M.C. White. Chem 153 C-H Activation -241- Week of november 4. 2002 The Holy grail of catalysis R CHeMI CH3 CHOR C-H activation: Process where a strong C-h bond (90-105 kcal/mol) undergoes substitution to produce a weaker C-M bond(50-80 kcal/mol) Functionalization: Metal-C bond is replaced by any bond except C-H Methods have been identified to regioselectivity effect C-H activation. Recall that there is both a kinetic and thermodynamic preference to form the less sterically hindered 1 C-M intermediate(see Structure Bonding, pg. 32). The challenge lies in finding ways to selectively form the C-M intermediate under synthetically useful, mild conditions that enable functionalization and catalyst renewal ARTHUR: Yes we seek the Holy grail(clears throat very quietly ) Our quest is to find the holy grail KNIGHTS: Yes it I ARTHUR: And so we're looking for it KNIGHTS: Yes we are BEDEVERE. We have been for some time KNIGHTS: Yes ROBIN: Months ARTHUR: Yes. and any help we get is. is very.. helpful Bergman Acc. Chem. Res. 1995(28)154. Exerpt from"Monty Python and the Holy Grail: 1974
The Holy Grail of Catalysis ARTHUR: Yes we seek the Holy Grail (clears throat very quietly). Our quest is to find the Holy Grail. KNIGHTS: Yes it is. ARTHUR: And so we’re looking for it. KNIGHTS: Yes we are. BEDEVERE: We have been for some time. KNIGHTS: Yes. ROBIN: Months. ARTHUR: Yes…and any help we get is…is very…helpful. Bergman Acc. Chem. Res. 1995 (28) 154. Exerpt from “Monty Python and the Holy Grail”; 1974. M.C. White, Chem 153 C-H Activation -241- Week of November 4, 2002 R CH3 R CH2[M] R CH2R' C-H activation: Process where a strong C-H bond (90-105 kcal/mol) undergoes substitution to produce a weaker C-M bond (50-80 kcal/mol). Functionalization: Metal-C bond is replaced by any bond except C-H. ? Methods have been identified to regioselectivity effect C-H activation. Recall that there is both a kinetic and thermodynamic preference to form the less sterically hindered 1o C-M intermediate (see Structure & Bonding; pg. 32). The challenge lies in finding ways to selectively form the C-M intermediate under synthetically useful, mild conditions that enable functionalization and catalyst renewal
M.C. White, Chem 153 C-H Activation -242 Week of November 4. 2002 Bergman C-H Activation via Late, Nucleophilic Complexes π- backbonding> Hydrido(alkyl)metal oxidative addition complex egioselectivity: sp C-H>10 sp'C-H> 2 C-H>>>30 sp'C-H. There is both a kinetic and thermodynamic preference to form the least sterically hindered C-M o bond. Kinetic preference: activation barrier to g-complex formation is lower for less sterically hindered C-H bonds and bonds with more s character. Thermodynamic preference: stronger C-M bonds are formed (see Structure and Bonding, pg. 32) prone to non-productive reductive elimination in the presence of oxidants and non-productive v or protonolysis in the presence of protic reagents H2 M=Ir. 1 代H ligand 16e- proposed coordinatively and Relative rate constants for attack at a single electronically unsaturated C-H bond by 1 and 2 at-60oC MLcO hvor△ C-H bond krel(rh, 2)krel (Ir, 1) low OS metals capable of cyclopropane 10.4 2.1 18e donating electrons in f-bond n-hexane( 19) 5.9 M=Ir, 3 formation. Highly prone to air with acyclic substrates n-hexane(2%) 0 Rh, oxidation the rh complex inserts ne(1°)26 JACS1982(104)352(Cmp.1) only into IC-H bonds nOM 1984(3)508(competition exp) 1.1 JACS1983(105)7190(Cmp.3) Bergman JACS 1994(116)9585(Cmp. 4) arbitrarily set at 1-+cyclohexane
