H y d ro g e n A t o m Tr a n s f e r b y H i g h - Va l e n t N i c k e l

Complexes
Mini Project Viva Voce Presentation

M S Va s u d e v
Under the Supervision of
M . S a n k a ra l i n g a m

N a t i o n a l Institute of Techno lo g y C a l i c u t
Department of Chemistry
M a y 7, 2024
Presentation Outline 2

• Introduction
• Synthetic strategies to
prepare High-Valent
Nickel complexes
• High-Valent nickel mediated HAT
• Conclusion and Future works
• References
Introduction
Historical Perspective and Early Developments 4

In the mid and Late twentieth century

► In the mid-20th century, transition metal catalysis, including nickel catalysis, began to
emerge as a field of interest in organic synthesis. Initial studies focused on
homogeneous nickel complexes as catalysts for various transformations, such as
cross-coupling reactions and hydrogenation.
► The late 20th century witnessed the initial forays into nickel-catalysed HAT reactions,
albeit in a limited capacity. The scientists began to explore the ability of nickel
complexes to facilitate HAT processes, particularly in the context of radical-mediated
transformations.
Mi l es to ne Di s co v ery 5

► The 2010s marked a turning point in the field, with seminal studies showcasing
the potential of high-valent nickel complexes for HAT reactions.
► One of the milestone contributions in the discovery of hydrogen atom transfer
(HAT) by high-valent nickel complexes can be attributed to the work of Sanford
and co-workers.
Mi l es to ne Di s co v ery 6

• Sanford and coworkers probed intramolecular C-H bond activation by using

scorpionate ligand bis(2-pyridyl) (2- Rphenyl)-fluoromethane as a model system. 1

R R

F F

CF3 CF3
NFTPT N NiIV
N NiII
CF3 CF3
CH2Cl2 N F
N
25oC, 10min
-HOTF
-Me3py

OTf
NFTPT=
N
F
Sy nthe ti c Str ate gi es to prepa re
Hi g h-Va l ent Ni cke l co mpl e x e s
Types 8

1. Oxidation Reactions

2. Ligand Exchange
Reactions
3. Redox Chemistry

4. Photo Chemical Methods

Ox i da ti o n Rea cti ons 9

► One of the most straightforward methods for preparing high-valent nickel complexes
is through oxidation reactions of lower-valent nickel species. This can be achieved
using various oxidizing agents, such as halogens, peroxides, or metal oxidants.

► For example, hillhouse and coworkers proposed a High-valent Nickel (III)

Intermediate after exposing the Ni (II) precursor(stabilized by bipyridyl ligand to either
O2 or I2 at room temperature2.
Li g a nd Ex cha ng e Rea cti o ns 10

► Ligand exchange reactions can also be employed to generate high-valent nickel

complexes by replacing labile ligands coordinated to nickel with stronger σ-
donating ligands. This can result in increased electron density on the nickel center,
leading to higher oxidation states.

► For example, Mirica and coworkers published a series of Ni(III) (aryl)halide

complexes stabilized by the ligand N,N ’-ditert-butyl-2,1 1-diaza[3,3](2,6)
pyridiophane. The Ni(III)aryl halide complex undergoes a rapid ligand exchange
reaction with Grignard reagent to yield a detectable Ni(III)(aryl)(alkyl) complex
followed by C-C bond formation 3.
Redo x Chemi s try 11

► Redox chemistry involving nickel complexes and external oxidants or reductants can
be employed to access high-valent nickel species. This approach often involves
reversible redox processes that allow for the generation and manipulation of different
oxidation states of nickel.

► For example, liang and coworkers designed and synthesized NiFeCu catalyst via sol-
gel method and demonstrated that the introduction of embedded Cu could regulate the
electron arrangement and effectively promote the formation of high-valent Ni sites 4.
Pho to c hemi ca l Methods 12

► Photochemical methods offer an alternative approach to generate high-valent nickel

complexes by utilizing light as an energy source to drive oxidation or reduction
reactions.
► For example, Jamison and coworkers reported the photochemical oxidation of Ni(II)
to Ni(III) to activate the nickel catalyst for reductive elimination using photoexcited
ruthenium and iridium complexes 5.
L i g a n d D e s i g n a n d t h e i r i n f l u e n c e o n t h e re a c t i v i t y o f 13
complexes

► Ligand design plays a critical role in modulating the reactivity of high-valent nickel
complexes, influencing their stability, selectivity, and catalytic activity in various
chemical transformations.
► Here is a note highlighting the importance of ligand design and its effects on the
reactivity of high-valent nickel complexes:
► Salen Ligands
► Ligand Flexibility
► Ancillary Ligands
Salen Ligands 14

