Organocuprate (copper) chemistry

Question 1

Organocuprates (organocopper reagents) can be made by…

Answer 1

… a transmetallation from an organolithium (or Grignard) and a copper salt

Question 2

What is a low-order cuprates (Gillman reagents)

Answer 2

• Reaction of 2 equivalents of a organolithium or grignards with a copper halide
• Adds two R groups and the M group onto the copper
• And a lithium halide

Question 3

What is a high-order cuprates (Lipshutz reagents)

Answer 3

• React two equivalnets of organolthium or Grignard wity Copper Cyanide
• Add two R groups onto the Copper

Question 4

What are 3 things which need to be considered when forming organocuprates?

Answer 4

• Need to use aprotic solvents (THF or Et₂O)
• Unstable at >0°C
• Prepared and used “in situ”

Question 5

What are the properties of organocuprates like?

Answer 5

• They are “softer” nucleophiles and less basic than Grignard or organolithium reagents
• This results in a different reactivity

Question 6

What happens if the following two reagent react together?

Answer 6

• Grignard/organolithium reagents are strong bases, and do not cleanly undergo Sₙ2 reactions with alkyl halides because of competing elimination reactions
• Can form a carbene, alkene or alkene

Question 7

Cuprates are less basic and undergo clean Sₙ2 reactions with alkyl halides or pseudohalides
What is the product of this reaction?

Answer 7

• Only one R group is transferred.
• CN group always stays on Cu

Question 8

What can x be in this reaction?

Answer 8

X = I, Cl, Br, OTs, OTf

Question 9

What is the product of this reaction?

Answer 9

• Only one R-group is transferred. CN group always stay on the Cu
• Sₙ2 means inversion of sterochemistry

Question 10

• Grignards or organolithiums are too basic and lead to elimination reactions in epoxide ring opening
• However cuprates can cleanly open epoxide rings
• What is the mechanism for this reaction

Answer 10

(note epoxide opening is selective for the less hindered position)

Question 11

Grignards or organolithiums are too basic and lead to elimination reactions in epoxide ring opening
What is the mechanism for this reaction?

Answer 11

Question 12

Grignard reagents are hard nucleophiles: direct 1,2-addition to α,β-unsatured ketones
What is the mechanism for the following reaction?

Answer 12

Question 13

Organocuprates are softer nucleophiles: conjuagate 1,4-addition
What is the mechanism for this reaction?

Answer 13

(soft reacts with soft - organocuprates is a soft nucleophile reacting with the soft enone)

Question 14

What is a hard nucleophile/electrophile?

Answer 14

• Small, high charge density
• e.g. RO⁻, H₂N⁻, R₂C=O, MeLi, MeMgBr
• Reactivity dominated by electrostatic interactions

Question 15

What is a soft nucleophile/electrophile

Answer 15

• delocalised charge in large, ‘diffuse’ orbitals
• e.g. RS⁻, I⁻, R₃P, Me₂CuLi, α,β-unsatured ketones + conjugated acids
• Reactivity dominated by HOMO-LUMO interactions

Question 16

The following reaction is a Sₙ2 reaction involving a soft nucleophile
What is the mechanism

Answer 16

(Soft reacts with soft)

Question 17

The same reagent can also react with the hard-nucleophile to form a different product
What is the mechansim

Answer 17

Question 18

Cuprates undergo syn-selective carbocupration reations with alkenes
The first part of this reaction involve reacting with four alkyne equivalents
What is the mechanism

Answer 18

Question 19

Cuprates undergo syn-selective carbocupration reaction with alkenes
What is the mechanism from this intermediate?

Answer 19

• Syn addition gives Z-alkenes
• Carbocupration can be used to make Z,Z dienes - very difficult to make any other way