McMurry Olefination

What Is McMurry Olefination?

Aldehydes and ketones undergo reductive dimerization under the action of low-valent titanium to form symmetrical alkenes. This is an accidental discovery. When trying to reduce the carbonyl group to methylene with LiAIH₄ modified by TiCI₃, the coupling product was unexpectedly obtained. Since the low-valent titanium reagent is insoluble in the reaction solvent, the reaction is a heterogeneous reaction. The low-valent titanium reagent is generally formed by the reduction of TiCI₃ with LiAIH₄ or alkali metal (Li, Na or K) or Mg or Zn (Cu). Zero-valent titanium may be an active catalytic species. The most widely used solvent in the McMurry reaction is tetrahydrofuran (THF), and dimethoxyethane (DME) is also an alternative. Activated zinc metal or zinc copper is a common reducing agent used in the McMurry reaction.

The coupling reaction of aldehydes and ketones can be carried out intermolecularly or intramolecularly, which is used for the synthesis of chain or cyclic olefins, respectively. From small ring olefins (three-membered rings) to macrocyclic olefins, including catenane and 72-membered macrocyclic tetraether aliphatic olefins can be formed.

Fig 1. McMurry coupling reaction and its mechanism. [1]

Mechanism of McMurry Olefination

In general, the McMurry coupling reaction is divided into two reaction steps. The first step is the reduction of the carbonyl substrate by single electron transfer of titanium to form a keto radical compound, which can dimerize to form an intermediate pinacol (metallic pinacol salt). By reducing the reaction temperature from reflux to 0°C, the intermediate pinacol can be isolated in high yield. The second step is to deoxygenate the metallic pinacol salt to form an olefin while maintaining the reflux temperature. [2]

Application Examples of McMurry Olefination

• Example 1-homo-McMurry coupling: The use of microwaves in organic synthesis is extended to the McMurry reaction, and the homologous McMurry reaction is completed within 10 minutes. [3]
• Example 2-cross-McMurry coupling: A two-step synthetic strategy for 2-arylbenzofurans involves a selective cross-McMurray coupling of salicylaldehyde or substituted salicylaldehydes with aromatic aldehydes and a sequential oxidative cyclization of the resulting o-vinylphenols. [4]
• Example 3-intramolecular McMurry coupling: The strategy for the simple and efficient synthesis of cyclopenta[l]phenanthrenes from substituted acetophenones is divided into three steps: first, the Mukaiyama aldol reaction is carried out in the presence of bis(trifluoromethane)sulfonyl imide as an acidic catalyst. Then, the resulting diketone is cyclized by an intramolecular McMurry coupling using Zn and TiCl₄ under Mukaiyama conditions. Finally, the photocyclization of diarylcyclopentenes in the presence of iodine and excess propylene oxide respectively produces the target phenanthrenes in high yield. [5]

Fig 2. Synthetic examples via McMurry coupling reaction.

Related Products

CAS No.	Structure	Product
10425-11-3		3-Aminopyrazole
1137-42-4		4-Hydroxybenzophenone
134-92-9		4-Hydroxy-4'-methylbenzophenone
611-99-4		4,4-Dihydroxybenzophenone
611-99-4		4,4'-Dihydroxybenzophenone
71372-37-7		(4-Hydroxyphenyl)(m-tolyl)methanone
7705-7-9		Titanium(III) chloride solution

References

1. Li, Jie Jack. Name Reactions: A Collection of Detailed Reaction Mechanisms, 2006, 323-325.
2. Bongso, Anthony, et al. RSC advances, 2022, 12(25), 15885-15909.
3. Stuhr-Hansen, Nicolai. Tetrahedron letters, 2005, 46(33), 5491-5494.
4. Duan, Xin-Fang, et al. The Journal of Organic Chemistry, 2007, 72(26), 10283-10286.
5. Connors, David M., et al. Organic Letters, 2016, 18(17), 4262-4265.