► Salen ligands (N,N’-bis(salicylidene)-1,2-cyclohexanediamine) are redox-active

ligands. These ligands can act as electron reservoirs, enhancing the reactivity of high-
valent nickel complexes.
► For example, Apparao and coworkers isolated and probed the nickel(III) salen
complex which exhibits hydrogen atom abstraction and oxygen atom transfer
reactivity6.
Salen Ligands 15

Nickel (III) salen complex which exhibits HAA reactivity. 6

3

7eq. mCPBA
CH3CN, -40O C
N N N N
Ni Ni
O O O C(CH3)3
3(H3C)C
O C(CH3)3 3 (H3 C)C

C(CH3)3 C(CH3)3 C(CH3)3

C(CH3)3
Ligand Flexibility 16

• The flexibility of ligands significantly impacts the reactivity of the nickel center. Different
ligand geometries can lead to distinct electronic structures and reactivity patterns.

• For example, ligands that allow for structural changes (such as bending or twisting) can
influence the activation of substrates and facilitate bond-breaking or bond-forming
processes7.
Ancillary Ligands 17

► Ancillary ligands are additional ligands in a coordination complex that are not
directly involved in substrate binding or catalysis. These ligands play a crucial
role in stabilizing high-valent species and influencing their reactivity.
► Bulky ancillary ligands hinder access to the metal center, preventing unwanted
side reactions. Chelating ancillary ligands form stable chelate rings, enhancing
the overall stability of the complex.
► By choosing specific ancillary ligands, researchers can fine-tune the selectivity
of high-valent nickel complexes in various transformations.
Ancillary Ligands 18

► Pyridinophane tetradentate ligands have been used to isolate and structurally

characterize well-defined organometallic nickel complexes. These ligands
stabilize high-valent nickel species relevant to C-C and C-O bond formation
reactions.
► For example, Mirica and coworkers reported the first isolated Ni(III)-dialkyl
complex stabilized by the N,N ’ -dimethyl-2,1 1-diaz[3,3](2,6) pyridinophane
ligand. 8
► NHCs are privileged ancillary ligands for nickel-catalyzed reactions. They
stabilize high-valent species and enable the activation of traditionally inert
bonds (e.g., C-H, C-O, C-N bonds) 9.
► Chiral NHCs have also been successful in endo-selective C-H cyclization
reactions of pyridines, pyrimidones, and pyrrolopyridines with alkenes 10.
High-Valent Nickel Mediated HAT
High-Valent Nickel Mediated HAT 20

Catalytic Functionalization of C-H bonds via HAT

► The selective functionalization of inert C-H bonds to more versatile functional group
has far reaching practical applications in many chemical industries.
► Nature has evolved a variety of remarkably efficient metalloenzymes that
functionalize inert hydrocarbons through oxidative hydroxylation, and desaturation,
C-X bond formation (X=O,N,S), and halogenation 11.
► Based on the catalytic studies of biomimetic halo-Fe IV=O model compounds of non-
heme iron halogenases, the Fe IV=O unit was postulated to perform HAT but still the
reactivity of HAT of metal-bound halide was not studied 12.
High-Valent Nickel Mediated HAT 21

• McDonald and coworkers isolated and probed the reactivity of a high-valent nickel
chloride complex which can perform HAT oxidation of phenolic O-H bonds and
hydrocarbon C-H bonds13.
NEt4

O O O
N N CAN(-400C) N
NEt4Cl or
N NiII NCCH3 N NiII Cl N NiIII Cl
magic blue (-80 0C)
CH3OH 25O C N
N N acetone
O O O
High-Valent Nickel Mediated HAT 22

• Mechanism of HAT by [Ni(III)(Cl)(L)] in C–H activation by HAT. 13

C
C
H HCl

(L)NiIII Cl (L)NiII
High-Valent Nickel Mediated HAT 23

► Groves and co-workers have demonstrated remarkably efficient oxidative

hydrocarbon fluorination using manganese porphyrin catalysts 14. The proposed
oxidant was an F– Mn V =O species that performed HAT, with rebound of the fluoride
ligand with the carbon-centred radical yielding the fluorinated product
► It is assumed the low yields of fluorinated product derive from competition with
hydroxylation rebound. The elimination of the oxo-ligand could enhance the
fluorination yield, which would be achieved through both HAT oxidation and halide
radical rebound by a high-valent metal-fluoride complex 15
High-Valent Nickel Mediated HAT 24

