M.C. White, Chem 253 Mechanism -43- Week of September 27th, 2004

Transcription

1 M.C. White, Chem 253 Mechanism -43- Week of September 27th, 2004 igand Exchange Mechanisms Associative ligand substition: is often called square planar substition because16 e-, d8 square planar complexes generally undergo ligand substitution via an associative mechanism (the M-u bond is formed before the M- bond breaks). The intermediate is 18e- and therefore provides a lower energy route to the product than a 14e- intermediate formed via dissociative substitution (the M- bond is fully broken before the M-u bond begins to form). Analogous in many ways to S 2 reactions. u empty, non-bonding p z orbital can act as an acceptor orbital for the e- density of the incoming nucleophile u M 16 e- M M u 18 e- intermediates M u M 16 e- u M = i(ii), d(ii), t(ii), h(i), Ir(I). Dissociative ligand substitution is most favored in coordinatively saturated 18e - complexes (e.g. d 10 tetrahedral, d 6 octahedral). In the dissociative mechanism, the M- bond is fully broken before the M-u bond forms thereby avoiding an energetically unfavorable 20e - intermediate. Analogous in many ways to S 1 reactions. - u: M 18e- M 16e- M 18e- u ote that in all ligand substition processes, there is no oxidation state change at the metal center. M = u(ii), Co(III), h(iii), Ir(III)

2 M.C. White, Chem 253 Mechanism -44- Week of September 27th, 2004 Associative Substitution:the nucleophile u ate = -d [t 2 ] = k 1 [t 2 ] k 2 [u][t 2 ] dt k 1 : first order rate constant that arises from substition of leaving group by solvent. k 2 : second-order rate constant for bi-molecular attack of u on metal complex. t II 16 e- Me, rt t II 16 e- u - u relative rate u relative rate Basicity of the incoming ligand (nucleophile) plays only a minor role in its reactivity for soft metal centers. In general, the softest (i.e. most polarizable) nucleophiles react fastest with soft metals like t(ii) via associative substitution. Steric hinderance at the nucleophile (i.e. picoline vs pyridine) can retard the rate of substition. Me C 3 C 2 - C F - C 3 - (Et) <100 <100 < < Br- I- C 6 11 C (C 3 ) 3 hs - h 3 Et , x x x x x x 10 8

3 M.C. White, Chem 253 Mechanism -45- Week of September 27th, 2004 Associative Substitution: Sterics Sterically shielding the positions above and below the plane of the square planar complex can lead to significant decreases in the rates of associative substition. Et 3 Et 3 t II, rt k 2 = 100,000 M -1 sec -1 Et 3 Et 3 t II y - Et 3 Et 3 t II, rt k 2 = 200 M -1 sec -1 Et 3 Et 3 t II y - Et 3 t II, rt Et 3 k 2 = 1 M -1 sec -1 Et 3 Et 3 t II y - earson J. Chem. Soc

4 M.C. White, Chem 253 Mechanism -46- Week of September 24, 2004 as the steric bulk of the imine backbone increases, the aryl groups become more rigidly locked perpendicular to the square plane making their ortho substituents more effective at blocking the axial sites above and below the plane. Associative Substitution: Sterics associative second order rate constants for ethylene exchange were examined by 1 M in CD 2 at -85 o C (BAr' 4 ) - (BAr' 4 ) - d (BAr' 4 ) - d d C 3 C 3 C 3 k = too fast to measure even at -100 o C. k = 8100 /mol/sec k = 45 /mol/sec Brookhart JACS 1995 (117) (BAr' 4 ) - = t C 3 uffo M 1998 (17) 2646.

5 M.C. White, Chem 253 Mechanism -47- Week of September 27th, 2004 Brookhart olymerization Catalysts d C 3 (BAr' 4 ) - d C 3 (BAr' 4 ) - olymer M w = 110,000 olymer M w = 390,000 d C 3 (BAr' 4 ) - (BAr' 4 ) - (BAr' 4 ) - insertion d C 3 polymer propagation d C 3 igh M w polymers β-hydride elimination (BAr' 4 ) - d C 3 d (BAr' 4 ) - C 3 associative displacement d (BAr' 4 ) - (BAr' 4 ) - d ow M w polymers Brookhart JACS 1995 (117) 6414.

