Hydroformylation and oxidation of olefins Textbook H: Chapter 16.6, 17.1 – 17.3 Textbook A: Chapter 16.1 – 16.2, 18.1 – 18.2

Outline Hydroformylation  Thermodynamics  Mechanism  Phosphine-modified catalysts Wacker reaction Monsanto process Katsuki-Sharpless asymmetric epoxidation of allylic alcohols Jacobsen asymmetric epoxidation of olefins Sharpless asymmetric dihydroxylation of olefins

Hydroformylation: Thermodynamics Thermodynamics at standard conditions: At higher temperatures the entropy loss becomes more important:  G will be less negative. The TD favored product is the alkane. The obtained product is the aldehyde because of kinetic control.

Mechanism of the Co-catalyzed hydroformylation All steps are reversible, except product formation, which is often rate- determining. Preferential formation of the linear product is due to steric interactions. Trapping of the alkyl by CO determines the regioselectivity.  -hydride elimination is suppressed due to the high CO pressure. Hydrogenolysis is the rate-determining step for simple terminal olefins.

Other mechanistic details Experimental evidence has been reported for both mechanisms under certain conditions. Heterometallic bimolecular formation of aldehyde has been observed. Direct reaction with H 2 was slower than the manganese hydride reaction. Last step Higher alkenes

Phosphine-modified catalysts Alkylphosphines are strong electron donors and thus dissociation of CO is retarded, leading to more stable, but also slower catalysts. A very effective ligand for Co is a phobane derivative:  The reaction is 100 times slower;  The selectivity to linear products increases;  The catalyst is more stable;  The catalyst acquires activity for hydrogenation Order of activity (195 °C, 36 bar)  Ph 2 EtP > PhBu 2 P > Bu 3 P > Et 3 P > PhEt 2 P > Cy 3 P Linear : branched ratio:  Bu 3 P > Et 3 P = PhEt 2 P = Cy 3 P = PhBu 2 P > Ph 2 EtP For Rh, PPh 3 works very well. HRh(CO)L 3 complexes are 100 to 1000 times more active than Co complexes and they operate under milder conditions (15 – 25 atm and 80 °C – 120 °C).

Acetic acid and acetyl chemicals Principal application of acetyl chemicals: solvents and vinyl acetate monomer for polymerization. Early production routes (ca 1850s): fermentation or wood distillation (still used in the USA in the mid-1960s). First synthetic route: Hg 2+ catalyzed H 2 O addition to HC≡CH to form CH 3 CHO.

The Wacker reaction: oxidation with O 2

Vinyl acetate synthesis Overall yields: 90 – 95% based on both ethylene and acetic acid. Homogeneous process was abandoned due to corrosion associated with the presence of acetic acid. Heterogeneous process uses PdCl 2 / CuCl 2 / C or PdCl 2 / alumina.

Monsanto carbonylation of methanol The rate-determining step is the OA of MeI to Rh(I). Other metals are active; Ir: the CATIVA process; Ni, Pd. In the CATIVA process Me migration becomes rate-determining (addition of metal salts to abstract I - ).

Katsuki-Sharpless asymmetric epoxidation of allylic alcohols Substitution patterns: Reference: Pfenninger, A. Synthesis 1986, 2, 89 Other tartrates are readily available. Small groups (COOEt) in  -position at considerable distance from the reactive center can induce high ee (> 98%): dimeric structure. Allylic tertiary alcohols are not successfully epoxidized.

Mechanistic considerations Dimeric Ti complex before coordination of substrate The kinetics of the reaction are in accordance with replacement of two i-PrO anions by a t-butylperoxyanion and an allyloxy anion. This intermediate has a very low concentration and has not been observed directly. The Ti alkoxide systems have several unique properties: - Exchange of the monodentate alkoxide ligands is rapid in solution. -Ti(IV) has a somewhat flexible coordination sphere. -Ti(IV) alkoxides are weak Lewis acids: they activate to a certain extent a coordinated alkylperoxo ligand towards nucleophilic attack by the double bond of the allylic alcohol. -The coordinated distal peroxo-O is transferred to the olefin. -The proximal peroxo-O interacts strongly with Ti in the TS. -The olefin pi* orbital must be in position to overlap with one of the lone pairs of the peroxo-O that is being delivered. The attack is centered along the axis of the O-O sigma-bond being broken.