2 + 2 Cu II 2 2 Cu I C 2 4 3 C 2 + 3 C II 0 II 4 Mechanistic Studies on the Wacker xidation 3 C Pamela Tadross Stoltz Group Literature Presentation ecember 8, 2008 8 PM, 147 Noyes II II II 3 II 2 + 2 2 +,
rigins of the Wacker xidation F. C. Phillips, 1894: 4 + C 2 4 + 2 (0) + C 3 C + 2 + 2 Phillips, F. C. Am. Chem. J. 1984, 16, 255-277. Smidt, J.; afner, W.; Jira, R.; Sieber, R.; Sedlmeier, S.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80.
rigins of the Wacker xidation F. C. Phillips, 1894: 4 + C 2 4 + 2 (0) + C 3 C + 2 + 2 Smidt, Wacker Chemie, 1959: (0) + 2 Cu 2 + 2 2 Cu + 4 2 Cu + 1/2 2 + 2 2 Cu 2 + 2 Phillips, F. C. Am. Chem. J. 1984, 16, 255-277. Smidt, J.; afner, W.; Jira, R.; Sieber, R.; Sedlmeier, S.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80.
rigins of the Wacker xidation 4 + C 2 4 + 2 (0) + C 3 C + 2 + 2 (0) + 2 Cu 2 + 2 2 Cu + 4 2 Cu + 1/2 2 + 2 2 Cu 2 + 2 Phillips, F. C. Am. Chem. J. 1984, 16, 255-277. Smidt, J.; afner, W.; Jira, R.; Sieber, R.; Sedlmeier, S.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80.
rigins of the Wacker xidation 4 + C 2 4 + 2 (0) + C 3 C + 2 + 2 (0) + 2 Cu 2 + 2 2 Cu + 4 2 Cu + 1/2 2 + 2 2 Cu 2 + 2 C 2 4 + 1/2 2 C 3 C Net Result: Air oxidation of ethylene to acetaldehyde! Phillips, F. C. Am. Chem. J. 1984, 16, 255-277. Smidt, J.; afner, W.; Jira, R.; Sieber, R.; Sedlmeier, S.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80.
rigins of the Wacker xidation 4 + C 2 4 + 2 (0) + C 3 C + 2 + 2 (0) + 2 Cu 2 + 2 2 Cu + 4 2 Cu + 1/2 2 + 2 2 Cu 2 + 2 C 2 4 + 1/2 2 C 3 C Net Result: Air oxidation of ethylene to acetaldehyde!! First organopalladium reaction applied on industrial scale.! First rendered commercial in 1960.! At one point was responsible for the production of over 2 billion pounds per year of acetaldehyde! Phillips, F. C. Am. Chem. J. 1984, 16, 255-277. Smidt, J.; afner, W.; Jira, R.; Sieber, R.; Sedlmeier, S.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80.
rigins of the Wacker xidation 4 + C 2 4 + 2 (0) + C 3 C + 2 + 2 (0) + 2 Cu 2 + 2 2 Cu + 4 2 Cu + 1/2 2 + 2 2 Cu 2 + 2 C 2 4 + 1/2 2 C 3 C Net Result: Air oxidation of ethylene to acetaldehyde!! First organopalladium reaction applied on industrial scale.! First rendered commercial in 1960.! At one point was responsible for the production of over 2 billion pounds per year of acetaldehyde!! Prior acetaldehyde production: a) xymercuration of acetylene b) ehydrogenation of ethanol! Wacker process eventually replaced because of more efficient ways of producing acetic acid (i.e. Monsanto process). Phillips, F. C. Am. Chem. J. 1984, 16, 255-277. Smidt, J.; afner, W.; Jira, R.; Sieber, R.; Sedlmeier, S.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80.
Early Kinetic Studies Conditions: [ II ] = 0.005-0.04 M [ ] = 0.1-1.0 M [ + ] = 0.04-1.0 M Rate = d[c 2 4 ] dt = k [ 4 ] [C 2 4 ] [ ] 2 [ + ]! First order in II! Second order inhibition! First order acid inhibition enry, P. M. J. Am. Chem. Soc. 1964, 86, 3246. Jira, R.; Sedlmeier, J.; Smidt, J. Liebigs Ann. Chem. 1966, 693, 99. Moiseev, I. I.; Vargaftik, M. N.; Syrkin, Ya. K. okl. Akad. Nauk. SSSR 1963, 153, 140.
Early Kinetic Studies Chloride Inhibition Conditions:! First order in II [ II ] = 0.005-0.04 M [ ] = 0.1-1.0 M [ + ] = 0.04-1.0 M Rate = d[c 2 4 ] dt = k [ 4 ] [C 2 4 ] [ ] 2 [ + ]! Second order inhibition! First order acid inhibition Source of Chloride Inhibition: + C 2 4 + 1 [ ] inhibition + 2 2 + 1 [ ] inhibition enry, P. M. J. Am. Chem. Soc. 1964, 86, 3246. Jira, R.; Sedlmeier, J.; Smidt, J. Liebigs Ann. Chem. 1966, 693, 99. Moiseev, I. I.; Vargaftik, M. N.; Syrkin, Ya. K. okl. Akad. Nauk. SSSR 1963, 153, 140.
Early Kinetic Studies Proton Inhibition Conditions: [ II ] = 0.005-0.04 M [ ] = 0.1-1.0 M [ + ] = 0.04-1.0 M Rate = d[c 2 4 ] dt = k [ 4 ] [C 2 4 ] [ ] 2 [ + ]! First order in II! Second order inhibition! First order acid inhibition 2 C 2 C 2 2 uter-sphere hydroxide attack: Predicted to be 10 3 times faster than diffusion controlled process enry, P. M. J. Am. Chem. Soc. 1964, 86, 3246. Jira, R.; Sedlmeier, J.; Smidt, J. Liebigs Ann. Chem. 1966, 693, 99. Moiseev, I. I.; Vargaftik, M. N.; Syrkin, Ya. K. okl. Akad. Nauk. SSSR 1963, 153, 140.
