cycloaddition 24 Zhu G Chen Z Jiang Q Xiao D Cao P Zhang X J Am Chem Soc 1997 119 3836 亲核催化反应亲核催化反应 3 2 Cycloaddition 25 Evans C A Miller S J J Am Chem Soc 2003 125 12394 亲核催化反应亲核催化反应 3 2 Cycloaddition 26 Wilson J E Fu G C Angew Chem Int Ed 2006 45 1426 亲核催化反应亲核催化反应 3 2 Cycloaddition 27 Cowen B J Miller S J J Am Chem Soc 2007 129 10988 亲核催化反应亲核催化反应 Deracemization of Allenic Ester 28 Cowen B J Miller S J J Am Chem Soc 2007 129 10988 亲核催化反应亲核催化反应 4 2 Annulation 29 Zhu X F Lan J Kwon O J Am Chem Soc 2003 125 4716 30 亲核催化反应亲核催化反应 4 2 Annulation 30 Wurz R P Fu G C J Am Chem Soc 2005 127 12234 亲核催化反应亲核催化反应 Ketene Substrates 31 X LG Product Br OR Cl OR F OR halo ester Imine lactam Aldehyde Ketone lactone H OR H NHR chiral ester amide 亲核催化反应亲核催化反应 Ketene Substrates 32 Pracejus H Matje H J Prakt Chem 4 Reihe 1964 24 195 Wynberg H Staring E J Am Chem Soc 1982 104 166 The Wynberg Method Pracejus s Chiral Ester Synthesis Br nsted Base catalysis Modest selectivities due to high background reaction Original method required the use of a ketene generator Limitations include the use of a highly electrophilic aldehyde Early Work 亲核催化反应亲核催化反应 Ketene Substrates Wynberg Modifications 33 Tennyson Reginald Romo D J Org Chem 2000 65 7248 Henry Riyad H Lee C Purohit V C Romo D Org Lett 2006 8 4363 Allows for in situ ketene generation Limitations still include the necessity of a highly electron deficient aldehyde overcome in intramolecular reactions with carboxylic acid activation lactones undergo a variety of useful transformations 亲核催化反应亲核催化反应 Ketene Substrates Utility of Lactones 34 Yang H W Romo D Tetrahedron 1999 55 6403 Yang H W Romo D J Org Chem 1999 64 7657 France S Guerin D J Miller S J Lectka T Chem Rev 2003 103 2985 亲核催化反应亲核催化反应 Ketene Substrates Lactam Products 35 Taggi A E Hafez A M Wack H Young B Ferraris D Lectka T J Am Chem Soc 2002 124 6629 Dudding T Hafez A Taggi A Wagerle T Lectka T Org Lett 2002 4 390 lactams are desirable targets because of their antimicrobial properties Subsequent manipulations are also possible Fu s PPY catalyst has also been shown to be effective in catalyzing these reactions 亲核催化反应亲核催化反应 Ketene Substrates Halogenations 36 France S Wack H Taggi A E Hafex A M Wagerle T R Shah M H Dusich C L Lectka T J Am Chem Soc 2004 126 4245 esterification must be fast enough to avoid racemization catalyst performs a dual role as both a Lewis and Bronsted base 亲核催化反应亲核催化反应 Ketene Substrates 37 Lectka T et al J Am Chem Soc 2004 126 4245 Org Lett 2001 3 2049 J Org Chem 2006 71 8946 deterioration of yield and ee at large scale Chlorination Bromination yield and ee consistent on gram scale 亲核催化反应亲核催化反应 Kinetic Resolution 38 s ln 1 C 1 ee ln 1 C 1 ee Where ee is enantiomeric excess of unreacted substrate Where ee is enantiomeric excess of product s kfast kslow Vedejs E Jure M Angew Chem Int Ed 2005 44 3974 Calculation of selectivity factor s Benchmark Values s 10 28 theoretical yield of unreacted substrate with ee 99 s 60 46 theoretical yield of unreacted substrate with ee 99 s ln 1 C 1 ee ln 1 C 1 ee 亲核催化反应亲核催化反应 Kinetic Resolution Pioneering Work by Evans and Vedejs 39 Evans D Anderson J C Taylor M Tetrahedron Lett 1993 34 5563 Vedejs E Chen X J Am Chem Soc 