1

Synthesis and Characterization of N-Heterocyclic Carbene Palladium(II) Complexes. The Catalytic

Application on Strecker Synthesis of α-Aminonitriles

學生：洪柏楷 指導教授：于淑君　博士

2010 / 07 / 29Department of Chemistry & Biochemistry

Chung Cheng University

2

Phosphine Ligand

Phosphines are electronically and sterically tunable.

Expensive.

Air/water sensitive and thermally unstable.

Metal leaching.

Chemical waste - water bloom.

P P PPO

OO

P(Bu)3 P(OiPr)3 P(Me)3 P(o-tolyl)3

25 mL 211.5 USD

25 G 396 USD

100 mL 31.9 USD

10G 135.5USD

3

N-Heterocyclic Carbenes

NHCs are stronger σ-donor and weaker π-acceptor than the most electron rich phosphines .

NHCs can be useful spectator ligands, because they are sterically and electronically tunable.

NHCs can promote a wide series of catalytic reactions like phosphine.

NHCs have advantages over phosphines and offer catalysts with better air- and thermal stability.

[M]

4

N-Heterocyclic Carbenes as Ligands- In the early 90's NHC were found to have bonding properties similar to trialklyphosphanes and alkylphosphinates.

- compatible with both high and low oxidation state metals

- examples:

- reaction employing NHC's as ligands:

Herrmann, W. Angew. Chem. Int. Ed. 2002, 41, 1290-1309.

Herrmann, W. A.; Öfele, K; Elison, M.; Kühn, F. E.; Roesky, P. W. J. Organomet. Chem. 1994, 480, C7-C9.

N NMe Me

W

COCOOCCOOC V

NHCCHN

NHCCHNCl

ClTi ClCl

ClCl

NN

N N

Me Me

MeMe

Re OO

OMe

N NMe Me Ru

PCy3

Ph

NNMesMes

ClCl

C-H Activation of Methane

Oxidation of Alcohols

Reductive Aldol Reaction

Allylation of Aldehydes

Strecker Reaction

5

The Catalytic Applications of Pd(II)

Heck reaction

Suzuki–Miyaura Reaction

Carbon-Surfur Coupling Reactions

Buchwald-Hartwig Reactions

Etherification Reaction

Ethylene-CO copolymerization Reaction

How does the life start on earth

6

Miller experiment – Water, methane, ammonia and hydrogen.

Stanley L. Miller . Science 1953, 117, 528-529.

7

Strecker Amino Acid Synthesis

The Strecker amino acid synthesis is a series of chemical reactions that synthesize an amino acid from an aldehyde (or ketone).

Adolph Strecker was the first to understand this organic reaction at 1850.

Two novel organogallium(III) complexes were tested in vitro against human tumour.

R1

O

HH2N

R2 NaCN

AcOH

HNR2

R1 CN

H+ HNR2

R1 CO2H

Santiago Gomez-Ruiz , Milena R. Journal of Organometallic Chemistry 2009, 694, 2191–2197.

Strecker, D. Ann.Chem. Pharm. 1850, 75, 27-45.

GaMe3

N OO

R COOH

R = H, Me

THF, hexane

NO

O R

O OGa

O OGa

R NO

O

1 R = H2 R = Me

8

Lewis Acid-Catalyzed Strecker Reactions Lewis acid catalysts Et3N 、 InCl3 、 Ga(OTf)3 、 BiCl3

Paraskar, A. S.; Sudalai, A. Tetrahedron Lett. 2006, 47, 5759-5762. Ranu, B. C.; Dey, S. S.; Hajra, A. Tetrahedron 2002, 58, 2529-2532. Surya Prakash, G. K.; Mathew, T. ; Panja, C.; Alconcel, S.; Vaghoo, H.; Do, C.; Olah, G. A. PNAS 2007, 104, 3703-3706. De, S. K. ; Gibbs, R. A. Tetrahedron Lett. 2004, 45, 7407-7408.

Transition metal Lewis acid catalysts RuCl3 、 NiCl2 、 Sc(OTf)3 、 Cu(OTf)2

De, S. K. Synth. Commun. 2005, 35, 653-656. De, S. K. J. Mol. Catal. A: Chem. 2005, 225, 169-171.

Lanthanide Lewis acid catalysts Pr(OTf)3 、 La(O-i-Pr) 、 Yb(OTf)3

De, S. K. Synth. Commun. 2005, 35, 961-966.

