M.C. White, Chem 153 Nu attack on olefins -327 Week of November 25, 2002 Olefin functionalization via metal promoted nu attack Recall that the balance of electron flow in olefin-metal bonding can be shifted predominantly in one direction pending on the electronic properties of the metal he metal is electron withdrawing. M-L o-bonding predominates and withdraws electron density from the bond of the olefin(see Structure and Bonding, pg 39). This results in the induction of a 8+ charge on the olefin that activates it towards nucleophilic attack. Duncanson model C-H o-donation to the electrophilic metal activates the metal alkyl towards lefin o-donation to the electrophilic metal activates it towards Nu attack B-hydride elimination ecall that the equilibrium for late T-backbonding etals lies towards the olefin form which is stabilized via T-backbonding Catalyst regeneration O,/2 HX Pd 2Cux 2 CuX Pall
M.C. White, Chem 153 Nu attack on Olefins -327- Week of November 25, 2002 Olefin functionalization via metal promoted Nu attack C C M Dewar-ChattDuncanson Model Recall that the balance of electron flow in olefin-metal bonding can be shifted predominantly in one direction depending on the electronic properties of the metal. If the metal is electron withdrawing, M-L σ-bonding predominates and withdraws electron density from the π-bond of the olefin (see Structure and Bonding, pg. 39). This results in the induction of a δ+ charge on the olefin that activates it towards nucleophilic attack. L PdII X X R Nu σ donation>> π-backbonding Nu L R PdII X X δ+ olefin σ-donation to the electrophilic metal activates it towards Nu attack C-H σ-donation to the electrophilic metal activates the metal alkyl towards β-hydride elimination. Nu L H PdII X R Nu R L PdII X H recall that the equilibrium for late metals lies towards the olefin form which is stabilized via π-backbonding. L PdII L H X L Pd0 L RE HX O2/ 2 HX 2 CuII X2 O O 2 HX stoichiometric oxidants L PdII L O O L PdII L O O H H H2O2 L PdII L X X O O Pd0 Ln O OH PdIILn O OH PdII Ln 2 CuI X Catalyst regeneration H+ H+ HO OH
M.C. White, Chem 153 Nu attack on olefins -328 Week of November 25, 2002 Wacker oxidation CuCh(cat) 2 mechanistic possibilities for hydroxypalladation HO. HCI The Wacker oxidation is used H,O nOH习y industrially to produce -4 million tons of acetaldehyde/year CI H0 1n2 O 2 CuCI H,0 2 CuCh Deuterium labeling study indicates that hydroxypalladation proceeds Ln Pd(o) via palladium-nucleophile anti-addition HCl H,0 H LmPd OH H,O 阝 hydride elimination HO merical production of hyde OH Binding specificity: terminal olefins Regioselectivity: 2 carbon Remote functionality tolerated Stille JOMC 1979(169)239
M.C. White, Chem 153 Nu attack on Olefins -328- Week of November 25, 2002 2 mechanistic possibilities for hydroxypalladation: Cl Pd H2O II OH R syn hydroxypalladation Cl PdII H2O OH R Cl Pd H2O Cl II R anti hydroxypalladation OH2 Cl Pd H2O II Cl OH R Deuterium labeling study indicates that hydroxypalladation proceeds via palladium-nucleophile anti-addition. LnPdII H D D H D H LnPdII OH H D OH2 H+ CO HD D H OH O PdII Ln O H D DH O Pd0 Ln Stille JOMC 1979 (169) 239. Wacker Oxidation H2O HCl 2 CuCl H2O 2 Cl Pd H2O II Cl OH2 Cl Pd H2O Cl II R Cl Pd H2O Cl II OH2 + R Cl Pd H2O II OH R H Cl Pd H2O H II OH R H2O Pd H2O II Cl H R R HO O R R O R HCl Commericial production of acetaldehyde β-hydride elimination LnPd(0) 2 CuCl 1/2 O2 + 2 HCl · Binding specificity: terminal olefins · Regioselectivity: 2o carbon · Remote functionality tolerated PdCl2 (cat) CuCl2 (cat) O2, H2O, HCl The Wacker oxidation is used industrially to produce ~ 4 million tons of acetaldehyde/year. hydroxypalladation
M.C. White, Chem 153 Nu attack on olefins -329- Week of November 25, 2002 Oxidation of terminal olefins Standard Wacker conditions Selective oxidation of terminal olefins PdCh(cat) CuCh(cat. yo DMF/HO Chadha Chem Soc. perkin /1979 2346 Cuprous chloride(Cucyozas the oxidant system leads to faster reactions with no chlorinated biproducts H H PdCl(30 mol%) PC2(20mo%) CuCI(1.6 CuCI(10 mol%)O, DMF/H2O(10: 1.2) DMF/H0(9: 1) H OTHI 77 H OTHP OTBS 91% Ikegami Tetrahedron 1981(37)4411 Cu(oAc)O, oxidant system Benzoquinone can be used as a stoichiometric oxidant. H Pd(oAch(10 mol%) PdCh(10 mol%) HCIO4(0.3M), CH3CN ao cose 20 mayo H H Smith JACS1999(121)10468 Santelli tl1994(35)6481
