C-C Bond Formation

Question 1

Other Cross Coupling Reaction

Answer 1

Metal = Boron - suzuki

= Tin - Stille

= Zinc - Negeishi

= Magnesium - kumada

Others are toxic or air/moisture sensitive/too reactive

Question 2

Suzuki Miyaura Catalytic Cycle

Answer 2

1. Oxidative Addition
2. transmetallation
3. reductive elimination

Question 3

Alkyl Halide Reactivity

Answer 3

I > Br/Otf >>> Cl

Question 4

Electronic Reactivity

Answer 4

Most electron deficient/electrophilic carbon is most reactivity to oxidative addition

EWG > nothing > EDG

Question 5

Benefits of Suzuki Miyaura

Answer 5

• functional group tolerance (carbonyls, acidic hydrogen)
• High steric tolerance

Question 6

Boronic acid syntheses

Answer 6

1. Classic Method

Grignard or lithium benzenes react with trialkyl borates

(ortholithiation)

2. Miyaura Borylation

suzuki reaction but with mild base

Question 7

Classic Method pros cons

Answer 7

pros

cheap reagents

simple chemistry

cons

no chemoselectivity

can’t use highly functionalised substrate (carbonyls, acidic H)

Question 8

Miyaura Borylation Pros and Cons

Answer 8

Pros

High functional group tolerance

create highly functionalised boronic acids

can make alkenyl/alkyl boranes (trans selectively)

more stable product

cons

more complex and expensive

Question 9

Why does miyaura borylation work

Answer 9

Mild base doesn’t form ate complex

Question 10

Carbon Monoxide Suzuki reaction

Answer 10

Inserts inbetween alkyl-metal bond after oxidative addition creating ketones

Question 11

Heck Reaction

Answer 11

reaction of aryl halide with alkene forming longer alkene

Trans selectively

Question 12

Heck reaction Catalytic cycle

Answer 12

1. oxidative addition
2. olefin coordination
3. alkyl migration
4. beta-H elimination
5. decoordination
6. reductive elimination of H-X

Question 13

Advantage of Intramolecular Heck Reaction

Answer 13

1. creates rings
2. can use much more sterically hindered substrates

forms most stable ring

alkene not always in same spot as initally

Question 14

pros cons of Heck Reaction

Answer 14

pros

High functional group tolerance

cons

can only use monosubbed alkenes for intermolecular

Question 15

Miyaura Borylation Details

Answer 15

alkyl halide reacts with pinacol borane in presence of Pd and mild base to form boronate ester

Question 16

Alkynyl Miyaura Borylation

Answer 16

react alkyne instead of alkyl halide

cis addition creates trans alkene boronate ester

Question 17

Akyl miyaura borylation

Answer 17

react alkene instead of alkyl halide

get alkyl boronate ester

still trans orientation