Early Kinetic Studies Proton Inhibition Conditions: [ II ] = 0.005-0.04 M [ ] = 0.1-1.0 M [ + ] = 0.04-1.0 M Rate = d[c 2 4 ] dt = k [ 4 ] [C 2 4 ] [ ] 2 [ + ]! First order in II! Second order inhibition! First order acid inhibition 2 C 2 C 2 2 uter-sphere hydroxide attack: Predicted to be 10 3 times faster than diffusion controlled process 2 2 C 2 C 2 2 + + uter-sphere water attack: Predicted to occur by an anti hydroxypalladation mechanism enry, P. M. J. Am. Chem. Soc. 1964, 86, 3246. Jira, R.; Sedlmeier, J.; Smidt, J. Liebigs Ann. Chem. 1966, 693, 99. Moiseev, I. I.; Vargaftik, M. N.; Syrkin, Ya. K. okl. Akad. Nauk. SSSR 1963, 153, 140.
Early Kinetic Studies Proton Inhibition Conditions: [ II ] = 0.005-0.04 M [ ] = 0.1-1.0 M [ + ] = 0.04-1.0 M Rate = d[c 2 4 ] dt = k [ 4 ] [C 2 4 ] [ ] 2 [ + ]! First order in II! Second order inhibition! First order acid inhibition 2 C 2 C 2 2 uter-sphere hydroxide attack: Predicted to be 10 3 times faster than diffusion controlled process 2 2 C 2 C 2 2 + + uter-sphere water attack: Predicted to occur by an anti hydroxypalladation mechanism 2 + + C 2 C 2 2 Inner-sphere hydroxyl attack: Predicted to occur by a syn hydroxypalladation mechanism enry, P. M. J. Am. Chem. Soc. 1964, 86, 3246. Jira, R.; Sedlmeier, J.; Smidt, J. Liebigs Ann. Chem. 1966, 693, 99. Moiseev, I. I.; Vargaftik, M. N.; Syrkin, Ya. K. okl. Akad. Nauk. SSSR 1963, 153, 140.
Kinetic Isotope Effects Early Evidence for an Inner-Sphere Syn ydroxypalladation Mechanism + 4 + 2 + 4 + 2 3 C 3 C + (0) + 2 + 2 + (0) + 2 + 2 k k = 1.07 enry, P. M. J. rg. Chem. 1973, 38, 2415. Kosaki, M.; Isemura, M.; Kitaura, K.; Schinoda, S.; Saito, Y. J. Mol. Catal. 1977, 2, 351. Saito, Y.; Schinoda, S. J. Mol. Catal. 1980, 9, 461.
Kinetic Isotope Effects Early Evidence for an Inner-Sphere Syn ydroxypalladation Mechanism + 4 + 2 + 4 + 2 3 C 3 C + (0) + 2 + 2 + (0) + 2 + 2 k k = 1.07 KIE for decomposition step determined by competitive isotope effect experiment: -shift 2 C + 4 + 2 ( 2 ) 2 k k = 1.70 -shift 2 C enry, P. M. J. rg. Chem. 1973, 38, 2415. Kosaki, M.; Isemura, M.; Kitaura, K.; Schinoda, S.; Saito, Y. J. Mol. Catal. 1977, 2, 351. Saito, Y.; Schinoda, S. J. Mol. Catal. 1980, 9, 461.
Kinetic Isotope Effects Early Evidence for an Inner-Sphere Syn ydroxypalladation Mechanism outer-sphere anti hydroxypalladation KIE 1.07 and competitive KIE of 1.70 indicates that the slow step occurs before decomposition. 2 + 2 2 C 2 C 2 + + + + + 3 C + 2 2 C 2 C 2 inner-sphere syn hydroxypalladation enry, P. M. J. rg. Chem. 1973, 38, 2415. Kosaki, M.; Isemura, M.; Kitaura, K.; Schinoda, S.; Saito, Y. J. Mol. Catal. 1977, 2, 351. Saito, Y.; Schinoda, S. J. Mol. Catal. 1980, 9, 461.
Kinetic Isotope Effects Early Evidence for an Inner-Sphere Syn ydroxypalladation Mechanism outer-sphere anti hydroxypalladation KIE 1.07 and competitive KIE of 1.70 indicates that the slow step occurs before decomposition. 2 + 2 2 C 2 C 2 + + fast slow + + + 3 C + 2 slow 2 C 2 C 2 fast inner-sphere syn hydroxypalladation anti pathway has decomposition as the slow step syn pathway has hydroxypalladation as the slow step enry, P. M. J. rg. Chem. 1973, 38, 2415. Kosaki, M.; Isemura, M.; Kitaura, K.; Schinoda, S.; Saito, Y. J. Mol. Catal. 1977, 2, 351. Saito, Y.; Schinoda, S. J. Mol. Catal. 1980, 9, 461.
Kinetic Isotope Effects Early Evidence for an Inner-Sphere Syn ydroxypalladation Mechanism outer-sphere anti hydroxypalladation KIE 1.07 and competitive KIE of 1.70 indicates that the slow step occurs before decomposition. 2 + 2 2 C 2 C 2 + + + + + 3 C + 2 slow 2 C 2 C 2 fast inner-sphere syn hydroxypalladation anti pathway has decomposition as the slow step syn pathway has hydroxypalladation as the slow step enry, P. M. J. rg. Chem. 1973, 38, 2415. Kosaki, M.; Isemura, M.; Kitaura, K.; Schinoda, S.; Saito, Y. J. Mol. Catal. 1977, 2, 351. Saito, Y.; Schinoda, S. J. Mol. Catal. 1980, 9, 461.
Early Stereochemical Studies Stille's Work Suggests Anti ydroxypalladation Mechanism 2 Na 2 C 3 C Key: C insertion proceeds with retention of stereochemistry at the migrating stereocenter. Stille, J. K. J. rganomet. Chem. 1976, 108, 401. Stille, J. K.; ivakarumi, R. J. J. rganomet. Chem. 1979, 169, 239.
Early Stereochemical Studies Stille's Work Suggests Anti ydroxypalladation Mechanism 2 Na 2 C 3 C Key: C insertion proceeds with retention of stereochemistry at the migrating stereocenter. C C anti hydroxypalladation syn hydroxypalladation Stille, J. K. J. rganomet. Chem. 1976, 108, 401. Stille, J. K.; ivakarumi, R. J. J. rganomet. Chem. 1979, 169, 239.
Early Stereochemical Studies Stille's Work Suggests Anti ydroxypalladation Mechanism 2 Na 2 C 3 C anti hydroxypalladation Stille, J. K. J. rganomet. Chem. 1976, 108, 401. Stille, J. K.; ivakarumi, R. J. J. rganomet. Chem. 1979, 169, 239.
