Transition metal complexes - the catalysts of organic ... · I.P. Beletskaya

I.P. BeletskayaChemistry Department of Moscow State University, Moscow, Russia

Transition metal complexes - the catalysts of organic reactions

2

Transition metal catalysis in industry

MeOH + CO MeCO2H

RCH=CH2 + CO H2 RCH2CH2CHO

CH2=CH2 + O2 CH3CHO

CH2=CHCH=CH2 + 2HCN NC(CH2)4CN

RCH=CH2 -[CRH-CH2]-

RCH=CH2 + H2 RCH2CH3

Rh,

Co, Rh

Pd with Cu

Ni

Ti, Zr, V

Rh, Ru

RhCl(PPh3)3, RhCl(CO)(PPh3)2, RhH(CO)(PPh3)2, [RhCl(C2H4)2]2, [RhCl(CO)2]2, PdCl2(MeCN)2,

PdCl2(PPh3)2, Pd(PPh3)4, [Pd(OAc)2]3, Pt(PPh3)4, Pt(PPh3)3, Cp2Co, Co2(CO)8, NiCl2(PPh3)2,

NiCl2dppm,NiCl2dppe, NiCl2dppp, NiCl2dppb, NiCl2diop, Ni(COD)2, IrCl(CO)(PPh3)2, RuCl2(PPh3)3

3

Transition metal catalysis in industry

MeOH + CO MeCO2H

RCH=CH2 + CO H2 RCH2CH2CHO

CH2=CH2 + O2 CH3CHO

CH2=CHCH=CH2 + 2HCN NC(CH2)4CN

RCH=CH2 -[CRH-CH2]-

RCH=CH2 + H2 RCH2CH3

Rh,

Co, Rh

Pd with Cu

Ni

Ti, Zr, V

Rh, Ru

RhCl(PPh3)3, RhCl(CO)(PPh3)2, RhH(CO)(PPh3)2, [RhCl(C2H4)2]2, [RhCl(CO)2]2, PdCl2(MeCN)2,

PdCl2(PPh3)2, Pd(PPh3)4, [Pd(OAc)2]3, Pt(PPh3)4, Pt(PPh3)3, Cp2Co, Co2(CO)8, NiCl2(PPh3)2,

NiCl2dppm,NiCl2dppe, NiCl2dppp, NiCl2dppb, NiCl2diop, Ni(COD)2, IrCl(CO)(PPh3)2, RuCl2(PPh3)3

4

Discovered : by W.H. Wollaston in 1803

Isolated in London, UK

Origin : The element is named after the

asteriod Pallas, also discovered in 1803.

Pallas was the Greek goddess of

wisdom.

Palladium

5

R M R' X+ R R' R' = Alk Wurtz

R M Ar (Het), vinyl, alkynyl R Ar (Het), vinyl, alkynyl

Kumada, Corriu (1972)

+cat

cat = Ni, Pd

aryl aryl (Ar-Ar, Ar-Het, Het-Het)

aryl alkenyl (Ar , Het )

R R

alkenyl alkenyl

aryl alkynyl (Ar R, Het R)

alkenyl alkynyl

aryl alkyl

6

Cross-coupling reactions

R Hal(OTf) + R R'

R=Ar, Vinyl; R'=Ar, Vinyl, Alk

R' M[Pd]

M = MgX (Tamao - Kumada)

= SnR3 (Migita - Kosugi - Stille)

= ZnX (Negishi)

= B(OH)2 (Suzuki - Miyaura)

= SiR3 (Hiyama)

7

R Hal(OTf) R R'R'[Pd], Cu

+

R=Ar, Vinyl; R'=Ar, Alk

base

Sonogashira - Hagihara

Cross-coupling reactions

8

Mizoroki-Heck reaction

RHal(OTf) +Z

[Pd]base

R

Z

R = Ar, vinylZ = Ar, COOH, COOR, CN

9

Carbonylation

R Hal +

R=Ar, Vinyl; HNu = H2O, ROH, RNH2, R2NH, RSH

R' M[Pd]

+ COR R'

O

R Hal + HNu[Pd]

+ COR Nu

Obase

10

Pd-catalyzed reactions

+ Pd(0)

R

X

Sonogashira

coupling

R'

R

H-E

(H-P,H-S, H-Se)

E

R

Buchwald - Hartwig

amination

HNR2'

R

NR2

(Nu=OH, OR,NR2)R

CONu

CO, Nu

Miyaura-Suzuki

coupling

R

Ar

ArB(OH)2

HC

Y

Z

R

CH

Y Z

Mizoroki-Heck

reaction

R

R'

R' CN

R

CN

R

PdX

11

Pd

R'

X

Pd

R'

X

RM

Pd(0) or Pd(II) precatalyst

L

L

L LPd

R'

R

Pd

R'

RL

L

L L

PdL2

R'X

RR'

catalyst pre-activation

oxidativeaddition

reductiveelimination

transmetalation

Pd metal

deactivation

L

Catalytic cycle of Pd-catalyzed reactions

Reactions in water or aq. solution (ligandless)

13

Stille reaction

Z

N2 X

+ Me4SnPd(OAc)2

MeCN:H2O, rt

Z

Z: o-, p-NO2, p-Br,

p-MeO, p-Me

Z

I X

+ RSnMe3

Pd(OAc)2

H2O, 60oC

Z

R

2

R: Me, m-MeC6H4

Z: H, m-NO2

Izv. Akad. Nauk SSSR, Ser. Khim., 1990, 2665; 1992, 2683

Z

X

+ RSnPdCl2 or PdCl2L2

H2O, 100oC

Z

R

X: Br, I

Z: m-CO2H, p-OH, p-Ac,

p-Me, o-NH2, o-OCH2CO2H

R: Me, Ph, etc.

