Carbenes Part 2: Cyclopropanation, C-H Insertion, and the Bamford-Stevens Reaction

Professor Dave Explains
13 Jan 202108:33
EducationalLearning
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TLDRThe script delves into the chemistry of carbenes, electron-deficient carbon species with two nonbonding electrons. It highlights cyclopropanation, where carbenes form three-membered rings with alkenes, and their role in insertion reactions, creating new bonds with existing sigma bonds. The distinction between singlet and triplet carbenes in terms of reactivity and stereochemistry is discussed, along with the Bamford-Stevens reaction, which converts ketones to alkenes using carbene chemistry. The summary underscores the versatility and importance of carbenes in synthetic organic chemistry.

Takeaways
  • 🧪 Carbenes are electron-deficient carbon species with two nonbonding electrons and a general formula of R2C.
  • 🔄 Carbenes can be prepared in situ from diazomethane, reacting with light as the slow step of the reaction.
  • 🔗 The cyclopropanation process involves carbenes reacting with alkenes or cycloalkenes to form three-membered rings with significant ring strain.
  • 🔑 Carbenes retain the stereochemistry of the original alkene during cyclopropanation, whether reacting with cis- or trans- alkenes.
  • 🌐 Halogenated carbenes can be used for cyclopropanation to introduce halogen functionality into the product.
  • 🌀 Singlet and triplet carbenes differ in their reactivity; singlet carbenes are more typical electrophiles, while triplet carbenes are diradicals.
  • 🔍 Singlet carbenes undergo stereospecific reactions, conserving the stereochemistry of the substrate, whereas triplet carbenes may lead to a mixture of isomers.
  • 📌 The presence of alpha hydrogens in carbene chemistry leads to the Bamford-Stevens reaction, converting ketones into alkenes.
  • 🔄 The Bamford-Stevens reaction involves the formation of a diazoalkane, which evolves nitrogen gas to form a carbene that inserts into a vicinal C-H bond.
  • 🔄 Carbenes can also perform insertion reactions into existing sigma bonds, often carbon-hydrogen bonds, to promote intramolecular cyclization.
  • 🔬 The stereochemistry of the product from reactions involving carbenes with alpha hydrogens, like in the Bamford-Stevens reaction, can be unpredictable, often yielding a mixture of E and Z alkenes.
Q & A

  • What are carbenes and what is their general formula?

    -Carbenes are electron-deficient carbon species containing two nonbonding electrons. The general formula for a carbene is R2C, where R can be alkyl, hydrogen, or other substituents.

  • Why are cyclopropanes difficult to synthesize?

    -Cyclopropanes are difficult to synthesize due to their high ring strain, which results from the 60-degree bond angles significantly deviating from the 109.5-degree angles preferred by sp3 hybridized carbons.

  • How do carbenes facilitate the synthesis of cyclopropanes?

    -Carbenes facilitate cyclopropane synthesis by reacting with alkenes or cycloalkenes, inserting themselves into the pi bond to generate the three-membered ring while retaining the stereochemistry of the alkene.

  • What is the slow step in the reaction of methylene carbene with cis-2-butene?

    -The slow step in the reaction of methylene carbene with cis-2-butene is the preparation of the carbene in situ from diazomethane in the presence of light, as carbenes are highly reactive once formed.

  • How do halogenated carbenes differ from methylene carbene in cyclopropanation?

    -Halogenated carbenes can be used instead of methylene carbene if there is a need for halogen functionality on the product. They can be generated through reactions like the one involving cyclohexene with chloroform in the presence of potassium hydroxide.

  • What is the difference between singlet and triplet carbenes in terms of their reactivity and reaction mechanisms?

    -Singlet carbenes have a lone pair and an empty p orbital, allowing them to act as nucleophiles or electrophiles, typically the latter, and they undergo concerted reactions in cyclopropanation. Triplet carbenes, being diradicals with two unpaired electrons, participate in stepwise radical additions, which is a slower process.

  • Why do singlet carbenes react in a stereospecific manner, while triplet carbenes may give a mixture of isomeric products?

    -Singlet carbenes react in a stereospecific manner because their reaction is concerted, conserving the stereochemistry of the alkene. In contrast, triplet carbenes undergo a slower stepwise process where the second bond formation is delayed until an electron flips its spin, allowing for the scrambling of stereochemistry and the formation of a mixture of cis and trans cyclopropanes.