M.C. White, Chem 153 C-H Activation -242- Week of November 4, 2002 Bergman:C-H Activation via Late, Nucleophilic Complexes Bergman JACS 1982 (104) 352 (Cmp. 1). Bergman OM 1984 (3) 508 (competition exp). Graham JACS 1983 (105) 7190 (Cmp. 3). Bergman JACS 1994 (116) 9585 (Cmp. 4). These hydrido(alkyl)metal complexes are prone to non-productive reductive elimination in the presence of oxidants and non-productive protonolysis in the presence of protic reagents Relative rate constants for attack at a single C-H bond by 1 and 2 at -60oC. C-H bond benzene cyclopropane n-hexane (1o) n-hexane (2o) propane (1o) propane (2o) cyclopentane cyclohexane krel (Rh, 2) 19.5 10.4 5.9 0 2.6 0 1.8 1.0 krel (Ir, 1) 3.9 2.1 2.7 0.2 1.5 0.3 1.1 1.0 arbitraril y set at 1 with acyclic substrates the Rh complex inserts only into 1o C-H bonds regioselectivity: sp2 C-H > 1o sp3C-H> 2o sp3 C-H >>> 3o sp3 C-H. There is both a kinetic and thermodynamic preference to form the least sterically hindered C-M σ bond. Kinetic preference: activation barrier to σ-complex formation is lower for less sterically hindered C-H bonds and bonds with more s character. Thermodynamic preference: stronger C-M bonds are formed (see Structure and Bonding, pg. 32). MI OC CO CO MI L MIII L M H I L H 18 ehv or ∆ 16 e- 18 e- proposed σ-complex intermediate ligand dissociation M = Ir, 3 Rh, 4 MIII Me3P H2 hv or ∆ M = Ir, 1 Rh, 2 oxidative addition coordinatively and electronically unsaturated intermediate H H π-donor low OS metals capable of donating electrons in σ-bond formation. Highly prone to air oxidation. H C M M H C π-backbonding>> σ-donation oxidative addition σ-complex Hydrido(alkyl)metal complex
gie Evidence for intermolecular o-complex formation Q Chen Chem 153 C-H Activation -243 Week of November 4. 2002 CD3 hv(flash), Kr(165K) Rh/ D roll.nD Rh一Co DC 18 0v(1946cm4) 0v(1947cm2) Bergman JACS 1994(116)958 CO v(2008 cm g-compler 0.020 1946m 1947cm 0.012 2008cm OC +(CD3)C 0.004 0.004+ Tm·(m) DyC CD3 The reaction of Cp*Rh(COh with neopentane-di2 was monitored using low-temperature IR nash kinetic spectroscopy. The CO stretch at 1946 cm" was assigned to the initial intermediate Cp"Rh(COXKr)complex, which after photolysis-mediated formation shows rapid decay. During this time, a second CO stretch at 1947 cm"grows in and decays; this absorption is assigned to a transient intermediate Rh--CD o-complex. The absorption at 2008 cm"is known to correspond to the product h(CODCs Du1), which increases steadily throughout the course of the reaction. Note that this entire process occurs in less than 1.5 ms
M.C. White, Q. Chen Chem 153 C-H Activation -243- Week of November 4, 2002 Evidence for intermolecular σ-complex formation CO D D2C CD3 D3C CD3 RhIII OC CD2 D CD3 D3C CD3 RhI [Kr] OC RhI OC CO RhI OC CD3 D3C CD3 CD3 18 ehv (flash), Kr (165K) CO v (1946 cm-1) CO v (1947 cm-1) σ-complex CO v (2008 cm-1) D D2C CD3 D3C CD3 RhI OC RhI [Kr] OC Rh OC CD2(C(CD3)3 D + (CD3)4C to products ∆G (kcal/mol) ‡ -3.2 kcal/mol + 6.9 kcal/mol The reaction of Cp*Rh(CO)2 with neopentane-d12 was monitored using low-temperature IR flash kinetic spectroscopy. The CO stretch at 1946 cm-1 was assigned to the initial intermediate Cp*Rh(CO)(Kr) complex, which after photolysis-mediated formation shows rapid decay. During this time, a second CO stretch at 1947 cm-1 grows in and then decays; this absorption is assigned to a transient intermediate Rh---CD σ-complex. The absorption at 2008 cm-1 is known to correspond to the product Cp*Rh(CO)(D)(C5D11), which increases steadily throughout the course of the reaction. Note that this entire process occurs in less than 1.5 ms. Bergman JACS 1994 (116) 9585