Others KSF 、 I2

Yadav, J. S.; Subba Reddy, B. V.; Eeshwaraiah B.; Srinivas, M. Tetrahedron 2004, 60, 1767-1771. Royer, L.; De, S. K.; Gibbs, R. A. Tetrahedron Lett. 2005, 46, 4595-4597.

9

Motivation

Using NHCs ligand to replace phosphine ligand in organomatallic catalysis.

Synthesis of NHC-Pd(II) complexes with well-defined structures.

Developing a practical and effective process for theStrecker Reactions.

Greener catalysis –solventless and microwave conditions.

10Toshikazu Hirao, Kenji Tsubata . Tetrahedron Letters 1978 , 18, 1535 - 1538.

Pd(II)Cl2(RNC)2 NH2CHCH(OC2H5)2R1 R2

PdCl

Cl

CNHR

NHCHCH(OC2H5)2

R1 R2

NHR

H -2C2H5OH

PdCl

Cl

CN

N

NHRR2

R1

R

H

24 h

rt

The First Palladium(II) Carbene Complexes

11

Lijin Xu, Weiping Chen Organometallics, 2000, 19, 1123-1127 .

Examples of Pd(II)-Carbene Complexes

trans-syn

NNMenBu

Br

Pd(OAC)2

THF reflux, 2h

trans-anticis-syn cis-anti

NN

NN

PdBr

Br

nBu

nBu

Me

Me NN

NN

PdBr

Br

Me

nBu

Bun

Me

N N

Pd

NN

Me

Me

nBu

nBu

N N

Pd

NN

Me

Bun

nBu

Me

BrBr BrBr

N

N

X

A: X = BrB: X = I

0.5 eq. Pd(OAC)2

DMSO, 120oC, 3h N

NPd

N

N

X

X

trans -1: X = Brtrans -2: X = I

Yuan Han, Han Vinh Huynh, Journal of Organometallic Chemistry, 2007, 692, 3606–3613.

12

Examples of Pd(II)-Carbene Complexes

Yuan Han, Han Vinh Huynh, Journal of Organometallic Chemistry, 2007, 692, 3606–3613.

2 AgO2CCF3

CH3CN

NN

Pd

NN

O2CCF3

O2CCF3

cis -3

N

NPd

N

N

X

X

trans -1: X = Brtrans -2: X = I

13

hmim = 1-hexyl-3-methylimidazolium

Synthesis of Palladium(Il) Carbene Complexes

NN

I

Pd(OAC)2

THF

2

90oC, 3 h

yield = 70%

Br NaI Iacetone

1

100oC, 24 h

yield = 90%

NNNN

I70oC, 8 h

yield = 95%

2

(hmim)HI

PdI2(hmim)2

3

N N

Pd

NN

II

N N

Pd

NN

II

trans-syn trans-anti

14

Synthesis of Pd(Il) Carbene Complex Catalyst

CH3CN, 3 h

yield = 90%

43

N N

Pd

NN

II

N N

Pd

NN

IIN

N

NN

PdO

O

CF3

O

CF3

O

AgO CF3

O

Pd(hmim)2(OOCCF3)2

15

1H NMR Spectra of (hmim)HI (2), PdI2(hmim)2 (3), and Pd(hmim)2(OOCCF3)2 (4)

*CDCl3

2HH

CH3

NN

I

(hmim)HI(2)

H

H H

NN

Pd

NN

O CF3

O

O CF3

O

Pd(hmim)2(OOCCF3)2(4)

N NH3C

Pd II

NNH3C

N NH3C

Pd II

NNCH3

trans-syn trans-anti

PdI2(hmim)2(3)

16

13C NMR Spectra of (hmim)HI (2), PdI2(hmim)2 (3), and Pd(hmim)2(OOCCF3)2 (4)

*CDCl3

C

C

CNN

C

Pd

NN C

O CF3

O

O CF3

O

Pd(hmim)2(OOCCF3)2(4)

N N

Pd II

NN

N N

Pd II

NNC

trans-syn trans-syn

PdI2(hmim)2(3)

C

C

C

NC

N

I(hmim)HI

(2)

q, 2J(C,F)= 36.0 Hz

q, 1J(C,F)= 288.0 Hz

19F NMR of Pd(hmim)2(OOCCF3)2 (4)

