Organic Chemistry

27. Transition Metals

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Organic Chemistry
27. Transition Metals

CONCEPT: THE ELECTRON CONFIGURATION

● Electron configurations represent the arrangement of electrons within ___________ & ___________.

Periodic Table (s, p, d, f blocks)

1A 8A
(1) (8)
2A 3A 4A 5A 6A 7A
1 (2) (3) (4) (5) (6) (7)

2 ___ - block
3B 4B 5B 6B 7B 8B 1B 2B
3 Si ___ - block

4
___ - block
5
___ - block
6

EXAMPLE: Write the full ground-state electron configuration for the following element:
Si (Z = 14)

Condensed Electron Configurations

● With condensed electron configurations, we start at the last ________________ before the desired element.

EXAMPLE: Write the condensed electron configuration for the following element:
Ca (Z = 20)

Charged Electron Configurations

● With a cation, we first remove electrons from the highest shell number (n value).
□ n value represents the _______________ quantum number and deals with the atomic orbital’s size and energy.
□ The quantum number provides the shell number or energy level of the electron.
1s2 2s2 2p6 3s2 3p6

n= n= n=

EXAMPLE: Write the condensed electron configurations for the element and its ion:
V (Z = 23) V3+ (Z = 23)

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CONCEPT: ELECTRON CONFIGURATIONS OF TRANSITION METALS

● The transition metals are the elements in the _____ – block or Group _____ of the periodic table.
□ Within a given period, a transition metal fills its ____ – orbital in the n quantum level followed by its ____ – orbital.

Periodic Table (s, p, d, f blocks)

Electron Orbital Diagrams

____ sub-level contains 1 electron orbital

3B 4B 5B 6B 7B 8B 1B 2B

Ti Co ____ sub-level contains 3 electron orbitals

____ sub-level contains 5 electron orbitals

____ sub-level contains 7 electron orbitals

EXAMPLE: Write the full ground-state electron configuration and electron orbital diagram for the following element:
Ti (Z = 22)

PRACTICE: Write the condensed configuration for the following element:

Co+ (Z = 27)

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Organic Chemistry
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CONCEPT: ELECTRON CONFIGURATION EXCEPTIONS

● Starting from chromium, as the atomic number (Z) ____________ exceptions to electron configurations can be observed.
□ s orbitals can be promoted to create half-filled orbitals with ___- elements.

Cr (Z = 24) Ar 4s23d4

Ar Ar

□ s orbitals can be promoted to create totally-filled orbitals with ___- elements.

Cu (Z = 29) Ar 4s23d9

Ar Ar

□ There are more advanced explanations for the exceptions, but for the scope of this course we won’t go into them.

Periodic Table (Transition Metals)

3B 4B 5B 6B 7B 8B 1B 2B

21 22 23 24 25 26 27 28 29 30
Period 4 Sc Ti V Cr Mn Fe Co Ni Cu Zn
39 40 41 42 43 44 45 46 47 48
Period 5 Y Zr Nb Mo Tc Ru Rh Pd Ag Cd
57 72 73 74 75 76 77 78 79 80
Period 6 La Hf Ta W Re Os Ir Pt Au Hg
89 104 105 106 107 108 109 110 111 112
Period 7 Ac Rf Db Sg Bh Hs Mt Ds Rg Cn

EXAMPLE: With an atomic number (Z) of 42, illustrate the exception to the electron configuration of molybdenum.
Mo (Z = 42)

EXAMPLE: Write the condensed electron configuration of the following ion:

Ag+ (Z = 47)

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Organic Chemistry
27. Transition Metals

CONCEPT: ELECTRON CONFIGURATION EXCEPTIONS

PRACTICE: Write the condensed electron configuration of the following ion:

PRACTICE: The palladium atom possesses a unique electron configuration, in which its d-orbital would prefer to be

completely filled. Based on this information, provide the electron configuration of both Pd 0 and Pd2+.

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CONCEPT: VALENCE ELECTRONS OF TRANSITION METALS

● The valence electrons represent the _________ shell electrons that are involved in the formation of chemical bonds.
□ For Main Group elements, the number of valence electrons is equal to the group number.

Group 1 Group 2 Group 3 Group 4 Group 5 Group 6 Group 7 Group 8

Na Mg Al Si P S Cl Ar

□ The valence of a transition metal (Metal M) is equal to ______ + ______ electrons.

