Ready; Catalysis Organometallics

Organometallic Reaction Mechanisms Ligand association/dissociation toluene CuBr + PBu3 (PBu3)nCuBr NOTE: No ox. state change insoluble soluble

P P P(tBu) P 2 P Pd + P Pd P Fe = P P P inactive catalyst active catalyst P(tBu)2 P for cross coupling Ligand Exchange: Associative - common for 16e- complexes rate = k[py][Pt] rate will depend on nature (sterics, electronics) of Nu and MLn

Cl Py + Et3P Cl Et P Cl Et P Py Et3P Py Py + Pt 3 Pt 3 Pt Pt + Cl- H PEt H PEt 3 H PEt3 H PEt3 3

Dissociative - common for 18 e- complexes Rate will depend on nature of leaving L, sometimes on new L' -L slow: - - PF - H PF Rate = k[ML] H 6 H PF6 6 R P H R3P H R P H 3 Ir -S 3 Ir Hydrogenation Ir S PR S PR3 S PR 3 +L' slow: S 3 18e- Rate = Kk [ML][L'] 16e- 18e- +L [L]

1 Ready; Catalysis Organometallics: ligand exchange

log 12.00 (krel) log (krel) Nu +MeI +Pt(Py)2Cl2 10.00 MeOH 0.00 0.00 8.00 AcO- 2.00 4.30 6.00 Et3N 3.07 6.66 4.00

Cl- 3.04 4.37 krel2)(rxn log 2.00 Py 3.19 5.23 0.00 I- 5.46 7.42 0.00 2.00 4.00 6.00 8.00 10.00 PhS- 7.23 9.92 log krel (rxn 1) Ph3P 8.99 7.00

Exchange rates vary over 20 orders of magnitude

[M] L [M] + L

From: David T. Richens, The Chemistry of Aqua Ions, 1997, Wiley (ISBN 0-471-97058-1); C/O Prof. Eric Meggers

2 Ready; Catalysis Organometallics

Oxidative Addition and Reductive Elimination X

oxidative addition O.A. and R.E. involve 2e- change (n+2) LnM(n) + X Y LnM at M, increase # ligands by 2 reductive elimination

Y "O.A" and "R.E." give NO information on mechanism: can be concerted 3-centered, SN2-like or radical

H H H Ph3P CO Ph3P CO Ir Note cis product from Ir H PPh3 concerted OA Cl PPh3 Cl

H2

H3C I CH3 CH3I Ph3P CO Ph3P CO Ph P CO Ir Ir 3 Ir Cl PPh3 Cl PPh3 H PPh3 I

EtBr

H2C CH3 CH3 Br Ph3P CO Radical chain mech. Ph3P CO Ir Ir H PPh3 Cl PPh3 Br

Ready; Catalysis Organometallics Sterochemical Issues

R2 OTBS R2 L I R1 SnBu3 + R1 + Pd X LnPd(0) CO2H X L R3 cat. Pd(II) R3 cis addition, olefin stereochemistry 65% is maintained OTBS X = I > Br ~ OTf >> Cl ~ OTs Smith, Jacs, 1998, 3935

CO2H

Vinyl and Aryl C-X much more reactive than alkyl C-X despite more e- rich alkyl C-X Why? precoordination R2

R1 X

R3 Pd Precoordination with allylic substrated allows O.A. to moderately activated bonds:

Pd Pd Backside (SN2-like) attack at C

OR OR OR = OAc, OCO2R, OP(O)(OR)2, OTs, I, Br, Cl

Precoordination can even allow activation of C-H bonds in some cases:

N N OTf-

H3C H3C N Pt N Pt NH H N N O Rhazinilam Sames, JACS, 2002, 6900

3 Ready; Catalysis Organometallics

Oxidative Addition: Thermodynamics Bond strength is reflected in ease of O.A., with exceptions

Rxn BDE (kcal/mol) est ΔG for O.A. of Cleaved Bond

Ir = Ir(I) CH3 L L L I Ir Ir + H3C I 56 -25 L L L L L

H L L L H Ir + H H Ir 104 -6 L L L L L

CH3 L L L CH3 Ir 88 +6 Ir + H3C CH3 L L L L L

H L L L CH3 Ir 104 +8 Ir + H3C H L L L L L

M-H bonds are stronger than we might predict O.A. to C-H and C-C remain very challenging, but could be valuable (more on this later in the course)

Ready; Catalysis Organometallics

A picture of oxidative addition from calculations.