Early Stereochemical Studies Stille's Work Suggests Anti ydroxypalladation Mechanism 2 Na 2 C 3 C anti hydroxypalladation Criticism:! lefin is unable to rotate into the square plane of the 2 making syn hydroxypalladation impossible! Ligand exchange to give (cod)( 2 ) would result in a cationic intermediate and is unlikely Stille, J. K. J. rganomet. Chem. 1976, 108, 401. Stille, J. K.; ivakarumi, R. J. J. rganomet. Chem. 1979, 169, 239.
Early Stereochemical Studies Stille's Work Suggests Anti ydroxypalladation Mechanism 2 Na 2 C 3 C anti hydroxypalladation 2 L n C L n 2 2 2 L n C L n Stille, J. K. J. rganomet. Chem. 1976, 108, 401. Stille, J. K.; ivakarumi, R. J. J. rganomet. Chem. 1979, 169, 239.
Early Stereochemical Studies Stille's Work Suggests Anti ydroxypalladation Mechanism 2 Na 2 C 3 C anti hydroxypalladation 2 L n C L n 2 2 2 L n C L n Stille, J. K. J. rganomet. Chem. 1976, 108, 401. Stille, J. K.; ivakarumi, R. J. J. rganomet. Chem. 1979, 169, 239.
Early Stereochemical Studies Stille's Work Suggests Anti ydroxypalladation Mechanism Criticism:! Solvent is acetonitrile not water.! Might proceed through a dimeric complex.! C (3 atm) is very coordinating and might occupy coordination sites prohibiting the ligation of water necessary for syn hydroxypalladation. anti hydroxypalladation 2 L n C L n 2 2 2 L n C L n Stille, J. K. J. rganomet. Chem. 1976, 108, 401. Stille, J. K.; ivakarumi, R. J. J. rganomet. Chem. 1979, 169, 239.
Bäckvall's Stereochemical Studies Further (More Convincing) Evidence for uter-sphere Anti ydroxypalladation [ ] < 1 M [Cu 2 ] < 1 M 3 C loss of stereochemical information C 2 4 + 4 2 2 Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Chem. Soc., Chem. Commun. 1977, 264. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Am. Chem. Soc. 1979, 101, 2411.
Bäckvall's Stereochemical Studies Further (More Convincing) Evidence for uter-sphere Anti ydroxypalladation [ ] < 1 M [Cu 2 ] < 1 M 3 C loss of stereochemical information C 2 4 + 4 2 2 [ ] > 3 M [Cu 2 ] > 2.5 M C 3 C + stereochemical information retained (maybe) Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Chem. Soc., Chem. Commun. 1977, 264. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Am. Chem. Soc. 1979, 101, 2411.
Bäckvall's Stereochemical Studies Further (More Convincing) Evidence for uter-sphere Anti ydroxypalladation [ ] < 1 M [Cu 2 ] < 1 M 3 C loss of stereochemical information C 2 4 + 4 2 2 [ ] > 3 M [Cu 2 ] > 2.5 M C 3 C + stereochemical information retained (maybe) Two Key Assumptions:! Chlorohydrin and acetaldehyde form from the same intermediate (i.e., [(C 2 C 2 )( 2 ) 2 ] ).! The steric course of the reaction is not affected by conditions containing high [ ] and high [Cu 2 ]. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Chem. Soc., Chem. Commun. 1977, 264. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Am. Chem. Soc. 1979, 101, 2411.
Bäckvall's Stereochemical Studies Further (More Convincing) Evidence for uter-sphere Anti ydroxypalladation 2 + 2 2 C 2 C 2 + + 2 Cu 2 + 2 Cu decomposition C 3 C! Chloride displacement of occurs with inversion of stereochemistry at carbon.! Chlorohydrin formation requires both high [ ] and high [Cu 2 ]. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Chem. Soc., Chem. Commun. 1977, 264. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Am. Chem. Soc. 1979, 101, 2411.
Bäckvall's Stereochemical Studies Further (More Convincing) Evidence for uter-sphere Anti ydroxypalladation 2 + 2 2 + + 2 Cu 2 anti hydroxypalladation Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Chem. Soc., Chem. Commun. 1977, 264. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Am. Chem. Soc. 1979, 101, 2411.
Bäckvall's Stereochemical Studies Further (More Convincing) Evidence for uter-sphere Anti ydroxypalladation 2 + 2 2 + + 2 Cu 2 anti hydroxypalladation 2 + 2 2 + + 2 Cu 2 syn hydroxypalladation Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Chem. Soc., Chem. Commun. 1977, 264. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Am. Chem. Soc. 1979, 101, 2411.
Bäckvall's Stereochemical Studies Further (More Convincing) Evidence for uter-sphere Anti ydroxypalladation 2 + 2 2 + + 2 Cu 2 anti hydroxypalladation 2 + 2 2 + + 2 Cu 2 syn hydroxypalladation Control Experiments:! Z/E isomerization is < 1% under the reaction conditions.! Cofirmed that cleavage of C bond with Cu 2 occurs with inversion at carbon.! Confirmed that chlorohydrin does not arise from an intermediate epoxide. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Chem. Soc., Chem. Commun. 1977, 264. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Am. Chem. Soc. 1979, 101, 2411.
Bäckvall's Stereochemical Studies An Apparent Contradiction with KIE Studies outer-sphere anti hydroxypalladation KIE 1.07 and competitive KIE of 1.70 indicates that the slow step occurs before decomposition. 2 + 2 2 fast C 2 C 2 + + slow + + + 3 C + 2 slow 2 C 2 C 2 fast innter-sphere syn hydroxypalladation anti pathway has decomposition as the slow step syn pathway has hydroxypalladation as the slow step enry, P. M. J. rg. Chem. 1973, 38, 2415. Kosaki, M.; Isemura, M.; Kitaura, K.; Schinoda, S.; Saito, Y. J. Mol. Catal. 1977, 2, 351. Saito, Y.; Schinoda, S. J. Mol. Catal. 1980, 9, 461.
Bäckvall's Stereochemical Studies Reconciling Stereochemical Results with Kinetic ata 2 + 2 2 C 2 C 2 + + Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Chem. Soc., Chem. Commun. 1977, 264. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Am. Chem. Soc. 1979, 101, 2411.