  • What is the main difference between the reactions of carbenes with substrates that have alpha hydrogens and those that do not?

    -When carbenes have alpha hydrogens, they can undergo an insertion into the vicinal C-H bond, leading to the formation of alkenes through a 1,2-shift of a hydride. This is different from the reactions without alpha hydrogens, which typically involve direct insertion into a pi bond.

  • What is the Bamford-Stevens reaction and how does it utilize carbene chemistry?

    -The Bamford-Stevens reaction is a method for converting ketones into alkenes using carbene chemistry. It involves the formation of a diazo compound from the ketone, which then evolves nitrogen gas to produce a carbene. The carbene then inserts into a vicinal C-H bond, resulting in the formation of an alkene.

  • Why is the Bamford-Stevens reaction synthetically useful in certain cyclic substrates?

    -The Bamford-Stevens reaction is synthetically useful in certain cyclic substrates because the cyclic nature and the presence of alpha hydrogens on only one side of the carbonyl produce torsional constraints that favor the formation of exclusively Z-alkenes.

  • What is the significance of the stereochemistry retention in the reactions involving carbenes?

    -The retention of stereochemistry in reactions involving carbenes is significant because it allows chemists to predict and control the spatial arrangement of atoms in the products, which is crucial for the biological activity and reactivity of the synthesized compounds.

Outlines
00:00
🧪 Carbene Chemistry and Cyclopropane Synthesis

This paragraph delves into the chemistry of carbenes, electron-deficient carbon species with two nonbonding electrons. It explains the general formula for carbenes and their applications, particularly in cyclopropane synthesis, a process known as cyclopropanation. Carbenes, once formed, can react with alkenes to form cyclopropane, a three-membered ring with significant ring strain due to its 60-degree bond angles. The paragraph also discusses the preparation of carbenes from diazomethane using light and the retention of alkene stereochemistry during the reaction. It further explores the use of halogenated carbenes and the differences between singlet and triplet carbenes in their reactivity and stereochemistry, highlighting the concerted nature of singlet carbene reactions and the stepwise radical mechanism of triplet carbenes.

05:03
🔍 Carbene Insertion and the Bamford-Stevens Reaction

The second paragraph expands on the versatility of carbenes by discussing their ability to insert into sigma bonds, commonly C-H bonds, leading to intramolecular cyclization reactions. It provides examples of such reactions, including the formation of five-membered rings and the use of superbases to generate carbenes from carbanions. The paragraph then introduces the Bamford-Stevens reaction, a method for converting ketones into alkenes using carbene chemistry. It describes the process of treating a ketone with N-tosylhydrazine to form an N-tosylhydrazone, followed by deprotonation and elimination to generate a diazoalkane, which then evolves into a carbene. The presence of alpha hydrogens allows for a unique insertion reaction, leading to the formation of alkenes with varying stereochemistry. The paragraph concludes by noting the limited synthetic utility of the Bamford-Stevens reaction due to the lack of stereochemical control, but highlights its usefulness in specific cyclic substrates where Z-alkenes are exclusively formed.

