M.C. White, Chem 153 Hydrozirconation -292 Week of november 18. 2002 Alkene/ Alkyne hydrozirconation orbital on zr via g-donation (T-backbonding is not possible ause the complex has no d electrons) Schwartzs reagent, 16e-(d0 Internally metalated omplexes rapidly isomerize at rt via 18e 6e-(d) B-hydride elimination, reinsertion sequences to the least sterically Moisture and O sensitive alkylzirconium SchwartzJACS 1974(96)8115 hindered 1 alkylzirconium produc product Olefin insertion into the Zr-C bond has never been observed Morokuma OM 1993(12)2777 nCI H Zr(CI)Cp2 Zr( ciCp nzene,rt, N2 84:16 Stereospecific cis hydrometallation occurs wit H regioselectivity in formation of the least sterically Zr(cl)cp2 vinylzirconium species. The use of excess Schwartz's reagent results in higher regioselectivities via formation of a dimetalated alkyl intermediate that preferentially p-hydride eliminates at the more sterically hindered Zr center Schwartz JACS 1975(97)679
M.C. White, Chem 153 Hydrozirconation -292- Week of November 18, 2002 Alkene/Alkyne Hydrozirconation ZrI V H Cl C6H13 (stoichiometric) benzene, rt, N2 ZrI V H Cl R 18e - (d0) Schwartz's reagent, 16e - (d0) ZrI V Cl 16e - (d0) R Moisture and O2 sensitive alkylzirconium product. Olefin insertion into the Zr-C bond has never been observed. Internally metalated alkylzirconium complexes rapidly isomerize at rt via β-hydride elimination, reinsertion sequences to the least sterically hindered 1o alkylzirconium product. Schwartz JACS 1974 (96) 8115. Morokuma OM 1993 (12) 2777. Olefin binds weakly to vacant d orbital on Zr via σ-donation (π-backbonding is not possible because the complex has no d electrons). ZrIV H Cl benzene, rt, N2 H Zr(Cl)Cp2 + Zr(Cl)Cp2 H 84:16 1 eq ZrI V H Cl benzene, rt, N2 catalytic Cp2(Cl)Zr H H Zr(Cl)Cp2 H Zr(Cl)Cp2 + Zr(Cl)Cp2 H 98:2 Stereospecific cis hydrometalation occurs with high regioselectivity in formation of the least sterically hindered vinylzirconium species. The use of excess Schwartz's reagent results in higher regioselectivities via formation of a dimetalated alkyl intermediate that preferentially β-hydride eliminates at the more sterically hindered Zr center. Schwartz JACS 1975 (97) 679
M.C. White, Chem 153 Hydrozirconation -293- Week of november 18. 2002 Functionalization HCI(dilute) >99% octane nCI D NCS also work lkylzirconium and alkenylzirco Reaction of Br2 with chiral alkylzirconiu mpounds react readily with affords alkyl bromides with retention of configuration H,0,, NaoH alkenylzirconium complexes react with Br2 to give vinyl bromides with retention of olefin 697 Because the alkylzirconium complex is formally product formation via an oxidative addition/ reductive ization is thought to proceed via a o-bond Schwartz ACIEE 1976(15)33 CO insertion/ zr acyl fictionalization HCI(dilute) h >99%I-heptanal Br, meoh R 5 1%methyl nNCl R R-HC-CH-R-CAHg, R=Ph, 69% insertion proceeds -CH CHr, R(CH,h OBn, r Ph, 74% with retention of SchwartzJACS 1975(97)228 HO, NaOH n-heptanoic acid, 77% Hanzawz ACIEE 1998(37)1696 M=AL, B, Cu, Hg, Wipf Tetrahedron 1996(52)12853
M.C. White, Chem 153 Hydrozirconation -293- Week of November 18, 2002 Functionalization Br2 O Cl Br R H R R O ZrIV Cl R ZrIV Cl Br R Br ZrI V Br Cl Schwartz ACIEE 1976 (15) 333. H2O2, NaOH HO R ZrI V Cl R Electrophilic functionalization CO insertion/ Zr acyl functionalization ZrI V Cl R O Br2, MeOH O R' H H2O2, NaOH O H R O MeO R OH R' O R O HO R Schwartz JACS 1975 (97) 228. Hanzawz ACIEE 1998 (37) 1696. 