Lecture 3

Question 1

What metals are typically used as catalysts in coupling reactions?

Answer 1

• Dominated by Pd(II)/Pd(0) systems

Question 2

What are the requirements for R1 in coupling reactions? (R1X)

Answer 2

• no beta hydrogens

- to prevent elimination

Question 3

What is X in a coupling reaction?

Answer 3

• halide or trifoliate

Order of reactivity:
I > OTf > Br > Cl

Question 4

What are the requirements for R2 in coupling reactions?

Answer 4

can be almost anything due to fast third step

Question 5

What are the requirements for M in coupling reactions?

Answer 5

can be a range of compounds

Question 6

What are examples of Pd(II) catalysts?

Answer 6

• reduced in situ and more stable than Pd(0) complexes
• PdCl2 (polymer, insoluable in many solvents)
• (RCN)2PdCl2 (R= Ph, Me more soluble)
• (PPh3)2Pd(Cl)2 which is air stable and easily prepared from PdCl2

Question 7

What are examples of Pd(0) catalysts?

Answer 7

• Pd(PPh3)4

- Pd2(dba)3

Question 8

Negishi reaction

Answer 8

• Zinc reagents

R-I + IZn-R’

Question 9

Stille reaction

Answer 9

• tin reagents, can be used to form polymers
• Br and SnMe3 couple
  cat = Pd2(dba)3. CHCl3
  Pd(o-tol)3

Question 10

Suzuki reaction

Answer 10

• boron reagents e.g. RB(OH)2, RB(OR)2, RBR2
• couple to bromine reagents
• sterochemistry of vinyl group maintained

Question 11

Hiyama-Denmark

Answer 11

• Silanolates and iodine
• NaH used to deprotonate most acidic proton
• then Pd2(dba)3. CHCl3 catalyst
• Reaction occurs via Pd-O-Si species

Question 12

Kumada

Answer 12

• Gringard reagents
• not useful if any =O or basic groups are present else a reduction will occur
• 1% mol Pd2(dba)3
• 4% mol iPr-HCl to generate a carbene in situ

Question 13

Sonagashria

Answer 13

• Copper acetylide reagents
• cat Pd2(dba)3 and CuI
• Pr2NH
• copper reacts with terminal alkyne to form reactive species

Question 14

Buchwalkd- Hartwig

Answer 14

• uses amines not R2-M
• Cat Pd2(dba)3
• cat racier BUNAP
• KOBut

Question 15

Oxidative coupling advantages and challenges

Answer 15

• removes need to synthesise substrates/ halides
• more atom efficient and green
• harder to get regioselectivity and reactivity right, relies heavily on directing groups