Olefin metathesis
Mechanism:
Such cycloaddition reactions between two alkenes to give cyclobutanes are
symmetry forbidden and occur only photochemically. However, the presence of dorbitals on the metal alkylidene fragment breaks this symmetry and the reaction is
quite facile.
Normally, the products are statistical, unless the reaction can be driven
in some way or the two alkenes have different reactivities.
Reference: Chem. & Eng. News 2002, Dec 23, 34-38
http://nobelprize.org/nobel_prizes/chemistry/laureates/2005/animation.html
Timeline
Reaction overview
Large-scale applications of OM

PHILIPS process (ARCO, Texas):

SHOP (Shell):


C8 and C16 internal olefins are metathesized in the course of a multi-step
process (ethylene oligomerization, isomerization, metathesis, hydroformylation)
leading to C11 – C15 primary alcohols (detergents).
Neo-hexene (musk scent for perfume industry) synthesis:
Mechanism: pair-wise vs. non pair-wise
Mechanism: sticky olefin

A system in which the metathesis products do not themselves
metathesize is needed such that the initial products are those
detected.

The results of this reverse double cross experiment showed a 1:2:1
mixture of d0, d2, and d4 isotopomers of the resulting ethylene.
Schrock catalysts: history
Reference: Schrock, R. R. J. Mol. Cat. A: Chem. 2004, 213, 21
Schrock catalysts
Stereogenic-at-Mo catalysts for Z-selective metathesis
R. Schrock, A. Hoveyda, et al. Nature 2011, 471, 461-466,
and Nature 2008, 456, 933-937
Grubbs catalysts
Reference: Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18
Mechanism with Grubbs catalysts
Ruthenium catalysts for Z-selective
olefin metathesis
Published in: Benjamin K. Keitz; Koji Endo; Paresma R. Patel; Myles B. Herbert; Robert H. Grubbs; J. Am. Chem. Soc. 2012, 134, 693699.
DOI: 10.1021/ja210225e
Copyright © 2011 American Chemical Society
ROMP: Observations

ROMP: strained cyclic olefins – driving force is the relief of ring strain.

It is difficult to ROMP tri- and tetrasubstituted olefins. Norbornene monomers
can be synthesized from the Diels-Alder reaction of cyclopentene.

Living polymerization: block copolymers
RCM: Observations

The ring to be formed cannot have appreciable strain.
Reaction is intramolecular most of the times (low dilution).

Asymmetric version: Schrock-Hoveyda catalyst

Comparison of catalysts
Schrock catalysts
Grubbs catalysts
Less functional group tolerant
More functional group tolerant, but
nitriles and amines are still a problem
More reactive, higher rates
Less reactive, slower rates
Asymmetric RCM works very well
Asymmetric RCM does not work as well
Perform ene-yne metathesis
Not known
Counterparts for alkyne metathesis
Not known (yet)
Alkyne metathesis
Although there are two types of metal carbynes, only Mo/W compounds were found to be
active for alkyne metathesis.
Alkyne metathesis is not applied commercially because acetylenes are made by other cheap
and easy methods and side reactions cannot be avoided during alkyne metathesis.
Reactions related to olefin metathesis
Polymerization of acetylenes
Metathesis of enynes: intermolecular mechanism
Fine Chemicals Manufacture
Homogeneous catalysis and fine
chemicals manufacture
Reaction
Catalyst
Product
Use
Cross-coupling
Hydroformylation
Pd
Rh
Diflunisal
Vitamin A
Pharmaceutical
Pharmaceutical
Hydrocaboxylation
Hydrogenation
Pd
Rh/DIPAMP
Ibuprofen
L-dopa
L-phenylalanine
Pharmaceutical
Food additive
Aroma chemical
Isomerization
Epoxidation
Rh/BINAP
Ti(OiPr)4/tBuOOH
di-iPr tartrate
L-menthol
Disparlure
Glycidol
Insect attractant
Intermediate
Pharmaceutical
Cyclopropanation
Cu/chiral Schiff
base
cilastatin
Diflunisal: cross-coupling
Giordano et al. Eur. Pat. Appl. 1992, 494419
Vitamin A: hydroformylation

High regioselectivity in the production of the branched aldehyde in
the hydroformylation step is key to the formation of the C5 building
block in the synthesis of vitamin A.
Ibuprofen and naproxen: asymmetric
hydrogenation
L-dopa
Hydrogenation – L-dopa
L-menthol: asymmetric isomerization
(+)-Disparlure: asymmetric epoxidation
Cilastatin:
cyclopropanation
cilastatin
renal enzyme inhibitor
Cu and Ru-enantioselective cyclopropanation
Outstanding levels of enantioselectivity have been achieved with Cu/C2 symmetric ligands and Rh2L*4.
Cu catalyst is Cu(I). Other Cu reagents generate Cu(I) in situ.
Ru catalysts give lower ee and yields than Cu or Rh, but they may offer some advantages.
Mechanistic considerations for Cu/Ru
Metallacyclobutane intermediate is more likely for Ru (same as olefin metathesis intermediate).
Reference: Kirmse, W. Angew. Chem. Int. Ed. 2003, 42, 1088