Bäckvall's Stereochemical Studies Reconciling Stereochemical Results with Kinetic ata 2 + 2 2 C 2 C 2 + + 2 C 2 C 2 slow 2 C 2 C 2 + 2 Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Chem. Soc., Chem. Commun. 1977, 264. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Am. Chem. Soc. 1979, 101, 2411.
Bäckvall's Stereochemical Studies Reconciling Stereochemical Results with Kinetic ata 2 + 2 2 C 2 C 2 + + 2 C 2 C 2 slow 2 C 2 C 2 + 2 Since decomposition occurs after the rate-limiting step a primary isotope effect would not be predicted. 2 C 2 C 2 fast 2 2 C C 3 3 C Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Chem. Soc., Chem. Commun. 1977, 264. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Am. Chem. Soc. 1979, 101, 2411.
Evidence for Syn ydroxypalladation The Isomerization of Allyl Alcohol Under Wacker Conditions + 4 + 2 2 + 4 + k 1 k 1 k 1 II k 1 k 2 oxidation products xidation of allyl alcohol is directed by the hydroxyl group Gregor, N.; enry, P. M. J. Am. Chem. Soc. 1981, 103, 681.
Evidence for Syn ydroxypalladation The Isomerization of Allyl Alcohol Under Wacker Conditions + 4 + 2 2 + 4 + k 1 k 1 k 1 II k 1 If hydroxypalladation is anti, isomerization should occur since hydroxypalladation is required to be an equilibrium process. k 2 oxidation products If hydroxypalladation is syn, isomerization should not occur since hydroxypalladation is rate limiting. xidation of allyl alcohol is directed by the hydroxyl group Rate = d[c 2 4 ] dt = k [ 4 ] [olefin] [ ] 2 [ + ] Gregor, N.; enry, P. M. J. Am. Chem. Soc. 1981, 103, 681.
Evidence for Syn ydroxypalladation The Isomerization of Allyl Alcohol Under Wacker Conditions + 4 + 2 2 + 4 + k 1 k 1 II k 1 k 1 If hydroxypalladation is anti, isomerization should occur since hydroxypalladation is required to be an equilibrium process. k 2 oxidation products If hydroxypalladation is syn, isomerization should not occur since hydroxypalladation is rate limiting. xidation of allyl alcohol is directed by the hydroxyl group Rate = d[c 2 4 ] dt = k [ 4 ] [olefin] [ ] 2 [ + ] Gregor, N.; enry, P. M. J. Am. Chem. Soc. 1981, 103, 681.
Evidence for Syn ydroxypalladation The Isomerization of Allyl Alcohol Under Wacker Conditions + 4 + 2 2 + 4 + k 1 k 1 II k 1 k 1 If hydroxypalladation is anti, isomerization should occur since hydroxypalladation is required to be an equilibrium process. k 2 oxidation products If hydroxypalladation is syn, isomerization should not occur since hydroxypalladation is rate limiting. Isomerization product was < 3% of the total deuterated allyl alcohol when the reaction was stopped after one half-life. ydroxypalladation is NT an equilibrium process! Gregor, N.; enry, P. M. J. Am. Chem. Soc. 1981, 103, 681.
Evidence for Syn ydroxypalladation The Isomerization of Allyl Alcohol Under Isomerization Conditions + 4 + 2 [ ] = 3.3 M 2 + 4 + k 1 k 1 II k 1 k 1 If hydroxypalladation is anti, isomerization should occur since hydroxypalladation is required to be an equilibrium process. k 2 oxidation products If hydroxypalladation is syn, isomerization should not occur since hydroxypalladation is rate limiting. Rate = d[c 2 4 ] dt = k [ 4 ] [olefin] [ ] nly isomerization observed. Gregor, N.; enry, P. M. J. Am. Chem. Soc. 1981, 103, 681.
Evidence for Syn ydroxypalladation The Isomerization of Allyl Alcohol Under Isomerization Conditions + 4 + 2 [ ] = 3.3 M 2 + 4 + k 1 k 1 II k 1 k 1 Reactions at high and low chloride do not proceed through the same mechanism. Formation of aldehyde and chlorohydrin does not occur through a common hydroxypalladation intermediate. If hydroxypalladation is anti, isomerization should occur since hydroxypalladation is required to be an equilibrium process. k 2 oxidation products If hydroxypalladation is syn, isomerization should not occur since hydroxypalladation is rate limiting. Rate = d[c 2 4 ] dt = k [ 4 ] [olefin] [ ] nly isomerization observed. Gregor, N.; enry, P. M. J. Am. Chem. Soc. 1981, 103, 681.
Anti ydroxypalladation at igh [ ] enry's Proposed Pathway + + + 2 C 2 C C 2 + + outer-sphere anti hydroxypalladation C 2 C C 2 + + + 2 Gregor, N.; enry, P. M. J. Am. Chem. Soc. 1981, 103, 681.
Anti ydroxypalladation at igh [ ] enry's Proposed Pathway + + + 2 C 2 C C 2 + + outer-sphere anti hydroxypalladation C 2 C C 2 + + + 2 Gregor, N.; enry, P. M. J. Am. Chem. Soc. 1981, 103, 681.
Reinterpreting Bäckvall's Results enry's Proposed Pathway 4 + C 2 4 + ligand loss prevented by high concentration of. + 2 C 2 C 2 Excess prevents this intermediate from undergoing decomposition to oxidation products. outer-sphere anti hydroxypalladation C 2 C 2 Cu 2 Assumption that oxidation products and chlorohydrin arise from a common intermediate is NT valid. Gregor, N.; Zaw, K.; enry, P. M. rganometallics 1984, 3, 1251.
Evidence for Syn ydroxypalladation A New Stereochemical and Kinetic Probe F 3 C + 4 + 2 2 + 4 + F 3 C 3 C F 3 C C 3 3 C C 3 Required Properties:! Substrate cannot undergo oxidation; can only isomerize. oxidation products! Substrate whose RLS is hydroxypalladation.! Substrate possesses stereochemistry that can be used to distinguish between syn and anti hydroxypalladation. oxidation products Francis, J. W.; enry, P. M. rganometallics 1991, 10, 3498.
Evidence for Syn ydroxypalladation A New Stereochemical and Kinetic Probe F 3 C + 4 + 2 2 + 4 + F 3 C 3 C F 3 C C 3 3 C C 3 k 1 k 1 k 1 k 1 oxidation products II F 3 C oxidation products 3 C C 3 Exchange is completely symmetric, thus the rate of isomerization depends only on the rate of formation of the hydroxypalladate and not on its equilibrium concentration. Francis, J. W.; enry, P. M. rganometallics 1991, 10, 3498.