17

F

NN

Pd

NN

O CF3

O

O CF3

O

Pd(hmim)2(OOCCF3)2(4)

4000 3500 3000 2500 2000 1500 1000 50040

45

50

55

60

65

70

75

80

85

90

95

100

tran

smitt

ance

(a.

u.)

wavenumber(cm-1)18

IR Spectra of (hmim)HI (2), PdI2(hmim)2 (3), and Pd(hmim)2(OOCCF3)2 (4)

(hmim)HI (2)

PdI2(hmim)2 (3)

Pd(hmim)2(OOCCF3)2 (4)

1868(C=O)

1166

1219

imidazole H–C–C & H–C–N bending

2953,2930,2857 1569

imidazole ring ν (C–H) aliphatic ν (C–H)

imidazole ν (ring stretching)

3079,3140

2954, 2928, 28573113, 3149

2957, 2933, 28613133, 3162

1566

1576

1190

19

Single-Crystal Structure of PdI2(hmim)2 (3)

bond lengths [Å] bond angles [deg]

Pd(1)-C(11)Pd(1)-I(1)

2.019(5)2.6066(5)

N(4)-C(11)-N(3)C(11)-Pd(1)-C(1) I(2)-Pd(1)-I(1)C(11)-Pd(1)-I(2)C(1)-Pd(1)-I(1)

105.0(5)179.8(2)179.22(2)89.62(15)90.27(14)

Pd(2)-C(21) Pd(2)-I(3)#1

2.032(6)2.6059(6)

N(5)-C(21)-N(6)C(21)-Pd(2)-C(21)#1I(3)-Pd(2)-I(3)#1C(21)-Pd(2)-I(3)#1C(21)#1-Pd(2)-I(3)

105.4(5)180.0(4)180.00(2)90.0(2)90.0(2)

dihedral angle8.20 °

Range of Pd(II)-C1.97 ~ 2.30 Å

20Lijin Xu, Weiping Chen Organometallics, 2000, 19, 1123-1127 .

trans-syn

NNMenBu

Br

Pd(OAC)2

THF reflux, 2h

trans-anticis-syn cis-anti

NN

NN

PdBr

Br

nBu

nBu

Me

Me NN

NN

PdBr

Br

Me

nBu

Bun

Me

N N

Pd

NN

Me

Me

nBu

nBu

N N

Pd

NN

Me

Bun

nBu

Me

BrBr BrBr

N-Heterocyclic Carbene Complexes of Palladium ---- cis / trans-Isomerization

trans-anti : trans-syn = 1:1

d-CDCl3

rt, 24 h

d-CDCl3

trans-anti : trans-syn = 5:1

PdI2(hmim)2 (3) trans-syn and trans-anti Isomerization

21

rt, 12h

PdI2(hmim)2 (3) recrystalized from toluene + hexane (1:15)

PdI2(hmim)2(3)

d-CDCl3

200 NMR

50 °C, 12h

trans-anti trans-syn : trans-anti = 1:1

4.3634.3254.287

+3.952

4.3804.3624.3304.3014.285

+3.9513.935

N N

Pd II

NN

trans-syn

22

Strecker Reaction

R1 R2

O

TMSCN cat.

R3 NH2 NH

R3R2

CN

R1

Jiacheng Wang, Yoichi Masui, Makoto Onaka Eur. J. Org. Chem. 2010, 1763–1771.

RCHO Me3SiCN R CN

OSiMe3

RCHO R1 NH2

NR1 R

H

cyanohydrin trimethylsilyl ether

(side product)

imine(intermediate)

Route 1

Side reaction

Me3SiCNR N

H

CN

R1

product

Noor-ul H. Khan, Santosh Agrawal . Tetrahedron Letters. 2008, 49, 640–644.

23

Examples of Catalytic Strecker Reaction of Ketones

R1 Me

OTMSCN

Fe(Cp)2PF6 (5 mol %)

neat, rt, 20 min R1 NH

R2

MeNC

R1= Ph, 4-MeC6H4, 2-BrC6H4, 4-O2NC6H4, 2-Naphthyl 73-94% yield

R2 NH2

R2 = Ph, PhCH2

Thomas Mathew, Chiradeep Panja, Steevens Alconcel. PNAS. 2007,104, 3703–3706.