6 M.C. White/Q.Chen Chem 253 Mechanism -48- Week of September 27th, 2004 η 5 to η 1 -Cp via Slipped η 3 -Cp Intermediate η 5 Cp slipped η 3 Cp η 1 Cp (C 3 ) 3 C (C 3 ) 3 C C e C 64 o C C e (C 3 ) 3 C C C e C (C 3 ) 3 1 (18 e-) proposed "slipped" η 3 Cp 2 (18 e-) intermediate 18 e- Based on the observation that the rate of reaction of 1 with (C 3 ) 3 to form 2 depends on both the concentration of 1 and (C 3 ) 3,an associative mechanism was proposed. To account for associative substition at a formally coordinatively and electronically saturated center, the authors propose an η 3 "slipped" Cp intermediate that forms concurrently with phosphine attack. Casey M 1983 (2)

7 M.C. White/M.W. Kanan Chem 253 Mechanism -49- Week of September 27th, 2004 η5 to η3 ing Folding W II C C C W II C 18 e- 18 e- 18 e- complexes with cyclopentadienyl, aryl, indenyl ligands may undergo "associative" substitution avoiding an energetically unfavorable 20 e- intermediate via ligand rearrangement from η5 to η3 or even η1 (cyclopentadienyl and indenyl). aptotropic rearrangement may take the form of ring "slippage" where the ring is acentrally bonded to the metal and its aromaticity is disrupted or ring "bending" where the conjugation of the π system is broken. 2.98Å: a non-bonding distance 2.28Å uttner J. rganometallic Chem (145) 329.

8 M.C. White, Chem 253 Mechanism -50- Week of September 27th, 2004 igand Exchange: Dissociative Mechanism h I 16 e slower at 25 o C h I 18 e- The rate-determining step in a dissociative ligand substition pathway is breaking the M- bond. Because of the late, product-like transition state for forming the coordinatively unsaturated intermediate in such a process, the M- BDE is a good approximation of the activation energy(e A ). rate of ethylene exchange via associative displacement at 25 o C is ~ 10 4 sec -1 rate of ethylene exchange via dissociative displacement at 25 o C is ~ 4 x sec -1 BDE = 31 kcal/mol E h I E A BDE h I rxn coordinate h 3 (mmol) k x 10 4 sec h I 18 e- Cramer JACS 1972 (94) o C h I 16 e- rate = -d [h(c 2 4 ) 2 ] dt = k 1 [h(c 2 4 ) 2 ] h 3 h I h 3 18 e a 6-fold increase in the concentration of nucleophile does not significantly affect the rxn rate. esults are consistent with a mechanism where the ratedetermining step is ethylene dissociation and is not affected by the concentration of the nucleophile.

9 M.C. White, Chem 253 Mechanism -51- Week of September 27th, 2004 igand dissociation: sterics Fe d 0 "ineffective catalyst" Fe Fe t-bu t-bu t-bu t-bu d 0 t-bu t-bu t-bu t-bu Fe catalyst "resting state" dissociative - The steric bulk of the bidentate phosphine ligand is thought to weaken the d- bond, thereby favoring ligand dissociation required to form the catalytically active species. Fe t-bu t-bu d 0 catalytically active species t-bu t-bu 2 at-bu also aryl Br, I, Ts also aniline, piperidine artwig JACS 1998 (120) 7369.

10 M.C. White, Chem 253 Mechanism-52- Week of September 27th, 2004 igand dissociation: or hv coordinatively and electronically unsaturated complexes capable of oxidatively adding into unactivated C- bonds. h I C hv or h I h III C C C C 18 e- 16 e- 18 e- ight-promoted ligand dissociation M-C M-C h I σ σ hv σ σ C proposed intermediate bond order = 1 bond order = 0 Bergman JACS 1994 (116) 9585.