M.C. White, Chem 153 C-H Activation -244- Week of November 4. 2002 Evidence for concerted c-H oxidative addition crossover experiment: evidence in support of a concerted mechanism. Ir—co cO 18 Less than 7% of the crossover products were observed by HNMR. This may be indicative of a minor radical pathway C Bergman JACS 1983(105 )3929
M.C. White, Chem 153 C-H Activation -244- Week of November 4, 2002 Evidence for concerted C-H oxidative addition IrI OC CO CO IrI OC IrIII OC H Bergman JACS 1983 (105) 3929. IrI OC D crossover experiment: evidence in support of a concerted mechanism. 18 ehv σ-complexes D12 IrII OC H IrII OC D H2C D11 H3C + IrI OC H IrIII OC D Less than 7% of the crossover products were observed by 1HNMR. This may be indicative of a minor radical pathway. IrIII OC Ir D III OC H D11 D11 D11
M.C. White, Chem 153 C-H Activation -245 Week of November 4. 2002 Dehydrogenation of alkanes to alkenes H2 generation via olefin dissociation and elimination of H. H2 must be rapidly and irreversibly removed to avoid olefin hydrogenation and isomerization H H p-hydride r ML 1.3 MLn-2, elimination, 3 ligands from the substrate in its oxidative addition ordination sphere mid-cycle H metal and m The first report (coe) PPh3 10 eq -10°C>40%C PhaP H CD2Cl2-60°C Phah PPh observed to form NMR recall: intermediate in cation call hydrogenation catal hydrogenation cataly Crabtree JACS 1979(101)7738
M.C. White, Chem 153 C-H Activation -245- Week of November 4, 2002 Dehydrogenation of alkanes to alkenes R R H2 -H2 Catalyst requirements: MLnx-3 "14e-" R MLn x 18e- 3 L H MLn-2x-1 H R H MLn-2x R H H β-hydride elimination 16e- 18eoxidative addition H2, R metal capable of shuttling between Mn and Mn-2 oxidation states complex capable of accomodating 3 ligands from the substrate in its coordination sphere mid-cycle regeneration via olefin dissociation and elimination of H2. H2 must be rapidly and irreversibly removed to avoid olefin hydrogenation and isomerization Ph3P Ir(III) PPh3 H H O + (BF4 - ) recall: intermediate in cationic hydrogenation catalysts 10 eq O CD2Cl2, -60oC (coe) Ph3P Ir(III) PPh3 H H + (BF4 - ) observed to form quantitatively by NMR -10oC->40o C Ir(I) PPh3 PPh3 + (BF4 - ) 75% recall: hydrogenation catalyst The first report: Crabtree JACS 1979 (101) 7738
M.C. White, Chem 153 C-H Activation -246- Week of November 4. 2002 Crabtree thermal dehydrogenation of alkanes to alkenes (p-FC6H43 Product distributions of linear alkenes are thought to result from isomerization of the initial kinetic I-ene product via intermediate Ir hydride species conditions gives similar olefin P(pFC6H小37lnM 4%0(3%) yields based on 55 mM frans-3-hexene 14%(18.5%) sacrificial H2 acceptor with cis-3-hexene 8%(7.5 %) 2d. 1. 4 tn 2d. 3 tn 2d.9 tn hydro proposed Mechanisn FCH小3 p-FC6l小3 OC(O)CH hydrogenation -CF2 hydrogenation (p-FC6H4)3l V-FC6H小 P(p-FC6H4) P(pFC6H4小3 OC(O)CF3 OC(OJCF isommerT-cTtIon (p-FC6H4)3l IrwIn>Cf (p-FC6H)3l P(p-FC6H03 tail-biting P(p-FC6HA3 P(p-FC6H43 (C6H乎-FB l43(P-FCH4)3P only trifluoroacetate complexes OC(O)CF3 were active in alkene HI (C6Hap-F)3P dehydrogenations. Their greater oxidative lability with respect to acetate (p-FC6H4)3l may allow more facile Plp-FC6H小3 (C6Hap-F3P interconversion from n' to n In-OC(O)CF3 necessary to provide an open (C,Hp-I coordination site for H Crabtree JACS 1987 (109)8025