Evidence for Syn ydroxypalladation A New Stereochemical and Kinetic Probe F 3 C + 4 + 2 2 + 4 + F 3 C 3 C F 3 C C 3 3 C C 3 k 1 k 1 k 1 k 1 oxidation products II F 3 C oxidation products 3 C C 3 For syn hydroxypalladation: For anti hydroxypalladation: Rate = d[c 2 4 ] dt = k [ 4 ] [olefin] [ ] 2 [ + ] Rate = d[c 2 4 ] dt = k [ 4 ] [olefin] [ ] Proton inhibition term must result from an equilibrium that occurs before the rate-limiting hydroxypalladation step. Proton inhibition term does not show up in the exchange rate because it results from this exchange equilibrium. Francis, J. W.; enry, P. M. rganometallics 1991, 10, 3498.
Evidence for Syn ydroxypalladation A New Stereochemical and Kinetic Probe F 3 C + 4 + 2 2 + 4 + F 3 C 3 C F 3 C C 3 3 C C 3 k 1 k 1 k 1 k 1 oxidation products II F 3 C oxidation products 3 C C 3 For syn hydroxypalladation: Rate = d[c 2 4 ] dt = k [ 4 ] [olefin] [ ] 2 [ + ] Proton inhibition term must result from an equilibrium that occurs before the rate-limiting hydroxypalladation step. bserved Kinetics under Wacker Conditions:! Rate expression had a first order proton inhibition term.! Rate expression was identical to the Wacker rate expression.! Consistent with syn hydroxypalladation mechanism. Francis, J. W.; enry, P. M. rganometallics 1991, 10, 3498.
Evidence for Syn ydroxypalladation A New Stereochemical and Kinetic Probe F 3 C + 4 + 2 2 + 4 + F 3 C 3 C F 3 C C 3 3 C C 3 k 1 k 1 k 1 k 1 oxidation products II F 3 C oxidation products 3 C C 3 bserved Kinetics under igh [ ] Conditions:! Rate expression had no first order proton inhibition term.! Rate expression was identical to what Bäckvall observed at high [ ].! Consistent with anti hydroxypalladation mechanism. For anti hydroxypalladation: Rate = d[c 2 4 ] dt = k [ 4 ] [olefin] [ ] Proton inhibition term does not show up in the exchange rate because it results from this exchange equilibrium. Francis, J. W.; enry, P. M. rganometallics 1991, 10, 3498.
Evidence for Syn ydroxypalladation A New Stereochemical and Kinetic Probe anti + F 3 C II C 3 C 3 + + II 2 3 C C 3 (R), Z F 3 C C 3 C 3 4 (R), E 2 Francis, J. W.; enry, P. M. rganometallics 1991, 10, 3498.
Evidence for Syn ydroxypalladation A New Stereochemical and Kinetic Probe anti + F 3 C II C 3 C 3 + + II 2 3 C C 3 (R), Z F 3 C C 3 C 3 4 (R), E 2 + syn F 3 C II C 3 C 3 + + II 2 F 3 C C 3 C 3 (S), E Francis, J. W.; enry, P. M. rganometallics 1991, 10, 3498.
Evidence for Syn ydroxypalladation A New Stereochemical and Kinetic Probe anti + F 3 C II C 3 C 3 + + II 2 3 C C 3 (R), Z product F 3 C C 3 C 3 4 substrate config % ee [ ] [catalyst] % isomerization % S % R (R), E 2 R R S 100 100 100 0.10 0.05 0.10 4 4 4 30 48 25 32.5 50.0 72.5 67.5 50.0 27.5 S 100 0.05 4 50 50.0 50.0 + syn F 3 C II C 3 C 3 + + II 2 F 3 C C 3 C 3 (S), E Francis, J. W.; enry, P. M. rganometallics 1991, 10, 3498.
Evidence for Syn ydroxypalladation A New Stereochemical and Kinetic Probe anti + F 3 C II C 3 C 3 + + II 2 3 C C 3 (R), Z product F 3 C C 3 C 3 4 substrate config % ee [ ] [catalyst] % isomerization % S % R (R), E 2 R R S 100 100 100 0.10 0.05 0.10 4 4 4 30 48 25 32.5 50.0 72.5 67.5 50.0 27.5 S 100 0.05 4 50 50.0 50.0 + syn F 3 C II C 3 C 3 + + II 2 F 3 C C 3 C 3 (S), E Francis, J. W.; enry, P. M. rganometallics 1991, 10, 3498.
Evidence for Syn ydroxypalladation A New Stereochemical and Kinetic Probe anti + F 3 C II C 3 C 3 + + II 2 3 C C 3 (R), Z F 3 C C 3 C 3 4 2 substrate config % ee [ ] % Z % isomerization % S % R R R 100 100 2.0 3.5 31 27 product 30 25 0.0 0.0 100 100 (R), E S 100 2.0 35 32 100 0.0 S 100 3.5 45 45 100 0.0 + syn F 3 C II C 3 C 3 + + II 2 F 3 C C 3 C 3 (S), E Francis, J. W.; enry, P. M. rganometallics 1992, 11, 2832.
Evidence for Syn ydroxypalladation A New Stereochemical and Kinetic Probe anti + F 3 C II C 3 C 3 + + II 2 3 C C 3 (R), Z F 3 C C 3 C 3 4 2 substrate config % ee [ ] % Z % isomerization % S % R R R 100 100 2.0 3.5 31 27 product 30 25 0.0 0.0 100 100 (R), E S 100 2.0 35 32 100 0.0 S 100 3.5 45 45 100 0.0 + syn F 3 C II C 3 C 3 + + II 2 F 3 C C 3 C 3 (S), E Francis, J. W.; enry, P. M. rganometallics 1992, 11, 2832.
Evidence for Syn ydroxypalladation A New Stereochemical and Kinetic Probe high [ ] anti + F 3 C II C 3 C 3 + + II 2 3 C C 3 (R), Z F 3 C C 3 C 3 4 Conclusions:! At low [ ] (Wacker conditions), syn hydroxypalladation is operative. (R), E 2! At high [ ] (Bäckvall's conditions), anti hydroxypalladation is operative. low [ ] + syn F 3 C II C 3 C 3 + + II 2 F 3 C C 3 C 3 (S), E Francis, J. W.; enry, P. M. rganometallics 1991, 10, 3498.
