The palladium-catalyzed C-C coupling between aryl halides or vinyl halides and activated alkenes in the presence of a base is referred as the "Heckp yReaction". Recent developments in the catalysts and reaction conditions have resulted in a much broader range of donors and acceptors being amenable to the Heck Reaction.g y One of the benefits of the Heck Reaction is its outstanding trans selectivity.Mechanism of the Heak ReactionRecent Literature●Trifunctional N,N,O-terdentate amido/pyridyl carboxylate Pd(II) complexes were highly active and stable phosphine-free catalysts for Heck and room-temperature Suzuki reactions with high turnover numbers.M. L. Kantam, P. Srinivas, J. Yadav, P. R. Likhar, S. Bhargava,J. Org. Chem.,2009,74, 4882-4885.●New N-Heterocyclic Carbene Palladium Complex/Ionic Liquid Matrix Immobilized on Silica: Application as Recoverable Catalyst for the Heck Reactionpp yB. Karimi, D. Enders,Org. Lett.,2006,8, 1237-1240.●Pd(quinoline-8-carboxylate)2as a Low-Priced, Phosphine-Free Catalyst for Heck and SuzukiReactionsX. Cui, J. Li, Z.-P. Zhang, Y. Fu, L. Liu, Q.-X. Guo,J. Org. Chem.,2007,72, 9342-9345.Recent Literature●Triethanolamine as an Efficient and Reusable Base, Ligand and Reaction Medium for Phosphane-Free Palladium-Catalyzed Heck ReactionsH. J. Li, L. Wang,Eur. J. Org. Chem.,2006, 5101-5102.●Triaryl phosphine-functionalized N-heterocyclic carbene ligands for Heck reactionA.-E. Wang, J.-H. Xie, L.-X. Wang, Q.-L. Zhou,Tetrahedron,2005,61, 259-266.A E Wang J H Xie L X Wang Q L Zhou259266p g p q●Heck Couplings at Room Temperature in Nanometer Aqueous MicellesB. H. Lipshutz, B. R. Taft,Org. Lett.,2008,10, 1329-1332.Recent Literature●Efficient Aqueous-Phase Heck and Suzuki Couplings of Aryl Bromides Using Tri(4,6-dimethyl-3-sulfonatophenyl)phosphine Trisodium Salt (TXPTS)L. R. Moore, K. H. Shaughnessy,Org. Lett.,2004,6, 225-228.●Poly(ethylene glycol) (PEG) as a Reusable Solvent Medium for Organic Synthesis. Application in the Heck ReactionS. Chandrasekhar, C. Narsihmulu, S. S. Sultana, N. R. Reddy,Org. Lett.,2002,4, 4399-4401.●Functionalized Ionic Liquid as an Efficient and Recyclable Reaction Medium for Phosphine-Free Palladium-Catalyzed Heck ReactionPalladium Catalyzed Heck ReactionL. Zhou, L. Wang,Synthesis,2006, 2649-2652.Recent Literature●Brønsted Guanidine Acid-Base Ionic Liquids: Novel Reaction Media for the Palladium-Catalyzed Heck ReactionS. Li, Y. Lin, H. Xie, S. Zhang, J. Xu,Org. Lett.,2006,8, 391-394.●Pd-m BDPP-Catalyzed Regioselective Internal Arylation of Electron-Rich Olefins by Aryl Halidesy y gS. Liu, N. Berry, N. Thomson, A. Pettman, Z. Hyder, J. Mo, J. Xiao,J. Org. Chem.,2006,71, 7467-7470.●Regioselective Heck Vinylation of Electron-Rich Olefins with Vinyl Halides: Is the Neutral Pathway in Operation?in Operation?M. McConville, O. Saidi, J. Blacker, J. Xiao,J. Org. Chem.,2009,74, 2692-2698.Recent Literature●The Heck Reaction of Electron-Rich Olefins with Regiocontrol by Hydrogen-Bond DonorsJ. Mo, J. Xiao,Angew. Chem. Int. Ed.,2006,45, 4152-4157.J Mo J Xiao Angew Chem Int Ed41524157●Palladium-Tetraphosphine Complex Catalysed Heck Reaction of Vinyl Bromides with Alkenes: Aj gPowerful Access to Conjugated DienesM. Lemhadri, A. Battace, F. Berthiol, T. Zair, H. Doucet, M. Santelli,Synthesis,2008, 1142-1152.