M.C. White, Chem 153 C-H Activation -246- Week of November 4, 2002 Crabtree:thermal dehydrogenation of alkanes to alkenes Crabtree JACS 1987 (109) 8025. solvent H Ir(III) H O O P(p-FC6H4)3 P(p-FC6H4)3 CF3 + t-Bu 7.1 nM 355 mM 150oC t-Bu 2d, 1.4 tn tn = turnover # 2d, 3 tn 2d, 9 tn 4% (3%) + 56% (54%) + 18% (17.5%) + trans-3-hexene 14% (18.5 %) cis-3-hexene 8% (7.5 %) yields based on catalyst. 14 days Product distributions of linear alkenes are thought to result from isomerization of the initial kinetic 1-ene product via intermediate Ir hydride species. Subjecting 1-hexene to the reaction conditions gives similar olefin distributions (in parentheses). sacrificial H2 acceptor with unusually high heat of hydrogenation H Ir(III) H O O P(p-FC6H4)3 P(p-FC6H4)3 CF3 H Ir(III) H OC(O)CF3 P(p-FC6H4)3 (p-FC6H4)3P t-Bu t-Bu Ir(III) H O O P(p-FC6H4)3 P(p-FC6H4)3 CF3 t-Bu (C6H4p-F)3P Ir(I) (C6H4p-F)3P O O CF3 (C6H4p-F)3P Ir(I) (C6H4p-F)3P OC(O)CF3 H Ir(III) H OC(O)CF3 P(p-FC6H4)3 (p-FC6H4)3P R H Ir(III) H OC(O)CF3 P(p-FC6H4)3 (p-FC6H4)3P R R t-Bu R H Ir(III) O O P(p-FC6H4)2 P(p-FC6H4)3 CF3 F R H Ir(III) H OC(O)CF3 P(p-FC6H4)3 (p-FC6H4)3P R 14 eoxidative addition β-hydride elimination "tail-biting" Ir(III) H OC(O)CF3 P(p-FC6H4)3 (p-FC6H4)3P H R isomerization pathway hydrogenation pathway R isomerization hydrogenation Proposed Mechanism: only trifluoroacetate complexes were active in alkene dehydrogenations. Their greater lability with respect to acetate may allow more facile interconversion from η3 to η1 necessary to provide an open coordination site for H2 acceptor binding
M.C. White, Chem 153 C-H Activation -247 Week of November 4. 2002 Crabtree photochemical dehydrogenation of alkanes to alkenes Under conditions of CF methylcyclohexane is product. This is thought to result from a kinetic preference to form the sterically less P(Cy)3 7. 1 nM Methylenecyclohexane subjected to the h(254mm) reaction conditions results in only 25% 7 days +1227m(6219m(38)085031103s1mn onversion to the thermodyn tn w/out tbe present(in parentheses) 355mM atios reflect more isomerization activity Proposed Mechanism P(Cy)3 nate wavelength promotes reductive elimination of the dihydride catalyst leading directly to the Isommterteanon catalytically active 14e-complex. It's interesting hy 254nm to note that no reaction takes place with tbe in (Cy)3 P(Cyl P(Cy)3 the absence of 254 nm light. This implies that acts as a H2 acceptor from a photochemically 1OC(O)CF3 . oC(O)CF3 excited intermediate (Cya bride P(Cyl (CyP in the presence (Cy)3P addition (Cy)3B, (OJCF3 Crabtree JACS 1987 (109)8025
M.C. White, Chem 153 C-H Activation -247- Week of November 4, 2002 Crabtree:photochemical dehydrogenation of alkanes to alkenes Proposed Mechanism: Crabtree JACS 1987 (109) 8025. Irradiation with light of the appropriate wavelength promotes reductive elimination of the dihydride catalyst leading directly to the catalytically active 14e- complex. It's interesting to note that no reaction takes place with tbe in the absence of 254 nm light. This implies that tbe acts as a H2 acceptor from a photochemically excited intermediate. H Ir(III) H O O P(Cy)3 P(Cy)3 CF3 (Cy)3P Ir(I) (Cy)3P O O CF3 (Cy)3P Ir(I) (Cy)3P OC(O)CF3 14 eH Ir(III) H OC(O)CF3 P(Cy)3 (Cy)3P R H