16e - (d0) CO (1.5 atm), rt 16e - (d0 ) HCl (dilute) >99% n-heptanal insertion proceeds with retention of configuration at C. 51% methyl n-heptanoate BF3· OEt2 -HC=CH-, R = C4H9, R'= Ph , 69% -CH2CH2 -, R = (CH2 )2OBn, R'= Ph, 74% n-heptanoic acid, 77% HCl (dilute) alkylzirconium and alkenylzirconium compounds react readily with a range of electrophiles. >99% octane 96% 80% 16e - (d0) 16e - (d0) Reaction of Br2 with chiral alkylzirconium complexes affords alkyl bromides with retention of configuration at the stereogenic carbon center. Likewise, alkenylzirconium complexes react with Br2 to give vinyl bromides with retention of olefin geometry. Because the alkylzirconium complex is formally d0 , product formation via an oxidative addition/ reductive elimination sequence is not reasonable. Functionalization is thought to proceed via a σ-bond metathesis mechanism. + 69% (note :NBS and NCS also work) Transmetallation of alkenylzirconocenes ZrIV Cl R 16e - (d0) LnM-X transmetalation M = Al, B, Cu, Hg, Ni, Pd, Sn, Zn R LnM ZrIV X + Cl Wipf Tetrahedron 1996 (52) 12853
M.C. White, Chem 153 Hydrozirconation -294- Week of november 18. 2002 Synthetic applications Hydrozirconation/transmetalation sequence in the total synthesis of Fostriecin Jacobsen ACIEE 2001 (40)3667 L [Cp2Zr(H)CI], CHCI 2. Me, Zn(-78 C). 10 minR Pro Zr(Ci)Cp2 ZnMe 45% Hydrozirconation/bromination sequence in the total synthesis of FK 506. Schreiber JACS 1990(112)5583 TIPSO 2. NBS, rt, 25 min Meo Me Hydrozirconation/Negishi coupling sequence in the total synthesis of FR901464 Jacobsen JACS 2000(122)10482 Cp(Ciz I 1. Cp Zr(h)CII ZnCl THE, OoC THF. 0C 3. Pd(PPh3)4(6.5mo%) TESO TESO btained via hydrozirconation/ iodination sequence
M.C. White, Chem 153 Hydrozirconation -294- Week of November 18, 2002 Synthetic applications i-PrO O H Me O O ZrIV Me Cl Me2Zn Me O R O ZnMe R Zr(Cl)Cp2 i-PrO O OH O 1. [Cp2Zr(H)Cl], CH2Cl2 2. Me2Zn (-78oC), 10 min 3. R ~ 45% Hydrozirconation/transmetalation sequence in the total synthesis of Fostriecin. Jacobsen ACIEE 2001 (40) 3667. Hydrozirconation/bromination sequence in the total synthesis of FK 506. Schreiber JACS 1990 (112) 5583. Me MeO TIPSO MeO TIPSO Br Me MeO TIPSO Zr(Cl)Cp2 Me 1. [Cp2Zr(H)Cl](3 eq), benzene, 30-40oC 2. NBS, rt, 25 min R 86% Hydrozirconation/Negishi coupling sequence in the total synthesis of FR901464. Jacobsen JACS 2000 (122) 10482. O I H O TESO O I O TESO Cp2(Cl)Zr 2. ZnCl2, THF, 0oC 3. Pd(PPh3)4 (6.5mol%) O N3 I obtained via hydrozirconation/ iodination sequence O I O TESO O N3 1. [Cp2Zr(H)Cl], THF, 0oC 80%
M.C. White, Chem 153 Hydrozirconation -295 Week of november 18. 2002 Hydridic character of schwartz's reagent H,0+ H pZr(cicp DH The hydridic character of the highly ionic Zr-H bond is demonstrated in its ability to reduce a variety of H carbonyl functionalities to Zr alkoxides at a rate R competative with olefin hydrozirconation. OH OR Schwartz ACIEE 1976(15)333 Reduction of 3 amides directhy to aldeIn Direct reduction of Evans N-acyl oxaolidinone(generally a 2 step procedure nvolving transamination to the Weinreb amide followed by lah reduction to the aldehyde) NO2C6H4,81% (1.5-2eq) OM THE rt 20-30 min R H MeoC(O)C8H16,74% Meo F. rt. 20-30 min 92% Why don' t the product aldehydes become reduced in situ? According to the proposed mechanism, the aldehyde is masked as iminium ion intermediate which decomposes upon aqueous workup to release the aldehyde product. OZr(H)Cp2 CI OZrCp2 CI R Cp2Zrh)CI HO Cp2Zr(O) JACS 20(