11 M.C. White, Chem 253 Mechanism-53- Week of September 27th, 2004 igand dissociation:weakly coordinating solvents First generation Crabtree hydrogenation catalyst Ir (Me)h 2 (F 6 - ) (Me)h 2 cat. 2, solvent (S) A glimpse into the catalytic cycle h 2 (Me) S Ir III S (F - 6 ) (F - 6 ) (F - 6 ) dissociative displacement h 2 (Me) h 2 (Me) Ir III Ir III (Me)h 2 S S (Me)h 2 catalytically active species S (Me)h 2 Solvent (S) Turnover Frequency (TF) ~ C TF = mol reduced substrate/mol catalyst/h Crabtree Acc Chem es 1979 (12) 331.

12 M.C. White, Chem 253 Mechanism-54- Week of September 27th, 2004 on-coordinating solvents: no such thing (BAr f - ) B Me 3 Ir C 3 = 3 C The first isolated chloromethane-metal complex. There are also similar complexes formed with C 2 2, and 3 C that have been characterized by M. Bergman JACS 2001 (123)

13 M.C. White, Chem 253 Mechanism-55- Week of September 27th, 2004 xidative Addition/eductive Elimination xidative Addition (A): metal mediated breaking of a substrate σ-bond and formation of 1or 2 new M- σ bonds. A requires removal of 2 electrons from the metal's d electron count. This is reflected in a two unit increase in the metal's oxidation state. The formation of 1 or 2 new M- σ bonds is accompanied by an increase in the metal's coordination number by 1 or 2 units respectively. The latter results in a 2 unit increase in the electron count of the metal complex (e.g.16 e - to 18 e - ). Currently, A of low valent, electron rich metals to polar substrates is the best way to form M-C σ bonds within the context of a catalytic cycle. The term oxidative addition confers no information about the mechanism of the reaction. M n "u:" "E " oxidative addition M (n2) reductive elimination or M (n2) - eductive elimination (E): microscopic reverse of oxidative addition where two M- σ bonds are broken to form one substrate σ bond. E results in the addition of two electrons into the metal d electron count. This is reflected in a two unit decrease in the metal's oxidation state. The breaking of 2 M- σ bonds is accompanied by a decrease in the metal's coordination number by 2 units. The result is a 2 unit decrease in the electron count of the metal complex (e.g. 18e- to 16 e-). The two M- σ bonds undergoing reductive elimination must be oriented cis to each other. Currently, E is the most common way to form C-C bonds via transition metal complexes. General A Mechanisms: Concerted (generally for non-polar substrates) ucleophilic displacement (generally for polar substrates) A A A x M n x M n x M (n2) x M n B B B 3-centered TS cis addition A δ δ - x M (n2) A - x M n A adical (both non-polar and polar) A A x M n x M (n1) A C x M (n2) C C

14 M.C. White, Chem 253 Mechanism -56- Week of September 27th, 2004 xidative Addition Metal Complex: electron rich metals in low oxidation states, with strong donor ligands and a site of coordinative unsaturation. d 10, tetrahedral, 18 e - --> d 10, M 2, 14e - --> d 8, M 4, square planar, 16e - (e.g. i 0, d 0, t 0 ) t-bu t-bu t-bu t-bu t-bu t-bu Fe t-bu t-bu t-bu t-bu d 0 t-bu t-bu Fe Fe d 0 t-bu t-bu A Fe d t-bu t-bu d 8, M 4, square planar, 16 e - --> d 6, M 6, octahedral, 18e - (e.g. h I, Ir I ) Ir I 16e- (Cy) 3 (F 6 - ) Ir III 2 (Cy) 3 Substrates: two groups segregated into non-polar and polar. Currently, the most facile way to form C-M σ bonds is with polar substrates (e.g. alkyl, aryl, and vinyl halides). on-polar substrates: - olar substrates: - where = I, Br,, Tf 2, 3 Si-, 2 B-, C 2 -,,,, 18 e- -, C 2 -,,,

15 M.C. White/M.S. Taylor, Chem 253 Mechanism -57- Week of September 27th, 2004 Transition Metal xidation States Ti V Cr Mn Fe Co i Cu Zr b Mo Tc u h d Ag f Ta W e s Ir t Au bserved positive oxidation state - Most stable oxidation state (aqueous solution) Mingos Essential Trends in Inorganic Chemistry; xford University ress, 1998.

