CHEM-E1130 Catalysis

Introduction to Homogeneous Catalysis

Jan Deska Laboratory of Organic Chemistry

11.2.2019 What is Homogeneous Catalysis?

Catalytic reaction in which both catalyst & reactant interact in the same phase (generally in the liquid phase, either in solution of in liquid reactant)

Nature of catalysts widespread in structure and complexity § acid or base catalysis (inorganic acids of bases) § biocatalysis (biomolecules i.e. proteins & cofactors) § organocatalysis (organic molecules e.g. amines, carbenes, organic acids, amphiphiles,...) § organometallic catalysis (transition metal complexes with organic and/or inorganic ligands)

Supporting literature, e.g.: Organotransition Metal Chemistry, J. F. Hartwig, University Science Books, 2010 The Organometallic Chemistry of Transition Metals, R. H. Crabtree, 3rd ed, Wiley, 2001 What is Homogeneous Catalysis?

Catalytic reaction in which both catalyst & reactant interact in the same phase (generally in the liquid phase, either in solution of in liquid reactant)

topic of today's lecture

Multiple Nobel prizes awarded to research on homogeneous catalysis

1963 Ziegler, Natta Metal-catalyzed polymerizations (e.g. PE, PP) 1973 Fischer, Wilkinson Sandwich organometallics (e.g. industrial hydrogenation catalysts) 1975 Cornforth Stereochemistry of enzyme reactions 2001 Knowles, Sharpless, Noyori Chirally catalyzed redox reactions (e.g. industrial asymmetric production of optically active amino acids) 2005 Chauvin, Grubbs, Schrock Olefin metathesis (e.g. ring-opening polymerization) 2010 Heck, Negishi, Suzuki Palladium-catalyzed cross coupling (e.g. key in pharma synthesis) 2018 Arnold Directed evolution of proteins (e.g. enzyme optimization) Heterogeneous vs Homogeneous Catalysis

Homogeneous Catalysis Heterogeneous Catalysis

activity high varies

selectivity high (also stereoselectivity) varies

reaction conditions limited to low temperatures high temperature & pressure

lifetime varies, potentially challenging long

catalyst poisoning low high

diffusion issues none often significant

catalyst separation challenging, expensive not required What is Organometallic Chemistry?

§ synthesis and reactions of molecular entities featuring carbon-metal bonds

Classical Organometallic Chemistry § main group metal-carbon compounds § Grignard reagents, Barbier-type organoaluminiums & -zincs, organolithium § no (subtle) redox chemistry, one redox state clearly prefered § characteristics: mainly highly reactive, used in stoichiometric transformations

Organotransition Metal Chemistry § transition metals as center of organometallic species § complex architecture, ligand structures and electronics crucial parameters § facile change of redox states often basis of catalysis

§ somewhere between organic chemistry and inorganic coordination chemistry Transition Metals – Structure & Bonding

The Transition Metals

d electrons in group 3 are easily removed via ionization, those in group 12 are stable and form part of the core electron configuration Transition Metals – Structure & Bonding

Valence electron count

for free (gas phase) transition metals: (n+1)s is Fe 2 6 4s 3d below (n)d in energy

CO CO for complexed transition metals: the (n)d levels are 8 OC Fe 3d below the (n+1)s and thus get filled first. CO OC

for oxidized metal centres, subtract the oxidation N 3d6 N Fe N state from the group # Mes Mes Cl Cl Transition Metals – Structure & Bonding

Valence orbitals

§ 9 Valence Orbitals: upper limit of 9 bonds may be formed. In most cases a maximum of 6 σ bonds are formed and the remaining d orbitals are non-bonding. It's these non-bonding d orbitals that give TM complexes many of their unique properties.

§ 18 electron rule: upper limit of 18 e- can be accommodated without using antibonding molecular orbitals (MO's).

§ Saturation: complexes with a filled valence shell, i.e. (n)d + (n+1)s + (n+1)p = 18 e–, are called saturated, complexes with less than 18 valence electrons are unsaturated Transition Metals – Coordination Geometries

Common geometries

§ governed by sterics § to a first approximation, geometry of TM complexes is determined by steric factors (VSEPR, valence shell electron pair repulsion). The M-L bonds are arranged to have the maximum possible separation around the metal centre.

