![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.](https://image.slidesharecdn.com/carbenes2-210215044048/85/Structure-and-Reactivity-of-Carbenes-14-320.jpg)
Structure and Reactivity of Carbenes
- 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