[RSn]: RSnCl3, Kn[RSn(OH)3+n]

L: TPPMS Ph2P

SO3M

Tetrahedron Lett., 1995, 36, 125

14

Suzuki-Miyaura reaction

ArB(OH)2 +cat

basesolvent

Ar'(Het)X Ar Ar'(Het)

cat = Pd(PPh3)4, Pd(OAc)2/L, Pd(OAc)2, Pd-cluster

base = Na2CO3, K2CO3, Cs2CO3, KF, K3PO4, PhONa, Ba(OH)2, TlOH

solvent = DMF, toluene, benzene, THF, dioxane, DMF-H2O, PhMe-H2O, H2O

X = I, Br, Cl, OTf

15Izv. Akad. Nauk SSSR, Ser. Khim., 1989, 2394

B(OH)2 X+Y Z

Pd(OAc)2 or PdCl2base, H2O, rt Y Z

X: Br, I; Y: H, p-F, p-(4-n-amylcyclohexyl); Z: m-, p-OH; o-, m-, p-COOH

B(OH)2 Br+

Y: H, F

Y OH

COOH

Y OH

COOH

+

COOH

I

PhB(OH)2Pd black, NaOH

H2O, rt

COOH

Ph

N

Z+

Z: NO2, NH2, OEt

BrPhB(OH)2Pd(OAc)2, Na2CO3

DMF-H2O, 90-130oC N

ZPh

16

Suzuki reaction

Metalloorg. Khim., 1989, 2, 1200

Izv. Akad. Nauk SSSR, 1989, 2394; Dokl. Akad. Nauk SSSR, 1995, 340, 775

Ph4BNa +Z base, H2O, rt

Pd(OAc)2 or PdCl2

ZPhX

HO2C BrPdCl2 (0.0004 mol%), Na2CO3

HO2C Ph

H2O, Ph4BNa+

4 HO2C Cl + Ph4BNaPdCl2, NaOH

H2O, 4 HO2C Ph

72%

X: Br, I;

Z: m-, p-OH;p-CHO;

m-, p-CO2H;

m-, p-NO2, etc.

Ph4BNa+2 Ar2IX1% PdCl2, Na2CO3

H2O, 80oC

4 ArPh

17

Heck reaction

Russ. Chem. Bull., 1992, 41, 2130

+

Z ZX CO2H

PdCl2, Na2CO3

DMF:H2O, HMPA:H2O,

or neat H2O, 100oC

CO2H

J. Organomet. Chem., 1989, 371, 397

+X CO2HK2CO3, 80

oC, 2h

K2CO3, KOAc, 50oC, 1h

CO2H

HO2C HO2CPdCl2, H2O

97%

98%

X: I, Br

Z: H, p-Cl, p-MeO, p-Ac, p-NO2,

p-CHO, p-OH, m-CO2H

X: I; Pd(OAc)2, 0.005%, K2CO3, H2O, 24h, 100oC, TON = 200 000

+(m-O2NC6H4)2I+X

- Pd(OAc)2, Na2CO3

H2O, rt, 1hCO2H

CO2HO2N

X: HSO4- (97%), BF4

- (80%)

Dokl.Akad. Nauk SSSR, 1990, 313, 107

18

Carbonylation

Dokl. Akad. Nauk SSSR, 1990, 312, 1129

ArIPd(OAc)2, 1 atm CO, K2CO3

DMF:H2O (2:1), 25-50oC

ArCOOH

Ar:

Z

Z: NO2, Cl, CN, Me, NH2, etc.

S

Z: m-, p-COOH; o-, m-, p-OH

Z

I

Pd(II), CO, base

H2O, 25-50oC

Z

COOH

19

Carbon-heteroatom bonds

Zh. Org. Khim., 1994, 30, 876

Tetrahedron Lett., 1998, 39, 5621

R

+ (EtO)2P

H

O A or BI

R

P(O)(OEt)2

NH

NN

+ Ph2IBF4

Pd(OAc)2, K2CO3

H2O, 100oC N

NN

+

Ph

NN

NPh

A: Pd(OAc)2, TPPMS, NaOH

Bu4NCl, PhH-H2O, 60oC

B: Pd(OAc)2, TPPMS, Et3N

MeCN-H2O, rt

20

Reaction in microemulsion

Reactions which can be readily run in microemulsion media at preparative scale

I

Z

COOH

Z

Ph

Z

Ar

Z

X

Z

CO (1 atm), PdCl2, K2CO3

Pd(OAc)2, Ph4BNa, KOH

Pd(OAc)2, ArB(OH)2, KOH

Pd(OAc)2, CH2=CHX, K2CO3

Z: Alk, NO2, OR, COOR, CN, Hal, etc.; X = COOR, Ar, 4-PyMicroemulsion media: surfactant (anionic, cationic, ornon-ionic) – co-surfactant (alkanol C2-C5, or alkyl ethers of mono or diethyleneglycol) – water (molar ratio 1:5-6:200)

Surfactant C17H33CO2K

PdCl2 (0.01 mol%), Yield 90%Heck reaction

TEM view of

Pd nanoparticles

oil water

21

1 Qualitative measure of sol stability in the reaction mixture. +++ the

sol rapidly forms and shows no signs of degradation during the

reaction; ++ the sol is formed readily but shows partial aggregation

and sedimentation; + the sol is formed but readily undergoes

sedimentation; - the sol is altogether not formed 2 Palladium sol freshly prepared in the same microemulsion3 Same sol aged for 3 months4 Same sol aged for 1 year

The correlation of perfomance of microemulsion media (surfactant - n-butanol -water) in Heck arylation with the stability of palladium sol in the same system

Surfactant Catalyst (mol %) Time, h Yield, % Sol stability 1

C17H33COOK PdCl2 (0.01) 8 90 +++

C15H31COOK PdCl2 (0.01) 8 78 +++

C13H27COOK PdCl2 (0.1) 8 32 ++

C11H23COOK PdCl2 (0.1) 8 10 +

C16H33NMe3Br PdCl2 (0.01) 8 86 +++

C16H33SO3K PdCl2 (0.1) 8 4 -

C17H33COOK Pd2 (0.1) 3 40 +++

C17H33COOK Pd3 (0.1) 3 47 +++

C17H33COOK Pd4 (0.1) 3 39 +++ TEM view of

Pd nanoparticles

oil water

22

I.P. Beletskaya"Palladium-catalyzed Organic Reactions in Aqueus Media."In: New Aspects of Organic Chemistry II.Organic Synthesis for Material and Life Sciences, 1992, 31.

I.P. Beletskaya, A.V. Cheprakov"Aqueous transition-metal catalysis."In: Organic Synthesis in Water.Ed. by P.A. Grieco, 1998, 141.

