Chapter: Synthesis and Reactions of Carbenes

1. Introduction to Carbenes

• Definition: Carbenes are neutral, highly reactive species containing a divalent carbon atom with two unshared valence electrons and two bonds to other atoms. The general formula is R2​C:.
• Electronic Nature: The carbon atom in a carbene possesses only six valence electrons, making it electron-deficient and highly electrophilic.
• Reactivity: Carbenes are extremely reactive intermediates due to their electron deficiency and the presence of unpaired electrons (in triplet carbenes). They typically have very short lifetimes.

2. Types of Carbenes: Singlet vs. Triplet

Carbenes exist in two main spin states, depending on the pairing of the two non-bonding electrons:

2.1. Singlet Carbene

• Structure: The two non-bonding electrons are paired and occupy a single sp2 hybridized orbital. The remaining p orbital is empty.
• Geometry: The carbon atom is sp2 hybridized, resulting in a bent geometry (bond angle typically around 103∘−105∘).
• Spin State: Overall spin is zero.
• Reactivity: Behaves as a nucleophile (due to the lone pair) and an electrophile (due to the empty p-orbital). It is typically more reactive and less selective than triplet carbenes in addition reactions.

2.2. Triplet Carbene

• Structure: The two non-bonding electrons are unpaired and occupy two different orbitals (one in an sp hybridized orbital and the other in a p orbital, or both in p orbitals depending on the substituents).
• Geometry: The carbon atom is typically sp hybridized, resulting in a linear geometry (bond angle closer to 180∘) or nearly linear for simpler alkyl carbenes. (However, often depicted as bent in simpler contexts for generality).
• Spin State: Overall spin is one (two parallel spins). Paramagnetic.
• Reactivity: Behaves as a diradical (radical-like). It is typically less reactive and more selective than singlet carbenes due to the need for spin inversion during reaction.

2.3. Singlet-Triplet Interconversion

• The ground state of a carbene (singlet or triplet) depends on the substituents. Electron-donating groups stabilize the singlet state. Electron-withdrawing groups can stabilize the triplet state.
• Interconversion can occur (e.g., singlet can convert to triplet via intersystem crossing).

3. Synthesis (Generation) of Carbenes

Carbenes are too reactive to be isolated and are usually generated in situ (in the reaction mixture).

3.1. From Diazo Compounds (R2​C=N2​)

• Diazo compounds are highly strained and can decompose to yield carbenes.
• Methods:
  • Thermolysis (Heat, Δ): Heating diazo compounds (e.g., diazomethane, CH2​N2​) causes the extrusion of N2​ gas and formation of a carbene.
    R2​C=N2​Δ​R2​C:+N2​↑
  • Photolysis (Light, hν): Irradiation with UV light is also effective, providing the energy for N2​ extrusion.
    R2​C=N2​hν​R2​C:+N2​↑
  • Transition Metal Catalysis: Using transition metals (e.g., Cu, Rh(II) complexes like Rh2​(OAc)4​) allows for the generation of metal-carbene complexes (carbenoids), which are often more selective and safer to handle than free carbenes. This is the most common method in modern synthesis.
    R2​C=N2​Cu or Rh(II) catalyst​Metal-carbene complex (These are often “ylides” or “carbenoids” that react like carbenes).

3.2. From Geminal Dihalides ( α-Elimination)

• α-Elimination (Alpha Elimination): A base abstracts a proton from the same carbon atom that bears a leaving group (usually a halogen).
• Dichlorocarbene (CCl2​): A classic example generated from chloroform (CHCl3​) and a strong base (e.g., KOtBu).
  1. CHCl3​+Base→CCl3−​+Base-H
  2. CCl3−​→CCl2​+Cl− (spontaneous expulsion of chloride)
• Other dihalocarbenes: Can be generated similarly from other geminal dihalides.

3.3. From Ketene (CH2​=C=O)

• Less common, but photolysis of ketene can generate methylene (CH2​:).

4. Reactions of Carbenes

Carbenes are highly versatile and undergo a variety of important reactions.