Periodic Table (Transition Metals)

3B 4B 5B 6B 7B 8B 1B 2B

Valence e– ____ ____ ____ ____ ____ ____ ____ ____ ____ ____
21 22 23 24 25 26 27 28 29 30

Period 4 Sc Ti V Cr Mn Fe Co Ni Cu Zn
4s23d1 4s23d2 4s23d3 4s13d5 4s23d5 4s23d6 4s23d7 4s23d8 4s13d10 4s23d10
39 40 41 42 43 44 45 46 47 48

Period 5 Y Zr Nb Mo Tc Ru Rh Pd Ag Cd
5s24d1 5s24d2 5s14d4 5s14d5 5s24d5 5s14d7 5s14d8 4d10 5s14d10 5s24d10
57 72 73 74 75 76 77 78 79 80
Period 6 La Hf Ta W Re Os Ir Pt Au Hg
6s25d1 6s25d2 6s25d3 6s25d4 6s25d5 6s25d6 6s25d7 6s15d9 6s15d10 6s25d10
89 104 105 106 107 108 109 110 111 112
Period 7 Ac Rf Db Sg Bh Hs Mt Ds Rg Cn
7s26d1 7s26d2 7s26d3 7s26d4 7s26d5 7s26d6 7s26d7 7s26d8 7s16d10 7s26d10

EXAMPLE: How many valence electrons are present in the following ion?

PRACTICE: Provide the condensed electron configuration and the number of valence electrons for the following ion:

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CONCEPT: COORDINATION COMPLEXES

● The most prevalent feature of transition metal chemistry is the formation of coordination complexes or compounds.
□ These structures are composed of a complex ion that is connected to anions or molecules called __________.
□ In order to maintain the overall neutrality of the compound a _______________________ is used.

[Ni(NH3)4]Cl2 +

Coordination Numbers
● The coordination number is the number of ligands bonded to the central metal cation.
□ The most common coordination numbers are _____, _____, and _____.

EXAMPLE: Correctly label all the components of the coordination complex: Na2[SnCl6].

EXAMPLE: Determine the number of ligands in the complex ion: [Cr(H2O)4Br2]F.

Molecular Geometry of Coordination Complexes

● Coordination complexes form predictable geometries based on their coordination and their electron configuration.
Coordination Number Configuration Geometry Example
__________________________________________________________________________________
__________________________________________________________________________________

__________________________________________________________________________________

□ Coordination of 4: A _____ electron configuration forms tetrahedral complexes. ______ forms square planar complexes.

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CONCEPT: COORDINATION COMPLEXES

EXAMPLE: Determine the geometry for the following complex ion: [Cr(NH3)4Cl2]+.

PRACTICE: Determine the geometry for the following complex molecule: Pd(H2O)4.

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CONCEPT: LIGANDS
● A ligand represents a _________ base because it bonds to a metal cation in a complex ion by using its lone pair.
□ Since ligands use their lone pair(s) to grab onto metal cations they are referred to as ______________ agents.
□ Ligands are typically either ____________ (L-Ligands) or ____________ charged (X-Ligands).

● The number of elements in a molecule that can donate a lone pair characterizes a ligand.
□ Ligands that possess the ability to donate _____ lone pair at a time are referred to as Monodentate ligands.
□ Ligands that possess the ability to donate _____ lone pairs at a time are referred to as Bidentate ligands.
□ Bidentate ligands give rise to ___________ in the complex ion form.

Ligand Name Abbreviation Type (X or L) Ligand Name Abbreviation Type (X or L)

_______________________________________________________________________________________________________________________________________________________________________________________

_______________________________________________________________________________________________________________________________________________________________________________________

_______________________________________________________________________________________________________________________________________________________________________________________

_______________________________________________________________________________________________________________________________________________________________________________________
_______________________________________________________________________________________________________________________________________________________________________________________
_______________________________________________________________________________________________________________________________________________________________________________________

H 2O aqua ____

NH3 ammine or ammino ____

triarylphosphino H 2C CH2
ethylenediamine
PR3 ____
trialkylphosphino H 2N NH2
Monodentate LIgands

C O carbonyl CO
Bidentate LIgands

H3CC N acetonitrilo MeCN

____
H 2C CH2 ethylene
2–
O O
benzene Ph C C oxalato
–O O –

–
X halo X

– ____
H hydrido
–
C N cyano CN

– ____
hydroxido O O
O H
acetylacetonato

cyclopentadienyl Cp

____
– allyl

EXAMPLE: Provide the complex ion structure when a Ti3+ ion combines with 4 ammonia molecules and 2 chloro anions.