180° L 120° 109.5° L M L M L L M L L L L coordination number: 2 coordination number: 3 coordination number: 4 linear trigonal planar tetrahedral

L L L L L L M 120° 180° M 90° L L L 90° L L coordination number: 5 coordination number: 6 trigonal bipyramidal octahedral Transition Metals – Coordination Geometries

Common geometries

§ governed by electronics § d electron count combined with the complex electron count must be considered when predicting geometries for TM complexes with non-bonding d electrons. Often this leads to sterically less favorable geometries for electronic reasons (e.g. coordination number 4, d8, 16 e- strongly prefers square planar geometry) .

180° 90-100° L L L L L L M L M 90° M 90° L L L 90° L L

coordination number: 3 coordination number: 4 coordination number: 5 T-shaped square planar square pyramidal Transition Metals – Electronic Configurations

Electron counting

the electronic configuration and the degree of saturation determine stability and reactivity of organometallic complexes

§ step 1: determine the oxidation state of the central metal ü To do this, balance the ligand charges with an equal opposite charge on the metal. This is the metal's formal oxidation state. ü To determine ligand charges, create an ionic model by assigning each M-L electron pair to the more electronegative atom (L). This should result in stable ligand species or ones known as reaction intermediates in solution. Transition Metals – Electronic Configurations

Electron counting

the electronic configuration and the degree of saturation determine stability and reactivity of organometallic complexes

§ step 2: determine the d electron count § step 3: determine the electron count of ü To do this, subtract the metal's the entire complex oxidation state from its group # ü To do this, add the number of electrons donated by each ligand to the metal's d electron count Transition Metals – Electronic Configurations

Hapticity (hn)

the number of atoms (n) of the ligand directly involved in binding to the metal

h ligands

Proposed intermediates in VO(acac)2 catalyzed directed epoxidation of allylic alcohols (Sharpless epoxidation).

µ ligands Transition Metals – Electronic Configurations

– anionic (2 e–) neutral (2 e ) Electron counting exercise

ligands = 4 x 2e–: 8 e– metal = d8: 8 e– Wilkinson's catalyst complex: 16 e– (unsaturated) Transition Metals – Electronic Configurations

Electron counting exercise

Noyori hydrogenation catalyst Transition Metals – Electronic Configurations

Electron counting exercise

Noyori hydrogenation catalyst ligands = 6 x 2e–: 12 e– metal = d6: 6 e– complex: 18 e– (saturated) Transition Metals – Electronic Configurations

Electron counting exercise

"Palladium tetrakis" (Tetrakis(triphenylphosphino)palladium) cross coupling catalysts Transition Metals – Electronic Configurations

Electron counting exercise

ligands = 4 x 2e–: 8 e– metal = d10: 10 e– "Palladium tetrakis" complex: 18 e– (saturated) (Tetrakis(triphenylphosphino)palladium) cross coupling catalysts Transition Metals – Electronic Configurations

Electron counting exercise

olefin hydroxylation catalyst Transition Metals – Electronic Configurations

Electron counting exercise

olefin hydroxylation catalyst ligands = 6 x 2e–: 12 e– metal = d6: 6 e– complex: 18 e– (saturated) Transition Metals – Electronic Configurations

Hapticity (hn) – part 2

unsaturated ligands offer higher degree coordination modes

as anionic ligands

M M M

h1-aryl h1-vinyl h1-alkynyl formal charge: –1 formal charge: –1 formal charge: –1 e donated: 2 e donated: 2 e donated: 2

as neutral ligands

M M M h6-arene h2-alkene h2-alkyne formal charge: 0 formal charge: 0 formal charge: 0 e donated: 6 e donated: 2 e donated: 2 Transition Metals – Electronic Configurations

Hapticity (hn) – part 2

unsaturated ligands offer higher degree coordination modes

as h1 ligand

H O M M M O h1-acetate h1-allyl h1-cyclopentadienyl formal charge: –1 formal charge: –1 formal charge: –1 e donated: 2 e donated: 2 e donated: 2

as hn ligand

O M M M O h3-acetate h3-allyl h5-cyclopentadienyl formal charge: –1 formal charge: –1 formal charge: –1 e donated: 4 e donated: 4 e donated: 6 Transition Metals – Electronic Configurations neutral (2 e–) Electron counting exercise – part 2 – anionic (2 e–) anionic (4 e )

ligands = 4 x 2 e– + 1 x 4 e–: 12 e– metal = d6: 6 e– Crabtree's hydrogenation catalyst complex: 18 e– (saturated) Transition Metals – Electronic Configurations