I.P. Beletskaya, A.V. Cheprakov"Aqueus Palladium Catalysis."In: Handbook of Organopalladium Chemistry for Organic Synthesis.Ed. by E. Negishi, 2002, Vol. 2, 2957.

I.P. Beletskaya, A.V. Cheprakov"Palladium (0)-catalysed Reactions in Aqueous Medium and Synthetic Applications"In: Transition Metal Catalysed Reactions.Ed. by S.-I. Murahashi, S.G. Davies, 1999, 55.

Palladium catalyst on soluble polymers

24

TEM image of Pd nanoparticles

stabilized by block copolymer micelles

Formation Pd nanoparticles in block copolymer micelles

(PS-PEO - polystyrene-poly(ethylene oxide)

CPC – cetylpyridinium chloride

No change of activity

after 1 year of storage

Langmuir, 2000, 16, 3626

J. Phys. Chem. B., 2001, 105, 9077

KBH4

25

Suzuki and Heck reactions in water

93% in air (96% in Ar)

4-7% of biphenyl (4-7%)

[Pd] 1 mol%

rt, KOH/H2O (10 h)C6H5B(OH)2

I

CO2H

C6H5

CO2H

+

I

OH

[Pd] 1 mol%

C6H5

OH

C6H5B(OH)2rt, KOH/H2O, Ar, 4 h

+

68% in Ar, 74% in 10 h

13-16% of biphenyl

CO2H

I

[Pd] 1 mol%

rt, KOH/H2O, 20 h

HO2C

S B(OH)2+

98%S

I

CO2H

[Pd] 1 mol%

O

O

C4H9

CO2H

O

O

C4H9+

Bu3N/H2O, 50oC, 3 d

98%

[Pd] 1 mol%

rt, KOH/H2O (20 h)C6H5B(OH)2

N

I

CO2H

N

C6H5

CO2H

+

98%

26

80

85

90

95

100

1 2 3 4 5

cycle number

Catalyst recycling (ultrafiltration)

50

60

70

80

90

100

1 2 3 4 5

cycle number

in water in methanol

Convers

ion, %

[Pd] 0.3 mol%

rt, KOH/H2O, 10 h

or 50 0C, MeOH, 7 h

C6H5B(OH)2

CO2H

I

CO2H

C6H5

+

27

Conversion >98%

Yield 81-85%

Catalyst recycling (centrifugation)

Suzuki-Miyaura reaction in methanol

run 1 2 3 4 5

yield, % 81 85 83 84 84

2306596878694Yield, %

55072>99>998898Conv. ,%

BrClBrIIIIX in

RC6H5X

p-Acp-NO2p-NO2p-NO2o-NO2p-CH3Om-CO2HR in

RC6H5X

[Pd] 1 mol%

rt, KOH/MeOH, 20 hC6H5B(OH)2+

X

R

Ph

R

I

[Pd] 1 mol%

KOH/MeOH, rt, 20 hC6H5B(OH)2+

28

before (A) and after Suzuki-Miyaura reaction (B for liquid phase, C for deposited phase)

and after interaction of the catalyst with m-iodobenzoic acid in the presence of KOH (D)

1.7 nm 1.9 nm

2.4-3.1 nm

Agglomerates

(2.6-7.2 nm)

of particles

(0.6-0.8 nm)

TEM images of the PdNPs

29

ArX + 2OH-

ArX+Ar'B(OH)2

+ 2OH-

ArPdX(OH)22-

ArPdAr'(OH)22-

ArAr' +2OH-

Ostwald ripening of PdNPs

Synlett, 2008, 1547

micelle

Pd

Pd

micelle

Pd

in the presence of ArX and in Suzuki-Miyaura reaction

micelle

Pd

Pd

Pd

Pd

Pd

30

Heck reaction

''Pd'': PdCl2 + PVI or PVI-PVC

PVI: poly(N-vinylimidazole)

PVI-PVC: co-poly(N-vinylimidazole-

N-vinylcaprolactam)

Run 1 2 3 4 5

Yield, % 99 99 91 94 98 ( PdCl2 : PVI-PVC=1:5)

97 99 96 92 92 ( PdCl2 : PVI-PVC=1:10)

I

OC4H9

O

OC4H9

O

+2 eq K2CO3

DMF, 100-120oC

1 mol% ''Pd''

N

N

N O

n m

31

Reactions of n-butyl acrylate with p-acetylphenyl bromide

Run 1 2 3 4 5

Yield, % 99 99 93 92 98

by 1H NMR

TEM images of the palladium nanoparticles

J.Organomet.Chem. 2007, 692, 4402

OC4H9

O

O

BrO

C4H9

O

O

+DMF, 120°C, 2h

1 mol% ''Pd''

2 eq K2CO3

''Pd'' = PdCl2/PVI-PVC=1:5

32

Novel recyclable catalyst for the cyanation of arylbromides

R: H, p-Ac, p-NO2,m-CHO, p-Me, p-OMe

0.1-1 mol % [Pd]

K4[Fe(CN)6], Na2CO3, DMF

80-97%

[Pd]: PdCl2 / poly(N-vinylimidazole-co-N-vinylcaprolactam) 1:5

120-140oC, 5-13 h

R

Br

R

CN

Br

O

CN

O5 mol% [Cu], K4[Fe(CN)6]

Na2CO3 , TBAB, DMF

140oC, 14 h

91%

[Cu]: CuI / poly(N-vinylimidazole -co-N-vinylcaprolactam) 1:5

Recycling: For R= p-Ac 5 consecutive cycles with constant yields ~93%

33

Alkoxycarbonylation of aryl iodides catalyzed by

polymer-supported palladium

Entry Catalyst Base Temp, oC

Pressure ofCO, atm

Yield, %

Influence of base and catalyst1 H2PdCl4 KOH 50 1 112 H2PdCl4 K2CO3 50 1 183 H2PdCl4 Et3N 50 1 324 K2PdCl4 KOH 50 1 455 K2PdCl4 K2CO3 50 1 536 K2PdCl4 Et3N 50 1 85

Influence of CO pressure 7 K2PdCl4 Et3N 50 1 708 K2PdCl4 Et3N 50 5 489 K2PdCl4 Et3N 50 30 41

