Organic synthesis reduction of reaction with mechanism

Organic synthesis

1. UNIVERSITY INSTITUTE OF SCIENCES DEPARTMENT OF CHEMISTRY M. SC. HONS. CHEMISTRY ORGANIC/ 2ND SEMESTER ORGANIC SYNTHESIS (24SHT-707) Unit No. 2 Chapter No. 1 Lecture No. 2.7-2.8 Topic : ___Heck Reaction___________________________ DR. NAVJOT SANDHU (E11857) ASSISTANT PROFESSOR Academic Session 2025-26 ODD Semester Jul-Dec 2025

2. Learning Objectives Learning Objective 1. Apply Key Name Reactions to Complex Molecule Synthesis Learning Objective 2. Select and Justify Organic Reagents for Target Transformations Learning Objective 3. Develop Retrosynthetic Strategies for Target Molecule Design 1

3. Recap of Previous Lecture Crown ethers are cyclic polyethers known for their ability to complex selectively with metal cations based on the size of their ring cavity. They consist of repeating –CH₂–CH₂–O– units forming a ring, typically named by the total number of atoms and the number of oxygens (e.g., 18-crown-6 has 18 atoms and 6 oxygen atoms). Crown ethers act as phase-transfer catalysts by encapsulating metal ions like K⁺, Na⁺, and Ca²⁺, increasing their solubility in organic solvents. They enhance reactions by transporting ionic species into nonpolar media and stabilizing cations via coordination to oxygen lone pairs. Selectivity depends on the size of the crown ether ring matching the ionic radius of the metal cation. Widely used in organic synthesis, ion transport, and analytical chemistry. 2

4. The first step is the oxidative addition of palladium to the halide to form the organopalladium species Reaction (metathesis) with base gives intermediate , which via transmetalation with the boron-ate complex (produced by reaction of the boronic acid with base) forms the organopalladium species Reductive elimination of the desired product restores the original palladium catalyst which completes the catalytic cycle. The oxidative addition is the rate determining step of the catalytic cycle. During this step, the palladium catalyst isoxidized from palladium(0) to palladium(II). The palladium catalyst is coupled with the alkyl halide to yield an organopalladium complex. The oxidative addition step breaks the carbon- halogenbond where the palladiumis now bound to both the halogen and the R group

5. Transmetalation is an organometallic reaction where ligands are transferred from one species to another. In the case of the Suzuki coupling the ligands are transferred from the organoboron species to the palladium(II) complex where the base that was added in the prior step is exchanged with the R1 substituent on the organoboron species to give the new palladium(II) complex . The organoboron compounds do not undergo transmetalation in the absence of base and it is therefore widely believed that the role of the base is to activate the organoboron compound as well as facilitate the formation of R2-Pdll-OtBu from R2-Pdll-X The final step is the reductive elimination step where the palladium(II) complex eliminates the product and regenerates the palladium(0) catalyst. The order of elimination is Ar-Ar > Ar -R > R-R

6. REFERENCES Textbooks / Reference Books   T1. Warren, S., Organic synthesis: The Disconnection Approach, John Wiley and Sons (1994). T2. Fieser, L.F., and Fieser , M., Reagents for Organic Synthesis , Vol. 1-16, Wiley- Interscience , New York. T3 . Corey, E.J. , Retrosynthetic Analysis. T4. Smith, M.B., Organic Synthesis, McGraw Hill Inc., New York (1995). T5. Carruthers, W. Modern Methods of Organic Synthesis, Cambridge University Press (1987)

7. Summary of the Lecture The Heck reaction is a widely used palladium-catalyzed carbon–carbon coupling between aryl or vinyl halides and alkenes to form substituted alkenes. It proceeds via oxidative addition of the aryl/vinyl halide to Pd(0), followed by alkene insertion and β-hydride elimination. The reaction forms C–C bonds with high regio- and stereoselectivity, typically giving trans-alkene products. Common catalysts include Pd(OAc)₂ with phosphine ligands, and bases like triethylamine or carbonate salts are used. The Heck reaction is useful in the synthesis of fine chemicals, pharmaceuticals, and natural products. It’s a key method for functionalizing alkenes and has been extensively applied in complex molecule construction. 6

8. Next Lecture Sonogashira Reaction 7

9. FAQ’s What does the Heck reaction do? It couples aryl or vinyl halides with alkenes to form substituted alkenes. Which catalyst is commonly used? Palladium(0) catalysts like Pd(OAc)₂ with phosphine ligands. What type of bonds does it form? It forms carbon–carbon (C–C) bonds with high regio- and stereoselectivity. What bases are used in the Heck reaction? Bases like triethylamine or carbonate salts are typically used. Where is the Heck reaction applied? Widely used in pharmaceuticals, fine chemicals, and natural product synthesis. 8

10. R eferences/ Articles/ Videos 1. https://ia601303.us.archive.org/25/items/Logic_of_Chemical_Synthesis_Corey_1989/Logic_of_Chemical_Synthesis_Corey_1989_text.pdf 2. https://www.ias.ac.in/article/fulltext/reso/024/10/1071-1086 9

11. Faculty-curated videos, NPTEL, Coursera, LinkedIn, or other relevant learning resources https://nptel.ac.in/courses/104105087 https://onlinecourses.nptel.ac.in/noc22_cy30/preview 10

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13. Thank You For queries Email: [email protected] 12