EXAMPLE: Provide the complex ion structure when Cu+ combines with ethylenediamine and 2 cyanide anions.

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CONCEPT: LIGANDS
PRACTICE: Provide the complex ion structure and geometry when a Ni atom combines with 2 chloro anions and 2 water
molecules.

PRACTICE: Provide the complex ion structure and geometry when a Co3+ ion combines with 3 ethylenediamines.

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CONCEPT: ELECTRON COUNTING

● In main-group chemistry, we use the ____________ rule as an indicator of reactivity.
□ If an element possessed less than 8 electrons around it then it would accept an electron pair.

● Electron count is also important in our understanding of the mechanistic basis of transition metal-catalyzed reactions.
□ To determine the electron count for a transition-metal complex we employ the following equation:

□ Valence of Metal M: ______ + ______ electrons.

□ QM = the _________ of the transition metal complex.

[Zn(H2O)4]2+ QM = _______ Pd(NH3)2Cl2 QM = _______

□ X-Type Ligands donate _____ electron(s) to the metal cation of the complex molecule or ion.
□ L-Type Ligands donate _____ electron(s) and doesn’t change the formal charge of the metal cation.

EXAMPLE: What is the electron count of the complex ion [Co(CN)6]3–?

PRACTICE: What is the electron count of the complex ion [Cr(NH3)4Cl2]+?

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Organic Chemistry
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CONCEPT: THE 18 AND 16 ELECTRON RULE

● Remember main-group elements want to follow the octet rule.
1A 8A
(1) (8)
2A 3A 4A 5A 6A 7A
1 (2) (3) (4) (5) (6) (7)

1A 2A 3A 4A 5A 6A 7A 8A 3B 4B 5B 6B 7B 8B 1B 2B
3
(1) (2) (3) (4) (5) (6) (7) (8)
3 4 5 6 7 8 9 10 4
2 Li Be B C N O F Ne
6.941 9.012 10.81 12.011 14.007 15.999 18.998 20.180 5
11 12 13 14 15 16 17 18
3 Na Mg Al Si P S Cl Ar
22.99 24.31 26.982 28.085 30.974 32.06 35.45 39.948 6

● In transition-metal chemistry, we use the 18 and 16-electron rule as an indicator for the reactivity of the transition metal.
□ The most stable transition-metal complexes in several cases have electron counts of _____ electrons.
□ This trend is called the ____ - electron rule.
□ This most stable number of electrons represents the number of total _____, _____, & _____ electrons.
1A 2A 3B 4B 5B 6B 7B 8B 1B 2B 3A 4A 5A 6A 7A 8A
(1) (3) (4) (5) (6) (7) (8)

___ ___ ___ ___ ___ ___ ___ ___ ___ ___
19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
4 K Ca Sc Ti V Cr Mn Fe Co Ni Cu Zn Ga Ge As Se Br Kr
39.10 40.08 44.956 47.867 50.942 51.996 54.938 55.845 58.933 58.693 63.546 65.38 69.723 72.630 74.922 78.971 79.904 83.798

18-Electron Rule Exceptions

● Exceptions happen most often with transition metals from the _____ to _____ valence electron groups.
□ The tendency of these metals to be happy with 16 electrons is called the ____ - electron rule.
□ _____ and _____ are the most common examples of transition metals following this rule.

EXAMPLE: What is the electron count of the neutral transition metal complex of Br2Pd(CO)2?

EXAMPLE: What is the electron count of the neutral transition metal complex of Pd(en)2?

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27. Transition Metals

CONCEPT: THE 18 AND 16 ELECTRON RULE

PRACTICE: How many NH3 ligands would need to be placed onto a nickel atom if we assume the resulting complex follows
the 18-electron rule?

PRACTICE: Using the 18-electron rule, explain why V(CO)6 can be easily reduced to [V(CO)6]–.

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CONCEPT: OVERVIEW OF CROSS-COUPLING GENERAL REACTIONS

● These reactions involve synthetic transformations that combine a(n) _____________ agent with a(n) ________________.
□ 2 driving forces: Formation of highly __________ products + the catalyst following the ____ or ____ electron rule.