M.C. White, Chem 153 Hydrozirconation -295- Week of November 18, 2002 Hydridic character of Schwartz’s reagent Reduction of 3o amides directly to aldehydes. O R NEt3 ZrIV H Cl O R H R = p-CNC6H4-, 90% p-NO2C6H4-, 81% p-OMeC6H4-, 99% MeOC(O)C8H16-, 74% O N O O H3C Ph MeO O H MeO Direct reduction of Evan's N-acyl oxaolidinone (generally a 2 step procedure involving transamination to the Weinreb amide followed by LAH reduction to the aldehyde). Cp2Zr(H)Cl (1.5-2.0 eq) THF, rt, 20-30 min 92% (1.5-2 eq) THF, rt, 20-30 min Why don't the product aldehydes become reduced in situ? According to the proposed mechanism, the aldehyde is masked as iminium ion intermediate which decomposes upon aqueous workup to release the aldehyde product. R O N R' R'' Cp2Zr(H)Cl R OZr(H)Cp2 N R' R'' Cl R OZrCp2 N R' R'' Cl H R H N R' R'' Cl H2O R H O Cp2Zr(O) Georg JACS 2000 (122) 11995. ZrI V H Cl O R H O R R' O R OR' OZr(Cl)Cp2 R R' H H3O+ OH R R' H H3O+ H3O+ OH R H H OH R H H The hydridic character of the highly ionic Zr-H bond is demonstrated in its ability to reduce a variety of carbonyl functionalities to Zr alkoxides at a rate competative with olefin hydrozirconation. δ+ δ- Schwartz ACIEE 1976 (15) 333
M.C. White. Chem 153 Alkene/C-M insertions-296- Week of Novem ber 18, 2002 Dimerization, Oligomerization, Polymerization 3-100 R=CH3, H R MR dime R R terminaTion B-hydride elimination note that there is no oxidation state change to the metal throughout LnM R addition MmH+ L MH B-lydride L LMa. K, has been found to depend on the It has been observed that with early, high-valent metals (e.g. Zr(IV), d) the equilibrium lies to the left(K2> substituents on the olefin Increased I)whereas with late, low-valent metals(e.g. Pd(in), d substitution and steric bulk of the the equilibrium lies to the right(K2< 1). Electron density olefin leads to decreased rates of binding to the metal complex at the metal is thought to favor the hydrido-alkene Hoffmann JACS 1976(98)1729 species via stabilizing T-backbonding into the olefin T' Labinger Aciee 1976(15)333
M.C. White, Chem 153 Alkene/C-M insertions -296- Week of November 18, 2002 LnMn H + R' K1 LnMn H R' K1 has been found to depend on the number and size of alkyl substituents on the olefin. Increased substitution and steric bulk of the olefin leads to decreased rates of binding to the metal complex. LnMn H R' ‡ LnMn R' H K2 β-hydride addition β-hydride elimination It has been observed that with early, high-valent metals (e.g. Zr(IV), d0) the equilibrium lies to the left (K2 > 1)whereas with late, low-valent metals (e.g. Pd(II), d8) the equilibrium lies to the right (K2 100 termination via β-hydride elimination propagation via insertion note that there is no oxidation state change to the metal throughout the cycle LnMn H R dimer termination via β-hydride elimination
M.C. White, Chem 153 EMPolymerization-297- Week of november 18. 2002 Ziegler natta polymerization What has guided my research has been solely the wish to do something that gave me jo that is a joy from finding, somehow or somewhere, something really novel.At least at the utset, the only thing of value aimed for is an accretion in knowledge, rather than new In an attempted distillation of ethyllithium, Ziegler such as Et2AlH displayed even higher activities observed ethylene and higher a-olefins. He reasoned towards ethylene n higher aluminum alkyls that could be readily that the following process was occuring hydrolyzed to pre alcohols - + Lih CAH tPC Ziegler found that traces of Ni salts (accidently Lih incorporated during cleaning the reactor)resulted only in butene and r,Alh AH+ Eisch Chem. Edu. 1983(60)1009 If traces of Ni salts could make such a dramatic impact on the The stereochemistry of polypropylene significantly influences its physical properties. Isotactic course of ethylene oligermerizations, Ziegler wondered what other polymers are the most useful commercially with such physical properties as high tensile etals may do. An exploration of this curiosity led to the strength and high melting points (165C) Cl/Et AlCI catalyzed Zeigler Natta polymerization(Nobel Prize, 63)which is currently used commercially to produce 15 million tons of