Ammonia in Transition Metal-catalyzed Reaction
Tatsuhiko Yoshino (D1)2011.4.20

Contents
1. Introduction
1-1. Ammonia As Nitrogen Source
1-2. Difficulty in Using Ammonia in Metal-catalyzed Reaction
2. Reactions Without Metal-Ammonia Coordination
2-1. Reductive Amination
2-2. Allylic Substitution
3. Amination of Aryl Halides
3-1. Pd-catalyzed Reactions
3-2. Cu-catalyzed Reactions
4. Hydroamination
4-1. Hydroamination with Amines
4-2. Hydroamination with Ammonia
5. N-H Activation of Ammonia
5-1. Multimetallic Activation
5-2. Monometallic Activation
Review: Chem. Rev. 1992, 92, 1.
6. Summary
Chem. Soc. Rev. 2010, 39, 2302.
Angew. Chem., Int. Ed. 2011, 50, 86.

1. Introduction
1-1. Ammonia As Nitrogen Source•Colorles, irritating smelling gas.
•Bp. –33.4 °C, Mp. –77.7 °C•pKa : 38 (H2O), pKAH+ : 9.2 (H2O)•N-H bond strength : 107 kcal/mol•Soluble in water, alcohol. and other polar organic solevents

N
H

H
H

Ammonia

Ammonia in Industry
Industrial Production: Haber-Bosch Process
Fe Catalyst
3H2 + N2

2NH3High Temperature : 400~500 °C
High Pressure : 10~35 MPa•Ammonia was f ormed industr ially around 100 million tonnes per year.
(almost the same amout by biological system)•1~2% of the total global ener gy demand annually.
For recent advances in N2 reduction and fixation
lit. Mr. Kimura 2010/4/21
lit. Dr. Yamaguchi 2009/2/21

Usage•Fertilizer (>80%)•Synthesis of amines
NH3 + RXNH2R

+ NHR2+ NR3•Synthesis of Inorganic acids and salts (nitric acid)
Most synthetic N-containing compounds can be derived back to ammonia.
11-2. Difficulty in Using Ammonia in Metal-catalyzed Reaction
Homogenios catalytic reactions using ammonia as a substrate are still limited.

•Metals and ammonia tends to form stable Werner complexs.
M

NH3

Werner complex•Low acidity and moderate basicity•Strong N-H bond (107 kcal/mol) : Difficulty in N-H activation•Ammonia is toxic gasous compound.
•Diffucult to supress over reactions.
Two r eactions using ammonia ar e litsted as "The 10 challenges f or catalysis"
Direct synthesis of anilines
NH3, [O]NH2
catalyst
anti-Markovnikov selective hydroamination of unreactive olefin
R

NH3

R

catalyst

NH2
C&EN, 1993, 23

Ammonia Surrogates
O
NH2

H2N

NHR

increased
nucleophilicity

BnNH2

H2N

O

O
CF3

H2N

OR

increased acidityof N-H bondNH
O

These protected ammonia equivalents are good substrates for several catalytic reactions.
However, deprotection step is required.

22. Reactions Without Metal-Ammonia Coordination
2-1. Reductive Amination
Hydroaminomethylation in Biphasic System Using Water Soluble System
Herwig, J.; Beller, M. et al. Angew. Chem., Int. Ed. 1999, 38, 2372.

[Rh(cod)Cl]2 (0.026 mol %)[Ir(cod)Cl]2 (0.21 mol %)TPPTS (11 mol %)CHOnNH3aq, MTBE, CO:H2=1:5 (65 bar)
NaO3S

n

+

+
CHO

iso

iso
+ secondary, tertialy amines

3

SO3Na

NH2

P

TPPTS =

n/ iso Selectivity depends on ligand.

NH2

Extraction EffectNH3 << alkyl amine
PAr2

NaO3S
NaO3S

PAr2
NH3 >> alkylamine
SO3Na

BINAS gave exclusively n-product.
(See the Table below)

Prim. Selective
Reaction proceeds in water.

3

Reductive Amination by Homogeneous Catalyst

Reductive amination using H2 as reducing reagents are well known in the case of heterogeneous catalyst.
O
+
R

R'

NH

NH3
R

NH2

Pd/C or other cat.
H2

R'

R

R'

H2O

Reductive Amination of Aldehyde and Ammonia

CHO[Rh(cod)Cl]2
TPPTS
H2O, THF, 135 °C
H2 (65 bar)

R

NH2
R
Beller, M. et al. Org. Lett. 2002, 4, 2055.

