Metathesis Reactions

3 Basic Types

1. Ring opening metathesis polymerization

2. Ring Opening/Closing metathesis

3. Cross metathesis

Catalysts

1. Hoyveda-Grubbs (Ru-based). Octahedral, w/ phosphine/NHC ligands 

2. Schrock (Mo based). Tetrahedral, w/ alkoxide/imido ligands, more reactive (less FG tolerance), more unstable than Ru Hoyveda-Grubbs catalysts 

Cross metathesis

Metathesis of two alkenes. Proceeds via consecuitive [2+2] additions and retro [2+2] additions. Shortcomings: Product distribution is hard to control (scrambling possible of cross-pdts, homodimers). Can mitigate w/excess of one olefin. Statistical distribution (=R1 + =R2):

25% homodimer R1=R1

50% R1=R2

25% R2=R2.

Homodimerization reduces with excess of R1:

=R1:=R2 (10:1)  

4 Olefin types 

Type 1: Rapid homodimerization, very reactive (terminal olefins)

Type 2: Slow homodimerization, homodimers react slowly with catalyst, moderately reactive (unhindered conjugated olefins, enones, allylic alcohols, epoxides)

Type 3: No homodimerization, somewhat reactive (1,1 disubstituted terminal olefins, 1,2,3-trisub olefins, hindered allyl groups, allyl phosphonates)

Type 4: Inert to metathesis, unreactive (but do not deactivate catalyst) (tetrasubstituted olefins, Nitro olefins, allyl ether 1,2 disubstituted allyl ethers)

Cross metathesis between Types of Olefins 

Type 4 will not react with any other type

Remember:

Most reactive to Least Reactive 

Type 1 > Type 2 > Type 3 > Type 4 

Type 1 + Type 2, Type 3 = most efficient cross product.

Ring-Closing metathesis

Most often terminal alkenes, ring size varies

Allylation is a good strategy for making these precursors 

Good for macrocyclization, bad for strained rings

Asymmetric Ring closing metathesis

Can run Asymmetrically with Schrock chiral catalysts

Only one terminal olefin reacts

Z-selective Ring closing metathesis (macrocycles)

For Z-selective metathesis, run at reduced pressure to induce volatile olefins to prevent scrambling 

Large alkoxy ligands are best for Z-selectivity, as R groups of metallocyclobutane intermediate point away from bulky ligand

Relay Ring closing metathesis

Let’s say you can’t cyclize a particular substrate due to sterics. You can increase the allyl chain by a particular number of carbons selective with an unhindered terminal alkene. Then, ring-closing metathesis occurs, spitting out a cyclic molecule of a particular size (i.e cyclopentene). Then, the real RCM occurs because the desired intermediate is already formed! Pretty clever. 

Ring Opening Metathesis (Polymerization)

Usually need strained alkenes.

Without a second olefin partner, polymerization occurs

Tandem Ring Opening-Ring closing metathesis

Enyne metathesis

Metathesis of an alkyne and alkene.

Olefin reacts first to form metallocyclobutane intermediate 

Conj. Diene formed 

Alkyne metathesis

Orthogonal to alkene metathesis! Totally chemoselective

Reaction of two alkynes to produce scrambled alkyne product

Same mechanism as OM

Tungsten, Molybdenum catalysts

Cross metathesis mechanism