Evidence for Syn ydroxypalladation A New Stereochemical and Kinetic Probe high [ ] anti + F 3 C II C 3 C 3 + + II 2 3 C C 3 (R), Z Criticism: F 3 C C 3 C 3 4! Trisubstituted alkenes are not standard Wacker substrates.! Substrate cannot undergo oxidation. (R), E 2! Would be best to study a substrate that can undergo both oxidation and isomerization under both low and high [ ] concentrations. low [ ] + syn F 3 C II C 3 C 3 + + II 2 F 3 C C 3 C 3 (S), E Francis, J. W.; enry, P. M. rganometallics 1991, 10, 3498.
Chirality Transfer Studies R 2 R 1 (R), Z reactive conformation amed,.; enry, P. M.; Thompson, C. J. rg. Chem. 1999, 64, 7745.
Chirality Transfer Studies [ ] > 2 M R 2 anti II 2 (S), Z R 1 R 2 R 1 4 + R 2 II R 1 [ ] = 0.1 M 0 + R 2 (S) R 1 2 (R), Z reactive conformation amed,.; enry, P. M.; Thompson, C. J. rg. Chem. 1999, 64, 7745.
Chirality Transfer Studies [ ] > 2 M R 2 anti II 2 (S), Z R 1 R 2 R 1 4 + R 2 II R 1 [ ] = 0.1 M 0 + R 2 (S) R 1 (R), Z reactive conformation 2 + R 2 R 1 [ ] > 2 M II 2 R 2 R 1 (R), E syn II [ ] = 0.1 M R 2 R 1 0 + amed,.; enry, P. M.; Thompson, C. J. rg. Chem. 1999, 64, 7745. (R)
Chirality Transfer Studies [ ] > 2 M R 2 anti II 2 (S), Z R 1 R 2 R 1 4 + R 2 II R 1 [ ] = 0.1 M 0 + R 2 (S) R 1 (R), Z reactive conformation 2 + R 2 R 1 [ ] > 2 M II 2 R 2 R 1 (R), E syn II [ ] = 0.1 M R 2 R 1 0 + amed,.; enry, P. M.; Thompson, C. J. rg. Chem. 1999, 64, 7745. (R)
Chirality Transfer Studies [ ] > 2 M Me Ph Me Me (R), Z reactive conformation Ph Me anti + + Me Me II Ph Me Me II 2 [ ] = 0.1 M 0 + [ ] > 2 M II 2 Me Me (S), Z Me Ph Me (S) Me Ph (R), E syn II Ph [ ] = 0.1 M Me Me 0 + amed,.; enry, P. M.; Thompson, C. J. rg. Chem. 1999, 64, 7745. (R) Ph
Chirality Transfer Studies [ ] > 2 M Me Ph Me Me (R), Z reactive conformation Ph Me anti + + Me Me II Ph must add syn regardless of the [ ] Ph Me Me II 2 [ ] = 0.1 M 0 + [ ] > 2 M II 2 Me Me (S), Z Me Ph Me (S) Me Ph (R), E syn II Ph [ ] = 0.1 M Me Me 0 + amed,.; enry, P. M.; Thompson, C. J. rg. Chem. 1999, 64, 7745. (R) Ph
Chirality Transfer Studies [ ] > 2 M Me Me Et 4 anti + Me II Et II 2 [ ] = 0.1 M 0 + Et (S), Z Me Et (S) (R), Z reactive conformation 2 + Me Et [ ] > 2 M II 2 Me Et (R), E syn II [ ] = 0.1 M Me Et 0 + amed,.; enry, P. M.; Thompson, C. J. rg. Chem. 1999, 64, 7745. (R)
Me Et (R), Z reactive conformation 4 2 Chirality Transfer Studies anti + + Me Me II Et Et [ ] > 2 M II 2 [ ] = 0.1 M [ ] > 2 M II 2 Me Me (S), Z Me 0 + the stereochemistry of hydroxypalladation(s) must be different at high and low [ ] (R), E Et Et Et syn II [ ] = 0.1 M Me Et 0 + amed,.; enry, P. M.; Thompson, C. J. rg. Chem. 1999, 64, 7745. (R)
Me Et (R), Z reactive conformation 4 2 Chirality Transfer Studies anti + + Me Me II Et Et [ ] > 2 M II 2 [ ] = 0.1 M II 2 Me (S), Z (R), E 0! Excess prevents syn hydroxypalladation + by Et prohibiting the ligation of water. (S)! Excess prevents "-hydride elimination to oxidation products by prohibiting the necessary dissociation of a ligand. [ ] > 2 M Me Et Me Et syn II [ ] = 0.1 M Me Et 0 + amed,.; enry, P. M.; Thompson, C. J. rg. Chem. 1999, 64, 7745. (R)
Mechanism for xidation of lefins under Wacker Conditions 1 [ ] inhibition 1 [ ] inhibition 2 C C 2 + 2 2 3 C + Cu 2 + 2 1 [ + ] inhibition + 2 2 + 2 syn hydroxypalladation enry, P. M. In andbook of rganopalladium Chemistry for rganic Synthesis; Negishi, E.-I., Ed.; John Wiley & Sons, Inc.: New York, 2002; Vol. 1, p 2119.
Mechanism for xidation of lefins under Wacker Conditions 1 [ ] inhibition 1 [ ] inhibition 2 C C 2 + 2 2 3 C + Cu 2 + 2 1 [ + ] inhibition + 2 2 + 2 syn hydroxypalladation enry, P. M. In andbook of rganopalladium Chemistry for rganic Synthesis; Negishi, E.-I., Ed.; John Wiley & Sons, Inc.: New York, 2002; Vol. 1, p 2119.
Mechanism for ecomposition to xidation Products Moiseev's Mechanism:!-hydride elimination dissociation tautomerize Smidt, J.; afner, W.; Jira, R.; Sieber, R.; Sedlmeier, J.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80. Moiseev, I. I.; Warhaftig, M. N.; Sirkin, J.. oklady Akad. Nauk UdSSR 1960, 130, 820. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Am. Chem. Soc. 1979, 101, 2411. enry, P. M. J. Am. Chem. Soc. 1964, 86, 3246.
