Peterson Olefination
TLDRThe video script delves into the synthesis of alkenes through the Peterson olefination, a method pioneered by Donald Peterson in 1968. It involves the metalation of alpha-halo silanes to form nucleophilic reagents that react with aldehydes or ketones to yield beta-hydroxy silanes, which upon treatment with acid or base, eliminate to form alkenes. The reaction's advantage lies in its stereoselectivity and the easy removal of the co-product, hexamethyl disiloxane, facilitating product purification. The script also discusses the stereochemistry of the reaction and its applications in natural product synthesis.
Takeaways
- 🔬 The script discusses the construction of alkenes through reactions that join carbon-based fragments to form a double bond.
- 🔑 The McMurry reaction is mentioned as the first of this type to be described for alkene synthesis.
- 🧪 The Peterson olefination is highlighted as another significant method for synthesizing alkenes, introduced by Donald Peterson in 1968.
- 🌟 The Peterson olefination involves two stages: metalation of an alpha-halo silane to form a nucleophilic reagent, and reaction with aldehydes or ketones to yield a beta-hydroxy silane.
- 💧 The intermediate beta-hydroxy silane can be treated with acid or base to cause elimination of a silanol and form the alkene.
- 🌀 A key advantage of the Peterson olefination is the co-product, trimethlysilanol, which spontaneously dimerizes and can be easily removed, simplifying purification.
- 🌐 The reaction is versatile, working with various substituted silanes and allowing for the synthesis of mono- and 1,2-disubstituted alkenes.
- 🧬 Isomerism is a consideration in the reaction, with the first step being irreversible and the elimination step being stereospecific, thus determining the product's stereochemistry.
- 🔍 The stereoselectivity of the addition can be influenced by the bulkiness of the R1 substituent and the choice of silyl group.
- 📉 The choice between acid and base for the elimination step leads to different stereochemical outcomes, with acid favoring an antiperiplanar conformation and base leading to an E olefin.
- ⚠️ Care must be taken with the primary product of the reaction, as it can fragment in situ, potentially affecting the desired stereochemistry of the final product.
- 🌿 The Peterson olefination is highlighted for its utility in natural product synthesis, exemplified by the synthesis of 3-hydroxybakuchiol.
Q & A
What is the main objective of the reactions discussed in the script?
-The main objective of the reactions discussed in the script is the construction of alkenes or olefins by joining two carbon-based fragments to form a double bond between them.
What is the McMurry reaction?
-The McMurry reaction is a method for synthesizing alkenes by joining two carbon-based fragments to form a double bond, though the script does not provide specific details about this reaction.
Who first described the Peterson olefination and when?
-The Peterson olefination was first described by American chemist Donald Peterson in 1968.
What are the two stages of the Peterson olefination reaction as mentioned in the script?
-The two stages of the Peterson olefination are: first, an alpha-halo silane is metalated, and second, the nucleophilic reagent reacts with aldehydes or ketones to yield a beta-hydroxy silane, which is then treated with acid or base to form the alkene.
What is the advantage of the Peterson olefination over other olefination methods?
-One main advantage of the Peterson olefination is that the co-product, trimethlysilanol, dimerizes spontaneously to form volatile hexamethyl disiloxane, which can be removed by evaporation, leaving no other substance in solution but the product.
How does the Peterson olefination handle isomerism issues?
-The Peterson olefination handles isomerism issues by having an irreversible first step and a stereospecific elimination step, which makes the stereochemistry of the nucleophilic addition stereochemistry-determining.
What factors influence the stereoselectivity of the addition reaction in the Peterson olefination?
-The stereoselectivity of the addition reaction in the Peterson olefination is influenced by the bulkiness of the R1 substituent and the type of silyl group, with TMS being less bulky than most alkyl groups.
How can one obtain the erythro product in the Peterson olefination?
-To obtain the erythro product, a bulkier silyl group, like triphenyl, can be used to increase torsional strain, making the erythro product more favorable.
What are the two choices for the elimination step in the Peterson olefination and what are their outcomes?
-The two choices for the elimination step are using acid or base. Acid leads to protonation of the alcohol, forming an alkene with antiperiplanar alignment, while base leads to the formation of a cyclic silanolate that fragments to yield an E olefin.
Why is it important to quench the alkoxide with acid below room temperature?