Influence of temperature10 K2PdCl4 Et3N 25 1 811 K2PdCl4 Et3N 40 1 6312 K2PdCl4 Et3N 55 1 92

1 mol % "Pd"5 mol %PVC-PVI

CO, baseMeOH

IO

O

PVI-PVC = poly(N-vinylimidazole-co-N-vinylcaprolactam)

34

Methoxycarbonylation of aryl iodides

I

R

1 mol % K2PdCl45 mol % PVC-PVI

CO (1 atm), Et3N

MeOH

55oC, 60 h

R

O

O

Yield of RC6H4C(O)OMe, %Entry R Cycle 1 Cycle 2 Cycle 3

1 H 95 92 932 Me 92 92 903 OMe 91 89 834 C(O)Me 97 95 94

Phosphorus

Greek ‘phosphoros’

means light bearing

Chemical phosphorus means:

1. Biological active compounds

2. Complexing agents

3. Ligands

4. Phosphorus containing polymers

5. Reagents for organic synthesis

and more ...

36

Synthesis of arylphosphonates

N

Cl5

N

Cl4

P(O)(OH)2

N

Cl4

N

Cl

NC NC

Cl

Cl

P(O)(OH)2

ArP(O)(OR)2ArHal + (RO)3PCat.

+ ( Me3SiO)3P1) NiCl2

2) MeOH

+ ( Me3SiO)3P

or

(AlkO)3P

1) NiCl2

2) MeOH

Alk = Et, Bu

- RHal

37

Synthesis of arylphosphonates

Z

X

Z

P(O)R2

R2P(O)H, [Pd]

R = AlkO, Ph

X = I, Br

[Pd] = Pd(OAc)2, Pd(OAc)2 + 2L

solvent free or aqueous solution (H2O or MeCN-H2O (1:1))

L = Ph3P, Fu3P, Ph2P(m-C6H4SO3Na)

70-80oC

70-100%

38

Synthesis of vinylphosphonates

OR (NEt 2)

X

R'

R

Br

R

OR (NEt 2)

P(O)(OEt)2

R'

R R

(EtO)2P(O)

R'

OR(NEt 2)

R'

OR(NR 2)

(EtO)2P(O)H, [Pd]

or

X = Br, ClR = H, Me

or

20 - 100oC

Tetrahedron Lett., 1999, 40, 569

39

Synthesis of arylphosphines

ArHal +Cat.

PR

R'P

R

R'

PR

H

SiMe3

PdCl2(MeCN)2

PR

H

Ar(Het)

PR

1

R2

SiMe3

PdCl2(MeCN)2

PR

1

R2

Ar(Het)

Ar (Het) X +

20 - 100oC

70 - 90%

Ar (Het) X +100oC

75 - 90%

ORO2C Br

[Pd]

ORO2C PRRP(SiMe3)2 +

100 - 120oC 2

SiMe3 Ar

40

Synthesis of vinylphosphines

VinPPh2VinHal + Ph2PHCat.

R

R'

X

OR(NEt 2)

Ph2PH, [Pd] R

R'

PPh2

OR(NEt 2)

Ph

Br

SiMe3

Br

Ph

Br

Et

Ph

PPh2

SiMe3

PPh2

Ph

PPh2

Et

100oC

Ph2PH, [Pd]

94-95%

EtO

Br

Ph

Br

H(O)C

Br

EtO

PPh2

Ph

PPh2

H(O)C

PPh2Ph2PH, [Ni]

Et3N, DMF, 120oC

75-98%

Et3N, PhH or PhMe, rt

R = H, Me, SiMe3

R' = H, Me

[Pd] = PdCl2(PPh3)2

92-96%

Tetrahedron Lett., 1999, 40, 573

41

Ni-catalyzed cross-coupling of terminal alkynes

with chlorophosphines

R R'2PCl

PhPCl2

PCl3

R

R

PR'2R

R

R

P Ph

R

R

P R

R = Ph, Am, t-Bu, TMS

R' = Ph, n-Bu, i-Pr, t-Bu

Cat. = Ni(acac)2, Ni(PPh3)2Br2, Ni(COD)2

Cat.

Et3N, PhMe, 80oC, 10 min

+

+

+

87-99%

~99%

~99%

Org. Lett, 5, 4309, 2003

42

Cu-catalyzed cross-coupling of terminal alkynes

with chlorophosphines

R R'nPCl3-n

CuX (1 mol%)PR'nR

S N

Ph2PCl, i-Pr2PCl, t-Bu2PCl, (i-PrO)2PCl, (Et2N)2PCl, PhPCl2, PCl3,

OPCl

O

+

Et3N, MePh, r.t., 6-8 h3-n

R = Pr, Am, 4-MeOC6H4, 4-Me2NC6H4, 3-CF3C6H4, MeOCH2, Me2NCH2, 2-Py, ,

R'nPCl3-n:

Synthesis, 2835, 2003

43

Hydrogenation of vinylphosphonic acids

P(OH)2

Ar

O

P(OH)2

Ar

O

*H2 (10 bar), (P*P)RuBr2 (1 mol%)

MeOH, 80oC, 100% conv.

Ar: Ph, 4-MeC6H4, 4-ClC6H4, 1-Naphtyl

77-86% ee

Tetrahedron Asymmetry, 12, 319, 2001

PPh2

PPh2

MeO

MeO

PPh2

PPh2

MeO

MeO

P

P

P

P

O

O

(S)-BINAP

2

2

(P*P):

(R)-MeO-BIPHEP (R)-2-furyl-MeO-BIPHEP (R,R)-Me-DuPHOS

48-82%

R + HP(O)(OEt)2(EtO)2P

R

O

Pd2(dba)3/PPh3 or Pd(PPh3)4 (3 mol%)

THF,

Hydrophosphorylation of alkynes

44

95% ee

P(O)(OEt)2

MeO

reveals anti-dopaminergic activitywithout extrapyramidal side effect

88% ee

P(O)(OEt)2

Ar = Ph, 4-BuiC6H4, 4-PhC6H4, 1-Naphtyl, 2-Naphtyl, 6-MeO-2-Naphtyl

88-95% ee

(EtO)2P

Ar

O

(EtO)2P

Ar

O

H2 (5 bar), [Ir(cod)L*]+ [BArF]- (1 mol%)

CH2Cl2, 40oC, 100% conv.