16 M.C. White, Chem 253 Mechanism -58- Week of September 27th, 2004 A: Concerted 3-centered (non-polar substrates) M π-backbonding>> σ-donation oxidative addition M σ-complex metal dihydride σ-complex: intermolecular binding of a substrate via it's σ-bond to a metal complex. σ-complexes are thought to be along the pathway for oxidative addition of non-polar substrates to low valent, e-rich metal complexes. Analogous to the Dewar-Chatt-Duncanson model for olefin metal-bonding, σ-bonding is thought to occur via a2way donor-acceptor mechanism that involves σ-donation from the bonding σ-electrons of the substrate to empty σ-orbital of the metal and π-backbonding from the metal to the σ* orbitals of the substrate. These bonding principles have been applied to non-polar σ-bonds such as -, C-, Si-, B- and even C-C bonds. x M n x M n 0.74Å 0.84Å x M n x M (n2) >1.6Å σ-complex π-backbonding>> σ-donation metal dihydride Concerted mechanism: σ-complex formation precedes an early (little σ-bond breaking), 3-centered transition state where strong π-backbonding results in oxidative addition of the bound substrate to the metal. The concerted mechanism is thought to operate primarily for non-polar substrates (i.e. -,C-, Si-, B-) with electron rich, low valent metals. The spectroscopic identification of metal dihydrogen σ-complexes with - bond distances stretched between the non-bonding (0.74Å ) and dihydride extremes (>1.6Å) provides strong support for this mechanism with 2.

17 M.C. White/M.W. Kanan Chem 253 Mechanism -59- Week of September 27th, 2004 Dihydrogen σ-complexes 3 C C W 3 C 0.84Å The first stable dihydrogen metal complex was isolated by Kubas. The lengthened - bond (0.84Å) is 20% greater than the - bond length in free 2 (0.74Å). This is thought to arise from metal backbonding into the - σ* orbital. Kubas Acc. Chem. es (21) 120.

18 M.C. White/M.W. Kanan Chem 253 Mechanism -60- Week of September 27th, 2004 Dihydrogen σ-complexes Å s Ac 2 2 The - bond distance is thought to be a measure of the metal's ability to backdonate its electrons. ow oxidation state metal complexes such as [s( 2 )(en) 2 (Ac)] with strong σ- and π-donor ligands are very effective π-backbonders as evidenced by the very long - bond in their M- 2 σ-complex. Taube JACS 1994(116) 4352.

19 M.C. White, Chem 253 Mechanism -61- Week of September 27th, 2004 sp 3 C- A via σ complex intermediates M π-backbonding>> σ-donation oxidative addition M ydrido(alkyl)metal complex C σ-complex C regioselectivity: sp 2 C- > 1 o sp 3 C-> 2 o sp 3 C- >>> 3 o sp 3 C-. 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- bonds and bonds with more s character. Thermodynamic preference: stronger C-M bonds are formed (see Structure and Bonding, pg. 32). Evidence in support of a σ-complex intermediate: CD 3 C h I 18 e- C D 3 C CD 3 CD 3 hv (flash), Kr (165K) C C h I [Kr] C v (1946 cm -1 ) C D h I D 2 C CD 3 D 3 C CD 3 C h III D 3 C D CD 2 CD 3 CD 3 C v (1947 cm -1 ) C v (2008 cm -1 ) σ-complex Bergman JACS 1994 (116) 9585.