4.1. Addition to Alkenes (Cyclopropanation)

• Definition: Carbenes add to alkenes to form cyclopropane rings. This is one of their most characteristic and synthetically useful reactions.
• Stereospecificity of Addition:
  • Singlet Carbene: Adds to alkenes in a stereospecific syn fashion. The relative stereochemistry of the substituents on the alkene is retained in the cyclopropane product. This is because the concerted addition is faster than rotation around the developing bonds in the transition state.
    • Example: cis-2-butene CH2​:​ cis-1,2-dimethylcyclopropane
    • Example: trans-2-butene CH2​:​ trans-1,2-dimethylcyclopropane
  • Triplet Carbene: Adds to alkenes in a non-stereospecific fashion. A diradical intermediate is formed first, allowing for bond rotation before the second bond forms. This leads to a mixture of cis and trans cyclopropane products from a given alkene.
• Simmons-Smith Reaction: A highly useful variation for stereospecific cyclopropanation. It involves the reaction of alkenes with diiodomethane (CH2​I2​) and a zinc-copper couple (Zn(Cu)). It generates an iodomethylzinc iodide species (ICH2​ZnI), often called a “carbenoid,” which adds to the alkene in a stereospecific syn fashion (like a singlet carbene). It’s safer and more practical than using free methylene.

4.2. Insertion Reactions

• Definition: Carbenes can insert into single bonds (e.g., C-H, O-H, N-H).
• C-H Insertion: Insertion into C-H bonds leads to chain extension or new branches.
  • Methylene (CH2​:), especially when generated by thermolysis or photolysis of diazomethane, is highly reactive and non-selective, inserting into primary, secondary, and tertiary C-H bonds almost equally, leading to mixtures of products.
  • Metal-carbenoids are much more selective and often favor insertion into weaker C-H bonds (e.g., tertiary C-H).
• O-H and N-H Insertion: Highly reactive carbenes can also insert into O-H bonds (e.g., converting alcohols to ethers) and N-H bonds (e.g., converting amines to secondary/tertiary amines). These are generally more selective than C-H insertion.

4.3. Rearrangements

• Unstable carbenes can undergo intramolecular rearrangements to form more stable products.
  • Wolff Rearrangement: A specific rearrangement of α-diazo ketones to ketenes, which then react with nucleophiles (e.g., water, alcohols) to form carboxylic acids or esters, often with chain shortening. This is a key step in the Arndt-Eistert synthesis.

4.4. Ylide Formation

• Carbenes can react with compounds having lone pairs (e.g., phosphines, sulfides) to form ylides.
  • Example: Reaction with phosphines to form phosphorus ylides (Wittig reagents). This is a general route for generating phosphorus ylides for the Wittig reaction.
    R3​P+R’2​C:→R3​P=CR’2​

5. Synthetic Applications

Carbenes and carbenoids are invaluable reagents in organic synthesis due to their ability to:

• Form cyclopropane rings (Simmons-Smith reaction being a prime example).
• Insert into various C-H, O-H, and N-H bonds (though selectivity can be an issue for simple carbenes).
• Generate other reactive intermediates like ylides.
• Facilitate rearrangements for building complex skeletons.

6. Summary of Key Distinctions

Multiple Choice Questions (MCQ) on Synthesis and Reactions of Carbenes

Instructions: Choose the best answer for each question.

1. What is the defining characteristic of a carbene? a) A positively charged carbon atom. b) A carbon atom with an unpaired electron. c) A neutral carbon atom with two unshared valence electrons and two bonds. d) A carbon atom bonded to three other atoms.

2. How many valence electrons does the carbon atom in a carbene possess? a) 4 b) 6 c) 8 d) 10

3. In a singlet carbene, the two non-bonding electrons are: a) Unpaired and in different orbitals. b) Paired and in a single sp2 hybridized orbital. c) Unpaired and in the same orbital. d) Not present.

4. What is the typical geometry of a singlet carbene? a) Linear b) Trigonal planar c) Tetrahedral d) Bent

5. A triplet carbene is characterized by two non-bonding electrons that are: a) Paired and in a single orbital. b) Unpaired and in two different orbitals. c) Delocalized across multiple atoms. d) Not involved in bonding.

