Shapiro Reaction
TLDRThis video explores the Shapiro reaction, a powerful modification of the Bamford-Stevens reaction, both dealing with the chemistry of sulfonyl hydrazones. The Shapiro reaction, invented by Robert H. Shapiro in 1967, involves the use of a strong base to form a dianion, leading to the formation of a vinyl lithium intermediate that can react with various electrophiles. The reaction's versatility is highlighted through its application in the total synthesis of Taxol, an important anticancer drug, showcasing its significance in complex organic syntheses.
Takeaways
- 🧪 The Shapiro reaction, invented by Robert H. Shapiro in 1967, is a powerful modification of the Bamford-Stevens reaction.
- 📚 Both reactions involve the fragmentation chemistry of sulfonyl hydrazones, which are derived from ketones.
- 🔍 The Bamford-Stevens reaction, developed in 1952, is often confused with the Shapiro reaction due to their close relation.
- ⚗️ The formation of sulfonyl hydrazones involves condensation of ketones with sulfonyl hydrazine and removal of water.
- 🔄 Tosyl hydrazones are typically crystalline and can be deprotonated by alkoxide bases due to their acidity.
- 🌡 The anionic salts of tosyl hydrazones are thermally unstable and decompose to form alkenes, nitrogen, and sulfinate salts.
- 🛤️ The mechanism of the Bamford-Stevens reaction involves two pathways, leading to the formation of alkenes with possible isomerism.
- 🧩 In the Shapiro reaction, two equivalents of a strong base are used to form a dianion, which undergoes fragmentation differently.
- 🏷️ The Shapiro reaction is selective, often forming the more acidic position of the tosyl hydrazone as the enolate.
- 💊 The reaction has applications in complex syntheses, including the total synthesis of the anticancer drug Taxol.
- 🔬 The trisyl hydrazone is preferred over the tosyl hydrazone for better yields in modern applications.
Q & A
Who invented the reaction discussed in the script and in what year?
-The reaction discussed in the script was invented by American chemist Robert H. Shapiro in 1967.
What is the relationship between the Shapiro reaction and the Bamford-Stevens reaction?
-The Shapiro reaction is a powerful modification of the classical Bamford-Stevens reaction, which was developed earlier in 1952. Both reactions are closely related and often confused for one another due to their similar subject matter involving the fragmentation chemistry of sulfonyl hydrazones.
What are the key components in the formation of sulfonyl hydrazones from ketones?
-The formation of sulfonyl hydrazones from ketones involves the condensation of the carbonyl compound with a sulfonyl hydrazine, typically p-tolyl hydrazine, with the removal of water, usually by azeotropic distillation.
Why are tosyl hydrazones usually solid and crystalline compounds?
-Tosyl hydrazones are usually solid and crystalline compounds due to their structure and properties, which makes their purification convenient.
What is the pKa range of sulfonamides and how does this relate to the acidity of tosyl hydrazones?
-The pKa of sulfonamides is in the range of 12-17, indicating their acidity. Tosyl hydrazones, being related to sulfonamides, are also acidic and can be deprotonated by alkoxide bases.
What products are formed when the anionic salts of tosyl hydrazones decompose thermally?
-When the anionic salts of tosyl hydrazones decompose thermally, they form alkenes, nitrogen gas, and sulfinate salts.
What are the two possible pathways for the Bamford-Stevens reaction mechanism?
-The Bamford-Stevens reaction mechanism can take two pathways: one where the tosyl hydrazone salt loses a leaving group to form a diazoalkane that decomposes to a carbene, and another in protic solvents where the diazo compound forms a diazonium salt that decomposes to a carbenium ion.
What is the difference in the base usage between the Bamford-Stevens reaction and the Shapiro reaction?
-In the Bamford-Stevens reaction, one equivalent of base is used, whereas in the Shapiro reaction, two equivalents of a very strong base, like butyllithium, are used to form a dianion.
What type of intermediate is formed in the Shapiro reaction after the addition of two equivalents of a strong base?
-In the Shapiro reaction, after the addition of two equivalents of a strong base, a dianion is formed, which then undergoes fragmentation to form a vinyl lithium species.
How is the selectivity achieved in the Shapiro reaction?
-The selectivity in the Shapiro reaction is achieved through the formation of an enolate before the fragmentation of the tosyl hydrazone, where the more acidic position is usually selected.
What is the significance of the Shapiro reaction in the total synthesis of Taxol?
-The Shapiro reaction is a key step in the total synthesis of Taxol, an important anticancer drug, as it allows for the formation of the desired ring structure with good yield and selectivity.