20 M.C. White, Chem 253 Mechanism -62- Week of September 27th, 2004 sp 3 C-: concerted vs. radical crossover experiment: evidence in support of a concerted mechanism. 3 C C Ir I C Ir III D 12 Ir I C hv Ir I C 18 e- C C Ir I D Ir III D C C D 11 D 11 σ-complexes ess than 7% of the crossover products were observed by 1 M. This may be indicative of a minor radical pathway. 2 C D 11 Ir II Ir II D Ir III Ir III D C C C C Bergman JACS 1983 (105) D 11

21 M.C. White, Chem 253 Mechanism -63- Week of September 27th, 2004 Agostic interactions: intramolecular σ-complex M C An agostic interaction is generally defined as an intramolecular σ-complex that forms between a metal and a C- bond on one of its ligands. Et h 3 5 mol% -C C h 3 u II h 3 Y Y Et Brookhart JMC 1983 (250) 395 Et u 0 (h 3 ) 3 Toluene, reflux Si(Et) 3 u 0 h 3 h 3 h 3 A u II h 3 h 3 h 3 The strategy of identifying substrates that can act as transient metal ligands has led to the only synthetically useful examples of C--> C-M (C- activation) to date. ike all substrate directed reactions, the scope of such processes is limited. Et Si(Et) 3 Trost JACS 1995 (117) 5371

22 M.C. White, Chem 253 Mechanism -64- Week of September 27th, 2004 A: sp 3 C C M C 3 C π-backbonding>> σ-donation oxidative addition M C σ-complex metal dialkyl complex Even though BDE's of C-C bonds are lower than those of analogous C- bonds (e.g. C 6 5 -C 3 :100 kcal/mol vs. C 6 5 -: 110 kcal/mol), transition metal mediated A's into C-C bonds are much more rare than those for analogous C- bonds. Formation of the σ-complex is kinetically disfavored by steric repulsion between the metal complex and the carbon substituents and by the high directionality of the sp3c-sp3c bond that localizes the σ bonding orbital deep between the carbon nuclei. Milstein and coworkers are able to overcome the kinetic barrier by approximating the C-C bond at the metal center. t-bu t-bu t-bu [(C 2 4 ) 2 h] 2-80 o C, tol h I -50 o C k = 2 x 10-4 /sec h III Et 2 Et 2 Et 2 Milstein JACS 2000 (122) o C observed by 1 M only product observed (no C- activation product)

23 M.C. White, Chem 253 Mechanism -65- Week of September 27th, 2004 A: sp 2 C-sp 3 C t-bu h III Et 2 only product observed (no C- activation product) Milstein M 1997 (16)3981.

24 M.C. White, Chem 253 Mechanism -66- Week of September 27th, 2004 A with C sp2 - bonds: aryl and vinyl halides x M n oxidative addition x M (n2) x Mn oxidative addition x M (n2) ote: retention of stereochemistry in A to vinyl halides ate of A = I>Br>>>F Three main mechanisms to consider for this process: 1. Concerted process with unsymmetrical, minimally-charged, 3-centered transition state 2. S Ar-like with highly charged transition state 3. Single-electron transfer processes with oppositely-charged, radical intermediates x M n C sp2 x M n x M (n1)( )

25 M.C. White, Chem 253 Mechanism -67- Week of September 27th, 2004 ammet plots (linear free energy relationships) - a valuable mechanistic probe See Carey and Sunberg: art A, 3 rd Edition. pp ecall the effect of e- withdrawing groups and e- donating groups on the acidity of benzoic acid resulting from stabilization and destabilization of the carboxylate anion, respectively: C 2 C 2 C 2 C 2 C 2 C 2 C 2 MeC Me CF 3 CMe Me pka Substituent group σ meta σ para C 2 Define: σ = pka - pka x CF CMe (by definition) Me Me Because these same substituents can often similarly stabilize or destabilize polar transtition states for reactions involving aryl substrates, a linear relationship can exist between σ and reaction rate for such processes. This type of "linear free energy relationship" can lend valuable insight into the charge characteristics of the transition state for various reactions.

