HYDROGENATION. Concerned with two forms of hydrogenation: heterogeneous (catalyst insoluble) and homogeneous (catalyst soluble)

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1 YDGEATI Concerned with two forms of hydrogenation: heterogeneous (catalyst insoluble) and homogeneous (catalyst soluble) eterogeneous Catalysis Catalyst insoluble in reaction medium eactions take place on catalyst surface ate of reaction and selectivity dependant on active sites on surface Active sites are the part of the catalyst substrate and hydrogen can adsorb on By blocking or poisoning active sites the reactivity of a catalyst is reduced and the selectivity increased Good poisons are metal cations, halides, sulfides, amines and phosphines eaction is a surface phenomenon and not fully understood catalyst surface 2 disassociation / activation * * predominantly syn hydrogenation adsorption of 2 alkene activation alkene adsorption * * * * * * * * Differences in catalyst arise due to ability of each metal to bind to various substrates and the different modes of binding rder of eactivity of Various Metals t = C= >> C=C > {} > Ar d = C=C > {} > C= > Ar u = C= > C=C > Ar > {} {} = hydrogenolysis C X C rder of Alkene eactivity > > > > ote: many other factors involved (eg. the release of ring-strain) Co-ordination of alkene on catalyst can lead to double bond isomerisation ossibility of migration related to the degree of reversibility of co-ordination d allows migration presumably via reversible co-ordination t essentially binds irreversibly resulting in no isomerisation Gareth owlands (g.rowlands@sussex.ac.uk) Ar402, eduction and xidation

2 tereoselectivity Mechanism (vide supra) indicates the addition is predominanly syn As substrate and hydrogen are both bound to surface addition occurs from the least hindered face as more readily binds to surface) roblem: isomerisation can lead to anti addition roblem: predicting which face will bind to surface not as simple as above statement suggests aptophilicity is the ability of a functional group to anchor to the surface and direct which face of alkene co-ordinates functional group functional group attracted to surface normally hydrogen adds from least hindered side Alkynes hydrogen adds from opposite face indlar catalyst (d / CaC 3 / b) optimum catalyst to prevent over-reduction and cis / trans isomerisation syn addition 2, indlar, Bu, rt 95 % eteroatom ydrogenations Carbonyl Moiety Can be hydrogenated tereoselectivity hard to predict so prefer hydride reagents latinum reagents preferred as C= faster than C=C (vide supra) especially when poisoned C 2 Et 2, t 2, Ac, 2 C 2 Et rder of carbonyl reduction () > > > > > 2 Gareth owlands (g.rowlands@sussex.ac.uk) Ar402, eduction and xidation

3 itriles Bn Boc Bn Bn Bn C 2, d() 2 / C, Me Boc 2 itro Group 1. 2, d / C 2 ( ) 3 C 4 11 ( ) 3 C (C 2 ) 2 Azides C 4 11 ( ) 3 3 h 2 h 2. 5 % d / C Me 2 C Me 2 C Gareth owlands (g.rowlands@sussex.ac.uk) Ar402, eduction and xidation

4 omogeneous Catalyst oluble in reaction medium Mechanisms much better understood Advantages: mild conditions (non-polar solvents which dissolve 2 better) Advantages: less catalyst required (each molecule is available for reaction and not just surface) Advantages: improved or complimentary selectivity (far more predictable) Advantages: directed hydrogenations Advantages: asymmetric hydrogenations Alkene ydrogenation 2 main types of homogeneous catalysts: dihydride and monohydride catalysts Dihydride Catalysts + 2 Examples: Wilkinson's Catalyst h(h 3 ) 3 (hydrogen adds prior to substrate) Crabtree's Catalyst [Ir(CD)(Cy 3 )(pyr)] + F 6 (substrate adds before 2 ) oxidative cis addition M n reductive elimination General Mechanism reductive elimination M n 2 Wilkinson's catalyst Crabtree's catalyst 2 Gareth owlands (g.rowlands@sussex.ac.uk) Ar402, eduction and xidation