Electron counting exercise – part 2

polymerization catalyst Transition Metals – Electronic Configurations

Electron counting exercise – part 2

polymerization catalyst ligands = 2 x 2 e– + 2 x 6 e–: 16 e– metal = d0: 0 e– complex: 16 e– (unsaturated) Transition Metals – Electronic Configurations

Electron counting exercise – part 2

hydroformylation catalyst Transition Metals – Electronic Configurations

Electron counting exercise – part 2

ligands = 1 x 6 e– + 1 x 4 e–: 10 e– metal = d8: 8 e– complex: 18 e– (saturated) hydroformylation catalyst Transition Metals – Bonding Modes

s-bonding

§ directional interaction of filled donor orbitals with empty acceptor orbitals

§ generally between the metal as acceptor and donor ligands

ü hydride, alkyl and tertiary amine ligands act purely as s-donors Transition Metals – Bonding Modes

p-bonding

ü 6 valence metal orbitals well oriented ü 3 valence metal orbitals don't match for s-bonding in an octahedral ü yet, suitable orientation and orbital environment symmetry for p-bonding ü (also consider hybridisation) Transition Metals – Bonding Modes

directionality in p-bonding

ü ligands with additional lone pairs or other filled orbitals can participate in additional p-donation

prim or sec. amides alkoxides halides Transition Metals – Bonding Modes

directionality in p-bonding

ü ligands with suitable empty orbitals can participate p-backbonding ü donation of e-rich metal centres into antibonding acceptors at the ligand

carbonyl complexes olefin complexes complexes with H2

complexes with push-pull complex with activation of H2 carbon monoxide alkenes (weakening of H-H-bond (similar with NO) (similar: side-on coordination through backbonding) of carbonyl groups) Common ligands in transition metal catalysis

§ stability and reactivity strongly affected by stabilizing ligands

§ phosphine-based ligand systems predominant

§ occasionally also bulky carbene donors employed From individual steps to catalysis

Various single-step reactions that can take place around a complexed transition metal centre

The right combination leads to the desired overall reaction outcome

Individual steps involve...

§ ligand exchange reactions

§ oxidative additions

§ transmetalations

§ reductive eliminations

§ migratory insertions & eliminations Ligand Exchange Reactions

Associative ligand substitution

§ Often found for 16 e–, d8 square planar complexes which undergo ligand substitution via an associative mechanism

§ Analogous in many ways to SN2 reactions.

empty non-bonding pz acts as acceptor for the e-density of the incoming nucleophile coordination number: 2 coordination number: 3 coordination number: 4 linear trigonal planar tetrahedral + Nu– – X–

observe: X– moves into an axial position prior to dissoziative loss Ligand Exchange Reactions

Dissociative ligand substitution

§ generally most favored in coordinatively saturated 18 e– complexes (e.g. d10 tetrahedral, d6 octahedral). § Avoids energetically unfavorable 20 e– intermediates, analogous in

many ways to SN1 reactions.

– X– + Nu–

ü Note: in all ligand substitution processes, there is no change in oxidation state of the central metal atom Oxidative Additions

§ metal mediated breaking of a substrate σ-bond and formation of 1 or 2 new M-L σ bonds. § OA requires removal of 2 electrons from the metal's d electron count, i.e. the metal's oxidation state increases by 2. § The formation of 2 new M-L σ bonds is accompanied by an increase in the metal's coordination number by 2 units. The latter results in a 2 unit increase in the electron count of the metal complex

depending on catalyst and substrate, different mechanisms can apply ü concerted oxidative addition ü nucleophilic replacement ü radical reactions Oxidative Additions

Non-polar Substrates § 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. § These bonding principles have been applied to non-polar σ-bonds such as H-H, C-H, Si-H, B-H and even C-C bonds.

ü two-way 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. Oxidative Additions

Polar Substrates § sp2 C-X bonds possibly break via three different mechanisms

Rate of oxidative addition: X = I > Br > Cl >> F

Concerted process with SNAr-like with Single-electron transfer processes unsymmetrical, minimally-charged, highly charged with oppositely-charged, radical 3-centered transition state transition state intermediates Transmetalation

§ the transfer of an organic group from one metal center to another. The process involves no formal change in oxidation state for either metal.