Cross-Coupling Reaction
M–Ln
R1 X + R2 C R1 R2 + CX

● The R1 group in the reaction can be an ___________, ___________, ___________, ___________, or ___________.
□ The carbon halide being used is dependent on the type of coupling reaction.

Carbon Halides
X
X
X
R1
X
R1 will be these two types + other(s)

C
C
R2 X

R2 is usually one of these types + other(s)

● The Coupling Agent (C group) in the reaction is also dependent on the type of coupling reaction.

EXAMPLE: The Heck reaction is a well-known coupling reaction that involves the combining of a carbon halide with an
alkene. Base on the example provided determine a possible coupling product.

PRACTICE: In the Stille reaction, an organostannane compound reacts with a carbon halide in order to form a new carbon-
carbon bond. What would be the final product from the following Stille coupling reaction?

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CONCEPT: CROSS-COUPLING REACTION MECHANISMS

● The detailed mechanisms for many of these reactions are still debated, but it is accepted that all of them follow 3 stages:
□ These stages include (1) oxidative addition, (2) transmetallation and (3) reductive elimination.

1. Oxidative Addition
● A transition metal complex, M––Ln, reacts with a carbon halide by inserting itself into the R1––X bond.

□ This step can happen by a variety of mechanisms, but a ______________ (one-step) process is most common.

Oxidative Addition
R1 X + M Ln

□ Both of the new bonds formed behave like ______-type ligands, which causes the electron count to ______ by 2.
□ Recall, this part of the cycle is driven by the _____ or _____ electron rule.
EXAMPLE: Determine the new palladium complex that forms during this oxidative addition step.

PRACTICE: Determine the new cadmium complex that forms during this oxidative addition step.

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Organic Chemistry
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CONCEPT: CROSS-COUPLING REACTION MECHANISMS

2. Transmetallation
● The R2 group of the coupling agent is transferred to the metal complex, while at the same time the ______ group leaves.

Transmetallation

R1 M L n + R 2 C
X

□ The term “transmetallation” generally involves the interchanging of ligands between two metals or metalloids.

EXAMPLE: Determine the product(s) formed in the following reaction sequence.

Pd(OAc)2 B(OCH3)3
Br
A B
Oxidative Addition Transmetallation

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CONCEPT: CROSS-COUPLING REACTION MECHANISMS

3. Reductive Elimination
● Both the _____ and _____ leave the metal complex and form a sigma bond between one another to end the reaction.
□ This step is basically the opposite of the oxidative addition step.
□ It is not always a typical elimination that generates a pi bond.

Stereochemistry
● Typically, reductive elimination generally results in the _________________ of stereochemistry.

EXAMPLE: Determine the final product in the following reaction.

□ Reduction is seen as the gaining of electrons and a ______________ in an element’s oxidation number.
□ When the two _____-type ligands are lost the oxidation state of the metal decreases by 2.
□ At the same time, the formation of a conjugated product allows for the unstable catalyst to be regenerated.
Mechanism Cycle
● These 3 stages together help to form a _______________ cycle to show product formation and catalyst regeneration.

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CONCEPT: HECK REACTION

● The Heck Reaction involves the coupling between a carbon halide and an alkene in the presence of a Pd catalyst.
□ The R group of the carbon halide is substituted for a(n) _______________ hydrogen of an alkene.

Cross-Coupling Reaction Heck Reaction

H R
[Pd] cat.
M–Ln R X HX
R1 X + R2 C R1 R2 + CX + Base +
Carbon Halide Coupling Agent Coupling Product Byproduct

□ The R1 group of the carbon halide is represented by a(n) vinyl, aryl + ____________ group.
□ The R2 group is represented by a(n) ____________ group.
□ The C group = ______.
□ The X leaving group of the carbon halide is represented by a Cl, Br, I or OTf group.
□ The Base = ________, ________ or ________.
Regioselectivity
● The reaction is highly regioselective, with the R1 group going to the ________ substituted position of the alkene.

Stereoselectivity
● If an E or Z configuration is possible at the alkene, the reaction is highly stereoselective, often giving _____ as the major.

EXAMPLE: Determine the product from the following Heck Reaction.

The Alkene
● The reactivity of the alkene (R2) _____________ with increasing substitution.
□ Highest yields are obtained for ___________ and _______________________ with electron withdrawing groups.