[Ir(cod)L*]+ [BArF]- =

CF3

CF3

B

4

-

P(o-Tol)2Ir

N

O

t-Bu

+

Hydrogenation of vinylphosphonates

Tetrahedron Asymmetry, 14, 1397, 2003

45

X

R P(OEt)2

O

NHPMP

R P(OEt)2

O

*

OH

R P(OEt)2

O

CH3

R P(OEt)2

O

Pd(OCOCF3)2/(R)-MeO-BIPHEP

1 atm., TFE, 80oC

R: Ph, 4-FC6H4, 4-MeOC6H4, 4-MeC6H4, 2-MeC6H4, 1-Ad, Me

up to 55% ee

[Rh(COD)2]+SbF6

-/(R)-BINAP

10 atm., MeOH, 60oC

R: Ph, 4-FC6H4, 4-MeC6H4, 2-thienyl

up to 94% ee

[Ir(COD)L]+[BArF]

-

5 atm., CH2Cl2, 40oC

R: Ph, 4-PhC6H4, 1-Np, 2-Np, 2-(6-MeO-naphthyl)

up to 94% ee

H2

X = NPMP, O, CH2

-Amino and -oxy phosphonic acids

46

P(O)(OR)2Ar P(O)(OR)2Ar

HCOONH4 (6 equiv.), 5 or 10%Pd/C (3 mol%)

H2O, , 2-10 h

R = H, Et

Ar = Ph, 4-MeC6H4, 4-BuiC6H4, 4-PhC6H4, 4-MeOC6H4,

1-Nf, 2-Np, 6-MeO-2-naphthyl, 3-Py, 3-Quinolyl, 6-Quinolyl

Isolated yield 70-90%

Reduction of -arylethylphosphonic acids and esters by

palladium catalysts on solid supports

Hydrogen Transfer Reduction:

Russ. J. Org. Chem. 2002, 38, 537

Ar = Ph, R = H; HCOOH (4 equiv.), PdCl2/Al2O3 (10 mol%), 2.5M NaOHaq, , 1 h: Cycles Yield, %

1 1002 1003 984 945 90

47

P(O)(OH)2Ph P(O)(OH)2Ph

H2 (1bar), [SiO2-GluCs-Pd] (3 mol%)

H2O, , 1h

Cycles Yield, %1 811 1002 1003 1004 985 99

O

CH2OH

NH2

OHO

CH2OH

NH2

OH O

PdCl2

O

O

CH2OH

N

OH OO

N

CH2OH

OOH

SiO2

n

n

palladium(II) complex immobilized to glutaraldehyde-crosslinked silica-supported chitosan

[SiO2-GluCS-Pd]:

or: H2 (1 bar), 10%Pd/C(en) (3 mol%), H2O, , 1h: Cycles Yield, %

1 1002 1003 1004 1005 100

Russ. J. Org. Chem. 2006, 42, 990

48

R

R

PPh2

R

Ph2P

R

Ph2P

PhH, 80oC or MeCN, 130

oC

R = Ph, n-Pr, n-Am, t-Bu,

CH2OCH3, CH2N(CH3)2

+ Ph2PHPd(0) or Ni(0) Pd

2+ or Ni

2+

Pd(0) or Ni(0), H+

-isomer-isomer

-isomer

Hydrophosphination of alkynes

Synlett, 497, 2004

49

R1,R2 = c-C6H11, c-C5H10, 1-Ad;

R1 = i-Pr, R2 = i-Pr;

R1 = Ph, R2 = Ph, Me;

R1= Me, R2= -Np, , ;

Z = c-C6H11, t-Bu, Bn.

NZ

R1

R2

EtO

P

O

HEtO

EtO

P

EtO

O

C

R1

R2

NHZ

CdI2

w+

EtO

P

O

HEtO

EtO

P

EtO

O

C

R1

R2

NHZ

CdI2

w

R1

C

R2

O ++ H2NZ

O

R1=Et, Pr, Ph; R2 =H.

Z = t-Bu, Ph, Ph(CH3)CH, c-C6H11

R1,R2 = c-C6H11, c-C5H10, Pr

Z = Ph(CH3)CH, c-C6H11

S

SynLett, 9, 1393, 2005

Russ. J. Org. Chem., 517, 2005

Synthesis of -aminophosphonates and

-aminophosphonic acids

(t = 45-90 sec., yield: 89-95%)

(t = 1,5 – 10 min., yield: 86-94 %)

(t = 10-25 min., yield: 72-92%)

50

O

O

EtO

P

O

HEtO

w

ClCH2CH2Cl

O

NHZP(O)(OEt)2

+ ZNH2+

24 min

~ 80%

(isolated yield)Z = Bn, t-Bu, Ph

N HN

NH N

MeOOC COOMe

O

H

N HN

NH N

MeOOC COOMe

O

HN HN

NH N

MeOOC COOMe

OH H

O

N HN

NH N

MeOOC COOMe

HO

O

H

N HN

NH N

MeOOC COOMe

O

O

Me

Me

12-18 min;

82-85%

(isolated yield)

-Aminophosphorylation of natural products

Synlett, 2193, 2003

Russ. Chem. Bull., 54, 262, 2005

Sulfur and Selenium

The Sanskrit ‘sulvere’ and the Latin

‘sulphurium’ both mean sulfur

Greek ‘selene’ means moon

Chemical sulfur and selenium mean:

1. Biological active compounds

2. Semiconductors and solar cells

3. Optical materials

4. Reagents for organic synthesis

and more ...