polyethylene and polypropylene annually Ziegler's original process for ethylene polymerization: 人人人人人人 TICI/AIR3 polyethylene stereochemistry at adjacent carbons bons Physical properties line with a melting Ziegler Angew. Chem. 1955 (67)54 Natta extends this to propylene polymerization. He finds that by regularity of the surface of the heterogeneous catalyst is increased. This results in a greater specificity in polymerization with the amount of desired isotactic polypropylene inreasing from 40% to 90%. atactic: stereorandom polymer that behaves as an amorphous 人 For other polymer tacticities see: Coates Chem. Rev. 2000(100)1223 Natta Angew. Chem. 1956(68)393
M.C. White, Chem 153 EM Polymerization -297- Week of November 18, 2002 Ziegler Natta Polymerization Natta Angew. Chem. 1956 (68) 393. "What has guided my research has been solely the wish to do something that gave me joy, that is a joy from finding, somehow or somewhere, something really novel...At least at the outset, the only thing of value aimed for is an accretion in knowledge, rather than new applications." Karl Ziegler. Li ∆ LiH Li ∆ LiH Al H 100oC Al Al Al Al H If traces of Ni salts could make such a dramatic impact on the course of ethylene oligermerizations, Ziegler wondered what other metals may do... An exploration of this curiosity led to the TiCl3/Et2AlCl catalyzed Zeigler Natta polymerization (Nobel Prize, 1963) which is currently used commercially to produce ~ 15 million tons of polyethylene and polypropylene annually. Ziegler's original process for ethylene polymerization: TiCl4/AlR3 n polyethylene Ziegler Angew. Chem. 1955 (67) 541. Natta extends this to propylene polymerization. He finds that by using crystalline TiCl3, the regularity of the surface of the heterogeneous catalyst is increased. This results in a greater stereospecificity in polymerization with the amount of desired isotactic polypropylene inreasing from 40% to 90%. TiCl3/AlR3 n polypropylene The stereochemistry of polypropylene significantly influences its physical properties. Isotactic polymers are the most useful commercially with such physical properties as high tensile strength and high melting points (~165oC). In an attempted distillation of ethyllithium, Ziegler observed ethylene and higher α-olefins. He reasoned that the following process was occuring: + β-hydride elimination propagation β-hydride elimination + Organoaluminum compounds such as Et2AlH displayed even higher activities towards ethylene resulting in higher aluminum alkyls that could be readily hydrolyzed to produce higher alcohols. Ziegler found that traces of Ni salts (accidently incorporated during cleaning the reactor) resulted only in butene and R2AlH. Ni salts + Eisch J. Chem. Edu. 1983 (60) 1009. isotactic: stereoregular material, long sequences having the same stereochemistry at adjacent carbons. Physical properties: crystalline thermoplastic. syndiotactic: long sequences having the opposite stereochemistry at adjacent carbons. Physical properties: semicrystalline with a melting temperature ~ 100oC. atactic: stereorandom polymer that behaves as an amorphous gum elastomer. For other polymer tacticities see: Coates Chem. Rev. 2000 (100) 1223
M.C. White, Chem 153 EMPolymerization-298- Week of november 18. 2002 Cossee mechanism for Ziegler Natta polymerizations According to the Cossee mechanism, propagation of the polymer occurs exclusively at the Ti center. The role of the alkyl aluminum pecies is thought to be that of initiator by alkylating the TiCI olefin coordination CHT cHI Representation of a TiCl lattice with an cis-carbometalation via a concerted 4-membered TS open coordination site on the surface Cossee190(17)12 Cossee stereochemical model for isotactic polypropylene formation Polvmer Polymer CHT si-face re-face Representation of a stereogenic Ti center on the edge of a chiral TiCl crystal. The growing polymer occupies the open quadrant. The olefin preferentially binds via its si-face placing its methyl substituent trans to the bulky polymer chain. Modem MgCl2-supported Ziegler Natta Cossee tz1960(17)17 catalysts are highly stereoselective resulting in formation of essentially Brintzinger ACIEE 1995(34)1143. only the isotactic polymer
