C-C Bond Formation Flashcards
Other Cross Coupling Reaction
Metal = Boron - suzuki
= Tin - Stille
= Zinc - Negeishi
= Magnesium - kumada
Others are toxic or air/moisture sensitive/too reactive
Suzuki Miyaura Catalytic Cycle
- Oxidative Addition
- transmetallation
- reductive elimination
Alkyl Halide Reactivity
I > Br/Otf >>> Cl
Electronic Reactivity
Most electron deficient/electrophilic carbon is most reactivity to oxidative addition
EWG > nothing > EDG
Benefits of Suzuki Miyaura
- functional group tolerance (carbonyls, acidic hydrogen)
- High steric tolerance
Boronic acid syntheses
- Classic Method
Grignard or lithium benzenes react with trialkyl borates
(ortholithiation)
- Miyaura Borylation
suzuki reaction but with mild base
Classic Method pros cons
pros
cheap reagents
simple chemistry
cons
no chemoselectivity
can’t use highly functionalised substrate (carbonyls, acidic H)
Miyaura Borylation Pros and Cons
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
Why does miyaura borylation work
Mild base doesn’t form ate complex
Carbon Monoxide Suzuki reaction
Inserts inbetween alkyl-metal bond after oxidative addition creating ketones
Heck Reaction
reaction of aryl halide with alkene forming longer alkene
Trans selectively
Heck reaction Catalytic cycle
- oxidative addition
- olefin coordination
- alkyl migration
- beta-H elimination
- decoordination
- reductive elimination of H-X
Advantage of Intramolecular Heck Reaction
- creates rings
- can use much more sterically hindered substrates
forms most stable ring
alkene not always in same spot as initally
pros cons of Heck Reaction
pros
High functional group tolerance
cons
can only use monosubbed alkenes for intermolecular
Miyaura Borylation Details
alkyl halide reacts with pinacol borane in presence of Pd and mild base to form boronate ester
Alkynyl Miyaura Borylation
react alkyne instead of alkyl halide
cis addition creates trans alkene boronate ester
Akyl miyaura borylation
react alkene instead of alkyl halide
get alkyl boronate ester
still trans orientation