Rh(I)-TPPTS catalyst is water soluble
and could be recycled after phase seperation.

aldehyde
H2

amine
THF
H2O

NH3

[Rh]

4

Synthesis of Amines from Alcohols
Milstein, D. et al. Angew. Chem. Int. Ed. 2008, 47, 8661.
Ru cat. (0.1 mol %)R

OHR
NH3 (7.5 atm)
toluene, reflux

NH2

Ru cat.

Reaction in water gave good results.

5

Synthesis of Secondary and Tertiary Amines
Yamaguchi, R.; Fujita, K. et al. Org. Lett. 2008, 10, 181.

[Cp*IrCl2]2 (1-5 mol %)NaHCO3 (2-30 mol %)ROH(3.6 eq)RR+

55-92% yield
R = aromatic and aliphaticNneat, 130 C, 17 h
R

NH4OAcR'R

OH

2.2 eq for prim.
3.0 eq for sec. alcohols+
NH4BF4R[Cp*IrCl2]2 (2-3 mol %)NaHCO3 (30 mol %)neat, 14 C, 17 h

HN
R'

R'

primary and secondary alcohols were used.
54-98% yield

R

Selectivity depends on acidity of ammonium salts.
Stronger acidic salts gave secondary amines. However, the reason for selectivity was unclear.

2-2. Allylic Substitution
R

R

M(n)

OAc

NH3

R
or

R

NH2

NH2

M(n+2)
M(n)Ir-catalyzed Asymmetric Allylic AminationPh

OCO2Me+cat (1) (2 mol %)[(COD)IrCl]2 (1 mol %)NH3(~ 2eq)Ph

H
N

EtOH/THF, rt

Ph

93% yield
94/6 dr No primary amine was
99% ee obtained.
Formed primary amine showed
higher reactivity than ammonia itself.

To obtain primary amine, they used ammonia surrogates.
O
KHN

CF3

or

Boc2NLi
Hartwig, J. F. et al. Org. Lett. 2007, 9, 3949.
6

Ir-catalyzed Asymmetric Allylic Amination to Primary Amines Using Ammonia
Hartwig, J. F. et al. J. Am. Chem. Soc. 2009, 131, 11312.

•Large excess NH3 was necessary to obtain primary amine.
•Additional Ir source was not tolerant with large amout of NH3. (entry 1)
This additional Ir captures ligand from catalyst to give active 16 electron complex.

X-ray Structure of -allyl Ir Complex

Ir-C47 : 2.377 Å
Nucleophilic Attack on C47 is favorable.
Ir-C45 : 2.240 Å(trans effect of P ligand)Hartwig, J. F. et al. J. Am. Chem. Soc. 2009, 131, 7228.
7

Pd-catalyzed Allylic Amination Using aqueous NH3

Kobayashi, S. et al. J. Am. Chem. Soc. 2009, 131, 4201.

Telomerization of Butadinene and Ammonia
Driessen-Hölscher, B. et al. Angew. Chem., Int. Ed. 1996, 35, 1708.
Driessen-Hölscher, B. et al. Chem. Eur. J. 1999, 5, 2069.

Pd(OAc)2 (0.2 mo l%)
TPPTS (0.8 mol %)2+ NH3
H2O/toluene, 80 °C, 1.5 h

NH2
+

NH2

+ secondary
tartiary amines

One pahse reaction mainly gave tertiary amines.

8

Proposed Reaction Mechanism

Relation between Ligand/Pd Ratio and Reactivity or Selectivity

Selectivity and Reactivity of Several Intermediates

NH3 : -donor ligand : deaccelerate the nucleophilic attack.
olefin, PR3 : -donor and -acceptor ligand : accelerate the nucleophilic attack.
These effects are larger at trans position to the ligand.

Summary of Reductive Amination and Allylic Substitution
In these reactions, ammonia reacts with substrates without participation of catalysts.
Main problem is the selectivity between primary, secondary and tertiary amines.
Biphasic reaction systems or use of large excess amount of NH3 could solve this problem.