M.C. White, Chem 153 EM Polymerization -298- Week of November 18, 2002 Cossee mechanism for Ziegler Natta polymerizations Cl Cl Ti Cl Cl Ti Ti Cl Cl Cl Ti Cl Cl Ti Ti Cl Cl Cl Ti Cl Cl Ti Ti Cl Cl Cl Ti Cl Cl Ti Ti Cl Representation of a TiCl3 lattice with an open coordination site on the surface According to the Cossee mechanism, propagation of the polymer occurs exclusively at the Ti center. The role of the alkyl aluminum species is thought to be that of initiator by alkylating the TiCl3. olefin coordination cis-carbometalation via a concerted 4-membered TS. Cossee TL 1960 (17) 12. Cossee mechanism for Ziegler Natta heterogeneous polymerization. Cossee stereochemical model for isotactic polypropylene formation: Cl Cl Ti Cl Cl Ti Ti Cl Polymer si-face favored Cl Cl Ti Cl Cl Ti Ti Cl Polymer re-face disfavored Representation of a stereogenic Ti center on the edge of a chiral TiCl3 crystal. The growing polymer occupies the open quadrant. The olefin preferentially binds via its si-face placing its methyl substituent trans to the bulky polymer chain. Modern MgCl2-supported Ziegler Natta catalysts are highly stereoselective resulting in formation of essentially only the isotactic polymer. Cossee TL 1960 (17) 17. Brintzinger ACIEE 1995 (34) 1143
M.C. White, Chem 153 EM Polymerization -299- Week of november 18. 2002 Metallocenes as homogeneous polymerization catalysts No reaction is observed in the absence of Et2 AICl or Et AL. Both EtAlCl and Et Al alone produce only oligomers. Unlike the heterogeneous Ziegler-Natta polymerization catalysts, these catalysts are ineffective at polymerizing a-olefins( propylene) EtAICI polyethylene Natta JACS 1957(79)2975 Breslow JACS 1957(79)5072 Breslow's proposed mechanism cr 8. CI EtAICl T代 Insertion Polarization of the Ti-CI bond by the Lewis acidic Al center promotes H Breslow JACS 1959(81)81
M.C. White, Chem 153 EM Polymerization -299- Week of November 18, 2002 Metallocenes as homogeneous polymerization catalysts TiIV Cl Cl Et2AlCl n polyethylene No reaction is observed in the absence of Et2AlCl or Et3Al. Both Et2AlCl and Et3Al alone produce only oligomers. Unlike the heterogeneous Ziegler-Natta polymerization catalysts, these catalysts are ineffective at polymerizing α-olefins (propylene). Natta JACS 1957 (79) 2975. Breslow JACS 1957 (79) 5072. Breslow's proposed mechanism: Breslow JACS 1959 (81) 81. TiIV Cl Al Cl δ+ δ- TiIV Cl Cl Et2AlCl σ-bond metathesis? Cl TiIV Cl Al Cl Cl TiIV Cl Al Cl δ+ δ- Cl cis- migratory insertion propagation TiIV Cl Al Cl Cl P β-hydride H elimination P TiIV H Cl Al Cl Cl TiIV H Cl Al Cl δ+ Cl (termination) Polarization of the Ti-Cl bond by the Lewis acidic Al center promotes ethylene coordination/insertion. P