From CHNF, figure 5.2

4 Ready; Catalysis Organometallics

Oxidative addition: reactivity trends Reaction rate increases with electron density on Pd

1

0.5 OMe y = -2.8259x - 0.4246

0 H

-0.5 CH3

-1 log[krel] F -1.5 Cl CF3 -2

-2.5 -0.4 -0.2 0 0.2 0.4 0.6 0.8 Hammett σ

Amatore, Organometallics, 1995, 1818

Ready; Catalysis Organometallics

Oxidative addition: reactivity trends Reaction rate decreases with electron density on ArX

2.5 NO2 2 y = 2.547x + 0.078 CN 1.5 CO2Et 1 CF3

log(krel) 0.5 Cl 0 H tBu -0.5 Me OMe -1 -0.4 -0.2 0 0.2 0.4 0.6 0.8 1 Hammett σ

Jutand, OM, 1995, 1810

5 Ready; Catalysis Organometallics

Oxidative addition: reactivity trends

Kink indicates change in mechanism

Ready; Catalysis Organometallics

Oxidative addition: reactivity trends With sp3 electrophiles, SN2 pathway dominates with Pd(0) Rxns show other traits of SN2 (solvent effects, leaving group trends)

From Fu, ACIEE, 2002, 3910 See also Fu, ACIEE, 2003, 5749

6 Ready; Catalysis Organometallics: Oxidative addition

Direct single electron OA: -3 -3 -3 -3 R X + 2 [Co(CN)5] R + X Co(CN)5] R Co(CN)5] + X Co(CN)5] X = halide

Net single electron OA CpFeIIIX (CO) + CpFeI(CO ) II [CpFe(CO)2]2 + X2 2 2 2 2 CpFe X(CO)2

Single electron OA in catalysis

O O N N N Br nC6H13 (iPrPyBox) 13 mol% (±)- + Hex ZnBr NiBr2-diglyme (10 mol%) 96% ee 89% yield

LnNi(0)

Br n-Hex NiLn NiLn

I + LnNi Br

achiral Fu, JACS, 2005, 10482

Ready; Catalysis Organometallics

Reductive elimination: reactivity trends (substrate) R

O PPh2 110 oC

Pd Fe R OMe O

PPh2 R % Yield OMe H 0 CN >90

CF3 Me

N PPh2 -15 oC

Fe Pd R CF3 N

PPh2 R kobs Me R H 3 Me 13 Hartwig, JACS, 2003, 16347 OMe 38 OM, 2003, 2775

7 Ready; Catalysis Organometallics

Reductive elimination: reactivity trends (substrate + catalyst) R

2 CN

P O

110 oC Fe Pd O NC OMe P OMe R % Yield H >90 kCF3/kH ~ 2 CF3 95 2

R

R

t-Bu2 O 110 oC P Pd O OMe

2 R OMe Fe R' R' R % Yield H 2-Me 5-25

Ph5 2-Me 66 Ph5 4-Me 0

Ready; Catalysis Organometallics

Oxidation-induced reductive elimination

H3C CH CH3 3 CH3 - ox. at M PF6

ClMg Ce(NH4)2(NO3)6 69% + MeO2C MeO2C Fe(CO) MeO2C Fe Fe 3 (CO) + CO Me (CO)3 3 2 - 18e- Fe(II) 17e Fe(III)

H3C CH3 H3C CH3 H3C CH3 H3C CH3 ox. at L H O -CO , -HO- ~70% 2 2 2 (1:1) O MeO C 2 Fe MeO2C Fe MeO2C Fe(CO) - 2 CO2Me (CO)3 (CO)2 - O OH 18e Fe(II) 18e- Fe(II) 16e- Fe(II)