52

Transition metal catalyzed synthesis of diaryl selenides

ArSeAr’

Tetrahedron Lett., 2003, 44, 7039

J. Organomet. Chem., 2000, 605, 96

X = Ac

Pd(PPh3)4, Toluene 1.5 % 87 %

Pd(PPh3)2Cl2 1.5 % 93 %

Ni(bpy)2Br2 10 % 91 %

Cu(phen)I 10 % 99 %

R

Se

XX

I

R

Se SnBu3

Bu3SnI(PPh3)2PdCl2

R = H, F

+DMF, 100C

5 h

+

83-95 %

X = H, Br, CH3O, NO2, CO2Et, CH3CO

53

Nickel catalyzed synthesis of diaryl selenides ArSeAr’

J. Organomet. Chem., 2000, 605, 96

Ni(PPh3)2Cl2Se SnBu3 OTf Se

+nBuOH, 100° C

LiBr, 12 h

Pd(PPh3)4, Toluene 1.5 % 0 %

Pd(PPh3)2Cl2, LiBr 1.5 % 60 %

Ni(PPh3)2Cl2 1.5 % 26 %

Ni(PPh3)2Cl2, LiBr 1.5 % 80 %

54

Copper catalyzed synthesis of diaryl selenides ArSeAr’

+ Bu3SnBr

(PPh3)Cu(phen)ISeSnBu3

F

SeAr(Het)

F

+ Ar(Het)Br

DMF, 110o C

4-27 h85-94 %

[Cat]

4-CF3C6H4SeC6H4F-4

(Bu3Sn)2Se

4-FC6H4SeSnBu3 + 4-CF3C6H4BrDMF, 110

o C

Bu3SnBr

+ +

(4-FC6H4)2Se+

Pd(PPh3)4, Toluene

(bpy)2NiBr2

(PPh3)Cu(phen)I

5%

10%

10%

0%

52%

97%

45%

18%

0%

N

Br Se

F N

SeSe

F F

SSe Se

FF Se Se

Se

F

FF

65%

83%

88%

67%

Tetrahedron Lett., 44, 7039, 2003

55

DMF, 110° C

10% (phen)CuI

Cl

SeNa Br

Ac

Se

AcCl

+

without additives 91% (26 h)

Bu3SnCl (10% mol) 93% (8 h)

microwave irrad. 92% (15 min)

Microwave, 300 W Heating, 110° C

ArBr ArSeAr’

t, min Isolated yield, % t, h Isolated yield, %

Br

Ac

Se

Ac Cl

15 92 8 93

Br

Me2N

Se

Me2N Cl

25 87 14 72

Br

H2N Me

Se

H2N Me Cl

25 65 18 41

N BrBr N SeSe

ClCl

20 90 7 85

N BrBr N Se

Cl

Br15 85 5 68

S

BrS

Se

Cl15 88 5 81

N

NN

BrN

NN

Se

Cl50 48 30

<15

(GC yield)

Copper(I) catalysed arylselenation of aryl bromides

R3SnCl co-catalysis. Microwave vs thermal activation

56

Hal = I, R=Ac

Hal = I, R=Ac

Hal = I, R=Me

Hal = I, R=Me

Hal = Br, R=CN

Hal = Br, R=CN

40

50

60

70

80

90

100

1 2 3 4

Copper(I) catalysed arylselenation of aryl bromides.

Catalyst recycling

57

R

EAr

R

ArE EAr

R

EAr

ArE

R

R

R

EAr

ArE

RR

EAr

R

R

R

ArE

Products of E-E and E-H bonds addition to alkynes

Chem. Rev., 106, 2320, 2006

J. Organomet. Chem., 687, 451, 2003

58

Pd

ArE

ArE EAr

R3P

Pd

ArE

EAr

Pd

EAr

PR3n

Pd

EAr

R3P EAr

R3P

Pd

EAr

ArE PR3

R3P

Pd

ArE

R3P EAr

ArE

Pd

EAr

PR3

Pd

ArE

ArE EAr

R3P

Pd

EAr

PR3

-PR3

-PR3PR3

-PR3PR3

KPd(PPh3)4-Cl

-PdCl2(PPh3)2ArE-EAr+

+

+

cis-

cis- trans-

trans-102.7 ppm 110.5 ppm

98.8 ppm101.2 ppm

insoluble

+ ArE-

Oxidative addition and substitution reactions

Organometallics, 2005, 24, 1414

K=0.0660.007 M

at 30oC

+-

31P NMR

E=S, Ar=Ph, PR3=P(Oi-Pr)3

59

R

PdL4

PdL2

ArE-EAr

oxidative

addition

coordinationinsertion

reductive

elimination

EAr

L2PdII

EAr

R

-LArE

PdIIL

EArL

L2PdII

EAr

EAr

R

EAr

R

ArE

60

Catalytic reaction under solvent free conditions

R

EAr

R

ArE

[Pd]

ArE-EAr

Z/E > 99/1

E=S, Se

+0.3 eq. PPh3 80-120

oC

meltsolvent-free

alkyne solution in the Ar2E2/PPh3 melt i

95-99%

Polymer-supported recyclable catalyst

Org.Biomol.Chem., 2004, 2, 284

Synlett, 2005, 1015; Russ.Chem.Bull., 2004, 53, 561

61

Addition reactions of Alk-EE-Alk (E = S, Se)

R + Alk2E2

Ni(acac)2/PMe2Ph (30 mol%)

neat, 100oC, 2h

AlkE

R

EAlk

Alk: Bu, Me, i-Pr, Cy

R: Bn, Ph, CH2OMe,

CH2NMe2, CMe2OH

R + Bu2S2

Pd2(dba)3/PCy2Ph (45 mol%)

neat, 140oC, 12h

BuS

R

SBu

R: Bu, SiMe3, CH2NMe2

OH

70 - 85%

83 - 89%

(~60% E = Se)

Chem. Eur. J., 2008, 14, 2420

62

R

RArE ArE

R

R

EAr

EArR'EAr

R' EAr

R

ArE

+ArE-H

60-80%, E/Z ~ 1/1E=S, Se

+hv (base)

Cat.