6. Which type of carbene is often described as behaving like a diradical? a) Singlet carbene b) Triplet carbene c) Metal-carbene complex d) Carbenoid

7. Which of the following is a common method for generating carbenes in situ? a) Hydrogenation of alkanes. b) Thermolysis or photolysis of diazo compounds. c) Nucleophilic substitution of alkyl halides. d) Electrophilic addition to alkenes.

8. What gas is typically extruded during the formation of a carbene from a diazo compound? a) CO2​ b) O2​ c) N2​ d) H2​

9. The generation of carbenes using transition metal catalysts (e.g., Cu, Rh) typically forms: a) Free, highly reactive carbenes. b) Metal-carbene complexes (carbenoids). c) Stable carbocations. d) Phosphorus ylides.

10. Dichlorocarbene (CCl2​) is commonly generated from which starting material and reagent? a) CH2​Cl2​ and NaOH b) CHCl3​ and strong base (e.g., KOtBu) c) CH2​N2​ and light d) CH3​Cl and Li

11. The process of generating a carbene from a geminal dihalide by abstracting a proton from the same carbon bearing a leaving group is called: a) Beta-elimination b) Alpha-elimination c) Gamma-elimination d) E2 reaction

12. What is the most characteristic and synthetically useful reaction of carbenes with alkenes? a) Insertion into C-H bonds. b) Formation of cyclopropane rings (cyclopropanation). c) Rearrangement reactions. d) Polymerization.

13. When a singlet carbene adds to a cis-alkene, what is the stereochemical outcome? a) A mixture of cis and trans cyclopropanes. b) Formation of only the trans-cyclopropane. c) Stereospecific syn addition, retaining the cis stereochemistry. d) Elimination to form an alkyne.

14. Addition of a triplet carbene to an alkene is typically: a) Stereospecific syn addition. b) Stereospecific anti addition. c) Non-stereospecific. d) Not possible.

15. The Simmons-Smith reaction is a method for synthesizing cyclopropanes using which reagents? a) CH2​Cl2​ and NaOH b) CH2​I2​ and Zn(Cu) (zinc-copper couple) c) CH2​N2​ and hν d) CHCl3​ and KOtBu

16. How does the Simmons-Smith reaction typically add to an alkene in terms of stereochemistry? a) Non-stereospecifically. b) Stereospecifically syn. c) Stereospecifically anti. d) Via a radical intermediate that racemizes.

17. What type of reaction involves a carbene inserting into a single bond (e.g., C-H)? a) Addition reaction b) Elimination reaction c) Insertion reaction d) Substitution reaction

18. When methylene (CH2​:), generated by photolysis of diazomethane, reacts with propane, what products might be formed? a) Only 1-methylpropane. b) Only 2-methylpropane. c) A mixture of 1-methylpropane and 2-methylpropane. d) Only cyclopropane.

19. Metal-carbenoids, generated with transition metal catalysts, are generally more selective for C-H insertion than free carbenes. Which type of C-H bond do they often favor? a) Primary C-H b) Secondary C-H c) Tertiary C-H d) Vinylic C-H

20. The Wolff rearrangement is a specific rearrangement of α-diazo ketones to: a) Aldehydes b) Ketones c) Ketenes d) Carboxylic acids

21. Carbenes can react with compounds possessing lone pairs (e.g., phosphines) to form: a) Carbocations b) Radicals c) Ylides d) Alkenes

22. What is the overall classification of carbene species in terms of electron count around the divalent carbon? a) Electron-rich b) Electron-deficient c) Neutral, with a full octet d) Positively charged

23. Which spin state (singlet or triplet) is typically more reactive and less selective in addition reactions due to its filled orbital and empty orbital? a) Singlet carbene b) Triplet carbene c) Both are equally reactive d) Neither is reactive

24. The term “carbenoid” often refers to: a) A carbene analog that is less reactive and more selective. b) A charged carbene. c) A radical intermediate. d) A carbene that has undergone rearrangement.

25. Which starting material would yield a carbene upon alpha-elimination? a) CH3​CH2​Cl b) CH3​COOH c) CH2​Br2​ d) CH2​N2​

26. Why are carbenes considered highly reactive intermediates? a) They have a positive charge. b) They have only six valence electrons, making them unstable and electrophilic. c) They are typically very large molecules. d) They are very stable.