1996 118 1809 亲核催化反应亲核催化反应 Kinetic Resolution 40 DMAP as an Esterification Catalyst Chiral Acylating Agent preformation of acylating agent necessary Reacts faster than alcohol with acylating agent catalytic step Acylammonium species is a better acylating agent than anhydride asymmetric induction step rate enhancements on the order of 104 compared to the uncatalyzed reaction 亲核催化反应亲核催化反应 Kinetic Resolution Fu s Planar Chiral Design 41 Fu G C J Org Chem 1996 61 7230 Fu G C Acc Chem Res 2000 33 412 18 electron complex A planar chiral azaferrocene 19 electron complex 18 electron complex A planar chiral DMAP 亲核催化反应亲核催化反应 Kinetic Resolution 42 Fu G C J Am Chem Soc 1998 63 2794 solventsolvent DMF CH3CN CH2Cl2 Acetone THF EtOAc Toluene Et2O t amyl alcohol conversion conversion after 1 0 hafter 1 0 h 6 10 14 8 4 6 13 8 36 s s 3 4 3 6 7 0 8 7 9 6 11 11 13 27 HO By combining with a catalyst enabling the racemization of secondary alcohol a DKR process could be realized 亲核催化反应亲核催化反应 Kinetic Resolution 43 Fu G C Acc Chem Res 2004 33 542 SbF6 as counterion 亲核催化反应亲核催化反应 Kinetic Resolution Fuji s Induced Fit Catalyst 44 Kawabata T Nagato M Takusa K Fuji K J Am Chem Soc 1997 119 3169 Induced fit type catalysts are most effective for resolution of cyclic diols e g deracemization of meso diols and kinetic resolution of monoesters 亲核催化反应亲核催化反应 Kinetic Resolution DHIP Catalysts 45 Disfavored Favored Origin of Stereoselectivity Birman V B J Am Chem Soc 2004 126 12226 Tetrahedron 2006 62 285 N N R X N N X H R O R H N N X H R H O R R C O 2 O 亲核催化反应亲核催化反应 Kinetic Resolution Resolution of Amines 46 s 11 27 s 9 8 31 s 50 520 Arai S Bellemin Laponnaz S Fu G C Angew Chem Int Ed 2001 40 234 Arp F Fu G C J Am Chem Soc 2006 128 14264 Birman V B Jiang H Li X Guo L Uffman E W J Am Chem Soc 2006 128 6536 亲核催化反应亲核催化反应 Kinetic Resolution Representative C Acylations 47 Fu G C Acc Chem Res 2004 33 542 Mermerian A H Fu G C J Am Chem Soc 2005 127 5604 Mermerian A H Fu G C Angew Chem Int Ed 2005 44 949 48 Chiral Br nsted Acid Outline 1 Definition 2 Catalytic models double hydrogen bonding single hydrogen bonding ion pairs 3 Catalysts thiourea guanidium diol catalysts phosphoric acid triflyl phosphoramides carboxylic acid etc 4 Reaction types as well as transition states 5 Summary and Outlook 49 Chiral Br nsted Acid Definition of Br nsted Acid An acid is a molecule or ion that is able to lose or donate a hydrogen cation proton H and a base is a species with the ability to gain or accept a hydrogen cation proton Br nsted Lowry theory J N Br nsted T M Lowry in 1923 50 Chiral Br nsted Acid Asymmetric Acid Catalysis Proton is the simplest Lewis acid Chiral Br nsted acids have emerged as a powerful organocatalyst over the last few years Catalytic Models Hydrogen bonding Ion pair vs 51 Chiral Br nsted Acid Asymmetric Acid Catalysis pKa value 52 Chiral Br nsted Acid Asymmetric Acid Catalysis stronger Br nsted acids 53 Chiral Br nsted Acid Chiral Thiourea Catalysts 53 Hine J et al J Am Chem Soc 1984 106 7980 Later Early Investigations Chiral Br nsted Acid Chiral Thiourea Catalysts 54 Jacobsen E N et al Chem Rev 2007 107 5713 Thiourea catalysts were originally designed as potential ligands for Lewis