●Heck Coupling with Nonactivated Alkenyl Tosylates and Phosphates: Examples of Effective 1,2-g y()Migrations of the Alkenyl Palladium(II) IntermediatesA. L. Hansen, J.-P. Ebran, M. Ahlquist, P.-O. Norrby, T. Skydstrup,Angew. Chem. Int. Ed.,2006,45, 3349-3353.Recent Literature●Synthesis of 2-Vinylic Indoles and Derivatives via a Pd-Catalyzed Tandem CouplingReactionA. Fayol, Y.-Q. Fang, M. Lautens,Org. Lett.,2006,8, 4203-4206.●Heck Vinylations Using Vinyl Sulfide, Vinyl Sulfoxide, Vinyl Sulfone, or Vinyl Sulfonate Derivativesy y y p p pand Aryl Bromides Catalyzed by a Palladium Complex Derived from a TetraphosphineA. Battace, T. Zair, H. Doucet, M. Santelli,Synthesis,2006, 3495-3505.●Direct Acylation of Aryl Bromides with Aldehydes by Palladium CatalysisJ. Ruan, O. Saidi, J. A. Iggo, J. Xiao,J. Am. Chem. Soc.,2008,130, 10510-10511.Protective Groups & StabilitiesFmoc‐NR29‐Fluorenylmethyl carbamate, FMOC amino, FMOC amine, FMOC amideH2O:pH < 1,100°CpH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RTpH > 12,100°CBases:LDA NEt3, Py t‐BuOK Others:DCC SOCl2Nucleophiles:RLi RMgX RCuLi Enolates NH3, RNH2NaOCH3 Electrophiles:RCOCl RCHO CH3I Others::CCl2Bu3SnH Reduction:H2/ Ni H2/ Rh Zn / HCl Na / NH3LiAlH4NaBH4 Oxidation:KMnO4OsO4CrO3/ Py RCOOOH I2, Br2, Cl2MnO2/CH2Cl2 T. W. Green, P. G. M. Wuts,Protective Groups in Organic Synthesis,Wiley Interscience New York503507736739Wiley-Interscience, New York,1999, 503-507, 736-739.Protective Groups & StabilitiesProtective Groups & Stabilities BOC‐NR2t‐Butyl carbamate, BOC amine, BOC amino, BOC amideH2O:pH < 1,100°CpH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RTpH > 12,100°CBases:LDA NEt3, Py t‐BuOK Others:DCC SOCl2 Nucleophiles:RLi RMgX RCuLi Enolates NH3, RNH2NaOCH3Electrophiles:RCOCl RCHO CH3I Others::CCl2Bu3SnH Reduction:H2/ Ni H2/ Rh Zn / HCl Na / NH3LiAlH4NaBH4Oxidation:KMnO4OsO4CrO3/ Py RCOOOH I2, Br2, Cl2MnO2/ CH2Cl2T.W.Green,P.G.M.Wuts,Protective Groups in Organic Synthesis, T. W. Green, P. G. M. Wuts,Protective Groups in Organic Synthesis, Wiley-Interscience, New York,1999, 518-525, 736-739.Protective Groups & StabilitiesProtective Groups & Stabilities Cbz‐NR2/ Z‐NR2Benzyl carbamateH2O:pH < 1,100°CpH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RTpH > 12,100°CBases:LDA NEt3, Py t‐BuOK Others:DCC SOCl2 NucleophileRLi RMgX RCuLi Enolates NH3, RNH2NaOCH3 s:Electrophiles:RCOCl RCHO CH3I Others::CCl2Bu3SnH Reduction:H2/ Ni H2/ Rh Zn / HCl Na / NH3LiAlH4NaBH4Oxidation:KMnO4OsO4CrO3/ Py RCOOOH I2, Br2, Cl2MnO2/ CH2Cl2T. W. Green, P. G. M. Wuts,Protective Groups in Organic Synthesis, Wiley-Interscience, New York,1999, 518-525, 736-739.Protective Groups & StabilitiesProtective Groups & Stabilities PhthalimideH2O:pH < 