9

3. Amination of Aryl Halides
3-1. Pd-catalyzed Reactions
Buchwald-Hartwig Amination Using Amines
Typical conditions
Pd: Pd(OAc)2, Pd2dba3
ligand: P(o-tol)3, BINAP, dppf
base: NaOtBu, K2CO3, CsCO3

Pd source
phosphine ligand

ArX+

ArNR1R2

1 2

base (stoich)

R R NH

Catalytic Cycle
ArNR2
ArX

LnPd(0)oxidative addition
NR2

X

LnPd(II)

LnPd(II)Ar
amido complex
HOtBu

Ar
HNR2 XNaX

LnPd(II)

Base promoted formationof amido complex

Ar

PointsStrong base was necessary for formation of
Pd-amido complex.

HNR2
coordination of amine

NaOtBuProblems of Aniline Syntesis by Ammonia•Ligands tends to be kicked out by the coordination of ammonia.
•Metal-amido complexes often favor the bridging structure and reductive elimination is difficult.
H2
N

R1
R2
M
M
R2
R1
N
H2
•Produced anilines are generally more reactive than ammonia.

Bulky, electron-rich, strongly coordinating ligands are suitable to overcome these problems.
•Ammonia would not kick out the ligands.
•Ligands could Inhibit the formation of dimer and promote reductive elimination.
•Sterically unhindered ammonia would react faster than produced anilines.
The First Report of Buchwald-Hartwig Amination Using NH3Hartwig, J. F. et al. J. Am. Chem. Soc. 2006, 128, 10028.
ArX
X=Cl, Br, I

PtBu2

LPdCl2 (1.0 mol %)+NH3(200 psi; ca. 14 atm)

DME, 90 °C

ArNH2

+

Ar2NH
L=

Fe PCy2
Josiphos10•Other ligands(PtBu3, Q-Phos, X-Phos, IPr, dppf, BINAP etc)
did not promote reactions.
•Lower NH3 pressure gave lower conversion
and lower A/B ratio.
•This condition also applicable reactions
using LiNH2 as N source.
Identification of Intermediates
Br AgOTf, NH
3
LnPd(II)
Ar

NH3

+

LnPd(II)Ar

CH2Cl2

mixture ofstereoisomers (4:1)
X-ray
NH2
LnPd(II)

C6D6, 90 °C

Ar

KHMDS

PPh3-d15

NMR
Ar2NH
ArNH2
+
45%
45%
Improved Reaction Conditions

Hartwig, J. F. et al. J. Am. Chem. Soc. 2009, 131, 11049.

They screened several catalyst precursors and found the combination of Pd[P(o-tol)3] andCyPF-tBu (Josiphos) in dioxane was the best conditions.

•No need to use excess amout of gasous ammonia.
•Results were sensitive to concentration.
•0.1 mol % catalyst gave excellent results.
•These conditions showed wide substrate scopewith ArX (Cl, Br, I) by using 0.1-2.0 mol % catalyst.
•When Pd(II) compounds were used as Pd sources,
Pd(0) generation seemed not efficient.
•Ester, ketone, nitrile are tolerant by changing thebase to K3PO4 and decreasing temp. to 70 °C.

Reaction using tosylates proceeded in mild conditions to give good results.
OTs
R

+

NH3
(5 eq)

Pd[P(o-tol)3] (2.0 mol %)CyPF-tBu (2.0 mol %)NaOtBu (1.4 eq)
1,4-dioxane (0.05-0.1 M)
50 °C, 24 h

NH2
R

+

Ar2NH

55-86% yield
17:1- >50:1 selectivity(Higher temp. promoted decomp. of tosyltes by base.)
11

Other Reported Reactions

Buchwald, S. L. et al. J. Am. Chem. Soc. 2007, 129, 10354.
Beller, M. et al. Chem. Eur. J. 2009, 15, 4528.
Stradiotto, M. et al. Angew. Chem., Int. Ed. 2010, 49, 4071.
Ph

t-Bu2P

N
Ph

N

P(1-Ad)2
PtBu2
N

NMe2

or

Buchwald et al.

Beller et al.

PtBu2

N
O

Stradiotto et al.

3-2. Cu-catalyzed Reactions
Ullmann Reaction
Cu salt, baseligandX+ R2NHNR2
solvent
Similiar mechanism to Pd is proposed (Cu(III),Cu(I) cycle)

Several reaction of halopyridines with ammonia were repoted from early 20th century.
However, high temperature (150-250 °C) were necessary.
First Mild and Practical Copper-catalyzed Amination
Br
R

Cu2O (0.5 w/2% to ArBr)
8M NH3 in ethylene glycol

Lang, F. et al. Tetrahedron Lett. 2001, 42, 3251.
NH2

R

80 °C
•Substrate scope was limited to electron-deficient aryl bromide or iodide.
(pyridine or benzene with electron-withdrawing groups)•Small amount of addition of ethylene glycol proceeded.