26 M.C. White, Chem 253 Mechanism -68- Week of September 27th, 2004 ammet plots (linear free energy relationships) - a valuable mechanistic probe See Carey and Sunberg: art A, 3 rd Edition. pp p- 2 m p- log k/k o 0 p-me p-me m- 2 log k/k o -0.8 slope (ρ) = 2.61 (positive ρ indicates build-up of negative charge in the TS) slope (ρ) = (negative ρ indicates build-up of positive charge in the TS) -1.6 p σ σ σ C 2 Et δ- δ - Et δ - C 2 δ - δ δ 2 - Et - 2

27 M.C. White, Chem 253 Mechanism -69- Week of September 27, 2004 xidative addition of aryl chlorides to tris(triphenylphosphine)nickel(0) 4 3 p-c p-ch p-cme m-c log k/k o 2 m-c 2 Me ρ = m- m-me p-me 0 p-h p-me m-h p σ x M n C sp2 (h 3 ) 3 i or (h 3 ) 2 i x M n Foa and Cassar J. Chem. Soc Dalton

28 M.C. White, Chem 253 Mechanism -70- Week of September 27th, 2004 A: C sp3 -:alkyl, allyl, and benzyl halides ucleophilic displacement (generally for polar substrates) x M n A x M n A δ δ - x M (n2) A - C 2 Me " Stereochemistry is the single most valuable type of mechanistic evidence in reactions that make or break bonds to tetrahedral carbon." G.M. Whitesides (JACS 1974 (96) 2814). Ac (h 3 ) 4 d 5 mol% Me 2 C Me 2 C inversion a (h 3 ) 2 d II Me 2 C Me 2 C C 2 Me δ (Ac - ) inversion C 2 Me C 2 Me C 2 Me net retention Trost Acc. Chem. es (13) 385. h Mes (Tf - ) d II 2 mol% Mes 2 Mes d II Mes h δ (Tf - ) 2 h h zawa JACS 2002 (124)

29 M.C White/M.W. Kanan, Chem 253 Mechanism-71- Week of September 27th, 2004 Transmetalation: Definition and Utility Definition: the transfer of an organic group from one metal center to another. The process involves no formal change in oxidation state for either metal. Commonly used transmetalation reagents and their associated cross-coupling reaction ' n M' ' n M ' n M' n M Transmetalation Transmetalation is often a reversible process, with the equilibrium favoring the more ionic M- bond. Subsequent reactivity of one n M- species can drive the equilibrium in one direction. This is often exploited in cross-coupling reactions, where a transmetalated intermediate undergoes a reductive elimination to generate a new organic product. Subsequent oxidative additions generates a new substrate for transmetalation reductive elimination ' n M ' (n2) ' r M' transmetalation ' r M' ' -M 1 -M 2 -M 1 -M 2 M 2 is typically group 10 eagent -coupling reaction i, Mg vinyl, aryl, allyl, alkyl Kumada ZrCp 2 vinyl, alkyl Zn vinyl, aryl, alkyl egishi Cu n alkynyl, aryl e.g. Sonagashira Sn' 3 vinyl, aryl, alkynl Stille B(') 2 vinyl, aryl Suzuki -9BB alkyl Suzuki-Miyaura Si' 3 aryl, vinyl,alkyl iyama Al 2, Al 2 alkyl M= i, d M r (n) r M (n2) oxidative addition In generalthe rates of transmetalation of follow the order :alkynyl> aryl,vinyl>alkyl

30 M.W. Kanan, Chem 253 Mechanism -72- Week of September 27th, 2004 Transmetalation: Mechanism The mechanism for transmetalation is the least-studied of the basic reaction steps. In a simple picture, the metal accepting the group is the electrophile and the M- bond being transferred is the nucleophile. M- bond formation may or may not be simultaneous with M - bond formation, depending on the nature of and the actual complexes involved. δ M δ M M' M' With this model, increasing the nucleophilicity of by altering the ligands on M and increasing the electrophilicity of M through its ligands will facilitate the transmetalation step. For weakly nucleophilic transmetalation reagents, an added nucleophile or base often facilitates the transmetalation. Transmetalation with the Suzuki coupling often requires added base ' B - ' B - n d II n d ' Suzuki Chem. ev (95) F - is thought to activate the organosilicon reagent for transmetalation via formation of a nucleophilic pentavalent silicate in a iyama coupling ' Si n F TBAF 3-n ' Si n F 4-n n d n d - ' iyama Tet. ett (31) 2719.