Electron Withdrawing Groups Nonsubstituted

Strong Moderate Weak
O O
+
N
+
_ NR3 CX3 SO3H CN C R H2C CH2
O

EXAMPLE: Rank the following alkenes in order of increasing reactivity towards the Heck Reaction.

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Organic Chemistry
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CONCEPT: HECK REACTION

PRACTICE: Determine the product from the following Heck Reaction.
O
Pd(OAc)2 , PPh3
OEt
+ I NaHCO3 , DMF

PRACTICE: Predict the product formed from the following intramolecular Heck reaction.

PRACTICE: Using ethyl-2-butenoate as your starting material, prepare the following compound by a Heck reaction.

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CONCEPT: HECK REACTION MECHANISM

● The Heck Reaction mechanism occurs via a catalytic cycle that is comprised of _____________________ intermediates.

Cross-Coupling Reaction Heck Reaction

H R
[Pd] cat.
M–Ln R X HX
R1 X + R2 C R1 R2 + CX + Base +
Carbon Halide Coupling Agent Coupling Product Byproduct

Coupling Mechanism
1) Oxidative Addition: Involves the addition of the carbon halide to the transition metal complex.
L
PdL2
R X Pd L

2) Syn Addition: The resulting complex reacts with the alkene and adds R1 and Pd across the pi bond on the same side.
L
H + Pd L

3a) Reductive Elimination 1: New complex undergoes a C–C bond rotation followed by syn elimination to give the alkene.

60º C––C Bond

Rotation Reductive Elimination

3b) Reductive Elimination 2: The base ( _________ or_________ ) removes HX to regenerate the palladium catalyst.
L
Base
H Pd L L Pd L
X

EXAMPLE: A Heck reaction between (Z)-3-hexene and bromoethene creates both (Z)-3-ethyl-1,3-hexadiene and (E)-3-
ethyl-1,4-hexadiene. Illustrate how both products can be formed.

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CONCEPT: STILLE REACTION

● In the Stille reaction, an organostannane compound reacts with a carbon halide in order to form a new C––C bond.
□ The reaction creates conjugated compounds composed of alkenes, __________ or __________ compounds.
Cross-Coupling Reaction Stille Reaction
M–Ln [Pd] cat.
R1 X + R2 C R1 R2 + CX R1 X + R2 Sn(R)3 R1 R2 + Sn(R)3X
Carbon Halide Coupling Agent Coupling Product Byproduct

□ The R1 group of the carbon halide is represented by a(n) vinyl, aryl + _________ group.
□ The R2 group of the organostannane is represented by a(n) vinyl, aryl + _________ group.
□ The C = Sn(R)3 with the R group of the organostannane is represented by a(n) _________ group.
□ The X group of the carbon halide is represented by a Cl, Br, I or OTf group.

● When creating conjugated dienes, the reaction is observed to be ___________________ with retention of configurations.

PRACTICE: Determine the product from the following Stille Reaction.

Br
Me3Sn Pd(PPh3)4
+
(E)-Alkene
(E)-Alkene
O

Coupling Mechanism
1) Oxidative Addition: Involves the addition of the carbon halide to the transition metal complex.
PdL2
R1 X'

2) Transmetallation: The R2 group transfers from the organostannane to the Pd metal complex.
L R
R1 Pd L + R2 Sn R
X R

3) Reductive Elimination: This step forms the coupling product.

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Organic Chemistry
27. Transition Metals

CONCEPT: STILLE REACTION

PRACTICE: Determine the product from the following Stille Reaction.

PRACTICE: Determine the product from the following Stille Reaction.

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CONCEPT: SUZUKI REACTION

● The Suzuki coupling reaction involves the coupling between a carbon halide and an organoboron compound (RBY 2).
□ The reaction creates conjugated compounds composed of alkenes, __________ or __________ compounds.
Cross-Coupling Reaction Suzuki Coupling Reaction
M–Ln [Pd] cat.
R1 X + R2 C R1 R2 + CX R1 X + R2 BY2
NaOEt or NaOMe
R1 R2 + BY2X
Carbon Halide Coupling Agent Coupling Product Byproduct

□ The R1 group of the carbon halide is represented by a(n) vinyl or aryl group.
□ The R2 group of the organoborane is represented by a(n) vinyl, aryl + _________ group.
□ The C group = BY2 with the Y group represented by a(n) ____ (boronic acid), ____ (boronic ester) or alkyl group.
□ The X group of the carbon halide is represented by a Cl, Br, I or OTf group.