Neither secondary nor tertiary amines were observed, which is common in Cu-catalyzed amination.
Using Aqueous Ammonia

Taillefer, M. et al. Angew. Chem. 2009, 121, 343.

12

O

O

ligand 6(entry 3)

For other examples, see review:Angew. Chem., Int. Ed. 2011, 50, 86.
Summary of Arylation
Pd-catalyzed Reactions•Bulky, electron-rich, phosphine ligands are essential to obtain desired product.
•Selectivity between primary and secondary amines are main problem.
Use of large excess amount of ammonia is effective for primary selective reaction.
•Wide substrate scope has been obtained. Even ArCl and ArOTs gave good resultswith low catalyst loading.
Cu-catalyzed Reactions•In most cases, primary amines are only product.
•Relatively high catalyst loading is necessary and substrate scope is limited.
Sensitive to steric hiderance. Reaction with ArCl is difficult.

13

4. Hydroamination
4-1. Hydroamination With AminesR

catalyst

+
HNRR'

R

NRR'

NRR'

+ R
linearbranchedanti-Markovnikov Markovnikov

anti-Markovnikov selective intermolecularhydroamination of olefin to give linear amines ishighly imortant and formidable challeng.

Rare-Earth Metal-catalyzed Hydroamination

This type reactions were well studied
using rare-earth metal-Cp* amido
complexs or related complexs.
Also alkaline-earth metal amido complex
are known to catalyze hydroamination.
However those reactions show
Markovnikov-selectivity.
For detail, see review:Chem. Rev. 2008, 108, 3795.

Late Transition Metal Catalyzed Markovnikov Selective Reactions

ArNH2 +R

Pd(PPh3)4 (2 mol %) / TfOH (20 mol %)orPd(TFA)2 (2 mol %) / DPPF (3 mol %) / TfOH (20 mol %)

NHAr
R

100 C

•Markovnikov Selectivity•Pd -benzyl complex is major species in reaction mixture(isolated and characterized by NMR and X-ray)•Addition of amines proceed via stereo inversion.

Hartwig, J. F. et al. J. Am. Chem. Soc. 2000, 122, 9546.
Mechanistic Study: J. Am. Chem. Soc. 2002, 124, 1167.
14

Substrate Induced anti-Markovnikov Selectivity[Rh(cod)2]BF4
+

N

N
H

N
N

THF, reflux
97%

Reaction seemed to proceed via cooridation of pyridine to Rh.
Beller, M. et al. Eur. J. Inorg. Chem. 1999, 1121.
Hydroamination via N-H Activation
Milstein, D. et al. J. Am. Chem. Soc. 1988, 110, 6738.

+

PhNH2

Ir(PEt3)2(C2H4)2Cl
ZnCl2 (0.2 eq to Ir cat.)

PhHN
up to 7.0 TON

THF, reflux
Stoichiometric Reactions Affording IntermediatesP

Ir(PEt3)3Cl+
PhNH2

THF, 50 °C

PClH
Ir NHPhP

Determined by NMR(Ir-1H : –21.47, coupled with P)

Ir(PEt3)2(C2H4)2Cl+

hexane, reflux

PhNH2

Proposed Catalytic Cycle

ZnCl2 would promote reductive elimination
by facilitating the dissociation of Cl anion andgeneration of 16 electton cationic complex.

Aysmmetric Version
Togni, A. et al. J. Am. Chem. Soc. 1997, 119, 10857.
[IrCl(S)-BINAP]2 (2 mol %) PhHN
P2-fluoride* (8 mol %)+P2-fluoride

PhNH2
neat, 75 °C, 72 h

22% yield
95% eeP2-fluoride as "naked" F- source
might coordinate to Ir andpromote oxidative addition.

15

Rh-catalyzed Anti-Markovnikov-selective Hydroamination
Hartwig, J. F. et al. J. Am. Chem. Soc. 2003, 125, 5608.