Jiacheng Wang, Yoichi Masui, Makoto Onaka Eur. J. Org. Chem. 2010, 1763–1771.

R1 = Ph, 4-MeOC6H4, 4-BrC6H4, 3-BrC6H4, t-BuR2 = Ph, 4-ClC6H4, 4-BrC6H4, n-Bu

63-99% yield

R1 Me

O

R2 NH2 TMSCNneat, rt, 0.75-4 h

Sn-Mont (1.9 mol %)

R1 NH

R2

CNMe

R1 Me

O

TMSCNCH2Cl2, rt, 3-7 h R1 N

H

R2

MeNC

R1 = Ph, 4-BrC6H4, 4-MeC6H4, CF3, CF2H, CH2F 75-98% yield

R2 NH2

R2 = Ph, 4-MeC6H4, 4-BrC6H4, 4-ClC6H4

Ga(OTf)3 (5 mol %)

24

Jamie Jarusiewicz, Yvonne Choe. J. Org. Chem. 2009, 74, 2873–2876.

R3 Me

OTMSCN

NHC-Pdll (3 mol %)

CH2Cl2, rt, 24 h R2 NH

R4

MeNC

R3 = 2-Naphthyl, 4-MeOC6H4, 4-BrC6H4, 4-O2NC6H4, 2-Furyl 15-92% yield

R4 NH2

R4 = Ph, PhCH2

NN

MeN

O

iPr

OCH3O

PdCl

NHC-Pdll

TMSCN R1 NH

R2R2 NH2R1 Me

O

toluene, 40oC, 24-48 h

cat. (10 mol %)

R1 = Ph, 4-FC6H4, 4-ClC6H4, 4-BrC6H4, 2-Naphthyl 79-99% yield

R2 = Ph, 4-MeOC6H4, 3-OMeC6H4, 4-BrC6H4, 4-ClC6H4

Me CN

O OP

OHO

cat.

Examples of Catalytic Strecker Reaction of Ketones

Jing Nie, Teng Wanga , Jun An Ma Org. Biomol. Chem. 2010, 8, 1399–1405.

25

H

O

H

O

Cl

CHOCHO

MeO

O H

O

S H

O

N

H

O

H

O

H

O

H

O

H

O

O O

MeOO

BrO

O

ON

O

O

MeO

NH2 NH2

NH2MeO

NH2

MeO

NH2

Me

NH2

Cl

NH

NH

O NH

NH2

Aldehyde Ketone Amine

Pd(II)-Catalyzed Strecker Reactions

NH

R3R2

CNTMSCN

cat. (3 mol %)R3 NH2

R1R1 R2

O

26

Pd(hmim)2(OOCCF3)2 (4) Catalyzed Strecker Reactions

Solvent Time

(min)

Conv.

(%)

Time

(min)

Conv.

(%)

toluene 5 52 25 62

CH2Cl25 55 25 87

THF 5 5 25 53

actonitrile 5 59 25 89

neat 5 >99 25 -

H

O

TMSCNNH2 N

H

CN cat. 4 (3 mol %)

rt, solvent

Reaction Conditions : Catalyst Loading = 3 mol % ; Benzaldehyde = 0.2 mmol; Aniline = 0.2 mmol, TMSCN = 0.4 mmol ; Sodium Sulfate = 0.7 mmol.The conversion is determined by 1H NMR.

27

EntryAldehyde

(R)Time (min)

Conv. (%)

Intermediate / Product /

Side product

1 Ph 1 >99 0/100/0

2 4-ClC6H4 1 >99 0/100/0

3 4-MeC6H4 1 >99 0/100/0

4 4-MeOC6H4 1 >99 0/100/0

5 2-furyl 1 >99 0/100/0

6 2-thienyl 1 >99 0/59/41

7 2-thienyl 1 >99 0/90/10a

8 3-pyridyl 3 >99 0/100/0

9 (E)-PhCH=CH 1 >99 0/100/0

10 butyl 1 >99 0/100/0

11 cyclohexyl 1 >99 0/100/0

12 t-butyl 1 >99 0/100/0

R H

OTMSCN R N

H

CN

NH2 no cat.

neat, rt

Reaction Conditions : Aldehyde = 0.2 mmol; Benzylamine = 0.2 mmol, TMSCN = 0.4 mmol.The conversion is determined by 1H NMR.aPdI2(hmim)2 (3) as catalyst (3 mol%).