5 Monohydride Catalysts Examples: u()(h 3 ) 3 Cp 2 1,2-insertion cis-addition reductive elimination metal centre oxidised n M 2 oxidative addition Wilkinson's Catalysis = solvent or vacant site h Very well studied catalytic species reductive elimination very fast; no isomerisation h+3 h h h+1 2 oxidative addition insertion D Gareth owlands (g.rowlands@sussex.ac.uk) Ar402, eduction and xidation h h h+3

6 electivity Ar 1 > = > > > > ( ) n = 1, ike heterogeneous catalysts there is a strong steric selectivity for the least hindered alkenes (C 2 ) 3 C 2 C 5 11 h(h 3 ) 3, 2 (C 2 ) 3 C 2 C 5 11 tereoselectivity As indicated in the mechanism reductive elimination is fast so no isomerisation can occur and syn addition results h Me h(h 3 ) 3, D 2 D h D Me ike heterogeneous catalysts, hydrogenation occurs from the least hindered face less substituted alkene addition from least hindered side h(h 3 ) 3, 2 ir ir Tr Me h(h 3 ) 3, 2 Tr Me Functional Group Compatibilty Compatible with most functional groups Aldehydes often undergo decarbonylation Cbz h(h 3 ) 3 95 % Cbz Gareth owlands (g.rowlands@sussex.ac.uk) Ar402, eduction and xidation

7 Directed ydrogenation A hydroxyl group in the substrate can displace a ligand from the catalyst resulting in directed hydrogenation This can reverse normal selectivity 2 same face Cy 3 Ir 24 : 1 Crabtree's catalyst Crabtree's catalyst much more reactive than Wilkinson's; so good for hindered alkenes Crabtree's catalyst gives superior directing effect for cyclic substrates For acyclic substrates use Wilkinson's catalyst If alkene isomerisation a problem use Wilkinson's catalyst at elevated pressure M vs disfavoured due to steric interactions M anti M vs M syn ote: only get stereocontrol if isomerisation is surpressed AYMMETIC YDGEATI Many asymmetric variants have now been developed Diphosphine ligands are very common h C 2 Me CMe h Ar Me h h > 95 % e.e. h C2 Me CMe Gareth owlands (g.rowlands@sussex.ac.uk) Ar402, eduction and xidation

8 Mechanism most stable complex C 2 Me h 2 slow D k major h major C 2 Me C 2 Me fast h h Ar CMe + Ar h h k minor : k major 573 : 1 fast minor complex reacts much faster Me 2 C Me 2 C h minor h 2 slow D k minor h h h h h C 2 Me Me 2 C h h h the major product comes from the minor complex C 2 Me CMe Me 2 C MeC h minor h major ote: ubstrate and metal must be complexed to get good e.e. Gareth owlands (g.rowlands@sussex.ac.uk) Ar402, eduction and xidation

9 on-co-ordinated Asymmetric Catalysts Catalysts that do not require co-ordination to the substrate to give good e.e.s still uncommon They offer the advantage of greater structural variety ne example is: Me h Me 3 mol% cat., 2 50 bar 99 % 98 % e.e. h BAF h h Ir tbu BAF = tetrakis{3,5-trifluoromethyl}phenyl borate Monohydride Catalyst rovides a second example X X 1. Bui 2. hi 3 2 ( psi) X 2 = 1,1'-binaphth-2,2'-diolate Mechanism group in space % % e.e. vs group clashes with ligand concerted 4-centre cleavage of Gareth owlands (g.rowlands@sussex.ac.uk) Ar402, eduction and xidation

10 Transfer ydrogenation + h h Ts u free crucial + Mechanism is given in the xidation ection of this course roblem: the reaction is reversible (hence the oxidation) If formic acid / triethyl amine is used as the reductant reaction irreversible + cat. Et 3 + C ydrogenolysis 2 X gives off C 2 hence irreversible Used to remove various functional groups I Me 2, i[] Me h I r protecting groups 2, d / C Ease of reduction of functional groups towards catalytic hydrogenation note how far down benzyl group is C C 2 2 C C' C=C' C C 2 C=C' C 2 C 2 ' C' C' ArC 2 ArC 3 + C C 2 2 Easiest C 2 ' C 2 + ' ardest ote: different catalysts have different propensities for functional groups so this is only a rough order Gareth owlands (g.rowlands@sussex.ac.uk) Ar402, eduction and xidation