+

H
N

O

[Rh(cod)2]BF4 (5 mol %)ligand (5 mol %)

O

N

N
+

toluene, 70 °C

O

amine

enamine

O

O

PPh2

PPh2

PPh2

Xantphos

O

Ph2P

PPh2

DPEphos

PPh2

PPh2

DBFphos

PPh2

BIPHEphos

Only DPEphos gave hydroamination product in moderate selectivity.

Primary amines gave no reactions.
Reason for selectivity have not been repoted.
Ru-catalyzed Highly Selective Hydroamination
Hartwig, J. F. et al. J. Am. Chem. Soc. 2004, 126, 2702.
J. Am. Chem. Soc. 2005, 127, 5756.

R+ HNRR'

Ru(cod)(2-methylallyl)2 (5 mol %)DPPPent (7 mol %)TfOH (10 mol %)NRR'R

dioxane, 100 °C, 24 h
•No enamine was observed.
•Only trace amout of branched product was observed under optimized conditions.
•No reaction occured in the absense TfOH or Ru cat.

16

Substrate Scope

Ru-arene complexes as Intermediates

These complexs showed slightly higher reactivity
when used as catalyst.
Proposed Reaction Mechanism

Electron deficient ligand showed higher reactivity.
H
NRR'
LnRu
Zwitterionic Intermediate
Stabilized by Ru Coordination
Problem: The reaction of this type mechanism can be applied to only aryl-vinyl substrates in principle.

4-2. Hydroamination With Ammonia

R+

catalyst

NH3

R

NH2

NH2

+ R
linearbranchedanti-Markovnikov Markovnikov

So f ar, ther e has been no report of selective homogeneous metal catalyst f or this pr ocess.
Heterogeneous Catalyst
aluminosilicate
catalyst+
1.5 eqNH3
1.0 eqNH2
300 °C
300 bar

9-17% conversion>95% selectivity
This process was commercialized by BASF.
Hayes, K. S. Applied Catalysis A: General 2001, 221, 187.
17

Alkali Metal-catalyzed Hydromination
Reactions between NH3 and olefin under extremely harsh conditions were reported.
R

+

R

Na

NH3

+ secondary amines + tertiary amines

NH2
175–200 °C
800–1000 atm

not selective, not high yield
Howk, B. W. et al. J. Am. Chem. Soc. 1954, 76, 1899.

Gold-catalyzed Hydroamination of Alkynes and Allenes with Ammonia
Bertrand, G. et al. Angew. Chem., Int. Ed. 2008, 47, 5224.

Dpp N
Au
NH3 B(C6F5)4R
C CH2NH3 (excess) +R(5 mol %)R

NH2+ secandary, tertialy amines

R

or

or

R

NH

C6D6, 110–165 °C

R

R

R

Proposed Reaction Mechanism
R
L
L
Au
Au
NH3
NH3
R

L

R

Au

R

H
N
H2

proton transfer or
hydride shift

R

H

R

Au

L
R

NH

R

L
Au
NH2

NH

+ NH3
R

R +

L
Au
NH3

One of The Hypothetical Mechanism of Hydroamination with Ammonia
NH2

R

M(n)
R

NH3

reductive
elimination

NH2

M(n)

M(n+2)

NH2
H

H
insertionRNH2oxidative
addition

Oxidative addition to form
M-NH2 complex is difficult.

NH2•Strong bonding energy•Stable Werner complex

M(n+2)

M(n+2)

H

H

M-NH2 complex often favors
stable mulinunlear complex

R18

5. N-H Activation of Ammonia
5-1. Multimetallic Activation
Oxidative Addition of Ir(I)
Casalnuovo, A. L.; Milstein, D. et al. Inorg. Chem. 1987.26. 971.
NH3
Ir(PEt3)2(C2H4)2Cl
THF, 25 C
90%[Ir(PEt3)2( -NH2)(NH3)]nCln
pyridine, 110 C
insoluble solids
50%(quant. conv.)
analyzed by solid-NMR
and elemental analysis

Electron rich Ir(I) could oxidatively added to NH3.

NaBPh443ax = BPh4

MeOH
50%
X-ray Structures of 3a and 4

Ligand exchanges
TlPF6

Ligandacetoneacetone4
TlPF6, Ligand
acetoneOxidative addition of NH3 gave
oligomeric metal amido hydride complexes.
These complexes were highly stableand only ligand exchange was possible.

