What Is the Barbier Reaction?
The Barbier reaction refers to the reaction of a halogenated hydrocarbon with a metal in the presence of an electrophilic reagent such as a carbonyl compound (aldehyde or ketone) to generate an organometallic reagent on site, which then reacts with the carbonyl compound (aldehyde or ketone) in the system to generate a secondary or tertiary alcohol. [1,2] Usually, the attacking reagent is a more active allylic halide, so the product obtained is a homoallylic alcohol.
In the Barbier reaction, the formation of the organometallic intermediate and the subsequent nucleophilic addition reaction are completed in one step in the same system. If the preparation of the organomagnesium reagent and its addition to the electrophilic reagent are completed in steps, it is usually called a Grignard reaction. This type of reaction requires oxygen-free and water-free operating conditions.
R1 and R2 can be hydrogen atoms, alkyl groups or aryl groups. R is usually a primary alkyl group, or a secondary alkyl group and an aromatic group. Tertiary alkyl groups are prone to elimination reactions when forming organometallic reagents. When R is an aromatic group or a large group, the reaction is slow, or even no reaction occurs. The size of R1 and R2 will also have a significant impact on the reaction. If both are aromatic groups, the reaction often fails to occur. When the carbonyl compound is an aldehyde, the reaction often proceeds well.
Fig 1. Overview of the Barbier reaction and its mechanism.
Intramolecular Barbier Reaction
The Barbier reaction can also be carried out intramolecularly. The metal involved in the reaction is a promoter rather than a catalyst, and usually requires more than stoichiometric amounts. There are a wide range of metals that can promote this type of reaction. Almost all main group metals and some transition metals (Zn, Cd, Mn, Cu, Fe, Co, Ni, Cr, Ti, Mo, etc.) and some lanthanide metals (Ce, La, Sm, Yb, etc.) can be used as promoters for the reaction. These metals are inserted into the C-X bond to form organometallic compounds to promote the reaction, so this type of reaction can also be promoted by many Lewis acids.
Fig 2. Barbier reaction occurring intramolecularly.
Application Examples of Barbier Reaction
The metal organic compounds in the Barbier reaction can also be replaced by certain elemental organic compounds, such as propyl silicide, allyl sulfide, allyl boride, etc., which can be used in the Barbier reaction. The reaction solvent is usually ether, tetrahydrofuran, N,N-dimethylformamide, alcohol and dichloromethane.
- Example 1: The figure below shows an example of the Barbier reaction promoted by metal indium. [3].
- Example 2: In addition to metals, samarium diiodide can also trigger the Barbier reaction as a single-electron reducing agent. [4]
- Example 3: With the development of environmentally friendly synthesis and green chemistry, the aqueous Barbier reaction has become one of the research hotspots of green synthesis methods. [5]
- Example 4: In recent years, the use of nano-metal promoters can not only increase the rate of the Barbier reaction, but also greatly increase the reaction yield and expand the reaction substrate aldehyde in the aqueous phase to ketone. [6] It also reduces the use of additives such as acids, bases, and phase transfer catalysts, making the Barbier reaction more environmentally friendly and more efficient and practical.
Fig 3. Research and development of Barbier reaction synthesis.
Related Products
References
- Barbier, P. Compt. Rend. 189, 128, 110.
- Yamamoto, Y., Asao, N., Chem. Rev. 1993, 93, 2207.
- Bennett, G.D., Paquelte, L. A., Org, Synth. 2002, 77, 107, 2004, Coll. Vol. 10, 541.
- Molander, G, A., Alonso-Alija , C. J., Org. Chem. 1998, 63, 4366.
- Keh, C.C.K., Wei, C.,Li , C.-J. J., Am. Chem. Soc. 2003, 125, 4062.
- Wang, Z-Y., Zha, Z-G., Zhou, C-L. Org. Lett., 2002, 4, 1683.