Strecker Reaction Under Catalyst-Free Conditions

28

EntryAldehyde

(R)Time(min)

Conv.(%)

Int./Product

no cat. condition

Conv.(%)

Int./Product

1 Ph 5 >99 3/97 >99 69/31

2 Ph 5 93 7/86a >99 69/31

3 4-ClC6H4 10 >99 30/70 >99 82/18

4 4-MeC6H4 2 >99 0/100 97 77/20

5 4-MeOC6H4 1 >99 0/100 97 58/39

6 2-furyl 2 >99 0/100 91 16/75

7 2-thienyl 10 97 13/84 93 77/16

8 3-pyridyl 15 97 17/80 96 69/27

9 (E)-PhCH=CH 4 >99 0/100 >99 52/48

10 cyclohexyl 1 >99 0/100 >99 0/100

R H

OTMSCN

NH2

R NH

CN cat. 3 (3 mol %)

neat, rt

Reaction Conditions : Catalyst Loading = 3 mol % ; Aldehyde = 0.2 mmol; Aniline = 0.2 mmol, TMSCN = 0.4 mmol.The conversion is determined by 1H NMR.a Pd(hmim)2(OOCCF3)2 (4) as catalyst.

PdI2(hmim)2 (3)-Catalyzed Strecker Reactions

29

H

O

TMSCN cat. 3 (3 mol %)

neat, rt

NH

CN

RR NH2

Reaction Conditions : Catalyst Loading = 3 mol % ; Benzaldehyde = 0.2 mmol; Amine = 0.2 mmol, TMSCN = 0.4 mmol.The conversion is determined by 1H NMR.

PdI2(hmim)2 (3)-Catalyzed Strecker Reactions

EntryAmine

(R)Time(min)

Conv.(%)

Int./ Product/ Side product

no cat. condition

Conv.(%)

Int./ Product/

Side product

1 butyl 1 95 0/90/5 >99 0/87/13

2 cyclohexyl 1 >99 0/94/6 >99 0/88/12

3 Ph 5 >99 3/97/0 >99 69/31/0

4 4-ClC6H45 >99 0/100/0 >99 78/22/0

5 4-MeC6H45 >99 0/100/0 98 63/35/0

6 piperidine 20 92 0/77/15 91 0/62/29

7 pyrrolidine 15 97 0/89/8 90 0/86/4

8 morpholine 20 >99 0/92/8 >99 0/82/18

30

EntryAldehyde

(R)Time(min)

Yield(%)

Reported Data

Time(min)

Yield(%)

Reference

1 Ph 5 97 6 96 Masui Y, Chem.Eur. J., 2010

2 4-ClC6H4 10 70 10 96 Najera C., Synthesis, 2007

3 4-MeC6H4 2 99 6 92 Masui Y, Chem.Eur. J., 2010

4 4-MeOC6H4 1 99 6 97 Masui Y, Chem.Eur. J., 2010

5 2-furyl 2 99 2 93 Masui Y, Chem.Eur. J., 2010

6 2-thienyl 10 84 20 86 Abaee M. S. , Tetrahedron Lett., 2009

7 3-pyridyl 15 80 30 83 Panja C., Synlett., 2007

8 (E)-PhCH=CH 4 99 30 81 Panja C., Synlett., 2007

9 cyclohexyl 1 99 60 86 Acosta F. C., Commun., 2009

R H

OTMSCN

NH2

R NH

CN cat. 3 (3 mol %)

neat, rt

Reaction Conditions : Catalyst Loading = 3 mol % ; Aldehyde = 0.2 mmol; Aniline = 0.2 mmol, TMSCN = 0.4 mmol.The conversion is determined by 1H NMR.