-Quenching the alkoxide with acid below room temperature is important to prevent the fragmentation that yields the E olefin, ensuring the desired Z olefin is obtained.
How has the Peterson olefination been applied in the synthesis of natural products?
-The Peterson olefination has been used in the synthesis of natural products, such as the synthesis of the terpene 3-hydroxybakuchiol by Professor David van Vranken at UC Irvine, demonstrating its utility in yielding high selectivity for the desired product.
Outlines
🧪 Peterson Olefination: Synthesis of Alkenes
The Peterson olefination is a method for synthesizing alkenes, first introduced by Donald Peterson in 1968. It involves the metalation of an alpha-halo silane to form a nucleophilic reagent, which then reacts with aldehydes or ketones to yield a beta-hydroxy silane. This intermediate, when treated with acid or base, undergoes elimination to form the desired alkene. The reaction's advantage lies in the co-product, trimethlysilanol, which spontaneously dimerizes to a volatile compound that can be easily removed, leaving the product pure. The method allows for stereocontrol and is applicable to various substituted silanes, including triphenyl and tert-butyl dimethyl, leading to 1,2-disubstituted alkenes with considerations for isomerism and stereoselectivity based on the bulkiness of substituents and the silyl group.
🔬 Applications and Considerations in Peterson Olefination
The Peterson olefination is widely used in the synthesis of natural and medicinal compounds, as demonstrated by Professor David van Vranken's synthesis of 3-hydroxybakuchiol. The reaction's stereochemistry is determined by the irreversible addition of the alpha-silyl carbanion to the carbonyl group and the stereospecific elimination step. The choice between acid and base for the elimination step leads to different stereochemical outcomes: acid leads to antiperiplanar desilylation for alkene formation, while base results in a syn-coplanar elimination yielding exclusively E olefins. However, functionalized silyl nucleophiles can lead to fragmentation issues, making it challenging to prevent the formation of unsaturated derivatives. The reaction's utility and the ease of co-product removal make it an essential tool for organic chemists, with the added benefit of facilitating product purification.
Mindmap
Keywords
💡Alkenes
💡McMurry Reaction
💡Peterson Olefination
💡Grignard Reagent
💡Lithiating Agent
💡Beta-Hydroxy Silane
💡Trimethlysilanol
💡1,2-Disubstituted Alkene
💡Stereoselectivity
💡Erythro and Threo Products
💡E2 Elimination
💡Syn-Coplanar Elimination
💡Functionalized Nucleophile
💡Natural Product Synthesis
Highlights
Exploring reactions for constructing alkenes by joining carbon-based fragments to form double bonds.
Introduction of the McMurry reaction for alkene synthesis.
The Peterson olefination, a key method for synthesizing alkenes, was first described by Donald Peterson in 1968.
The Peterson olefination involves two stages: metalation of alpha-halo silane and nucleophilic addition to aldehydes or ketones.
Beta-hydroxy silane intermediates are formed and can be isolated.
Acid or base treatment of intermediates leads to elimination of silanol and formation of alkenes.
Advantage of the Peterson olefination is the co-product trimethlysilanol spontaneously dimerizes, leaving no other substances in solution.
The reaction is compatible with various substituted silanes and can yield 1,2-disubstituted alkenes.
Stereochemistry of the nucleophilic addition is stereochemistry-determining due to the irreversible first step and stereospecific elimination.
Stereoselectivity can be influenced by the size of the R1 substituent and the choice of silyl group.
Transition state analysis and Newman projections illustrate the preference for threo product formation.
Use of a bulkier silyl group like triphenyl can favor erythro product formation.
Elimination can be carried out with acid or base, leading to different stereochemical outcomes.
Acidic elimination leads to antiperiplanar desilylation and formation of the alkene.
Basic elimination results in syn-coplanar fragmentation, yielding exclusively E olefins.
Quenching the primary alkoxide product with acid below room temperature can yield Z olefins.
Silyl-containing nucleophiles can be functionalized with nitrile, ester, or imine groups, leading to further elimination.
The Peterson olefination is frequently used in the synthesis of natural products and medicinal substances.
Example of synthesizing terpene 3-hydroxybakuchiol using the Peterson olefination with high selectivity for the threo product.
The Peterson olefination allows for stereocontrol in the olefin product and easy co-product removal, facilitating product purification.
The Peterson olefination is an essential tool for practicing organic chemists.
Transcripts
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