Ligand = CO gas or tBuNC
Oxidative addition also occured without -donating ligands.
See: Milstein, D. et al. Angew. Chem., Int. Ed. 1991, 30, 707.
19

Oxidative Addition of Pd(I) Dimer Comlex
Ozerov. O. V. et al. J. Am. Chem. Soc. 2007, 129, 10318.
Photolytic Generation of Pd(I)-Dimer

Pd has distorted square-planar.
Pd-Pd length indicates existence of Pd-Pd bond.
Equilibrium betweem Monomer and DimerR
PHiPr2
1

2

N

NMR analysis shows the Pd-dimeris almost diamangnetic.

Pd(0)PHiPr2

But EPR spectrum indicatesexistence of "organic radicals".

R
Bimetallic Oxidative Addition of Ammonia
Reaction mechanism was unrevealed.

5-2. Monometallic Activation
Oxidative Addition of NH3 to Form Monomeric Ir Complex
Hartwig, J. F. et al. Science 2005, 307, 1080.

X-ray Structure of 5

Geometry between trigonal bipyramidal andsquare pyramidal indicated -donation from amido p orbital
to Ir center.

Mechanistic studies, reaction using ND3 and kinetic experimetns, supported the path of
direct oxidative addition after ligand dissociation,
20

Hartwig, J. F. et al. J. Am. Chem. Soc. 2003, 125, 13644.

Electron-donating alkyl backbone is essential.

Amido hydride complex rapidly gaveammonia (Werner) complex at rt.
(stable < –30 °C)
Oxidative additon of anilines
is thermodyamically favorable.

Thermodyanmics with Alkyl Backbone Ligand
Surprisingly, anilido complex is less favorable
than parent amido complex.
They said this is due to the steric factor orstronger -donation of NH3.
(But neither of them can explain the differece
between aryl and alkyl backbone ligands.)
If the coodination of olefin (good -acceptor) does not affect the equilibrium,..

Ir

+ NH3

PtBu2

+

Ir

NH3

PtBu2

This [PCP]Ir(H)NH2 was not so kinetically stable.
PtBu2
NH2
Ir
(5 mol %)H
PtBu2
C6D6, rt, 20 h

+

PhNH2

PtBu2

PtBu2
NH2
Ir
H
PtBu2

PtBu2
Ir

PtBu2

PtBu2
NH2
Ir
H
PtBu2

PtBu2

PtBu2
Ir
PtBu2

+ PhNH2

PtBu2
NHPh
Ir
H
PtBu2

PtBu2
NHPh
Ir
H
PtBu2

Hartwig, J. F. et al. Angew. Chem., Int. Ed. 2008, 47, 5785.
DD
D(>96% D)21

More Stable [PSiP]Ir(H)NH2 Complex

Turculet, L. et al. J. Am. Chem. Soc. 2009, 131, 14234.

TMSCH2Li

ammonia or anilines–Me4Si

cyclohexane-d 12
65 °C

R = Ph (qant.)
R = H (72%)
M = IrAmido Exchange by Unrevealed Mechanism
PCy2

PCy2

NH2
Me2Si Ir
H
PCy2

PhNH2
rt, cyclohexane-d 12
quant.

NPh
Me2Si Ir
+
H
PCy2

PCy2
NH2
Me2Si Ir
H
PCy2

NH3

PCy2

ND3
25 °C, cyclohexane-d 12
quant.

ND2
Me2Si Ir
Simple reductive elimination/oxidative addition
mechanism cannot explain.
H
PCy2

Reductive Elimination
PCy2

PCy2

C6D5

NH2
Me2Si Ir
H
PCy2

C6D6

Me2Si IrD
PCy2This reaction proceeded at only higher temp (>100 °C).

6. Summary
Recently, several transitionmetal-catalyzed reactions using NH3 has been achieved.
Reactions which don't require formation of M-NH2 ,reductive amination, allylic substitutions,
could be achieved by relatively small modification of reaction conditions to inhibit over reactions.
Excellent reaction conditions for Buchwald-Hartwig amination and Ullmann amination were also achieved.
Key for the former is using bulky, electron rich ligand, which is recent standard strategy used in severaltransitionmetal catalyzed reactions.
Hydroamination is one of the most important but challenging reaction and has not been achieved.
To discover and develop new catalytic reactions, several groups are challenging oxidative addition of NH3.
So far, only stoichiometric processes have been reported.

22