Ir(III) H OC(O)CF3 P(Cy)3 (Cy)3P R R t-Bu R oxidative addition β-hydride elimination Ir(III) H OC(O)CF3 P(Cy)3 (Cy)3P H R isomerization pathway H Ir(III) H O O P(Cy)3 P(Cy)3 CF3 * hv, 254nm t-Bu H2 H2 Some free H2 is formed even in the presence of tbe. solvent H Ir(III) H O O P(Cy)3 P(Cy)3 CF3 + t-Bu 7.1 nM tbe 355 mM hv (254 nm) t-Bu 2.77tn (1.6) + 2.19 tn (3.84) + 7 days Under conditions of hv and tbe, methylcyclohexane is the preferred product. This is thought to result from a kinetic preference to form the sterically less hindered M-C bond. Methylenecyclohexane subjected to the reaction conditions results in only 25% conversion to the thermodynamically more stable 1-methylcyclohexene. Although the reaction proceeds w/out tbe, the product ratios reflect more isomerization activity. + + H2 0.85 tn (0.32) 1.26 tn (0.82) tn w/out tbe present (in parentheses)
M.C. White. Chem 153 C-H Activation -248 Week of November 4. 2002 Tanaka: photochemical dehydrogenation PMe3 (solvent) 27h, 155 tn 1:79:20 138 tn, 17h 930tn,69h H a theoretical amount N, stream of H, was det Added phosphine ligand decreases the efficiency of in the gas phase the regioselectivity When a N, stream PMe3/Rh time(h) 12.3 towards formation if 1-hexene. Within the same PMe3/Rh ratio, an erosion in regioselectivity is increased to 195 tn 54 observed upon prolonged reaction times. This is 1241 18.7 10 Could this ratio also be reflective of the rates of 10 103417.2 olefin hydrogenation? Exposure of 1-hexene to the reaction conditions results in 2-hexene (35%)and hexane(63%)after 22h Proposed mechani CI.aPMe3 Added phosphine ligand may take up a acant coordination site cis to the M-alkyl, preventing formation of the gastic interaction necessary to effect B-hydride elimination. a decrease in both alkane dehydrogenation and h ht-promoted reductive P-Rh@"PMe3 14 elimination PMe
M.C. White, Chem 153 C-H Activation -248- Week of November 4, 2002 Tanaka: photochemical dehydrogenation Proposed Mechanism: 0.7mM hv, rt, N2 138 tn, 17 h A theoretical amount of H2 was detected in the gas phase. When a N2 stream was used, tn increased to 195 tn. 930 tn, 69h N2 stream + 1:79:20 + 27 h, 155 tn Me3P Rh(I) OC PMe3 Cl (solvent) H2 + PMe3/Rh 2 5 5 10 10 time (h) 1 3 22 3 22 hexenes 1- 2- 3- 1 12 6 28 10 11 4 4 4 3.4 2 1 1 1 1 TN 5.4 4.0 18.7 0.6 7.2 Added phosphine ligand decreases the efficiency of the reaction but increases the regioselectivity towards formation if 1-hexene. Within the same PMe3/Rh ratio, an erosion in regioselectivity is observed upon prolonged reaction times. This is indicative of catalyst mediated alkene isomerization. Could this ratio also be reflective of the rates of olefin hydrogenation? Exposure of 1-hexene to the reaction conditions results in 2-hexene (35%) and hexane (63%) after 22 h. Me3P Rh(I) OC PMe3 Cl 16 ehv CO Me3P Rh(I) PMe3 Cl 14 eR Rh(III) PMe3 Cl H PMe3 R H Rh(III) PMe3 Cl H PMe3 R H intermediate in Wilkinson hydrogenation R H2 light-promoted reductive elimination of H2 ?? Rh(III) PMe3 Cl H PMe3 H R Added phosphine ligand may take up a vacant coordination site cis to the M-alkyl, preventing formation of the agostic interaction necessary to effect β-hydride elimination. A decrease in both alkane dehydrogenation and olefin isomerization results. β-hydride elimination reductive elimination