Comparison of 3-Catalyzed Strecker Reactions with Reported Data

31

EntryAmine

(R)Time(min)

Yield(%)

Reported DataTime(min)

Yield(%)

Reference

1 butyl 1 90 6 95 Masui Y, Chem.Eur. J., 2010

2 cyclohexyl 1 94 13 90 Najera C., Synthesis, 2007

3 Ph 5 97 6 96 Masui Y, Chem.Eur. J., 2010

4 4-ClC6H4 5 99 6 90 Masui Y, Chem.Eur. J., 2010

5 4-MeC6H4 5 99 8 94 Abaee M. S. , Tetrahedron Letters, 2009

6 piperidine 20 77 20 90 Azizi N., Synthetic Communications, 2004

7 pyrrolidine 15 89 20 90 Azizi N., Synthetic Communications, 2004

8 morpholine 20 92 20 96 Desai U. V., Monatshefte fur Chemie., 2007

H

O

TMSCN cat. 3 (3 mol %)

neat, rt

NH

CN

RR NH2

Reaction Conditions : Catalyst Loading = 3 mol % ; Benzaldehyde = 0.2 mmol; Amine = 0.2 mmol, TMSCN = 0.4 mmol.The conversion is determined by 1H NMR.

Comparison of 3-Catalyzed Strecker Reactions with Reported Data

32

Neat Neat + 100 mg Na2SO4

Time (h)

Conv. (%) Time (h)

Conv. (%)cat. 3 cat. 4 cat. 3 cat. 4

12 - <5 12 44 <515 43 - 15 50 18 - - 18 -24 54 <5 24 48 <5

Reaction Conditions : Catalyst Loading = 3 mol % ; Acetophenone = 0.2 mmol; Aniline = 0.2 mmol, TMSCN = 0.4 mmol .The conversion is determined by 1H NMR.

PdI2(hmim)2 (3) and Pd(hmim)2(OOCCF3)2

(4)-Catalyzed Strecker Reactions of Ketone

NH

H3C CNO

TMSCN cat. 3 or cat. 4 (3 mol%)

rt

NH2

33

Entry MWcat. 3 cat. 4

Time(s)

Conv.(%)

Time(s)

Conv.(%)

1 150

120 - 120 52160 - 160 83180 85 180 88200 91 200 86220 89 220 -

2 30030 77 30 7140 82 40 7250 72 50 -

3 450 40 72 40 694 600 40 70 40 60

Microwave-Assisted PdI2(hmim)2 (3) and Pd(hmim)2(OOCCF3)2 (4)-Catalyzed Strecker

Reaction of Ketones

Reaction Conditions : Catalyst Loading = 3 mol % ; Acetophenone = 0.2 mmol; Aniline = 0.2 mmol, TMSCN = 0.4 mmol .

The conversion is determined by 1H NMR.

NH

H3C CNO

TMSCNcat. 3 or cat. 4 (3 mol%)NH2

2 drops (Bmim)PF6, MW

34

Microwave-Assisted PdI2(hmim)2 (3) and Pd(hmim)2(OOCCF3)2 (4)-Catalyzed Strecker Reactions

Entry R1 R2

cat.3 cat.4Time

(s)Conv.(%)

Time(s)

Conv.(%)

1 Ph 200 91 180 882 3-MeOC6H4 200 85 220 803 Ph 4-MeOC6H4 200 90 200 884 4-MeC6H4 200 92 180 885 4-ClC6H4 220 94 220 766 4-MeOC6H4 Ph 200 79 240 727

4-BrC6H4

Ph 220 83 240 688 4-MeOC6H4 200 87 180 799 Ph 220 84 240 85

10 2-naphthyl 4-MeOC6H4 200 93 220 8611 3-MeOC6H4 220 84 220 8212 2-furyl Ph 200 89 200 8213

3-pyridylPh 220 81 200 75

14 4-MeOC6H4 200 89 200 84

154′-methoxy

propiophenonePh 180 68 180 63

Reaction Conditions : Catalyst Loading = 3 mol % ; Ketone = 0.2 mmol; Amine = 0.2 mmol, TMSCN = 0.4 mmol; (Bmim)PF6 = 2 drops; Power = 150W.The conversion is determined by 1H NMR.

NH

R2H3C CN

TMSCN cat. 3 or cat. 4 (3 mol %)

2 drops (Bmim)PF6, MWR2 NH2

R1R1

O

35

PdI2(hmim)2 (3)-Catalyzed Strecker Reactions

Benzyl amine (pKb= 4.67) Aniline (pKb= 9.3)

Me3SiCN

Me3Si CN

H2N H2N

O

CN

OSiMe3

TMSCN

O

cat. 3 (3 mol %)

2 drops (Bmim)PF6, MW

NH2

CN

MeOTMS

TMSCN

N

O

N

cat. 3 (3 mol %)

2 drops (Bmim)PF6, MW

NH2

CN

MeOTMS

Kobayashi S.; Tsuchiya Y.; Mukaiyama T. Chemistry Letters, 1991, 537-540.

