The Heck Reaction: Mechanistic Insight into a ... - The Stoltz Group

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Preactivation of Catalyst • if a Pd(II) source is used in a Heck reaction, it must be reduced to Pd(0) before entering the catalytic cycle Reduction by Phosphines outer shell mechanism nucleophillic attack H 2 O L n Pd II PR 3 L n Pd(O) + NuPR 3 Nu H + O PR 3 Nu phosphonium inner shell mechanism Nu reductive elimination H 2 O L n Pd II PR 3 L n Pd(O) + NuPR 3 Nu H + O PR 3 phosphonium • electron-withdrawing group on phosphine increases rate of Pd(II) to Pd(0) reduction, because phosphine is more susceptible to attack by nucleophile • hard nucleophiles assist Pd(II) to Pd(0) reduction (eg. - OH, - OR, H 2 O, AcO - /H 2 O, F - /H 2 O) Preactivation of Catalyst - continued • in the absence of phosphines, Pd(II) can be reduced to Pd(0) by other means Reduction by Tertiary Aliphatic Amines L n Pd II X X coordination R 2 N R L X R 2 N Pd H R !-hydride elimination R 2 N R L n Pd II X H reductive elimination HX L n Pd(0) Reduction by Olefins (Wacker-Type Process) L n Pd II X X coordination R L n Pd II R X Wacker-type attack Nu H L n Pd II X Nu R !-hydride elimination R L n Pd II X H reductive elimination HX L n Pd(0) Nu • when a high catalyst loading is used, the yield may be diminished if the substrate olefin undergoes this Wacker-type reaction Reduction by Other Functional Groups • phosphonium and 4° ammonium salts can also reduce Pd(II) to Pd(0) (via oxid. addn. to C-N or C-P) 2
Preactivation of Catalyst - continued • to enter the catalytic cycle, Pd(0) must have a proper coordination shell (eg. L 2 Pd(0) ) there can be no more than 2 strongly bound ligands on palladium there is a a restriction on the choice of ligands and their concentration in solution The Proper Coordination Shell for Pd(0) in Monodentate Phosphine Assited Catalysis • too much phosphine inhibits catalysis by generating a coordinatively saturated complex: PR 3 R 3 P Pd 0 PR 3 PR 3 R 3 P Pd 0 PR 3 Ar Br PR 3 ligand ox. addn. assoc. Ar R 3 P Pd II Br PR 3 Heck • but with too little phosphine, the active dicoordinated Pd 0 (PR 3 ) 2 disproportionates to a stable tricoordinate Pd 0 (PR 3 ) 3 and unstable low-ligated complexes, which leads to Pd aggregation and cluster formation: 2Pd(PR 3 ) 2 Pd(PR 3 ) 3 + Pd(PR 3 ) Pd n L m Pd-black (stable) Preactivation of Catalyst - continued The Proper Coordination Shell for Pd(0) Complexes Generated from Pd(dba) 2 • once again, with too little phosphine (or other L-type ligand) the active dicoordinated Pd 0 L 2 disproportionates to a stable tricoordinate Pd 0 L 3 and unstable low-ligated complexes, which leads to Pd aggregation and cluster formation: Pd(dba) 2 + 2L 2dba + PdL 2 PdL 3 + PdL Pd n L m Pd-black • with too little phosphine there may also be incomplete deligation of dba, which requires at least 4 equivalents of phosphine • Pd(dba) 2 + excess PR 3 may lead to a coordinatively saturated complex, which may not react with less reactive substrates preformed Pd(PPR 3 ) 4 may be more reactive thanPd(dba) 2 + excess PR 3 Electronic Influences on the Proper Coordination Shell for Pd(0)-Triaryl Phosphine Complexes • there's a fine balance in choosing a triaryl phosphine ligand with the proper electronices electron withdrawing group on arylphosphine higher concentration of reactive Pd 0 (PAr 3 ) 2 via deligation of PAr 3 electron donating group on arylphospine higher rate of oxidative addition 3
Page 1: The Heck Reaction: Mechanistic Insi
Page 5 and 6: Migratory Insertion - continued (3)
Page 7 and 8: Regioselectivity in Migratory Inser
Page 9: !-Hydride Elimination Ph Pd L X R H

The Heck Reaction: Mechanistic Insight into a ... - The Stoltz Group

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