M.C. White, Chem 153 EM Polymerization-300- Week of november 18. 2002 Activation by MA0 considered a poison arly transition metal Activation by MAO sts. Trace amounts of water were reported to cause a in the rates of ethylene polymerization by Dimetyl=iconium complex Cp2TiEtCI/AlEtCl2 system. It was later found that water activated It is postulated that the highly Lewis acidic Al centers in MAO"abstract"CH3-resulting analogous Zr complexes which were typically unreactive towards even in a cationic Zr complex and a weakly coordinating(CH3-MAO) counterion that may or ethylene polymerizations to highly active catalysts for both ethylene and may not be weakly associated with the metal H3CAI(MAO Me mAo RiAl H3G-AI(MAO +H,o atactic polypropylene Me H3C一 AlMAC) In sit formation of mao(methylalumino oxane). Hydrolysis of AIMe3 by water results in the formation of a mixture of oligomeric aluminoxanes(exact compositions and structures are still not known) polypropylene Preformed MAO is equally effective as an activator of Cp2ZrMer and Cp2ZrCl2 catalysts towards olefin polymerizations MAO MAO nAMEs Kaminsky ACIEE 1976(15)630 MAo(methlylalumino oxane Kaminsky ACIEE 1980( 19)390 Barron JACS 1995(117)6465 Brintzinger ACIEE 1995(34)1143
M.C. White, Chem 153 EM Polymerization -300- Week of November 18, 2002 Activation by MAO In situ formation of MAO (methylalumino oxane). Hydrolysis of AlMe3 by water results in the formation of a mixture of oligomeric aluminoxanes (exact compositions and structures are still not known). Preformed MAO is equally effective as an activator of Cp2ZrMe2 and Cp2ZrCl2 catalysts towards olefin polymerizations. nAlMe3 nH2O Al Me O n O Al Al O O Al Al O Me Me Me Me n MAO (methlylalumino oxane) Barron JACS 1995 (117) 6465. Activation by MAO: ZrIV Me Me It is postulated that the highly Lewis acidic Al centers in MAO "abstract" CH3_ resulting in a cationic Zr complex and a weakly coordinating (CH3-MAO)- counterion that may or may not be weakly associated with the metal. MAO ZrI V Me H3C Al(MAO) ZrI V Me H3C Al(MAO) ZrI V H3C Al(MAO) δ- δ+ δ- δ+ polypropylene Dichlorozirconium complex Dimethylzirconium complex ZrI V Cl Cl MAO ZrI V Me Me ligand exchange (via σ-bond metathesis?) MAO as above Kaminsky ACIEE 1976 (15) 630. Kaminsky ACIEE 1980 (19) 390. Brintzinger ACIEE 1995 (34) 1143. atactic polypropylene ZrIV R' R' R3Al + H2O n R' = Me or Cl No polymerization activity Water is generally considered a poison for early transition metal polymerization catalysts. Trace amounts of water were reported to cause a significant increase in the rates of ethylene polymerization by Cp2TiEtCl/AlEtCl2 system. It was later found that water activated analogous Zr complexes which were typically unreactive towards even ethylene polymerizations to highly active catalysts for both ethylene and propylene polymerization. or or n
M.C. White, Chem 153 EMPolymerization-301 Week of november 18. 2002 Cationic metallocene catalysts First preformed and spectroscopically characterized cationic complex capable of ethylene polymerization. This work supports the proposal that cationic Zr and Ti complexes formed upon olefin inding are the active polymerization catalysts. The low polymerization activity was attributed to the coordinated THF which competes with ethylene for binding -BPh CH3 AgBPhg(l eq) THE H3 Jordan JACS 1986(108)7410 First well-characterized cationic zirconocene catalyst capable of propylene polymerization at high rates. H3C-B(C6 F5)3 B(C6F5)(1 eq). Marks JACS 1991(113)3623
M.C. White, Chem 153 EM Polymerization -301- Week of November 18, 2002 Cationic metallocene catalysts ZrI V CH3 CH3 AgBPh4 (1 eq) THF ZrIV CH3 O BPh4 First preformed and spectroscopically characterized cationic complex capable of ethylene polymerization. This work supports the proposal that cationic Zr and Ti complexes formed upon olefin binding are the active polymerization catalysts.The low polymerization activity was attributed to the coordinated THF which competes with ethylene for binding. Jordan JACS 1986 (108) 7410. First well-characterized cationic zirconocene catalyst capable of propylene polymerization at high rates. ZrIV CH3 CH3 B(C6F5)3 (1 eq) C6H6 ZrI V CH3 H3C B(C6F5)3 Marks JACS 1991 (113) 3623