31 M.W. Kanan, Chem 253 Mechanism -73- Week of September 27th, 2004 Transmetalation with advanced intermediates Suzuki-Miyaura Bn Bn Bn TBS 9BB TF, rt Bn Bn Bn TBS 9BB Tf Bn 3M aq. Cs 2 C 3, DMF d(h 3 ) 4, 0 C 71% Bn Bn Bn Bn TBS Bn Synthetic studies on Ciguatoxin Bn Takakura ACIEE, 2001 (40) 1090

32 M.C. White/Q. Chen Chem 253 Mechanism -74- Week of September 27th, 2004 eductive Elimination eductive elimination is a key transformation in transition metal mediated catalysis, often representing the product forming step in a catalytic cycle. General trend for reductive elimination from d 8 square planar complexes: M > M > C(sp) M C(sp 2 ) > M > C(sp 3 ) M C(sp 3 ) C(sp 3 ) Best overlap rbitals with more s character are less directional and lead to better overlap in the transition state for reductive elimination (E). ote: cis orientation of the ligands is required for E to occur. Worst overlap 1.51Å 1.55Å 1.52Å 1.55Å 1.96Å C Å C 3 d 73 o 1.73Å d metal dihydride 51 o 1.33Å Transition state (TS) Calculated E = 1.55 kcal/mol d- bond is stretched only 2% in TS d 1.95Å 80 o 2.39Å C 3 hydrido(alkyl)metal complex d 51 o 1.57Å 1.99Å C 3 Transition state (TS) Calculated E = 10.4 kcal/mol d 92 o 2.82Å 1.96Å C 3 metal dimethyl d 56 o 2.11Å C 3 Transition state (TS) Calculated E = 22.6 kcal/mol d- bond is stretched ~10% in TS Goddard JACS 1984 (106) Dedieu Chem. ev Computational studies suggest that the spherical symmetry of the s orbitals of allows the simultaneous breaking of the M- σ bonds while making the new σ bond of the product.

33 M.C. White Chem 253 Mechanism -75- Week of September 27th, 2004 E can be promoted by: Increasing the bite angle of the ligand Increasing electrophilicity of metal center (e.g. π-acids) igand dissociation E: Bite Angle Effects TMS d II C 2 TMS C 80 o C d II k C 2 TMS C d II C bite angle h 2 C 2 TMS d II C h 2 bite angle: 85 o k = 2.1 x 10-6 h 2 C 2 TMS h 2 d II d II C C h 2 h 2 bite angle: 90 o bite angle: 100 o k = 5.0 x 10-5 k = 1.0 x 10-2 C 2 TMS arge bite angles of diphosphines have been shown to enhance the rates of reductive elimination from square planar complexes presumably by bringing the two departing ligands closer together. Moloy JACS 1998 (120) 8527.

34 M.C. WhiteChem 253 Mechanism -76- Week of September 27th, 2004 E: π-acid Effects E can be promoted by: Increasing the bite angle of the ligand Increasing electrophilicity of metal center (e.g. π-acids) igand dissociation i II F 3 C Bu I 10 mol% i II Bu ent 2 Zn F 3 C 50 mol% possible intermediate Bu 70% yield, 1h ent w/out π-acid: 20%, 15h Knochel ACIEE 1998 (37) 2387.

35 M.C. White, Chem 253 Mechanism-77- Week of September 27th, 2004 Migratory Insertion/De-insertion: Alkyl, Cossee-Arlman Mechanism for alkyl migration to a coordinated olefin C 3 Zr C 3 Zr C 3 Zr Brintzinger catalyst for Ziegler atta polymerizations no oxidation state change at M -2e from the electron count The π-bonding electrons of the olefin are used in σ-bond formation with a M-alkyl σ*. Formation of the new C-C and M-C σ bonds are thought to occur simultaneously with breaking of the π-bond and alkyl-m σ bond through a 4-centered concerted transition state. Migratory insertion of a hydride into a coordinated olefin (the microscopic reverse of β-hydride elimination) is thought to procede via the same mechanism. For metal alkyls, the equilibrium lies to the right, whereas for metal hydrides it lies to the left. Early TS Grubbs and Coates Acc. Chem es (29) 85. ate TS