Mindmap
Keywords
💡Carbenes
Carbenes are electron-deficient carbon species with two nonbonding electrons, typically represented by the formula R2C, where R can be alkyl or hydrogen. They are central to the video's theme as they are the main reactants in the reactions discussed, such as cyclopropanation and insertion reactions. For example, methylene carbene is mentioned as a specific type of carbene that can be generated from diazomethane in the presence of light.
💡Cyclopropane Synthesis
Cyclopropane synthesis, or cyclopropanation, is a key application of carbenes highlighted in the video. It involves the formation of a three-membered ring with significant ring strain due to the 60-degree bond angles, which are different from the preferred 109.5-degree angles of sp3 hybridized carbons. The process is exemplified by the reaction of methylene carbene with cis-2-butene, where the stereochemistry of the alkene is retained in the product.
💡Stereochemistry
Stereochemistry is the study of the spatial arrangement of atoms in molecules and is crucial in the context of the video as it pertains to the retention or change of spatial arrangement during chemical reactions. The script discusses how the stereochemistry of alkenes is retained during cyclopropanation with carbenes and how triplet carbenes can lead to a loss of stereochemistry due to the stepwise radical addition.
💡Insertion Reaction
An insertion reaction is a type of chemical reaction where a molecule inserts itself into an existing chemical bond, often a carbon-hydrogen bond in the context of the video. Carbenes are shown to be capable of such reactions, leading to the formation of new rings or altering the structure of the substrate. The script provides examples of intramolecular cyclization and C-H insertion with carbenes.
💡Bamford-Stevens Reaction
The Bamford-Stevens reaction is a method for converting ketones into alkenes using carbene chemistry, which is discussed in the video. It involves the formation of a diazo compound, which upon evolution of nitrogen gas, forms a carbene that can undergo a 1,2-hydride shift to form an alkene. The reaction is noted for its limited synthetic utility due to the lack of stereochemical control, except in specific cyclic substrates.
💡Diazomethane
Diazomethane is a compound that is used in the script as a precursor to generate carbenes in situ, particularly methylene carbene, under the influence of light. It is an example of a diazo compound that plays a significant role in the synthesis of cyclopropanes.
💡Halogenated Carbenes
Halogenated carbenes are a type of carbene that contains a halogen atom, such as chlorine, as part of its structure. The script mentions their use in cyclopropanation reactions where the halogen functionality may be desired in the final product, as in the reaction of cyclohexene with chloroform in the presence of potassium hydroxide.
💡Singlet and Triplet Carbenes
Singlet and triplet carbenes are different electronic states of carbenes that influence their reactivity and the type of reactions they undergo. Singlet carbenes, having a lone pair and an empty p orbital, typically engage in concerted reactions like cyclopropanation, preserving the stereochemistry of the reactants. In contrast, triplet carbenes, being diradicals, participate in stepwise radical additions, leading to a loss of stereochemistry. The script explains these differences in the context of their reactions with alkenes.
💡Concerted Reaction
A concerted reaction is a type of chemical reaction where all bond-making and bond-breaking steps occur simultaneously in a single transition state. The script uses this term to describe the cyclopropanation reaction with singlet carbenes, emphasizing that it is a one-step process that retains the stereochemistry of the alkene.
💡Diradicals
Diradicals are species with two unpaired electrons, and in the context of the video, they refer to triplet carbenes. The script explains that triplet carbenes, being diradicals, undergo a stepwise radical addition process in their reactions, which contrasts with the concerted reactions of singlet carbenes.
💡Phosphorescence
Phosphorescence is a process where an electron in an excited state returns to the ground state by emitting light, which is mentioned in the script as one of the mechanisms by which an electron in a triplet carbene can change its spin to facilitate the formation of the second bond in a stepwise radical addition.
Highlights

Carbenes are electron-deficient carbon species with two nonbonding electrons and the general formula R2C.

Cyclopropane synthesis, or cyclopropanation, is an important application of carbenes.

Cyclopropane has a three-membered ring with significant ring strain due to 60 degree bond angles.

Carbenes can be generated in situ from diazomethane in the presence of light.

Carbenes react with alkenes to form cyclopropanes, retaining the stereochemistry of the alkene.

Halogenated carbenes can be used for cyclopropanation to introduce halogen functionality.

Singlet and triplet carbenes react differently in cyclopropanation due to their electronic configurations.

Singlet carbenes undergo stereospecific concerted reactions, conserving alkene stereochemistry.

Triplet carbenes participate in stepwise radical additions, leading to mixtures of isomeric products.

The difference in stereochemistry between singlet and triplet carbenes can be used to determine their identity.

Carbenes can insert into existing sigma bonds, often C-H bonds, to promote intramolecular cyclization.

Carbenes with no alpha hydrogens undergo different reactions compared to those with alpha hydrogens.

The Bamford-Stevens reaction converts ketones into alkenes using carbene chemistry.

The Bamford-Stevens reaction involves the formation of an N-tosylhydrazone intermediate.

An anionic intermediate is formed by deprotonation of the N-H bond in the hydrazone.

Elimination of the tosyl group generates a diazoalkane, which evolves nitrogen to form a carbene.

The carbene undergoes insertion into a vicinal C-H bond, followed by a 1,2-hydride shift to form an alkene.

The Bamford-Stevens reaction lacks stereochemical control, producing a mixture of E and Z alkenes.

The reaction is synthetically useful with particular cyclic substrates that produce exclusively Z-alkenes.

Transcripts

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CarbenesCyclopropaneSynthesisReactionsOrganic ChemistryInsertionStereochemistryBamford-StevensDiazomethaneKetonesAlkenes