M.C. White, Chem 153 Nu attack on Olefins -329- Week of November 25, 2002 Oxidation of terminal olefins Selective oxidation of terminal olefins O PdCl2 (cat.) CuCl2 (cat.)/O2 DMF/H2O O O 70% Chadha J. Chem. Soc. Perkin I 1979 2346. Cuprous chloride (CuCl)/O2 as the oxidant system leads to faster reactions with no chlorinated biproducts. H H OTHP O H H OTHP O O PdCl2 (30 mol%) CuCl (1.6 eq)/O2 DMF/H2O (10:1.2) 77% Ikegami Tetrahedron 1981 (37) 4411. H PdCl2 (20 mol%) CuCl (10 mol%)/O2 DMF/H2O (9:1) 91% OTBS O O H OTBS O O O Money Tetrahedron 1996 (52) 6307. Benzoquinone can be used as a stoichiometric oxidant: H H H O O H Pd(OAc)2 (10 mol%) HClO4 (0.3M), CH3CN O O 85% H H H O O H O Santelli TL 1994 (35) 6481. Cu(OAc)2/O2 oxidant system: O O PdCl2 (10 mol%) Cu(OAc)2 (20 mol%)/O2 DMF: H2O (7:1) O O O Smith JACS 1999 (121) 10468. Standard Wacker conditions:
M.C. White, M.s. Taylor Chem 153 Olefin Nu attack -330 Week of November 25, 2002 Palladium(1-mediated 3, 3/-sigmatropic rearrangements OAc PdCl(MeCN) (10mo%) Bno BnO OB THF.23° OAc 82% BnOH2( BnOc (10mol%) Clpd ChPd THF.23°C Chpd- CH3 Saito tl1988(29)1157 The vinyl ether I is unreactive to Pd(ii) catalysis. However, the similar substrate 2 shows good reactivity PdCl(Mech PdCl(MeCN)h (10mol%) Recovered starting THF23°C kelhaupt1986(27)6267 The authors speculate that when reacting with 1, Pd(n) binds preferentially to the electron-rich vinyl ether olefin over the terminal olefin. Such binding does not lead to a productive reaction. When the steric bulk of the vinyl ether is increased, as in 2, binding to the vinyl ether is less favourable Pd(in)coordination to the terminal allylic olefin occurs resulting in catalysis of the Claisen rearrrangement. Note that these structural requirements limit the scope of this reaction
M.C. White,M.S. Taylor Chem 153 Olefin Nu attack -330- Week of November 25, 2002 Cl2Pd O O CH3 R BnOH2C BnO OBn OAc OAc Cl2Pd O O R BnOH2C CH3 BnO OBn OAc OAc Cl2Pd O O CH3 R BnOH2C PdCl2(MeCN)2 (10 mol%) THF, 23°C 82% BnO OBn OAc OAc PdCl2(MeCN)2 (10 mol%) THF, 23°C Palladium (II)-mediated [3,3]-sigmatropic rearrangements Saito TL 1988 (29) 1157. Et O Et O Me Et O Me The vinyl ether 1 is unreactive to Pd(II) catalysis. However, the similar substrate 2 shows good reactivity: PdCl2(MeCN)2 (10 mol%) THF, 23°C Recovered starting material 1 PdCl2(MeCN)2 (10 mol%) THF, 23°C 71% The authors speculate that when reacting with 1, Pd(II) binds preferentially to the electron-rich vinyl ether olefin over the terminal olefin. Such binding does not lead to a productive reaction. When the steric bulk of the vinyl ether is increased, as in 2, binding to the vinyl ether is less favourable. Pd(II) coordination to the terminal allylic olefin occurs resulting in catalysis of the Claisen rearrrangement. Note that these structural requirements limit the scope of this reaction. 2 Bickelhaupt TL 1986 (27) 6267
M.C. White, Chem 153 Nu attack on olefins -331 Week of novem ber 25. 2002 Cyclic ether formation Pd(oAch(20 mol%) Cu(OAch(50 mol%)o Meoh/ho Pd(oac)2 Pd(oac)z 2Cu(OA)、/12O2 OAc Cycle A Cvcle B +2 HOAc <甲 2 Cu(oAch H20 HOAc H10::1mm!m195(48)153. Asymmetric version 5 membered ring formation Pd(ococF3h2(10 (S, S-boxax(10 D mol%) Meoh OH 0 5-exo-trig 6 membered ring formation Pd(ococF3)2 (10 mol%) (S, S)boxx(10 mol%) oOCOCF3 OCOCF3 6-exo-trig 61% yield Hayashi JACS 1997(119)506 97%ee
M.C. White, Chem 153 Nu attack on Olefins -331- Week of November 25, 2002 N O R O N R PdII OCOCF3 OCOCF3 Asymmetric version: OH Pd(OCOCF3)2 (10 mol%) (S,S)-boxax (10 mol%) MeOH O O (4 eq) O OH Pd(OCOCF3)2 (10 mol%) (S,S)-boxax (10 mol%) MeOH O O (4 eq) 5 membered ring formation 6 membered ring formation O * 71 % yield 93 % ee 61 % yield Hayashi 97 % ee JACS 1997 (119) 5063. OH Pd(OAc)2 (20 mol%) Cu(OAc)2 (50 mol%)/O2 MeOH/H2O O 54% OH PdII O OAc O O PdII H O O HOAc LnPdII H OAc Pd(OAc)2 LnPd0 Pd(OAc)2 HOAc 2 Cu(OAc)2 2 Cu(OAc) 1/2 O2 + 2 HOAc H2O Cycle A Cycle B Hosokawa Bull. Chem. Soc. Jpn. 1975 (48) 1533. Cyclic ether formation 5-exo-trig 5-exo-trig 6-exo-trig