• Mc Donald and coworkers reported the reactivity of a high-valent fluoride complex

which can undergo oxidation of hydrocarbons through HAT 15.
• The high-valent nickel-fluoride complex is denoted as [NiIII(F)(L)], where L=
N,N’-(2,6-dimethylphenyl)-2,6-pyridinedicarboxamidate.
• It was prepared by oxidizing the precursor [NiII(F)(L)] using selectfluor.
NnBu4

O O O
N N selectfluor N
n
Bu4NF
N NiII NCCH3 N NiII F N NiIII F
acetone
THF 25oC N
N N 0oCor 40oC
O Inert atm O O
inert atm.
High-Valent Nickel Mediated HAT 25

• Proposed mechanism of HAT by high-valent nickel fluoride complex. 15

C
C
H HF

(L)NiIII F (L)NiII

(L)NiIII F NiII(L)
C C +

1/2 PPh3 II
(L)NiIII F F2PPh3 + (L)Ni
High-Valent Nickel Mediated HAT 26

Reactivity in C−H Activation Mediated by Nickel-Oxo Complexes

► In 2012, Ray and coworkers reported the generation of Ni(III)−oxo/hydroxo species 16
during the reaction of [NiII(TMG 3tren)]2+ {TMG3tren = tris[2-(N-
tetramethylguanidyl)ethyl] amine} with m-CPBA at low temperature.
► Rate constants for C-H activation of 9,10dihydroanthracene, 1,4-cyclohexadiene,
xanthene, and 1-benzyl-1,4- dihydronicotinamide in CH 2Cl2 at -30oC were found to
decrease with an increase in the C-H BDE of the substrates.
► Moreover, a deuterium kinetic isotope effect of 3.9 was obtained in the oxidation of
9,10- dihydroanthracene-d 4. These results support H atom abstraction as the rate-
determining step in the C−H activation reactions 16.
High-Valent Nickel Mediated HAT 27

Generation of Ni(III)−oxo/hydroxospecies during the reaction of [NiII(TMG 3tren)]2+

with m-CPBA16
O
N N N
HO O C Ar
N N
N NiII N N NiIII
N N N
-HOTf N
N OH N
N O O
N
O Ar
High-Valent Nickel Mediated HAT 28

► In 2015, Company and co-workers reported the formation of a metastable

nickel−oxygen species, [NiIII(O·)(L)] (L is a tetradentate dianionic macrocyclic
ligand with two amidate, one pyridine, and one aliphatic amine groups), by reaction of
a nickel(II) precursor with m-chloroperbenzoic acid at low temperature.
► [NiIII(O·)(L)] was only sufficiently stable and could perform hydrogen atom
abstraction of hydrocarbon substrates such as fluorene, 1,4-cyclohexadiene, 9,10-
dihydroanthracene, and xanthene. The rate constants were found to be correlated
linearly with C−H BDE of substrates, providing strong evidence for hydrogen-atom
abstraction as the rate-determining step for the oxidation 17.
High-Valent Nickel Mediated HAT 29

Scheme 8: Reaction of Nickel(II) precursor with mCPBA to form [NiIII(O•)(L)] 17.

O
O
O N OH LNiIII LNiIII O
+ O OH O
N NiII N +
O
N Ar ArCOOH
Cl

decomposition of NiIII species

High-Valent Nickel Mediated HAT 30

► Recently, the same group reported a new high-valent Ni−OCl intermediate supported
by the same macrocyclic tetradentate ligand during the reaction with NaOCl.
Interestingly, this species behaves as a strong oxidizing agent both toward alkanes and
alkenes, with reaction rates that surpass those previously reported for related
nickel−oxygen species.
► Moreover, corrected second-order rate constants values were found to correlate
linearly with the BDE values of the substrates providing strong evidence for
hydrogen-atom abstraction as the rate-determining step for the oxidation. 18
Conclusion
Conclusion 32

► Hydrogen atom transfer (HAT) reactions represent pivotal processes in organic

synthesis and catalysis due to their potential to facilitate the construction of complex
molecular architectures.
► C-H functionalization via HAT has opened new avenues for late-stage
functionalization and retrosynthetic disconnections in complex molecules. Continued
research in the field of C-H activation mediated by high-valent nickel-oxo complexes
is focused on developing more efficient catalytic systems, expanding the substrate
scope, and improving selectivity and sustainability.
Reference 33

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“ I f you have knowledge, let others light
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Margaret
Fuller

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