● When creating conjugated products, the reaction is observed to be ______________ with retention of configurations.

EXAMPLE: Determine the product from the following Suzuki Coupling Reaction.
CH2CH3
Br Pd(Ph3)4
B + NaOEt
CH2CH3

Coupling Mechanism
1) Oxidative Addition: Involves the addition of the carbon halide to the transition metal complex.
PdL2
R1 X

2) Transmetallation: The R2 group transfers from the organoborane to the Pd metal complex.
L
R1 Pd L + R2 BY2
X

3) Reductive Elimination: This step forms the coupling product.

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CONCEPT: SUZUKI REACTION

PRACTICE: Determine the product from the following Suzuki Reaction.
Pd(OAc)2
+ B(OH)2 NaOEt
Br

PRACTICE: Predict the structures of organoborane compound A and coupling product B in the following reaction
sequence.
O
B H
O Br
A B
Pd(PPh3)4 , NaOMe

PRACTICE: Beginning from 1-pentyne, synthesize the following compound via a Suzuki Coupling Reaction.

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CONCEPT: SONOGASHIRA COUPLING

● The Sonogashira Coupling reaction involves the coupling between an aryl or vinyl halide and a terminal alkyne.
□ Co-catalysts: A pair of ___________________ catalysts that improve each others’ catalytic performance.
□ Generally, the reaction uses a Pd catalyst and a Cu co-catalyst to form a ________ or ________ alkynyl product.
Cross-Coupling Reaction Sonogashira Coupling Reaction
M–Ln [Pd] cat., [Cu(I)] cat.
R1 X + R2 C R1 R2 + CX R1 X + R2 H R1 R2 + HX
Base
Carbon Halide Coupling Agent Coupling Product Byproduct

□ The R1 group of the carbon halide is represented by a(n) vinyl or aryl group.
□ The R2 group of the alkyne is represented by a(n) vinyl or aryl group.
□ The C group = _______.
□ The X group of the carbon halide is represented by a Cl, Br, I or OTf group.
□ The Base group = _______.
EXAMPLE: Determine the product from the following Sonogashira Coupling Reaction.

Pd(PPh3)4 , CuI
OTf + Et3N

Coupling Mechanism
● The Sonogashira Coupling is a Pd-catalyzed reaction of a Cu(I)-alkynyl complex with a vinyl or aryl halide.
0) Co-catalyst Formation: Created by the reaction of a terminal alkyne with CuI and an amine.

1) Oxidative Addition: Involves the addition of the carbon halide to the transition metal complex.

2) Transmetallation: The alkynyl group of the Cu(I)-alkynyl compound transfers from Cu to the Pd complex.

3) Reductive Elimination: This step forms the coupling product.

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CONCEPT: SONOGASHIRA COUPLING

PRACTICE: Determine the product from the following Sonogashira Reaction.

+ H Pd(PPh3)4 , CuI

I Et2NH

PRACTICE: Determine compounds A, B, and C from the following reaction sequence.

Otf
1) Br2, hv 1) Br2
A B C
2) NaOtBu 2) NaNH2 (xs) Pd(PPh3)4
CuI, Et3N
3) H2O

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CONCEPT: FUKUYAMA COUPLING

● The Fukuyama Coupling reaction involves the coupling between a thioester and an organozinc halide with a Pd catalyst.
□ The reaction creates a ______________ product.
Cross-Coupling Reaction Fukuyama Coupling Reaction
O O
M–Ln [Pd] cat.
R1 X + R2 C R1 R2 + CX + R2 ZnI + ZnI SEt
R1 SEt Toulene R1 R2
Carbon Halide Coupling Agent Coupling Product Byproduct

□ The R1 group of the thioester is represented by a(n) vinyl or aryl group.

□ The R2 group of the organozinc halide is represented by a(n) _______ group.
□ The C group = _______.

EXAMPLE: Determine the product from the following Fukuyama Coupling Reaction.
O
PdBr2(PPh3)2
SEt + Et ZnI
Toulene

Coupling Mechanism
● Unlike the Grignard Reagent, the organozinc halide stops at the ketone instead of proceeding to a _____ alcohol.
1) Oxidative Addition: Involves the addition of the thioester to the Pd complex.
O [Pd] cat.
Toulene
R1 SEt
2) Transmetallation: The R2 group of the organozinc compound transfers from Zn to the Pd complex.
O

R1 Pd SEt + R2 ZnI
3) Reductive Elimination: This step forms the coupling product.