R: CH2R'

+ +

Addition of S-H and Se-H bonds to alkynes

Ogawa, A.; Ikeda, T.; Kimura, K.; Hirao, T. J.Am.Chem.Soc., 1999, 121, 5108

63

Ni-catalyzed S-H and Se-H bonds addition

[Ni]R R' ArEH

R

EAr

R' R'

EAr

R

+20-40

oC,

~1-3 h70-95%

+

[Ni]R ArEH

R

EAr

+20-40

oC,

~20-30 min70-95%

The catalyst from Pd(OAc)2

precursor

The catalyst from Ni(acac)2

precursor

Eur. J. Org. Chem., 2007, 3431

Organometallics, 2006, 25, 1970

64

R

ArEH

acacH

Ni(acac)2

ArE

NiEAr

NiArE

ArE

n

ArE

NiEAr

NiArE

n

R

ArE

ArEH

EAr

R

65

Relative activity of the self-organized catalysts

0

10

20

30

40

50

60

70

80

0 1 2 3 4 5 6 7

Particle size, μm

Yield, %

Organometallics, 2007, 26, 740

66

OH

nBu

NMe2

SCy

OH

SCy

nBu

SCy

NMe2

99 (92) >99:1

98 (75) 95:5

96 (87) 91:9

Ph

OH

NMe2

SCy

Ph

SBn

OH

SBn

NMe2

98 (77) 84:16

88 (74) >99:1

68 (57) 97:3

R

SAlk

R

+5% Pd(OAc)2AlkSH

w

Alkyne Product Yield, % Selectivity Alkyne Product Yield, % Selectivity

Pd-catalyzed AlkSH addition

J. Am. Chem. Soc.,2007, 129, 7252

C-N bond formation

68

Beginning of the era of the catalytic aryl halides amination

Br

R

Bu3SnNEt2

NEt2

R

+

PdCl2(P(o-Tol)3)2

Kosugi, Kamayama, Migita, 1983

I

R

Ph2NH

NPh2

R

+Pd(OAc)2, CuI

H2O, BuOH, CTMAB

Davydov, Beletskaya, 1995

X

R

NR'R''

R

+ R'R''NH

Pd(dppf)Cl2 orPd(BINAP)Cl2

tBuONa, dioxane

Buchwald, Hartwig, 1995

69

Arylation of benzotriazole

SO

O

O Na

P

O

N

N

I

O

IS

Br

N

BrN

O

O-

3

tppts =

Cu2+

Cu(II) =

HetHal =

Ar(Het)

NN

N

H

NN

N

Ar(Het)Hal

PdCl2L2 (2%)

K2CO3/CetMe3Br

Cu(II) (2%)

DMF, 100oC

+

79-96%

Ar

NN

N

H

NN

N

Pd(OAc)2 (2%)

2 tppts, NaOH

Cu(II) (2%)

H2O, 100oC

+

90-95%

2 2Ar2I+BF4

-

Ar

NN

N

H

NN

N

Pd(OAc)2 (2%)

2 tppts, NaOH

H2O, 100oC

+

90-95%

Ar2I+BF4

-N Ar

N

N

+

Ar(Het)

NN

N

H

NN

N

Ar(Het)Hal

PdCl2L2 (2%)

K2CO3/CetMe3Br

DMF, 100oC

+

79-96%

N Ar(Het) N

N

+

Ar: Ph, p-MeC6H4, p-MeOC6H4,

p-ClC6H4

70

Arylation of tetrazoles

Tetrahedron Lett., 2002, 43, 6217

Tetrahedron Lett., 2002, 43, 6221

NNH

N

N

R

Ar2I+BF4

-N

NN

NR

Ar

NN

N

N

R

Ar++

t-BuONa, t-BuOH

80oC, 8h

~ 1.5:1

42 - 52%

NNH

N

N

R

Ar2I+BF4

-+ N

NN

NR

Ar

92 - 98%

Pd(dba)2(rac-BINAP) (2%)

Cu(II) (2%), rac-BINAP (2%)

t-BuONa, t-BuOH, 80oC, 8h

Ar: Ph, p-MeC6H4, p-MeOC6H4, p-ClC6H4

R: Ph, p-MeC6H4, p-BrC6H4, p-MeOC6H4, 4-Py

Ph

CO2

2

Cu2+Cu(II):

71

Br

R

H2NHN

OR

HN

HN

R(H)

OH(Ph)+

Pd2dba3, L

Cs2CO3, dioxane,

100°C

OPPh2PPh2

CF3

CF3

OPAr2PAr2

62-98%

64-92%L =

L =

Ar =

Arylation of urea

Tetrahedron Lett., 2001, 42, 4381

Tetrahedron Lett., 2003, 44, 4791

R: p-CN, p-CF3, p-NO2

p-PhC(O), p-CO2Et

R: o-, p-Cl o-, m-, p-Me, o-MeO

72

N

N

N

MeO

N

CO2Et

N

NR1

O

N

R2

R1 N N

O

N

N

NHPri

Me

Me

R2

R

R= Me, Bn

= ; ; ;

Pd2dba3, 2-[di(t-butyl)phosphino]biphenyl, toluene, t -BuONa, 100°C

Palladium-catalyzed amination and amidation of

bromoindoles and their derivatives

Amination of bromoindoles and bromotetrahydrocarbazolones

NN

NN

ON

N

NN

HN

O

Pd2dba3, Xantphos, dioxane, Cs2CO3, 100°C.

Amidation of bromotetrahydropyrazinocarbazole

73

O

NO

N

R1

R2

N

O

R1

R2N

O

O

NH

O

NH

NO

NN

ON

O

R R

X

MeO

HN

CO2Et

O

N

Me

CO2Et

NN

ON

Me

EtO2C

Me Me

N

Me

CO2Et

HN

HN

ON

Me

EtO2C

Me Me

R

= ; ;

R= Me, BnX = O, NMe

Pd2dba3, Xantphos, dioxane, Cs2CO3, 100°C.