M.C. White. Chem 153 C-H Activation -249- Week of November 4. 2002 Goldman Wilkinson 's Catalyst Varient A variety of sacrificial alkenes work in the Me3P 59 tn 53 tn dehydrogenation of cyclooctane,an especially reactive substrate. Cyclooctene H2(0ps9.60°C has a very low heat of hydrogenation (solvent) probably resulting from transannular steric alkane 4 tn severe in cyclooctene sacrificial alkene n-hexane gave hexenes in mode tn(9.) with norbornene as the h2 acceptor. No mention was made to the isomer distributions 9492. Proposed mechanism A PMe H2 PMe of octahedral dihydride comple initiate ligand dissociation. Wilkinson,'s hydrogenation catalyst(see hydrogenation, pg. 142), known to dissociate PMe3 PPh3 upon H2 oxidative addition, is cited as precedent for HRE this. There is no evidence that Co dissociates preferentially over PMe,. The authors invoke this to arrive at the same 14 e- ntermediate proposed in Tanaka's photochemical system PM PMe Me P- R"PMe3
M.C. White, Chem 153 C-H Activation -249- Week of November 4, 2002 Goldman: Wilkinson’s Catalyst Varient Proposed Mechanism: Goldman JACS 1992 (114) 9492. Me3P Rh(I) OC PMe3 Cl 16 eH2 Me3P Rh(III) H PMe3 Cl H CO Rh(III) PMe3 Cl H PMe3 18eH CO 16 ePh3P Rh(III) H PPh3 Cl H Me3P Rh(I) PMe3 Cl Tanaka's 14 e- intermediate Rh(III) PMe3 Cl H PMe3 H 0.7mM H2 (1000 psi), 60oC 1.5 h, x tn Me3P Rh(I) OC PMe3 Cl sacrificial alkene + + alkane , 59 tn , 106 tn , 53 tn t-Bu , 4 tn sacrificial alkenes n-hexane gave hexenes in modest tn (9.6) with norbornene as the H2 acceptor. No mention was made to the isomer distributions. A variety of sacrificial alkenes work in the dehydrogenation of cyclooctane, an especially reactive substrate. Cyclooctene has a very low heat of hydrogenation probably resulting from transannular steric repulsions in cyclooctane which are less severe in cyclooctene. (solvent) Formation of octahedral dihydride complex is thought to initiate ligand dissociation. Wilkinson's hydrogenation catalyst (see hydrogenation, pg. 142), known to dissociate PPh3 upon H2 oxidative addition, is cited as precedent for this. There is no evidence that CO dissociates preferentially over PMe3. The authors invoke this to arrive at the same 14 eintermediate proposed in Tanaka's photochemical system
M.C. White. Chem 153 C-H Activation -250 Week of November 4. 2002 Substrate directed dehydrogenation via c-H activation Possible intermediates HaCO (OTT 0 (OTr) H3C00 (OTT) F3CH2OH 70°C,60h CH Sames constructs a ligand for the metal from the requisite functionality of the target that directs C-H activation towards only one of the 2 ethyl substituents. This results in selective dehydrogenation to give the platinum hydride in 产0 (OTr) >90% yield. The reaction is stiochiometric in HcQ 0 platinum and the metal must be removed via treatment with aqueous potassium cyanide Sames JACS2000(122)6321
M.C. White, Chem 153 C-H Activation -250- Week of November 4, 2002 Substrate directed dehydrogenation via C-H activation N N O H3CO N PtIICH3 N N O H3C O N Pt N H N O H3CO O H CF3CH2OH N N O H3CO N PtIVCH3 H N N O H3CO N PtII H (OTf- ) + (OTf- ) + 70oC, 60 h Rhazinilam (OTf- ) + (OTf- ) + CH4 Possible intermediates: Sames constructs a ligand for the metal from the requisite functionality of the target that directs C-H activation towards only one of the 2 ethyl susbstituents. This results in selective dehydrogenation to give the platinum hydride in >90% yield. The reaction is stiochiometric in platinum and the metal must be removed via treatment with aqueous potassium cyanide. Sames JACS 2000 (122) 6321