Mechanism for ecomposition to xidation Products Moiseev's Mechanism:!-hydride elimination dissociation tautomerize + 4 + 2 3 C + (0) + 2 + 2 + 4 + 2 3 C + (0) + 2 + 2 lack of proton incorporation from solvent means that tautomerization mechanism is invalid Smidt, J.; afner, W.; Jira, R.; Sieber, R.; Sedlmeier, J.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80. Moiseev, I. I.; Warhaftig, M. N.; Sirkin, J.. oklady Akad. Nauk UdSSR 1960, 130, 820. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Am. Chem. Soc. 1979, 101, 2411. enry, P. M. J. Am. Chem. Soc. 1964, 86, 3246.
Mechanism for ecomposition to xidation Products enry's Model + (0) + II -assisted hydride shift Smidt, J.; afner, W.; Jira, R.; Sieber, R.; Sedlmeier, J.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80. Moiseev, I. I.; Warhaftig, M. N.; Sirkin, J.. oklady Akad. Nauk UdSSR 1960, 130, 820. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Am. Chem. Soc. 1979, 101, 2411. enry, P. M. J. Am. Chem. Soc. 1964, 86, 3246.
Mechanism for ecomposition to xidation Products enry's Model + (0) + II -assisted hydride shift Bäckvall's Model!-hydride elimination reinsertion + (0) +!-hydride elimination from oxygen Smidt, J.; afner, W.; Jira, R.; Sieber, R.; Sedlmeier, J.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80. Moiseev, I. I.; Warhaftig, M. N.; Sirkin, J.. oklady Akad. Nauk UdSSR 1960, 130, 820. Bäckvall, J.-E.; Åkermark, B.; Ljunggren, S.. J. Am. Chem. Soc. 1979, 101, 2411. enry, P. M. J. Am. Chem. Soc. 1964, 86, 3246.
Mechanism for ecomposition to xidation Products Computational Studies Bäckvall's Model 3 C II + (0) +!-hydride elimination from oxygen Goddard's Computations Keith, J. A.; xgaard, J.; Goddard, W. A., III J. Am. Chem. Soc. 2006, 128, 3132. Keith, J. A.; Nielsen, R. J.; xgaard, J.; Goddard, W. A., III J. Am. Chem. Soc. 2007, 129, 12342.
Mechanism for ecomposition to xidation Products Computational Studies Bäckvall's Model II 3C + (0) +!-hydride elimination from oxygen Goddard's Computations 4-membered TS: 36.3 kcal/mol Keith, J. A.; xgaard, J.; Goddard, W. A., III J. Am. Chem. Soc. 2006, 128, 3132. Keith, J. A.; Nielsen, R. J.; xgaard, J.; Goddard, W. A., III J. Am. Chem. Soc. 2007, 129, 12342.
Mechanism for ecomposition to xidation Products Computational Studies Bäckvall's Model II 3C + (0) + β-hydride elimination from oxygen Goddard's Computations 4-membered TS: 36.3 kcal/mol -mediated reductive elimination TS: 18.7 kcal/mol Keith, J. A.; xgaard, J.; Goddard, W. A., III J. Am. Chem. Soc. 2006, 128, 3132. Keith, J. A.; Nielsen, R. J.; xgaard, J.; Goddard, W. A., III J. Am. Chem. Soc. 2007, 129, 12342.
From Industrial Process to Synthetic Method Preparations of Methyl Ketones from Terminal lefins ement, 1964: 2 (10 mol%) oxidant 2 (12-17%), 2 MF oxidant = Cu 2 2 2 (10 mol%) or p-benzoquinone ement, W..; Selwitz, C. M. J. rg. Chem. 1964, 29, 241. Tsuji, J. Synthesis 1984, 369.
From Industrial Process to Synthetic Method Preparations of Methyl Ketones from Terminal lefins ement, 1964: 2 (10 mol%) oxidant 2 (12-17%), 2 MF oxidant = Cu 2 2 2 (10 mol%) or p-benzoquinone Me Me Zearalenone 19-Nortestosterone intermediate to ichroanone TP Nootkatone Brevicomin intermediate to Coriolin ement, W..; Selwitz, C. M. J. rg. Chem. 1964, 29, 241. Tsuji, J. Synthesis 1984, 369.
Moritani, 1973: From Industrial Process to Synthetic Method xidative Cyclizations Give Access to eterocyclic Compounds R Na + 2 (PhCN) 2 (1 equiv) Ph R osokawa, T.; Maeda, K.; Koga, K.; Moritani, I. Tetrahedron Lett. 1973, 10, 739.
Moritani, 1973: From Industrial Process to Synthetic Method xidative Cyclizations Give Access to eterocyclic Compounds R Na + 2 (PhCN) 2 (1 equiv) Ph R (dba) 2 (5 mol%) KC 3 (1.1 equiv) (Ac) 2 (2 mol%) Cu(Ac) 2 2 (1 equiv) air, MS, 2 60 C air, MF, 100 C no co-oxidant! Roshchin, A. I.; Kel'chevski, S. M.; Bumagin, N. A. J. rganomet. Chem. 1998, 560, 163. Larock, R. C.; Wei, L.; ightower, T. R. Synlett 1998, 522.
Moritani, 1973: From Industrial Process to Synthetic Method xidative Cyclizations Give Access to eterocyclic Compounds R Na + 2 (PhCN) 2 (1 equiv) Ph R (dba) 2 (5 mol%) KC 3 (1.1 equiv) (Ac) 2 (2 mol%) Cu(Ac) 2 2 (1 equiv) air, MS, 2 60 C air, MF, 100 C no co-oxidant! (TFA) 2 (10 mol%) ligand (20 mol%) p-benzoquinone (4 equiv) Me, 60 C 96% ee i-pr N N i-pr Uozumi, Y.; Kato, K.; ayashi, T. J. rg. Chem. 1998, 63, 5071.
From Industrial Process to Synthetic Method xidative Cyclizations Give Access to eterocyclic Compounds Me 2 C Boc N Bn Bn Bn N NTs N N Ts N osokawa, T.; Murahashi, S.-I. In andbook of rganopalladium Chemistry for rganic Synthesis; Negishi, E.-I., Ed.; John Wiley & Sons: New York, 2002; Vol. 2, pp 2169-2192.