acidic metals representative catalysts Chiral Br nsted Acid Chiral Thiourea Catalysts 55 Asymmetric Strecker Reactions Jacobsen E N J Am Chem Soc 1998 120 4901 List B Angew Chem Int Ed 2007 46 612 Tolerates a wide range of aryl and aliphatic aldimines Work well with methylketimines but no other examples The less problematic acetyl cyanide can be used instead of toxic HCN for the highly enantioselective acyl Strecker type reaction Imine Electrophiles Chiral Br nsted Acid Chiral Thiourea Catalysts 56 1 Potassium cyanide KCN and sodium cyanide NaCN represent inexpensive alternative cyanide sources 2 Adaptable to large scale synthesis 3 Ketimine is not adaptable Jacobsen E N Nature 2009 461 968 Chiral Br nsted Acid Chiral Thiourea Catalysts 57 Jacobsen E N J Am Chem Soc 2004 126 4102 Tolerates a wide range of aryl and aliphatic aldimines An efficient asymmetric synthesis of aminophosphonic acids Imine Electrophiles Jacobsen E N Angew Chem Int Ed 2007 46 1315 Imine allylation Tolerates a wide range of aromatic and hetero aromatic acylhydrazones Chiral Br nsted Acid Chiral Thiourea Catalysts 58 Mannich reaction Mechanism not well understood and structure mechanism studies showed that Schiff base on original catalyst are unnecessary tolerates a wide range of aryl groups no aliphatic example Jacobsen E N J Am Chem Soc 2002 124 12964 Nitro Mannich Jacobsen E N Angew Chem Int Ed 2005 44 466 Chiral Br nsted Acid Chiral Thiourea Catalysts Michael addition reactions mediated by bifunctional thiourea This methodology has also been applied to enantioselective additions of substituted ketoester Takemoto Y J Am Chem Soc 2003 125 12672 Org Lett 2004 6 625 60 Chiral Br nsted Acid Chiral Thiourea Catalysts Additions of Oxindoles to Nitroolefins Barbas III C F J Am Chem Soc 2009 131 8758 Products bearing successive chiral centers containing a quaternary center in good yield with good to excellent dr and ee Application of this methodology to the formal synthesis of esermethole Other nucleophiles such as thiophenol nitromethane etc also could be well applied in the reaction with nitroolefins 61 Chiral Br nsted Acid Chiral Thiourea Catalysts Aldol Reaction Hiemstra H Angew Chem Int Ed 2006 45 929 The first example of a highly enantioselective organocatalytic Henry reaction of aromatic aldehydes No aliphatic aldehyde example was shown 62 Chiral Br nsted Acid Chiral Thiourea Catalysts 62 Ricci A Angew Chem Int Ed 2005 44 6576 Friedel Crafts Addition of Indoles The hydroxy group in the catalyst is crucial for the enantiocontrol Deng L J Am Chem Soc 2006 128 8156 Tolerates a wide range of aryl and aliphatic aldimines with excellent ees Chiral Br nsted Acid Chiral Thiourea Catalysts 63 Pictet Spengler reaction Acetyl chloride is crucial for the activation of the imines Jacobsen E N J Am Chem Soc 2004 126 10558 Jacobsen E N J Am Chem Soc 2007 129 13404 Substituent and counterion effect studies point to a novel mechanism of catalysis involving rate limiting anion abstraction and binding by the thiourea Chiral Br nsted Acid Chiral Thiourea Catalysts 64 Jacobsen E N Science 2010 327 986 Povarov reaction Kinetic isotope effect data suggest that a concerted albeit highly asynchronous 4 2 