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CONCEPT: FUKUYAMA COUPLING

PRACTICE: Determine the product from the following Fukuyama Reaction.
O
PdCl2(PPh3)2
SEt + Me ZnI Toulene
Br

PRACTICE: Determine compounds A, B, and C from the following reaction sequence.

O ZnI

SOCl2 EtSH
OH A B C
pyridine TsOH Pd(PPh3)4
Toulene

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CONCEPT: KUMADA COUPLING

● The Kumada Coupling reaction involves the coupling between a carbon halide and Grignard Reagent.
□ The reaction uses a Pd or Ni catalyst in the formation of _________ or _________ products.
□ The use of a Pd or Ni catalyst allows for stereoselectivity with the Grignard reagent.
Cross-Coupling Reaction Kumada Coupling Reaction
M–Ln [Pd] cat or [Ni] cat.
R1 X + R2 C R1 R2 + CX R1 X' + R2 MgX R1 R2 + XMg X'
Carbon Halide Coupling Agent Coupling Product Byproduct

□ The R1 group of the carbon halide is represented by a(n) vinyl or aryl group.
□ The R2 group of the Grignard reagent is represented by a(n) vinyl, aryl + _________ group.
□ The C group = MgX with the X group represented by a(n) ______, ______ or ______.
□ The X’ group of the carbon halide is represented by a(n) Cl, Br, I or OTf group.

EXAMPLE: Determine the product from the following Kumada Coupling Reaction.

NiCl2(PPh3)2
Br + Me MgBr

Stereoselectivity
● The stereochemistry of a vinyl halide is ____________ when an alkyl Grignard reagent is used in the reaction.
Br [NiCl2(dpe)] [NiCl2(dpe)]
+ Et MgBr + Et MgBr
(Z)-Alkene Br
(E)-Alkene

● A _______________ of products are possible when a vinyl or aryl Grignard reagent is used in the reaction.
Cl [NiCl2(dpe)]
+ Ph MgBr
(Z)-Alkene

Chemoselectivity
● The Grignard reagent does not readily couple with aryl _______________.
Br MgBr
[NiCl2(dpe)]
+

Cl

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Organic Chemistry
27. Transition Metals

CONCEPT: KUMADA COUPLING

PRACTICE: Determine the product from the following Kumada Reaction.
MgBr
Br PdCl2(PPh3)2
+

PRACTICE: Determine the coupling product for the following Kumada reaction.
I I
O MgBr
+ [NiCl2(dpe)]

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Organic Chemistry
27. Transition Metals

CONCEPT: NEGISHI COUPLING

● The Negishi reaction involves the coupling between a carbon halide and an organozinc halide with a Pd or Ni catalyst.
□ The reaction uses a Pd or Ni catalyst in the formation of _________ or _________ products.
Cross-Coupling Reaction Negishi Coupling Reaction
M–Ln [Pd] cat or [Ni] cat.
R1 X + R2 C R1 R2 + CX R1 X' + R2 ZnX R1 R2 + ZnX X'
Carbon Halide Coupling Agent Coupling Product Byproduct

□ The R1 group of the carbon halide is represented by a(n) vinyl, aryl + _______, _______, or _______ group.
□ The R2 group of the organozinc halide is represented by a(n) vinyl, aryl + _______, _______, or _______ group.
□ The C group = ZnX with the X group represented by a(n) _____ or _____.
□ The X’ group of the carbon halide is represented by a Cl, Br, I or OTf group.

EXAMPLE: Determine the product from the following Negishi Coupling Reaction.
Br Pd(PPh3)4
+
BrZn

Coupling Mechanism
1) Oxidative Addition: Involves the addition of the carbon halide to the transition metal complex.

PdL2
R1 X

2) Transmetallation: The R2 group of the organozinc compound transfers from Zn to the Pd complex.

L
R1 Pd L + R2 ZnX
X

3) Reductive Elimination: This step forms the coupling product.