Stereochemistry of xidative Cyclizations L n R anti oxypalladation R R Ln!-hydride elimination R L n syn oxypalladation R R Ln!-hydride elimination
Stereochemistry of xidative Cyclizations Stoltz Group Studies (TFA) 2 (5 mol%) pyridine (20 mol%) Na 2 C 3 (2 equiv) MS3Å, 2 (1 atm) PhC 3, 80 C 95% yield Trend, R. M.; Ramtohul, Y. K.; Ferreira, E. M.; Stoltz, B. M. Angew. Chem. Int. Ed. 2003, 42, 2892.
Stereochemistry of xidative Cyclizations Stoltz Group Studies (TFA) 2 (5 mol%) pyridine (20 mol%) Na 2 C 3 (2 equiv) MS3Å, 2 (1 atm) PhC 3, 80 C 95% yield C 2 Et NTs NBn 90% yield 88% yield 63% yield 82% yield 87% yield 93% yield 62% yield Trend, R. M.; Ramtohul, Y. K.; Ferreira, E. M.; Stoltz, B. M. Angew. Chem. Int. Ed. 2003, 42, 2892.
Stereochemistry of xidative Cyclizations Stoltz Group Studies E [ II ] E E [ II ] E E E anti oxypalladation C 2 Et C 2 Et E E [ II ] E E [] E E syn oxypalladation Trend, R. M.; Ramtohul, Y. K.; Stoltz, B. M. J. Am. Chem. Soc. 2005, 127, 17778.
Stereochemistry of xidative Cyclizations Stoltz Group Studies E [ II ] E E [ II ] E E E anti oxypalladation C 2 Et C 2 Et C 2 Et C 2 Et + C 2 Et C 2 Et E E [ II ] E E [] E E syn oxypalladation Trend, R. M.; Ramtohul, Y. K.; Stoltz, B. M. J. Am. Chem. Soc. 2005, 127, 17778.
Stereochemistry of xidative Cyclizations Stoltz Group Studies E E [ II ] anti oxypalladation E [ II ] E E E C 2 Et C 2 Et E E [ II ] syn oxypalladation E E [] E E Trend, R. M.; Ramtohul, Y. K.; Stoltz, B. M. J. Am. Chem. Soc. 2005, 127, 17778.
Stereochemistry of xidative Cyclizations Stoltz Group Studies E E [ II ] anti oxypalladation E [ II ] E E E C 2 Et C 2 Et C 2 Et C 2 Et E E [ II ] syn oxypalladation E E [] E E Trend, R. M.; Ramtohul, Y. K.; Stoltz, B. M. J. Am. Chem. Soc. 2005, 127, 17778.
Stereochemistry of xidative Cyclizations ayashi Group Studies (MeCN) 4 (BF 4 ) 2 (5 mol%) (S,S)-ip-boxax (/L* = 1/2) benzoquinone (4 equiv) Me, 40 C, 4 h A:B:C: = 16:46:29:9 A B syn oxypalladation C ayashi, T.; Yamasaki, K.; Mimura, M.; Uozumi, Y. J. Am. Chem. Soc. 2004, 126, 3036.
Stereochemistry of xidative Cyclizations ayashi Group Studies (MeCN) 4 (BF 4 ) 2 (5 mol%) (S,S)-ip-boxax (/L* = 1/2) benzoquinone (4 equiv) Me, 40 C, 4 h A:B:C: = 16:46:29:9 A B syn oxypalladation C 2 (MeCN) 2 (10 mol%) Na 2 C 3 (2 equiv) Li (2 equiv) benzoquinone (1 equiv) TF, 65 C, 24 h A:B:C: = 6:5:7:82 A B anti oxypalladation C ayashi, T.; Yamasaki, K.; Mimura, M.; Uozumi, Y. J. Am. Chem. Soc. 2004, 126, 3036.
Stereochemistry of xidative Cyclizations Stahl Group Studies anti aminopalladation L n Ts N Ts N Ts N Ts N NTs L n Ts N Ts N Ts N syn aminopalladation Ts N Liu, G.; Stahl, S. S. J. Am. Chem. Soc. 2007, 129, 6328.
Stereochemistry of xidative Cyclizations Stahl Group Studies anti aminopalladation L n Ts N Ts N Ts N Ts N NTs No additive: L n 2:1 ratio syn:anti aminopalladation products Ts N Ts N Ts N syn aminopalladation Ts N Liu, G.; Stahl, S. S. J. Am. Chem. Soc. 2007, 129, 6328.
Stereochemistry of xidative Cyclizations Stahl Group Studies anti aminopalladation L n Ts N Ts N Ts N Ts N NTs C 2 Additive: L n 1:2 ratio syn:anti aminopalladation products Ts N Ts N Ts N syn aminopalladation Ts N Liu, G.; Stahl, S. S. J. Am. Chem. Soc. 2007, 129, 6328.
Stereochemistry of xidative Cyclizations Stahl Group Studies anti aminopalladation L n Ts N Ts N Ts N Ts N NTs NaAc or Na 2 C 3 Additive: L n exclusively syn aminopalladation products Ts N Ts N Ts N syn aminopalladation Ts N Liu, G.; Stahl, S. S. J. Am. Chem. Soc. 2007, 129, 6328.
Conclusions Source and Ligands Additive Effects (co-oxidant, acid, base, salts) syn vs. anti heteropalladation or carbopalladation Solvent Effects ( 2, R, MS, etc.) lefin Sterics and Electronics Nucleophile Sterics and Electronics
The Wacker xidation ne-stage Process purge C 2 4 C 2 4, 2 Reactor 2, Cu 2, C 2 4, C 3 C Separation Equipment! Required brick and rubber-lined reactors and titanium pipes.! Requires an 2 plant.! perates at 60-70 C, 3 atm, and p between 0.8 and 3.0.! Yields >95% acetaldehyde. C 3 C Wiseman, P. Introduction to Industrial rganic Chemistry; 2nd Ed.; Applied Science Publishers: London, 1979; pp. 116-120.
The Wacker xidation Two-Stage Process! Required brick and rubber-lined reactors and titanium pipes.! Uses ambient air as 2 source and impure mixtures of ethylene. C 3 C! perates at 90-100 C, 10 atm.! Yields >95% acetaldehyde. C 2 4 2, Cu 2, xidation Reactor 2, (Cu) 2, + C 3 C Separation Equipment 2, (Cu) 2, N 2 Regeneration Reactor air Wiseman, P. Introduction to Industrial rganic Chemistry; 2nd Ed.; Applied Science Publishers: London, 1979; pp. 116-120.