University:
Rutgers University Newark
Course:
CHEM 336 | Organic Chemistry ||
Academic year:

2024
Views:

278

Pages:

23
Author:

Mahitab S.

CHAPTER 24 Part 2 CATALYTIC CARBONCARBON BOND FORMATION ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions • Nobel Prize Chemistry 2010 • http://www.nobelprize.org/nobel_prizes/chemistry/ laureates/2010/ CATALYSIS ©2018 Cengage Learning. All Rights Reserved. PALLADIUM Nobel Prize Chemistry 2010 • Applications in everyday life: plastics, electronics, drugs, paints, car fuel, materials ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions • Palladium-catalyzed cross coupling solved the problem of joining C–C bonds and provided chemists with a more precise and efficient tool to work with. ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions - Applications • Examples of drugs and late-stage drug candidates where Suzuki cross-coupling was used to form key carbon–carbon bonds (shown in blue) find p s p p b 7 ©2018 Cengage Learning. All Rights Reserved. a Cross-Coupling Reactions - Types • In the Heck reaction, an olefin reacts with aryl halide R-CH=CH2 + Ar-X • In the Negishi reaction, an organozinc reacts with aryl halide: Ar-ZnX + Ar’-X • In the Suzuki reaction, an organoboron reacts with aryl halide: Ar-BR2 + Ar’-X • The carbon atoms meet on a palladium atom • Cross-coupling reactions allow to join C-C bonds under mild conditions and with very high precision ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions - Types • Instead of the Grignard reagent Heck began to use olefins. In an olefin the carbon atom is naturally slightly activated and when it binds to palladium it becomes even more likely to react with another carbon atom • Organozinc: variant of the Grignard reagent when he substituted magnesium for zinc carbon becomes less reactive when using zinc • Organoboron: the mildest activator so far and is even less toxic than zinc, which is an advantage when it comes to large-scale applications ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions - Mechanism ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions - Mechanism ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions - Applications • Precision – the key to gigantic molecular constructions • One of the most spectacular examples of Pd-catalyzed cross-coupling is synthesis of palytoxin – a naturally occurring poison with the help of Suzuki reaction ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions - Catalytic Cycle • Cross-coupling of aryl halides (Ar-X) - Example 1 Suzuki • Cycle ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions - Catalytic Cycle • Cross-coupling of aryl halides (Ar-X) - Example 2 Stille • Cycle ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions - Catalytic Cycle • Cross-coupling of aryl halides (Ar-X) - Example 3 Negishi • Cycle ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions - Catalytic Cycle • Cross-coupling of aryl halides (Ar-X) - Example 4 Heck • Cycle ©2018 Cengage Learning. All Rights Reserved. Aryl vs Acyl Cross-Coupling • In chapter 18, five classes of organic compounds related to carboxylic acids are discussed • Under the general formula of each functional group is an illustration to show how the group is formally related to a carboxylic acid and organic halide (R-C(O)-X ≈ R-X) ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions - Catalytic Cycle • Cross-coupling of acyl halides (RC(O)-Cl) Acyl parol • Cycle pdin pdlol ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions - Catalytic Cycle • Cross-coupling of esters (RC(O)-OR’) Ester • Cycle ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions - Catalytic Cycle • Cross-coupling of amides (RC(O)-NR’R’’) Amide • Cycle ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions - Acyl Groups • Carboxylic acid derivatives discussed in this class have relative reactivity toward acyl substitution (Relative resonance stabilization & leaving group ability) (Ch. 18) least reactive most reactive • Similar trend is observed in cross-coupling reactions • Acyl chlorides >> esters >> amides (important) • Special activating groups for esters and amides must be used to break resonance stabilization • For esters: OPh; For amides: N-Ph/SO2Ph ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions - Examples • Examples of Suzuki, Negishi and acyl cross-coupling Br Suzuki electrophilic Muliophilic Negishi electrophilic acyl electrophilic nucleophilic Nudiophilic ©2018 Cengage Learning. All Rights Reserved. Cross-Coupling Reactions - Summary • (1) Type of Cross-coupling (Suzuki, Stille, Negishi, Heck) • (2) Catalytic cycle • (3) Steps in catalytic cycle + oxidation state of Pd • (4) Acyl cross-coupling (acyl halides, esters, amides) • (5) Be able to draw disconnections • (6) Be able to draw products pdil ©2018 Cengage Learning. All Rights Reserved. pain Suzuki Heck 10 Redimtiation I CI o II I I Example Rotation