27. What would be the major product of the reaction of 1-butene with dichlorocarbene (CCl2​) generated from CHCl3​ and KOtBu? a) 1,1-dichlorobutane b) 1,1-dichloro-2-ethylcyclopropane c) 1,1-dichloro-2-propylcyclopropane d) A mixture of 1,1-dichloro-2-ethylcyclopropane and 1,1-dichloro-3-ethylcyclopropane.

28. If a carbene is generated by heating a diazo compound, what term describes this process? a) Photolysis b) Thermolysis c) Hydrolysis d) Electrophoresis

29. What is the approximate bond angle in a singlet carbene? a) 180∘ b) 120∘ c) 103−105∘ d) 90∘

30. Which of the following is an example of an O-H insertion reaction of a carbene? a) R-H+CH2​:→R-CH3​ b) R-OH+CH2​:→R-OCH3​ c) R-NH2​+CH2​:→R-NHCH3​ d) R-CH=CH2​+CH2​:→cyclopropane

31. The driving force for the decomposition of diazo compounds to carbenes is the formation of: a) A stable carbocation. b) A very stable N2​ molecule. c) A highly reactive radical. d) An ylide.

32. The Wittig reaction utilizes phosphorus ylides, which can be prepared from carbenes reacting with: a) Alkenes b) Carbonyl compounds c) Phosphines d) Alkyl halides

33. Which of the following statements about methylene (CH2​:) generated by photolysis is true? a) It is highly selective for tertiary C-H bonds. b) It is very reactive and relatively non-selective for C-H insertion. c) It primarily undergoes elimination reactions. d) It is a stable, isolable compound.

34. In the Simmons-Smith reaction, the active species that acts as a “carbenoid” is: a) CCl2​ b) CH2​N2​ c) ICH2​ZnI d) Cu(OAc)2​

35. If a trans-alkene reacts with a triplet carbene, what would be the expected stereochemical outcome for the cyclopropane product? a) Only trans-cyclopropane. b) Only cis-cyclopropane. c) A mixture of cis and trans cyclopropanes. d) No reaction would occur.

36. What is the primary method to control the stereoselectivity and regioselectivity of carbene reactions in modern organic synthesis? a) Using extremely high temperatures. b) Using highly reactive, free carbenes. c) Employing transition metal catalysts to form carbenoids. d) Performing reactions in non-polar solvents.

37. Which reaction is a classic example of an α-elimination process generating a carbene intermediate? a) Dehydration of alcohols. b) Reaction of chloroform with strong base. c) Wittig reaction. d) Grignard reaction.

38. The Arndt-Eistert synthesis, which can lengthen a carbon chain by one carbon, uses which carbene-related rearrangement? a) Simmons-Smith reaction. b) Peterson olefination. c) Wolff rearrangement. d) Corey-House synthesis.

39. A carbene with two identical substituents (e.g., CH2​:, CCl2​) is considered to be: a) Achiral. b) Chiral. c) Racemic. d) Optically active.

40. What is the relative reactivity of singlet carbenes compared to triplet carbenes in addition reactions? a) Singlet carbenes are generally less reactive. b) Singlet carbenes are generally more reactive. c) Reactivity depends entirely on the solvent. d) They have similar reactivities.