36 M.C. White, Chem 253 Mechanism -78- Week of September 27th, 2004 β-ydride Elimination A significant decomposition pathway for metal alkyls is β-hydride elimination which converts a metal alkyl into a hydrido metal alkene complex. d II C 3 (BAr ' 4 ) - donative agostic interaction β hydride elimination (BAr ' 4 ) - C 3 d II concerted transition state d C 3 (BAr ' 4) - β-hydride elimination can occur when: cis to the alkyl group there exists is a site of coordinative unsaturation on the metal which corresponds to a site of electronic unsaturation (empty metal orbital). the M-C-C- unit can take up a coplanar conformation which brings the β-hydrogen in close enough proximity to the metal to form an agostic interaction. the metal is electrophilic resulting in an agostic interaction that is primarily electron donative in nature (i.e. σ-donation>>π-backbonding). M C σ-donation >> π-backbonding σ-complex

37 M.C. White, Chem 253 Mechanism -79- Week of September 27th, 2004 Wacker xidation d 2 2 Binding specificity: terminal olefins egioselectivity: 2 o carbon emote functionality tolerated 1/ Cu 2 Cu 2 d 2 d(0) - 2 d 2 * protonolysis * d d d β-hydride elimination Commericial production of acetaldehyde

38 M.C. White Chem 253 Mechanism -80- Week of September 27th, 2004 β-ydride Elimination Computational studies suggest that the higher energy of the i(ii) vacant d orbital ( hartree) with respect to that of the analogous d(ii) complex ( hartree) results in a weaker donative agostic interaction with the βc σ bond. The energetically optimized geometries of the agostic complexes show a greater lengthening of the βc- bond in the d(ii) complex than in the i(ii) complex, indicative of greater σ-donation in the former. These computational results are consistent the experimentally observed greater stability of i alkyls towards β-hydride elimination that d alkyls and can be rationalized based on the greater electronegativity of d(ii) vs i(ii) as reflected in their respective second ionization potentials. 1.10Å i II Å d II 3 second ionization potential i(ii): ev recall: sp 3 C- is 1.09Å second ionization potential d(ii): 19.9 ev Morokuma JACS 1985 (107) 7109.

39 M.C. White, Chem 253 Mechanism-81- Week of September 27th, 2004 Migratory Insertion/De-insertion: C Mechanism for C insertion : via alkyl migration to coordinated C 3 C 88.8 o C 88.2 o d II 3 C 3 C o o d II 3 3 C C d II 3 alkyl groups migrate preferentially over hydrides Computational studies suggest that in the TS, the methyl group has moved up half way towards the carbonyl. no oxidation state change at M -2e from the electron count Experimental evidence also suggests that carbonyl insertion occurs via alkyl migration (not C migration) Morokuma JACS 1986 (108) d II C C d II C insertion 3 C d II β-hydride elimination 3 C d II reductive elimination cis-diethyl complex 3 d II 3 C d II C C insertion 3 d II C reductive elimination trans-diethyl complex Yamamoto Chem. ett

40 M.C. White, Chem 253 Mechanism-82- Week of September 27th, 2004 Migratory Insertion/De-insertion: C 3 t II 3 t II t II C C C monomer dimer (no dimer observed) h < Me Electron donating substituents on aryl groups promote migrations whereas electron withdrawing substituents inhibit them. < C 2 h < Me < h < Et Anderson Acc. Chem. es (17) 67. Monomer Dimer 0% 100% Me 12% 88% Me 24% 76% 46% 54% 73% 27% C 100% 0% Cross J. Chem. Soc., Dalton Trans. 1981, 2317.

41 M.C. White Chem 253 Mechanism -83- Week of September 27th, 2004 eck Arylation Me Me I Me C 2 Me oxidative addition d(h 3 ) 4 cat. Et 3, C 3 C 80 o C Me Me I d() 2 Me C 2 Me I h 3 associative displacement Me d h 3 Me migratory insertion Me I h 3 d Me Me C 2Me reasonable intermediates Me C 2Me β-hydride elimination Me Me Me C 2 Me Me 93% yield C 2Me Me C 2Me (±)-F Danishefsky JACS 1993 (115) 6094.