Coupling reactions (CHY-412)

Cross-Coupling reactions (CHY-412)

HECK (1972)
SONOGASHIRA (1975)
NEGISHI (1977)
STILLE (1978)
SUZUKI-MIYAURA (1979)
Cross-Coupling reactions (CHY-412)
Cross-Coupling reactions (CHY-412)
 HECK Cross-Coupling reaction (CHY-412)

The Mizoroki–Heck Reaction

 HECK Cross-Coupling reaction (CHY-412)

The Mizoroki–Heck Reaction

 HECK Cross-Coupling reaction (CHY-412)

In the late 1960s, Heck

 HECK Cross-Coupling reaction (CHY-412)

In 1971, Mizoroki et al

In 1972, Heck and Nolley

HECK Cross-Coupling reaction (CHY-412)
 HECK Cross-Coupling reaction (CHY-412)

Mechanism of the Mizoroki–Heck Reaction when the Catalytic Precursor is Pd(OAc)2 in the Absence of Ligand
HECK Cross-Coupling reaction (CHY-412)
 HECK Cross-Coupling reaction (CHY-412)

Mechanism of the Mizoroki–Heck Reaction when the Catalytic Precursor is Pd(OAc)2 Associated with
Monophosphine Ligands

Pd(0) Formation from Pd(OAc)2 in the Presence of a Monophosphine Ligand

 HECK Cross-Coupling reaction (CHY-412)

Phosphine, Amines and Alkenes as Factors Affecting the Rate of the Oxidative Addition

that excess PPh3 slows down the oxidative addition by formation

 HECK Cross-Coupling reaction (CHY-412)

The oxidative addition is also slower when performed in the presence of NEt3, which stabilizes Pd0(PPh3)2(OAc)− versus its
decomposition by protons to the most reactive bent Pd0(PPh3)2
HECK Cross-Coupling reaction (CHY-412)
 HECK Cross-Coupling reaction (CHY-412)

Multiple Role of the Base

the base stabilizes Pd0(PPh3)2(OAc)− versus its decomposition to Pd0(PPh3)2 by protons

the base slows down the oxidative addition
the base accelerates the carbopalladation step by increasing the concentration of the reactive PhPd(OAc)L2
HECK Cross-Coupling reaction (CHY-412)
 HECK Cross-Coupling reaction (CHY-412)

electron-poor alkenes generally react smoothly, delivering mainly the trans-isomer of the b-substituted product.

Vinyls with an electron-donating substituent generally form a mixture of the products in the presence of
monodentate ligands (or without ligands)
HECK Cross-Coupling reaction (CHY-412)
HECK Cross-Coupling reaction (CHY-412)
 HECK Cross-Coupling reaction (CHY-412)

weakly coordinating triflate or tosylate is used as the leaving group,

the reaction proceeds via the cationic route.

strongly coordinating bidentate ligands

aryl halides as aryl palladium precursors

the neutral intermediate predominates

To achieve a high α-selectivity with aryl bromides

and iodides, an additive, often a silver or a thallium salt, is required to
scavenge the halide

α-regioselectivity with both organic bromides and aryl iodides by simply

increasing the polarity of the reaction system (ionic liquids or water.

The regioselectivity for electron-rich alkenes is determined by the nature of the π-complex.
In a positively charged π-complex, the organopalladium moiety is generally stabilized by an uncharged bidentate phosphine or nitrogen ligand (Figure 3.1, cationic route)
In a neutral π-complex, palladium coordinates one ligand and one anionic counter ion, usually a halide (Figure 3.1, neutral route).

The positively charged π-complex will lead to the α-product, while the neutral π-complex will give rise to a mixture of the α- and β-substituted products
HECK Cross-Coupling reaction (CHY-412)
HECK Cross-Coupling reaction (CHY-412)
 HECK Cross-Coupling reaction (CHY-412)

Cyclic Alkenes and Double-Bond Migration

HECK Cross-Coupling reaction (CHY-412)
Sonogashira coupling reaction (CHY-412)

Br

O OH

CO2Me
Negishi Cross-Coupling Reaction (CHY-412)
Nigishi Cross-Coupling Reaction (CHY-412)
Nigishi Cross-Coupling Reaction (CHY-412)
Stille Cross-Coupling Reaction (CHY-412)
Suzuki cross coupling reaction (CHY-412)
Organosilicon chemistry (CHY-412)
Organosilicon chemistry (CHY-412)
Buchwald-Hartwig Coupling (CHY-412)