Answer Key with Explanations

1. c) A neutral carbon atom with two unshared valence electrons and two bonds.
   • Explanation: This definition precisely describes a carbene: a neutral carbon atom with a valence of two, possessing two non-bonding electrons.
2. b) 6.
   • Explanation: The divalent carbon in a carbene forms two bonds (4 electrons) and has two non-bonding electrons, totaling 6 valence electrons around the carbon atom.
3. b) Paired and in a single sp2 hybridized orbital.
   • Explanation: In a singlet carbene, the two non-bonding electrons are paired in a single hybridized orbital (typically sp2), leaving an empty p-orbital.
4. d) Bent.
   • Explanation: The sp2 hybridization of the carbene carbon in a singlet carbene, along with the lone pair, leads to a bent molecular geometry.
5. b) Unpaired and in two different orbitals.
   • Explanation: A triplet carbene has two unpaired non-bonding electrons, each occupying a separate orbital (e.g., one sp hybridized and one p, or two p orbitals).
6. b) Triplet carbene.
   • Explanation: Because a triplet carbene has two unpaired electrons with parallel spins, it behaves like a diradical, undergoing reactions that involve single electron transfers.
7. b) Thermolysis or photolysis of diazo compounds.
   • Explanation: Diazo compounds are the most common precursors for carbene generation, breaking down upon heating (thermolysis) or irradiation (photolysis) to release N2​ and form the carbene.
8. c) N2​.
   • Explanation: The stability of the diatomic nitrogen molecule (N2​) is a major driving force for the decomposition of diazo compounds to carbenes.
9. b) Metal-carbene complexes (carbenoids).
   • Explanation: Transition metal catalysts interact with diazo compounds to form metal-carbene complexes, which are often more controlled and selective in their reactions than free carbenes.
10. b) CHCl3​ and strong base (e.g., KOtBu).
    • Explanation: Dichlorocarbene (CCl2​) is typically generated by α-elimination from chloroform (CHCl3​) using a strong base, which deprotonates chloroform to form a trichloromethyl anion, followed by expulsion of a chloride ion.
11. b) Alpha-elimination.
    • Explanation: Alpha-elimination (or α-elimination) is the process where both the proton and the leaving group are removed from the same carbon atom.
12. b) Formation of cyclopropane rings (cyclopropanation).
    • Explanation: The addition of carbenes (or carbenoids) to alkenes to form cyclopropanes is a cornerstone reaction in synthetic organic chemistry.
13. c) Stereospecific syn addition, retaining the cis stereochemistry.
    • Explanation: Singlet carbenes add to alkenes in a concerted, stereospecific syn fashion. This means the relative positions of substituents on the alkene are maintained in the resulting cyclopropane.
14. c) Non-stereospecific.
    • Explanation: Triplet carbenes add to alkenes in a stepwise manner, forming a diradical intermediate. This intermediate allows for rotation around the developing single bonds, leading to a mixture of cis and trans cyclopropane products from a single alkene isomer.
15. b) CH2​I2​ and Zn(Cu) (zinc-copper couple).
    • Explanation: The Simmons-Smith reaction uses these reagents to generate an iodomethylzinc iodide “carbenoid” species, which provides a safer and stereospecific method for cyclopropanation.
16. b) Stereospecifically syn.
    • Explanation: The Simmons-Smith reaction is known for its highly stereospecific syn addition, adding the methylene group to the same face of the alkene.
17. c) Insertion reaction.
    • Explanation: Carbenes are capable of inserting into existing single bonds, such as C-H, O-H, and N-H bonds.
18. c) A mixture of 1-methylpropane and 2-methylpropane.
    • Explanation: Free methylene (CH2​:), especially from photolysis/thermolysis of diazomethane, is very reactive and relatively non-selective. It will insert into primary and secondary C-H bonds of propane, leading to a mixture of butane (from primary C-H) and isobutane (from secondary C-H). (My answer in thought was 1-methylpropane and 2-methylpropane, which are isobutane and butane, which is correct).
19. c) Tertiary C-H.
    • Explanation: Metal-carbenoids are more selective than free carbenes and typically prefer to insert into the weakest C-H bonds, which are tertiary > secondary > primary.
20. c) Ketenes.
    • Explanation: The Wolff rearrangement is a specific rearrangement of α-diazo ketones to form highly reactive ketenes.
21. c) Ylides.
    • Explanation: Carbenes can react with compounds containing lone pairs (like phosphines or sulfides) to form zwitterionic species called ylides.