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Organic Chemistry
27. Transition Metals

CONCEPT: NEGISHI COUPLING

PRACTICE: Determine the product from the following Negishi Coupling Reaction.
Br
Pd(PPh3)4
+ BrZn

PRACTICE: Determine the product from the following Negishi Coupling Reaction.
Br + [NiCl2(PPh3)2]
ClZn

Br

PRACTICE: Determine compounds A and B from the following reaction sequence.

Cl
Zn
A B
I Et2O Pd(PPh3)4

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Organic Chemistry
27. Transition Metals

CONCEPT: BUCHWALD-HARTWIG AMINATION

● The Buchwald-Hartwig Amination reaction involves the coupling between an aryl halide and an amine with a Pd catalyst.
□ The reaction creates a bond between C––N in the formation of an _________________.
Cross-Coupling Reaction Buchwald-Hartwig Amination
R2 R2
M–Ln [Pd] cat
R1 X + R2 C R1 R2 + CX X + N H N + HX
R3 Base R3
Carbon Halide Coupling Agent Coupling Product Byproduct

□ The R1 group of the carbon halide is represented by a(n) _________ group.

□ The R2 group of the amine are represented by a(n) H, _________ or _________ group.
□ The R3 group of the amine are represented by a(n) H, _________ or _________ group.
□ The C group = ______.
□ The X group of the carbon halide is represented by a Cl, Br, I or OTf group.
□ The Base group = ______
EXAMPLE: Determine the product from the following Buchwald-Hartwig Amination Reaction.

Pd(OAc)2
+ N NaOtBu
Br H

Coupling Mechanism
0) Partial Dissociation: The coupling mechanism begins with the partial dissociation of the palladium catalyst.

PdL2

1) Oxidative Addition: Involves the addition of the aryl halide to the transition metal complex.

PdL + Ar X

2) Ligand Substitution: The transmetallation step is replaced by this step with the amine compound.

R2NH
Ar Pd L Base
X
3) Reductive Elimination: This step forms the coupling product.

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Organic Chemistry
27. Transition Metals

CONCEPT: BUCHWALD-HARTWIG AMINATION

PRACTICE: Determine the product from the following Buchwald-Hartwig Amination Reaction.
Cl H
N
Pd(PPh3)2
+
NaOtBu
O

PRACTICE: Determine compounds A and B from the following reaction sequence.

NH2
OH Tf2O
A B
CH2Cl2 Pd(OAc)2
NaOtBu

PRACTICE: Outline the synthetic pathway for the creation of p-dimethylaminoacetophenone from bromobenzene.
O

p-dipropylaminoacetophenone

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Organic Chemistry
27. Transition Metals

CONCEPT: EGLINTON REACTION

● The Eglinton Coupling Reaction involves the coupling between 2 identical terminal alkynes with a Cu catalyst and base.
□ The reaction uses a Cu catalyst in the formation of a ______________ product.
□ Like coupling reactions, the driving forces are forming of ___________ products and the catalyst’s electron count.
□ Unlike the other coupling reactions, it doesn’t use a catalytic cycle and instead ___________.

Eglinton Coupling Reaction

Cu(I), [Cu(II)] cat.
R1 H + R2 H R1 R2
pyridine

□ The R1 group of the terminal alkyne is represented by a(n) vinyl, aryl + ___________ or ___________ group.
□ The R2 group of the terminal alkyne is represented by a(n) vinyl, aryl + ___________ or ___________ group.

EXAMPLE: Determine the product from the following Eglinton Coupling Reaction.

Coupling Mechanism
1) Deprotonation: The slight acidity of the terminal alkyne hydrogen allows it to be deprotonated by the pyridine base.

R1 H +
N
2) Substitution: The alkylnide ion formed during deprotonation undergoes a substitution with CuOAc.

R1 + Cu OAc

3) Radicalization: The newly formed C––Cu bond undergoes homolytic cleavage in order to form an alkylnide radical.
AcO OAc
R1 Cu + Cu
4) Dimerization: The final step involves the dimerization of the two alkylnide radicals that have been formed.

R1 + R2

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Organic Chemistry
27. Transition Metals

CONCEPT: EGLINTON REACTION

PRACTICE: Determine compounds A and B from the following reaction sequence.
Cl
Cl
1) NaNH2 (excess) Cu(OAc)2
2) H2O
A pyridine
B

PRACTICE: Predict the product formed from the following intramolecular Eglinton reaction.
Cu(OAc)2
3 pyridine

Page 35