36

Entry R1 R2

cat. 3 Reported DataTime

(s)Conv.(%)

Time(h)

Conv.(%)

1 Ph 200 91 0.33 94b

2 3-MeOC6H4 200 85 24 99c

3 Ph 4-MeOC6H4 200 90 24 87c

4 4-MeC6H4 200 92 6 85a

5 4-ClC6H4 220 94 0.75 95e

6 4-MeOC6H4 Ph 200 79 1 92e

74-BrC6H4

Ph 220 83 3 95a

8 4-MeOC6H4 200 87 24 82c

9 Ph 220 84 0.33 88b

10 2-naphthyl 4-MeOC6H4 200 93 24 80c

11 3-MeOC6H4 220 84 24 86c

12 2-furyl Ph 200 89 24 83d

133-pyridyl

Ph 220 81 24 40d

14 4-MeOC6H4 200 89 24 90c

154′-methoxy

propiophenonePh 180 68 3 91e

Reaction Conditions : Catalyst Loading = 3 mol % ; Ketone = 0.2 mmol; Amine = 0.2 mmol, TMSCN = 0.4 mmol; (Bmim)PF6 = 2 drops; Power = 150W.

The conversion is determined by 1H NMR.a Ga(OTf)3,

bFe(Cp)2PF6, cBINOL-derived phosphoric acid, dPdII-NHC, eSn-Mont

Comparison of 3-Catalyzed Strecker Reactions with Reported Data

NH

R2H3C CN

TMSCN

cat. 3 (3 mol %)

2 drops (Bmim)PF6, MWR2 NH2 R1R1

O

37

Entry R1 R2

cat. 4 Reported DataTime

(s)Conv.(%)

Time(h)

Conv.(%)

1 Ph 180 88 0.33 94b

2 3-MeOC6H4 220 80 24 99c

3 Ph 4-MeOC6H4 200 88 24 87c

4 4-MeC6H4 180 88 6 85a

5 4-ClC6H4 220 76 0.75 95e

6 4-MeOC6H4 Ph 240 72 1 92e

74-BrC6H4

Ph 240 68 3 95a

8 4-MeOC6H4 180 79 24 82c

9 Ph 240 85 0.33 88b

10 2-naphthyl 4-MeOC6H4 220 86 24 80c

11 3-MeOC6H4 220 82 24 86c

12 2-furyl Ph 200 82 24 83d

133-pyridyl

Ph 200 75 24 40d

14 4-MeOC6H4 200 84 24 90c

154′-methoxy

propiophenonePh 180 63 3 91e

Reaction Conditions : Catalyst Loading = 3 mol % ; Ketone = 0.2 mmol; Amine = 0.2 mmol, TMSCN = 0.4 mmol; (Bmim)PF6 = 2 drops; Power = 150W.

The conversion is determined by 1H NMR.a Ga(OTf)3,

bFe(Cp)2PF6, cBINOL-derived phosphoric acid, dPdII-NHC, eSn-Mont

Comparison of 4-Catalyzed Strecker Reactions with Reported Data

NH

R2H3C CN

TMSCN cat. 4 (3 mol%)

2 drops (Bmim)PF6, MWR2 NH2

R1R1

O

38

Proposed Mechanism for Strecker Reaction

NN

Pd

NN

O CF3

O

O CF3

O

R1 R2

O

R NH2

H2O

NR R1

R2

NHC-Pd2+ NHC-Pd2+

NC Si

R1

R2

CNNR

Si

H2O

SiOH

NR

H R2

R1CN

N N

Pd II

NN

cat. 3 cat. 4

or

39

ConclusionsWe have successfully synthesized NHC-carbene Pd(II) complexes (3) and (4) , and characterized them by using 1H- ,13C , 19F-NMR, IR spectrocopies, as well as X-ray crystallography.

We have successfully demonstrated the highly effective activity of the Pd(II) NHC-carbene complex catalyst towards the Strecker reactions.

Not many successful synthetic protocols for Strecker reactions of ketones has been reported. We have demonstrated in this study that our target Pd(II) NHC-carbene catalyst (3) and (4) is highly active for the Strecker reactions of ketones under microwave irradiation conditions.