A supplement to Clayden, Greeves, and Warren's Organic Chemistry, Chapter 40. Covers the first half of the chapter.

1. CARBENE
S
Organic Chemistry. Clayden,
Greeves, & Warren 2e. Chapter 40:
Synthesis and Reactions of Carbenes

2. WHAT REAGENTS WOULD
YOU USE TO MAKE THE
METHYL ESTER?

3. DIAZOMETHANE IS BASIC
AND NUCLEOPHILIC AT
CARBON
Nitrogen: World’s best
leaving group
Proximity Effect:
Carboxylate and
diazonium methane are
close and react first (so
no unwanted byproducts
are formed)

4. Dry Ice Condenser
N-Nitroso-N-methyl-p-toluenesulfonamide
KOH in Ether
Distilled Ethereal Diazomethane
Diazomethane Exploding

5. MAKING DIAZOMETHANE FROM N-
NITROSO-N-METHYL-P-
TOLUENESULFONAMIDE
1. Nucleophilic substitution at sulfonate (similar to substitution at an acid chloride)
2. Protonation
3. Deprotonation
4. Loss of 𝑂𝐻− to generate diazomethane

6. WHAT IF DIAZOMETHANE
DECOMPOSED?
Carbene: A compound containing a neutral carbon atom
containing 6 valence electrons instead of 8
Carbene Reactivity: Act like simultaneous electrophile and
nucleophiles (empty p orbital and lone pair)
Hybridization: sp2 hybridized so that they can contain an
empty p orbital
Electronic Configuration: Singlet vs. Triplet
Singlet Carbene Triplet Carbene
(rare)

7. CARBENES PREPARED
FROM DIAZO-
COMPOUNDS
1) Nucleophilic Acyl
Substitution
2) Diazo-
exchange
What are the two
other byproducts?
Nitrogen and Methyl
Chloride

8. THE BAMFORD-STEVENS
REACTION
Diazocarbonyl compounds are resonance
stabilized; however, diazoalkanes are very
unstable and explosive
Alpha-elimination: Two substituents attached to the same atom are removed (eliminated)

9. CARBENES PREPARED
FROM ALPHA-
ELIMINATION
Chloroform
Dichloroalkanes
Chloroalkanes
Beta-elimination

10. CARBENOIDS AND “ENOID”
REAGENTS: CARBENE
EQUIVALENTS
“Enoid” Reagents: Electrophilic and
nucleophilic bifunctionality
Leaving Group: Electrophilic
Character
Lone Pair: Nucleophilic Character
Oxenoid

11. N-HETEROCYCLIC
CARBENES: A NEW
ORGANOMETALLIC
LIGAND
Hoveyda-Grubbs Catalyst: NHC stabilizes
Ruthenium complex
Lone pairs stabilize
unfilled p orbital on
carbene

12. TRIPLET
CARBENE
S
Triplet carbenes are favored when
no adjacent lone pairs are present

13. SINGLET
CARBENE
S
Singlet carbenes are favored when
adjacent lone pairs are present

14. SINGLET CARBENE
REACTIVITY:
CHELETROPIC
REACTIONS
Cheletropic Reaction: a [1+n]-cycloaddition between an
“enoid” reagent and a (4q + 2)s component
Carbene
“Docking”
Stereospecific reaction. Single, concerted
step does not allow more stable trans-
cyclopropane to be formed.

15. TRIPLET CARBENE
REACTIVITY: RADICAL
“CHELETROPIC” REACTIONS
Stereoselective NOT stereospecific because of free bond rotation
The slow spin inversion means the single bond
has time to rotate to favor the more
thermodynamically favorable trans-
cyclopropane
Thermodynamic
trans-alkene

16. CARBENES ARE NEUTRAL
AND REACT LIKE
RADICALS
Reactions between most compounds are based on polar interactions, which favor delta positive reagents and
delta negative reagents interacting.
However, carbenes are completely neutral, so reactions are based on the smallest bond dissociation enthalpy
(BDE). This results in weird reactions, such as the insertion into a C-H bond!
Is the O-H bond or the C-H bond
weaker?

17. WE WILL CONTINUE WITH THE
APPLICATIONS OF CARBENES IN SYNTHESIS
IN OUR NEXT LECTURE