The Rainier Metathesis Reaction

The Rainier Metathesis Reaction

Original paper from Takai and Utimoto et al.: J. Org. Chem. 1994,59, 2668-2670

[1] DOI:

[2] DOI:

[3] DOI:

Bryostatin 1:

It’s still January and time for another review… This time I will present to you a short summary of a reaction which catched my eye in the Bryostatin 1 synthesis recently published from Keck et al.. One of their key steps is a Rainier Metathesis reaction:

Scheme 1

Originally published by Takai, Utimoto et al. the group around Rainier optimized the reaction conditions and expanded the scope of this reaction from an olefination to an olefination/metathesis process.

In 1978, Takai and Utimoto published an approach to olefins from carbonyl compounds by employing a reagent mix of CH2Br2 – Zn – TiCl4. After several groups were unable to replicate the results it was found that the zinc powder Takai and Utimoto employed was contaminated with lead. In 1994 another paper was published in which they described optimized conditions and expanded the scope of the reaction to esters.

Scheme 2

Lead, or lead salts, proved to be essential to accelerate the reaction rate. A mechanism was also published in this paper in which the role of lead halides becomes clear:

Scheme 3

First the geminal halide 1 reacts with activated zinc powder to form 2. Without lead the second metal-halogen displacement is extremely slow so it was proposed that before the second metal-halogen displacement takes place a transmetallation between 2 and PbCl2 forms the organo-lead-species 3. This is reactive enough to produce a geminal bisorganometallic species 4 which in turn reacts with in situ formed zinc halide to give 5.

Then TiCl4 is added which displaced one or two of the zinc atoms to form a metallocyclobutane ring 6 or a Schrock carbene 7. Whatever product is formed it reacts with a carbonyl compound like the Tebbe or Petasis reagent to form an olefin.

This was all known for some time before Nicolaou discovered that the Tebbe reagent can be used in a tandem olefination/metathesis reaction.

In 2007 Rainier published a paper in which he showed that by employing Takai-Utimoto’s protocol on olefins it was possible to get metathesis products. The reaction was used to build cyclic ether of various ring sizes from ester and ethers [1], [2]. Also (bis)lactams can be accessed from amides or lactams [3]:

Scheme 4

If you are interested in more stuff check the related paper on the JACS page. Maybe one of you careful readers tried this reaction? I would be interested in some front news…

Btw: I will review the full story of Bryostatin 1 but I am currently a bit busy with my exams so be patient… J

4 Responses

  1. Looking forward to bryo 1 story.

  2. hai, i have a question on the metathesis

    what ever that comes in the place of the c=o to c=c is from the dibromoethane and Ti complex, via formation of shrock carbene. is it after that there is metathesis between the double bonds that make it a glycan (in synthesis of bryostatin). if it is correct . what is the metal that mediates the metathesis process.

    Also in scheme 3, for the transformation of 7 and 8 to 9 are we missing any carbon on the olefin ( RCH2 instead of R), please correct me if I am wrong.

  3. Hey, thx for the question.
    If i understand you properly the answer should be that you first form the exo methylene (or in this case ethenylene) group from the ester which in turn is coupled with the other terminal olefin to give the DHP-ring. both processes are catalysed by the Ti=C-carbene which, as demonstrated with this reaction, can mediate olefinations and metathesis reactions.

    does this answer your first question?

    to the second one: yes you’re right… i fixed the scheme 😉

  4. thanks, very useful to get quick overview on Rainier Metathesis.

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