McMurry Reaction
TLDRThis tutorial delves into olefination reactions, pivotal in organic synthesis, focusing on the McMurry reaction, a reductive coupling process invented in 1974. It discusses the reaction's mechanism involving titanium reagents and its challenges, such as E/Z selectivity and product distribution. The script highlights the McMurry reaction's utility in intramolecular couplings, natural product synthesis, and the creation of strained olefins, showcasing its versatility and ongoing research to refine its mechanism and applications.
Takeaways
- 🧪 Olefination reactions are crucial in organic synthesis, involving the formation of double bonds between two carbon units.
- 🔍 Olefins, or alkenes, can be produced through various methods, including elimination and redox reactions, but the focus here is on skeletal construction steps.
- 🌟 The Wittig reaction is an example of an olefination reaction that results in a mixture of E and Z alkenes, highlighting the importance of stereoselectivity in such reactions.
- 📚 The McMurry reaction, discovered in 1974, is a reductive coupling of two carbonyl compounds to form an olefin, typically using a low-valent titanium species as a reagent.
- 🛠 The initial step in the McMurry reaction involves reducing titanium tetrachloride in an ether solvent like THF under anhydrous and oxygen-free conditions.
- 🔬 Various reducing agents have been used in the McMurry reaction, including lithium aluminum hydride and other metals, but the exact active species of titanium remains unclear.
- 🤔 The mechanism of the McMurry reaction is not fully understood, but it is believed to involve ketyl radicals and titanium pinacolates, leading to the formation of E and Z olefins.
- ⚠️ The McMurry reaction may be limited to homo-coupling, making it challenging to control product distribution in reactions involving different ketones.
- 🔄 The reaction's major challenge is controlling E/Z isomerism, a common issue in olefination reactions.
- 🌿 The McMurry reaction is particularly useful in intramolecular reactions, as demonstrated in the synthesis of Compactin, a natural cholesterol-lowering agent.
- 🔬 Beyond ketones and aldehydes, the McMurry reaction can also be applied to other carbonyl compounds like esters and amides for the synthesis of heterocycles.
- 💡 The McMurry reaction is uniquely suited for preparing highly strained olefins, which are difficult to synthesize by other methods.
Q & A
What are olefination reactions in organic synthesis?
-Olefination reactions in organic synthesis are processes used to form carbon-carbon double bonds, also known as alkenes, by joining two activated carbon units.
What is the Wittig reaction?
-The Wittig reaction is a type of olefination reaction that involves the formation of a double bond between two carbon units, resulting in a mixture of E and Z alkenes.
What is E or Z selectivity in the context of olefination reactions?
-E or Z selectivity refers to the control over the formation of either the E (trans) or Z (cis) isomer of an alkene during an olefination reaction.
Who invented the McMurry reaction and when?
-The McMurry reaction was invented in 1974 by American chemist John McMurry of Cornell University.
What is the key chemical transformation in the McMurry reaction?
-The key chemical transformation in the McMurry reaction is the reductive coupling of two carbonyl compounds (such as ketones or aldehydes) to yield an olefin.
Which reducing agents are commonly used in the McMurry reaction?
-Common reducing agents used in the McMurry reaction include lithium aluminum hydride, lithium, sodium, potassium, magnesium, zinc, and zinc-copper couple.
What are ketyl radicals and their role in the McMurry reaction?
-Ketyl radicals are intermediates in the McMurry reaction that dimerize to yield titanium pinacolates, which then eliminate to give E and Z olefins.
What challenges are associated with the McMurry reaction?
-Challenges include controlling E/Z isomerism and limiting the reaction to homo-coupling, as two different ketones would yield a mixture of four products.
How has the McMurry reaction been applied in complex natural product synthesis?
-The McMurry reaction has been used in complex natural product synthesis, such as the synthesis of Compactin, by creating bicyclic dienic structures with intramolecular reactions.
Can the McMurry reaction be used with carbonyl compounds other than ketones and aldehydes?
-Yes, the McMurry reaction can also be applied to other carbonyl compounds, such as esters and amides, to synthesize heterocycles like indoles and benzofurans.
Outlines
🔬 Olefination Reactions and the McMurry Reaction
The script introduces olefination reactions, crucial in organic synthesis, focusing on the McMurry reaction, a reductive coupling process invented by John McMurry in 1974. It involves the coupling of two carbonyl compounds to form an olefin, typically using a low-valent titanium reagent. The script discusses the challenges of E/Z selectivity and the reaction's limitations, such as homo-coupling and isomerism issues. It also highlights the McMurry reaction's utility in intramolecular reactions and its application in the synthesis of complex natural products like Compactin, with an emphasis on optimizing reaction conditions for yield and selectivity.
🌿 Versatility of the McMurry Reaction in Organic Synthesis
This paragraph delves into the versatility of the McMurry reaction, noting its application beyond ketones and aldehydes to include other carbonyl compounds like esters and amides, facilitating the synthesis of heterocycles. It underscores the reaction's unique suitability for creating highly strained olefins, which are challenging to synthesize by other methods. The paragraph provides examples of specific olefins prepared via the McMurry reaction and mentions the ongoing research to understand the complex mechanism of this reaction, as well as its synthetic extensions in organic chemistry.
Mindmap
Keywords
💡Olefination Reactions
💡Alkenes
💡Wittig Reaction
💡E/Z Selectivity
💡McMurry Reaction
💡Reductive Coupling
💡Titanium Species
💡Intramolecular Reactions
💡Compactin
💡Heterocycles
💡Strained Olefins
Highlights
Olefination reactions are widely utilized in organic synthesis, with olefins also known as alkenes.
Olefins can be made through refunctionalizations like elimination or redox reactions, as well as skeletal construction steps.
The Wittig reaction is an example of an olefination reaction that produces a mixture of E and Z alkenes.
E/Z selectivity is a key theme in olefination reactions, determining how to achieve it and the controlling parameters.
The McMurry reaction, invented in 1974, is a reductive coupling of two carbonyl compounds to yield an olefin.
The McMurry reagent is typically a low-valent titanium species generated in situ by a reducing agent.
Lithium aluminum hydride was the initial reducing agent used by McMurry, but other metals have since been introduced.
The exact reduced species of titanium that is active in the McMurry reaction is not clear.
The proposed mechanism for the McMurry reaction involves ketyl radicals and titanium pinacolates.
The McMurry reaction may be limited to homo-coupling reactions, leading to challenges in controlling product distribution.
The problem of E/Z isomerism is a significant challenge in the McMurry reaction.
The McMurry reaction is primarily used in intramolecular reactions for complex natural product synthesis.
Intramolecular McMurry reactions benefit from more favorable entropy of activation, leading to the desired hetero-coupling product.
The synthesis of Compactin, a natural cholesterol-lowering agent, utilized an intramolecular McMurry reaction as a key step.
Potassium on graphite was found to be the ideal reducing agent for the McMurry reaction in the synthesis of Compactin.
The McMurry reaction is not limited to ketones and aldehydes; esters and amides can also undergo the reaction.
The reaction is useful for building hindered indoles and synthesizing benzofurans.
The McMurry reaction is uniquely suitable for the preparation of very strained olefins with four bulky substituents.
Despite challenges, the McMurry reaction has found extensive use in organic synthesis and continues to be studied for its complex mechanism.
Transcripts
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