Amidation of bromoindoles and bromotetrahydrocarbazolones

Possible biological activity: Antidepressant, Psychotropic, Anxiolytic, Psychosexual disfunction treatment

74

Solvent-free amination

Br Z

O

N

OO

O

N CF3F3C

O

NH

NH

ZZ

O

H2N NH2

O

H2N

O

HN

Z

NH2

PhS

O2N

PhS NO2

NH

F3C

NH2

NH

CN

Z = CN, CF3

Reaction conditions:

100oC, graphite,

Base: Cs2CO3 or t-BuONa

[Pd]: Pd2(dba)2, Pd(OAc)2

L: Xantphos, DPEPhos

diaza-18-crown-6

60%, 10 h

72%, 4 h70%, 3 h70%, 8 h

Z = CF3, 75%, 5 hZ = CN, 65%, 6 h

Mendeleev Commun., 2003, 4, 13

75

Hal

H2N NH

NH2

H2N NH

NH R

NH

NH

NH RR

N NH

NRR

R R

H2N NH

NH

NH

NH

NH2

R

Hal = Cl, Br, I

n nx

n = 0, 1; x = 0, 1, 2, 3, 4

+

n nx

n nx

n nx

n nx

n nx

R = Hal1

Mono-, di-, and polyarylation of linear polyamines

Tetrahedron Lett., 1997, 38, 2287

Synlett, 1999, 1459; Eur. J. Org. Chem., 2005, 261

76

Z

H2N X NH2

Hal1

Hal2

HN X

NH

NHN NH

X

NH2N X NH

NH

X NH2

NHN NH

X

HN

X

NHN

Hal1, Hal

2 = Cl, Br

n nm

n = 0, 1; m = 1, 2, 3, 4

+

X = NH, O

Z = CH, N

n

n

m

n nm

n nm

n nm

n n

n n

Amination of dihalobenzenes and dihalopyridines with

polyamines

Tetrahedron Lett., 2008, 49, 3950

Tetrahedron Lett., 2003, 44, 1433

77

A new family of polyazamacrocycles

N

HN

NH

X

N

HN

NH

X

HN

NH

X

HNHN

X

Z

Z

HN

NH

X

Z

Z

NH HN

X

Synlett, 2005, 87; Chem. Lett., 2005, 110

Tetrahedron Lett., 2006, 47, 2691; 2001, 42, 4983, 4987; 2003, 44, 1433

Z

Z

Cl Cl

Z = CH, CO

Z

Z

Cl

Cl

Hal

Hal

Hal

Hal

Hal = Cl, Br

NHal Hal

N

Hal Hal

X NH2H2N

Pd(dba)2/BINAP 4-8 / 4.5-9 mol%

t-BuONa or Cs2CO3

dioxane, 6 - 72 h

+

X: NH(CH2)2NH, NH(CH2)3NH, CH2NH(CH2)2NHCH2,

CH2NH(CH2)3NHCH2, NH[(CH2)2NH]2, NH[(CH2)2NH]3,

O(CH2)2O, CH2O[(CH2)2O]2CH2, CH2O(CH2)4OCH2

78

OCl

ClOO

NH

HN

O

OO

NH2

O O

H2N

[Pd]

30%

+

79

Ar X NH2NHX HNH2N

Ar HalArHal X NHHN

X

NH

HN

X

NH

NH

X HNNH

Ar

ArAr

+

Pd(dba)2/BINAP

t-BuONa or Cs2CO3

cyclotrimers

Ar HalArHal X NHHN

X NH2H2N

X

NH

NH

X

HN

HN

Ar

Ar

+Pd(dba)2/BINAP

t-BuONa or Cs2CO3

cyclodimers

Helv. Chim. Acta, 2005, 88, 1983

80

Z

Z

Cl

Cl

H2N X NH2Z

Z

NHNH

X

Z

Z

HNHN

X

X

HN

HN Z

Z

Z

Z

Z

Z

Z

Z

NHNH

X

HN

NH X HN

HN

X

Z = CH, CO

n nm

n = 0, 1; m = 2, 3, 4

X = NH, O

+

nn

m

n

nn

n

n

n

n

n

n n

Intramolecular amination of dichloroanthracenes and

anthraquinones

Helv. Chim. Acta, 2005, 88, 1983

Eur. J. Org. Chem., 2005, 281; Tetrahedron Lett., 2001, 42, 4983

81

O

O

Br

Br

H

HN

O

BrH

OX

NH

O

OBr

H

XNH2H2NH

H

H

HH

HH

HH

B

0.5 equiv.

O

O

NH

HN

X NH2

X

H2NH

O

Br

Br

HO

X NH2H2N

2.5-3 equiv.

HH

HHHH

A

O

O

NH

HN

X

H

O

Br

Br

HO

X NH2H2N

Pd(dba)2/BINAP 8/9 mol%tBuONa, dioxane reflux

HH

HHHH

1 equiv.

82

O

NH

NH

HO X

HN

O

O

HN

H

X

NH2 NH2

X

O

NH NH

H

O

O

H

O

NH

NH

X

X

H

H

HH

H H

H

HH

H

HH

+

or

B

A

+

O

Br

Br

HO

H

HH

Chem. – Eur. J., 2005, 11, 1730

83

Mono-, bis- and triscyclen structures with polyamine linkersX

NH2NH2

NH N

N HN

Br

Br

NH N

N HN HN

HN

X

XHN

HN

NH N

N HN

N HN

NH N

Br Br

[Pd]

[Pd]

[Pd]

Y

NH

NH HN

N

N

NH

HN

NH

NH

X

N

N

HN

H2N X NH2NH2YH2N

+

1 equiv.

X = CH2NH(CH2)2NHCH2,

X = CH2NH(CH2)3NHCH2,

X = CH2O(CH2)2O(CH2)2OCH2,

X = CH2O(CH2)2OCH2,

X = CH2,

cyclodimer

X = Y = O(CH2)2O,

X = CH2O(CH2)2OCH2

Y = CH2

40%

36%

65%

69%

61%

37%

38%

NHN

NHN

NH

X

NH

N

N

N

N

HNN

NNH

HN

X

HN

Br Br

+

Tetrahedron Lett., 2008, 49, 3950

X = CH2O(CH2)2OCH2,X = CH2,

54%

15%

84

Acknowledgements

Afanas'ev V.V.

Ananikov V.P.

Artamkina G.A.

Averin A.D.

Bessmertnykh A.G.

Cheprakov A.V.

Davydov D.V.

Ganina O.G.

Goulioukina N.S.

Kabachnik M.M.

Prof. Guilard R.

Prof. Genet J-P.

Prof. Pfaltz A.

Financial support: INTAS, RFBR, CRDF, President grant for Leading School

Cooperation:Kashin A.N.

Kazankova M.A.

Latyshev G.V.

Lukashev N.V.

Orlov N.V.

Ranyuk E.R.

Shukhaev A.V.

Shulyupin M.O.

Sigeev A.S.

Titanyuk I.D.

Zobnina E.V.