22. b) Electron-deficient.
    • Explanation: With only six valence electrons around the carbon, carbenes are inherently electron-deficient and act as strong electrophiles.
23. a) Singlet carbene.
    • Explanation: Singlet carbenes have both a filled orbital (the lone pair) and an empty p-orbital, allowing them to act as both a nucleophile and an electrophile simultaneously, leading to higher reactivity and lower selectivity in some reactions.
24. a) A carbene analog that is less reactive and more selective.
    • Explanation: Carbenoids are metal-carbene complexes that behave chemically like carbenes but are generally less reactive, more stable, and more selective, often leading to cleaner reactions.
25. c) CH2​Br2​.
    • Explanation: Geminal dihalides like CH2​Br2​ (dibromomethane) can undergo α-elimination with a strong base to generate a carbene (CHBr: or CH2​: if both bromines leave sequentially, depending on conditions). CH2​Cl2​ also works for generating dichlorocarbene.
26. b) They have only six valence electrons, making them unstable and electrophilic.
    • Explanation: The incomplete octet on the carbene carbon makes it highly unstable and eager to react to achieve a stable electron configuration.
27. c) 1,1-dichloro-2-propylcyclopropane.
    • Explanation: 1-butene is CH2​=CH-CH2​CH3​. Dichlorocarbene adds across the double bond. The carbene carbon forms bonds to the two carbons of the double bond. The propyl group would be a substituent on the cyclopropane ring. So it would be 1,1-dichloro-2-propylcyclopropane. (The “2-ethyl” in b is wrong as it is on a 2 carbon chain)
28. b) Thermolysis.
    • Explanation: Thermolysis refers to the chemical decomposition of a compound by heat.
29. c) 103−105∘.
    • Explanation: Due to sp2 hybridization and the presence of a lone pair in a hybridized orbital, singlet carbenes adopt a bent geometry with bond angles in this range.
30. b) R-OH+CH2​:→R-OCH3​.
    • Explanation: This reaction shows the insertion of a carbene (CH2​:) into the O-H bond of an alcohol to form an ether.
31. b) A very stable N2​ molecule.
    • Explanation: The extrusion of a highly stable molecule like N2​ gas is the thermodynamic driving force for the decomposition of diazo compounds into carbenes.
32. c) Phosphines.
    • Explanation: Phosphorus ylides (Wittig reagents) are typically prepared by reacting a phosphine (e.g., triphenylphosphine) with an alkyl halide to form a phosphonium salt, which is then deprotonated to yield the ylide. (Carbenes can also react with phosphines to directly form ylides).
33. b) It is very reactive and relatively non-selective for C-H insertion.
    • Explanation: Methylene generated from photolysis/thermolysis of diazomethane is a highly energetic and reactive species that does not discriminate much between different types of C-H bonds, leading to mixtures.
34. c) ICH2​ZnI.
    • Explanation: The Simmons-Smith reagent combination (CH2​I2​ and Zn(Cu)) generates the active iodomethylzinc iodide species, which is the “carbenoid” that adds to the alkene.
35. c) A mixture of cis and trans cyclopropanes.
    • Explanation: Triplet carbenes add non-stereospecifically. A diradical intermediate is formed, allowing rotation around the single bonds before ring closure, resulting in a mixture of diastereomers regardless of the starting alkene stereochemistry.
36. c) Employing transition metal catalysts to form carbenoids.
    • Explanation: Modern synthesis heavily relies on metal-catalyzed carbene reactions because the metal-carbenoid complexes offer greater control over reactivity, regioselectivity, and stereoselectivity.
37. b) Reaction of chloroform with strong base.
    • Explanation: This reaction (e.g., CHCl3​+KOtBu) is the classic method for generating dichlorocarbene via an α-elimination pathway.
38. c) Wolff rearrangement.
    • Explanation: The Arndt-Eistert synthesis uses the Wolff rearrangement of an α-diazo ketone to a ketene, which then undergoes nucleophilic attack, effectively lengthening the carbon chain.
39. a) Achiral.
    • Explanation: A carbene with two identical substituents (e.g., CH2​:, CCl2​) has a plane of symmetry (or in the case of CH2​:, also C2​ axis and center of inversion, depending on exact geometry/spin state), making it achiral.
40. b) Singlet carbenes are generally more reactive.
    • Explanation: Singlet carbenes, with their electrophilic empty orbital and nucleophilic lone pair, can react in a concerted fashion and are typically more reactive than triplet carbenes, which must undergo a spin inversion to form a stable product.