Corey House Reaction

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Corey House Synthesis

The reaction of an alkyl halide with a lithium dialkyl cuprate to form a new alkane, an organocopper compound and a lithium halide is Corey house synthesis. It is useful to synthesize alkane with an odd number of carbons that are not possible with the Wurtz reaction in which a mixture of alkanes is formed. If we are considering tertiary alkyl halide for a reaction then due to the steric hindrance of three alkyl groups sn2 reaction, substitution does not take place instead there exists a greater possibility of elimination reaction, leading to elimination product. R part of R2CuLi acts as a strong conjugate base and this leads to elimination.

Corey House Synthesis Mechanism

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Organic reactions are chemical reactions involving chemical compounds. Basically in this Corey synthesis, this reaction occurs in three steps:-

  • The lithium metal is treated with an alkyl halide and solvated in dry ether, which converts the alkyl halide into an alkyl lithium compound, R-Li. The starting (R-X)compound  can be primary, secondary, or tertiary alkyl halide:

R-X + 2Li → R-Li + Li-X

  • The second step requires cuprous (CuI) treated with an alkyl lithium compound. This creates a lithium dialkyl cuprate compound. These compounds were first synthesized by Henry Gilman of Iowa State University, and are usually called Gilman reagents in honour of his contributions:

2RLi + CuI → R2CuLi + LiI

  • The second alkyl halide is then treated with the lithium dialkyl cuprate, which couples to the compound:

R'-X + R2CuLi → R-R' + RCu + LiX

  • Cross-products are formed If the second alkyl halide is not the same as the first.

  • For this reaction to work successfully it is important to note that the second alkyl halide must be a methyl halide, benzyl halide, primary alkyl halide, or a secondary cycloalkyl halide. For synthesizing organic compounds the relative simplicity of this reaction makes it a useful technique.

  • As R and R' are different then it is important to note that only the cross product obtained is R–R'. but both the products i.e R–R or R'–R' are not formed in significant quantities. An example of a cross-coupling reaction is Corey house reaction. The Corey–House synthesis is one of the earliest transition metal-mediated (or catalyzed) cross-coupling reactions to be discovered.

Importance of Corey House Synthesis

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Corey House is a powerful and practical tool for the synthesis of complex organic molecules. This reaction usually takes place at room temperature. 

  • One of the features of Corey house synthesis is that the operation is a very simple, easily accessible reaction. It can be used for preparing straight-chain, branched-chain, symmetrical, or unsymmetrical alkanes. For a better product, the alkyl halide used should be primary.

  • In the case of tosylates and alkyl bromides when a configurationally pure alkyl electrophile is used inversion of configuration is observed. To give a copper(III) species the reaction is believed to process via sn-2 like mechanism which undergoes reductive elimination to give the coupling product.

  • When alkyl iodides are used and cyclization products are observed, the scrambling of configuration is also observed to form for alkyl iodides with an olefin tether, both of which are indicative of the involvement of radicals.

  • For this reaction to work successfully the alkyl (pseudo)halide coupling partner must be methyl, benzylic, allylic, 1° alkyl, or 2° cycloalkyl. In most cases, acyclic 2° electrophiles and 3° give unsatisfactory results. (However, see below for recent modifications that allow 2° electrophiles to be used successfully).

  • On the other hand, sterically hindered organocopper reagents, including 3° and other branched alkyl reagents, are generally tolerated, However, aryl bromides, iodides, and sulfonates, which do not ordinarily undergo nucleophilic substitution in the absence of a transition metal, can be used successfully as coupling partners. 

FAQ (Frequently Asked Questions)

1. What are the advantages of Corey house reaction over Wurtz reaction?

Ans. The advantages of Corey house reaction over Wurtz reaction are listed below.

  • The formation of alkyl lithium is the first step in Corey house synthesis. We can prepare only even carbon numbers of alkane in Wurtz reaction but in Corey house synthesis we can prepare oddly and even and carbon number alkane. 

  • A mixture of alkanes will be a product that is difficult to separate. For unsymmetrical alkane use Corey house synthesis.

  • In the reaction of 2 different alkyl halides, we can implement the Wurtz reaction but due to 3 different possibilities, there will be 3 different products formed.  

2. By using Corey house reaction how can n-butane be prepared?

Ans. N butane is an alkane. It is a gas at room temperature, easily liquified gas, highly inflammable, colourless gas. By reacting alkyl halide with lithium and ether we can synthesize n-butane. Then this product is further reacted with lithium dialkyl copper and then treated with an alkyl halide. After all this reaction the final product will be alkane and this reaction is Corey's house reaction. The lithium di organyl cuprate reacts with organyl halide to form a new alkane. So, that’s how n-butane can be prepared by using Corey house reaction.