1,100°CpH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RTpH > 12,100°CBases:LDA NEt3, Py t‐BuOK Others:DCC SOCl2Nucleophiles:RLi RMgX RCuLi Enolates NH3, RNH2NaOCH3Electrophiles:RCOCl RCHO CH3I Others::CCl2Bu3SnH/Reduction:H2/ Ni H2/ Rh Zn / HCl Na NH3LiAlH4NaBH4Oxidation:KMnO4OsO4CrO3/ Py RCOOOH I2, Br2, Cl2MnO2/ CH2Cl2T. W. Green, P. G. M. Wuts,Protective Groups in Organic Synthesis, Wiley-Interscience, New York,1999, 518-525, 736-739.Protective Groups & StabilitiesProtective Groups & Stabilities Bn‐NR2BenzylamineH2O:pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°CBases:LDA NEt3, Py t‐BuOK Others:DCC SOCl2Nucleophiles:RLi RMgX RCuLi Enolates NH3, RNH2NaOCH3Electrophiles:RCOCl RCHO CH3I Others::CCl2Bu3SnH Zn / HCl LiAlH NaBH Reduction:H2/Ni H2/Rh n Na/NH3iAlH4Na H4Oxidation:KMnO4OsO4CrO3/ Py RCOOOH I2,Br2, Cl2MnO2/ CH2Cl2T. W. Green, P. G. M. Wuts,Protective Groups in Organic Synthesis, Wiley-Interscience, New York,1999, 518-525, 736-739.R H'Aldol'is an abbreviation of aldehyde and alcohol.When the enolate of an aldehyde or a ketone reacts at theα‐h l f ld h d k hcarbon with the carbonyl of another molecule under basicor acidic conditions to obtainβ‐hydroxy aldehyde or ketone,ketonethis reaction is called Aldol Reaction.Mechanism of the Aldol AdditionMechanism of the Aldol AdditionMechanism of the Aldol AdditionUnder conditions of kinetic control,the mixed Aldol Addition can be used to prepare adducts that are otherwise difficult to obtain selectively.This process begins with the irreversible generation of the kinetic enolate,e.g.by employing a sterically hindered lithium amide base such as LDA(lithium diisopropylamide). With an unsymmetrically substituted ketone,such a non‐nucleophilic,t i ll b tit t d k t h l hili sterically‐demanding,strong base will abstract a proton from the least hindered side.Proton transfer is avoided with lithium enolates at low temperatures in ethereal solvents,so that addition of a second carbonylsolventspartner(ketone or aldehyde)will produce the desired aldol product.Recent Literature●Highly Enantioselective Organocatalytic Direct Aldol Reaction in an Aqueous MediumV. Maya, M. Raj, V. K. Singh,Org. Lett.,2007,9, 2593-2595.V Maya M Raj V K Singh Org Lett25932595●Chiral Amine-Polyoxometalate Hybrids as Highly Efficient and Recoverable Asymmetric Enamine Catalysts. S. Luo, J. Li, H. Xu, L. Zhang, J.-P. Cheng,Org. Lett.,2007,9, 3675-3678.Catalysts S Luo J Li H Xu L Zhang J P Cheng Org Lett36753678●A Highly Efficient Organocatalyst for Direct Aldol Reactions of Ketones with AldedydesZ. Tang, Z.-H. Yang, X.-H. Chen, L.-F. Cun, A.-Q. Mi, Y.-Z. Jiang, L.-Z. Gong,J. Am. Chem.Z Tang Z H Yang X H Chen L F Cun A Q Mi Y Z Jiang L Z Gong J Am ChemSoc.,2005,127, 9285-9289.Recent Literature●The First Direct and Enantioselective Cross-Aldol Reaction of AldehydesA. B. Northtrup, D. W. C. MacMillan,J. Am. Chem. Soc.,2002,124, 6798-6799.●Enantioselective organocatalytic aldehyde–aldehyde cross-aldol couplings. The broad utility of α-thioacetal aldehydes。