What is the preferred hydrazone used in modern applications of the Shapiro reaction?
-The trisyl hydrazone, which means 1,3,5-trisopropylphenyl hydrazone, is generally preferred over the tosyl hydrazone in modern applications of the Shapiro reaction due to slightly better yields.
Outlines
🧪 Shapiro and Bamford-Stevens Reactions Overview
This paragraph introduces the Shapiro reaction, a powerful modification of the Bamford-Stevens reaction, both involving the chemistry of sulfonyl hydrazones. The Shapiro reaction was developed by Robert H. Shapiro in 1967 and is closely related to the Bamford-Stevens reaction, which was developed earlier in 1952. The paragraph explains the process of creating sulfonyl hydrazones from ketones and their acidic nature, leading to their deprotonation by alkoxide bases. It details the thermal instability of the anionic salts of tosyl hydrazones, which decompose to form alkenes, nitrogen, and sulfinate salts. The mechanism of the reaction is discussed, highlighting two possible pathways involving the formation of diazoalkanes, carbenes, and the subsequent formation of alkenes. The paragraph also differentiates the Shapiro reaction by its use of two equivalents of a strong base to form a dianion, leading to a vinyl lithium species that can be quenched with various electrophiles, showcasing the reaction's versatility in complex syntheses.
💊 Taxol Synthesis Featuring the Shapiro Reaction
The second paragraph focuses on the application of the Shapiro reaction in the synthesis of Taxol, an important anticancer drug originally derived from the yew tree. It describes the use of trisyl hydrazone in modern Taxol synthesis, which yields better results than the traditional tosyl hydrazone. The paragraph explains how the vinyl lithium intermediate, formed through the Shapiro reaction, is quenched by a complex aldehyde at low temperatures, leading to a high-yield condensation product. The reaction's selectivity in forming the new stereogenic center, matching the desired stereochemistry, is highlighted. The paragraph concludes by emphasizing the significance of the Shapiro reaction as a key step in the synthesis of complex molecules like Taxol, as demonstrated by Professor Nicolaou's work at the Scripps Research Institute.
Mindmap
Keywords
💡Robert H. Shapiro
💡Bamford-Stevens Reaction
💡Sulfonyl Hydrazones
💡Wolff-Kishner Reaction
💡Azeotropic Distillation
💡Alkoxide Bases
💡Diazoalkanes
💡Carbenes
💡Shapiro Reaction
💡Vinyl Iodide
💡Allylic Alcohol
💡Taxol
💡Trisyl Hydrazone
Highlights
The Shapiro reaction, invented by Robert H. Shapiro in 1967, is a powerful modification of the classical Bamford-Stevens reaction.
Both the Shapiro and Bamford-Stevens reactions involve the fragmentation chemistry of sulfonyl hydrazones.
Tosyl hydrazones can be easily prepared from ketones by condensation with p-tolyl hydrazine and removal of water.
Tosyl hydrazones are acidic and can be deprotonated by alkoxide bases.
The anionic salts of tosyl hydrazones are thermally unstable and decompose to form alkenes, nitrogen gas, and sulfinate salts.
The alkenes formed in the Bamford-Stevens reaction are a mixture of E and Z isomers with two possible regiochemistries.
The reaction mechanism involves two possible pathways, with diazoalkanes losing nitrogen to form carbenes, which then undergo 1,2-hydride shifts.
The Shapiro reaction uses two equivalents of a strong base like butyllithium to form a dianion, which undergoes fragmentation to form a vinyl lithium species.
The vinyl lithium intermediate in the Shapiro reaction can be quenched with various electrophiles, such as iodine, TMS chloride, aldehydes, or protons.
The Shapiro reaction is a key step in the total synthesis of Taxol, an important anticancer drug.
Taxol is synthesized using the trisyl hydrazone, which gives better yields and is generally preferred over the tosyl hydrazone.
The Shapiro reaction is highly selective in forming the new stereogenic center with the correct stereochemistry in Taxol synthesis.
The versatility of the Shapiro reaction has been demonstrated in complex syntheses, as exemplified by its use in Taxol synthesis.
The Bamford-Stevens reaction works in both protic and aprotic solvents via two different mechanisms.
The Shapiro reaction is a critical step in joining ring A and C in the synthesis of Taxol.
Tosyl hydrazones from aldehydes are not suitable for the Shapiro reaction due to butyllithium addition to the C=N double bond.
The Shapiro reaction has found numerous applications in complex organic syntheses beyond Taxol.
Transcripts
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