ü Transmetalation is often a reversible process, with the equilibrium favoring the more ionic M-X bond. ü Often exploited in cross-coupling reactions, where a transmetalated intermediate undergoes a reductive elimination to generate a new organic product. Reductive Elimination

§ key transformation in transition metal mediated catalysis, often representing the product forming step in a catalytic cycle. § strict requirement: cis-orientation of the two bond-forming ligands!

R (n+2) (n) M Ln M Ln + R R' R'

ü during the process, the product is "squeezed out" from the complex Reductive Elimination

can be promoted by increased bite angle ligands

ü large bite angle, bidentate ligands favour reductive elimination by bringing the departing ligands in closer proximity to each other Migratory Insertion and reverse

§ 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 concerted 4-centred 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.

no change in oxidation state! loss of 2 e– in electron count (16 e– to 14 e–)

+ +

ü here: elemental step in Ziegler-Natta-type ethylene polymerizations Migratory Insertion and reverse

b-hydride elimination § significant decomposition pathway for alkylmetals which converts a metal alkyl into a hydrido metal alkene complex. § but also: crucial elemental step in important processes such as Wacker oxidations and Heck reactions

agostic interaction concerted 4-centre transition state Migratory Insertion and reverse

insertion and elimination of CO § alkylmetal carbonyl complexes can transform into acyl metal species § proceeds via concerted 3-centre transition state, where alkyl and CO approach similarly to reductive elimination § reversiblity often requires high CO pressures for productive carbonylations

alkyl groups migrate more no change in oxidation state! readily than hydrides loss of 2 e– in electron count (16 e– to 14 e–)

ü crucial step in e.g. Monsanto acetic acid process or hydroformylations A real-life example

Hydroformylation (aka Oxo process) § oldest and one of the most significant processes based on homogeneous catalysis § valorization of simple alkenes to give aldehydes (and alcohols)

syngas O H (H2 + CO) O R and/or R H catalyst R linear (n) branched (iso) Catalyst systems § unmodified cobalt-catalyzed hydroformylation (Otto Roehlen, 1938) o no organic ligands o high pressure required to maintain complex stability (typical conditions: P=300 bar, T=150C) CO o no control over n/iso ratio (approx 1 : 1) CO H Co o aka BASF-oxo or Exxon/Kuhlmann-oxo CO CO Hydroformylation – the mechanism

HCo(CO)4

de-coordination O – CO H

HCo(CO)3 H +I CO reductive coordination Co H elimination O +III CO OC CO H Co CO oxidative CO H addition 2 migratory insertion +I H CO Co H CO migratory coordination CO Co insertion CO CO Co O CO CO CO CO CO CO +I Co +I +I CO CO CO Further developments

Hydroformylation (aka Oxo process) § oldest and one of the most significant processes based on homogeneous catalysis § valorization of simple alkenes to give aldehydes (and alcohols)

syngas O H (H2 + CO) O R and/or R H catalyst R linear (n) branched (iso) Catalyst systems § Union Carbide (today Dow, 1970's) H PPh o rhodium as central metal with phosphine ligands 3 Ph3P Rh o typical conditions: P = 30 bar, T = 120 C PPh3 CO o high selectivities for n-butyraldehyde (>92%) o today widely used for valorization of short-chain alkenes

PPh3 = P Further developments

Hydroformylation (aka Oxo process) § oldest and one of the most significant processes based on homogeneous catalysis § valorization of simple alkenes to give aldehydes (and alcohols)

syngas O H (H2 + CO) O R and/or R H catalyst R linear (n) branched (iso) Catalyst systems § Rhône-Polenc (1980's, by Ruhrchemie & Rhône-Poulenc) o still rhodium but with water-soluble phosphine ligands Rh(acac)(CO)2 + TPPTS o typical conditions: P = 50 bar, T = 120 C – + SO3 Na o high selectivities for n-butyraldehyde (>92%) TPPTS = o simple catalysts recycling in biphasic systems (water as second layer) P o limited to propene and butene (due to low solubility of – + – + higher alkenes in water) SO3 Na SO3 Na