Donaldson, OL, 2005, 2047

8 Ready; Catalysis Organometallics

Ready; Catalysis Organometallics

Oxidative addition: applications of Sn2-like OA and carbonylation

9 Ready; Catalysis Organometallics

agostic interactions: stable intermediates on the way to α- or β-hydride elimination • Stable interactions often found with electron-poor metals • Especially common with do metals • Computation with Ti(carbene) and W(carbyne) estimates BDE ≤ 10 kcal/mol (OM, 2006, 118)

Schrock, et al

Things to note Ta(III) carbene (d2) Small Ta-C-H angle (78o) Long C-H bond (1.14A, average here is 1.085A) i.e. weakening of C-H bond Big Ta-C-C angle (170o) Unrelated to agostic interactions: Ethylene C’s out of plane (average 0.33A out of 4H plane) Long ethylene C-C distance (1.48 v. 1.34 when free)

Ready; Catalysis Organometallics Agostic interactions are likely unobserved intermediates in normal tranisition metal-catalyzed reactions:

Heck Rxn: L

I Pd(0) I Pd L Pd(H)I + + H n

base

Generation of Pd(0) H

H3C Et Zn -CH2CH2 H3C -CH3CH3 2 II PdCl Pd II L Pd(0) 2 Pd H red. elim. n transmetalation β-Hydride elim L L α-agostic interactions can happen, too likely intermediate in α-elimination: + Cp*TaClBn H 3 lewis acid Cp2ZrCl2 Zr H Ph H H -PhCH3 LnTa Ta Ph Cl Bn catalyst for ethylene polymerization Cp* cation stabilized by agostic interaction Schrock, Accts, 1979, 98

10 Ready; Catalysis Organometallics

Agostic interaction can be dynamic

Nolan, ACIEE, 2005, 2512

PF PF PF6 6 C(CD3)3 6 H H N D D C(CD3)3 N N N H2 D Ir N 2 N N Ir Ir N N N N H N H D D

CD3 D3C CD3 D C D D 'cyclometalated' Ir(III)bis(NHC) 3 DD

Ready; Catalysis Organometallics

A C-H complex observed crystallographically :

Milstein, JACS, 1998, 12539

Reversible deprotonation with Et3N to form Ar-Rh bond

11 Ready; Catalysis Organometallics

Hydroformylation (7 bil Kg/yr) cat. Rh(I) R H H2/CO (syn gas) R + R CHO O linear branched

R H HRh(CO)2L2

O H H L HRh(CO)L2 Rh R L R CO O H2

R OC L Rh R H L L Rh O L CO

H H H Rh(CO)2L2 Rh(CO)L2 R CO R

R Rh(CO)L2 R CHO

Ready; Catalysis Organometallics

4-centered reactions: R 2+2 N see Eur. JOC, 2003, 935 cat. Cp2Zr(NHR)2 RNH2 + R' R' R' R' NR NR - ZrCp2 ZrCp2 R' R' R R R' R R' N N N

Zr Zr Zr Cp Cp Cp Cp NHR R' Cp R' Cp

σ-bond metathesis Cp*

Sc CH3 -HCMe3 Cp* CH3

Tilley, Jacs, 2003,7971 Cp* Cp* Sc Sc Cp* H Cp* H2C CH4

12 Ready; Catalysis Organometallics

Transmetallation R-M + M'-X R-M' + M-X

Stoichiometric Use: Great way to make Grinards, alkyl zincs, cuprates, stannanes etc. Esp useful on small scale where O.A. to R-X not possible

BuLi MgBr , -100 oC, 5min NC I NC Li 2 NC MgBr 3 3 3 Tet, 1996, 7201

In catalytic cycle: TMS Cl cat. NiCl (DPPP) TMS MgBr 2 + TMS Cl Ln L via n Ni -MgBrCl Ni

-T.M. usually from more eletropositive M to more electronegative M -Endothermic T.M.'s can be part of catalytic cycle if R-M' subsequently reacts -Likely by associative mech for coordinatively unsaturated M -Likely metathesis for coordinatively saturated

13