cycloaddition was involved Chiral Br nsted Acid Chiral Phosphoric Acid Catalysts bifunctional catalysts 66 Chiral Br nsted Acid Chiral Phosphoric Acid Catalysts Review a Terada M Synthesis 2010 12 1929 b Tsogoeva S B et al Org Biomol Chem 2010 8 5262 1 Mannich Reaction 2 Friedel Crafts Reaction 3 Hydrogenation 4 Michael Reaction 5 Diels Alder Reaction 6 Strecker Reaction 7 Aldol Reaction 8 Robinson Cyclization 9 Biginelli Reaction 10 Counteranion Catalysis etc Chiral Br nsted Acid Chiral Phosphoric Acid Catalysts 67 Terada M et al J Am Chem Soc 2004 126 5356 Akiyama T et al Angew Chem Int Ed 2004 43 1566 Akiyama and Terada independently discovered Nine membered cyclic transition state Only aromatic aldimines were adaptable 68 Chiral Br nsted Acid Chiral Phosphoric Acid Catalysts Friedel Crafts reaction The first asymmetric phosphoric acid catalyzed Friedel Crafts alkylation Terada M J Am Chem Soc 2004 126 11804 You S L J Am Chem Soc 2007 129 1484 A large scaleup for imine 10 mmol and catalyst recycling were successfully demonstrated Chiral Br nsted Acid Chiral Phosphoric Acid Catalysts 69 N alkylation of indole Huang H Angew Chem Int Ed 2011 50 5682 Ten membered cyclic transition state Various substituted indoles were adaptable Chiral Br nsted Acid Chiral Phosphoric Acid Catalysts 70 Pictet Spengler reaction Special substrates were employed to enhance the enantiocontrole Aromatic or aliphatic aldehydes were adaptable Hiemstra H Angew Chem Int Ed 2007 46 7485 List B J Am Chem Soc 2006 128 1086 Chiral Br nsted Acid Chiral Phosphoric Acid Catalysts 71 Limitation of PS reaction Nucleophiles was limited to electron rich arenes such as indoles pyrroles Electron rich benzene derivatives usually yield poor enantiocontrol Tolerates a wide range of aryl or aliphatic aldehydes with excellent ees Wang Y G Lin X F Chem Eur J 2012 18 3148 New catalysts Chiral Br nsted Acid Chiral Phosphoric Acid Catalysts 72 Nucleophilic Addition to Aldimines Akiyama T Org Lett 2005 7 2583 Strecker Reaction Rueping M Angew Chem Int Ed 2006 45 2617 Mechanism not well studied No ketimine examples Chiral Br nsted Acid Chiral Phosphoric Acid Catalysts Terada M Angew Chem Int Ed 2006 45 2254 Rueping M Org Lett 2007 9 1065 Aza Ene Type Reaction 74 Chiral Br nsted Acid Chiral Phosphoric Acid Catalysts Diazoesters as Nuc Two reaction route Terada M J Am Chem Soc 2005 127 9360 FC type reaction Chiral Br nsted Acid Chiral Phosphoric Acid Catalysts 75 Use of less acidic pyridinium salt suppressed decomposition of Brassard s diene in the reaction medium Akiyama T J Am Chem Soc 2006 128 13070 Aza Diels Alder Reactions Akiyama T Angew Chem Int Ed 2006 45 4796 The presence of the OH moiety on the N aryl group is essential for attaining high enantioselectivity Chiral Br nsted Acid Chiral Phosphoric Acid Catalysts Carbonyl Compounds DFT computational studies suggest the presence of a double hydrogen bond between the catalyst and ethyl glyoxylate the first example of aldehyde activation by a BINOL derived phosphoric acid but restricted to glyoxylates as reactive aldehydes 77 Chiral Br nsted Acid Chiral Triflyl Phosphoramide Catalysts pKa Yamamoto H J Am Chem Soc 2006 128 9626 The first example in which