SYNTHESIS, STRUCTURE AND CATALYTIC APPLICATION OF NOVEL CARBENE COMPLEXES WITH BENZOTHIAZOLIN 2 YLIDENE LIGANDS 1

The NNHC 1.1-1.3 derived from imidazole, imidazoline and benzimidazole have been successfully employed as ancillary ligands in catalysis.5 One way to “enrich” a NNHC is to attach hetero

Chapter One: Introduction Introduction

Chapter One

Introduction

Carbenes, the simplest being methylene CH2, are defined as neutral divalent carbon species bearing two non-bonding electrons.1 The existence of CH2 was first postulated in the 1930s.1 However, definitive evidence for its existence did not come until 1959. 1

Carbene chemistry has fascinated and challenged chemists for decades, and in recent years this field has experienced tremendous growth The first stable

nucleophilic N, N-heterocyclic carbene (NNHC) was isolated by Arduengo in 1991.2

Conceptually, NHCs may be considered as phosphine mimics.3 NHC ligands are regarded as strong -donors with some degree of back-donation possible.3

Fig 1.1 N-heterocyclic carbenes.5

Most of the carbene work in literature is focused on N,N-heterocyclic carbenes

(NNHC) The NNHC (1.1-1.3) derived from imidazole, imidazoline and

benzimidazole have been successfully employed as ancillary ligands in catalysis.5

One way to “enrich” a NNHC is to attach heteroatoms to the parent N,N-heterocycle

Synthesis, Structure and Catalytic Application of Novel Carbene Complexes with Benzothiazolin-2-ylidene

1

Chapter One: Introduction Introduction

2

carbene moiety Such a strategy is being used to tune the electronic properties and the donating abilities of NHC ligands.6 Carbene complexes with thiazolin-2-ylidene (1.4) and benzothiazolin-2-ylidene (1.5) ligands are more acidic compared to their imidazolin-2-ylidene (1.1) and benzimidazolin-2-ylidene (1.3) analogues The replacement of N-R by S in the 1-position makes 1.4 and 1.5 better -acceptors due to

the availability of empty d-orbitals.7 This larger sulfur atom bears no exocyclic substituent and might be expected to diminish p-p interactions between the carbene center and the neighboring heteroatoms (nitrogen) in this case.8

Prior to this project, there were only a few reports of N,S-heterocyclic carbene

(NSHC) complexes and their use as catalysts.8-14 As the electronic configuration of NSHC and the chemical properties of its metal carbene bond, as well as the catalytic activity are less known than NNHC,3 it would be in our interest to explore this type of compound In this chapter, the development of NSHC ligands and their complexes will be reviewed and its application in catalysis is discussed

1.1 The Development of N,S-Heterocyclic Carbene

Complexes

Early work by Breslow described the application of N,S-heterocyclic carbene

or thiazolin-2-ylidene (1.6) as organocatalysts such as the vitamin B1 catalyzed

benzoin condensation reactions (Fig 1.2). 15-16

Transition metal complexes of NSHC were explored quite early Lappert et al and Stone et al are among the pioneers in synthesizing NNHC and NSHC (Table

1.1).9-10 Rh(I)-NSHC complex (1.7) was reported in 1974 by Lappert.9 Stone and his co-workers managed to synthesize some cationic NSHC carbene complexes of Ir(III),

Chapter One: Introduction The Development of N,S-Heterocyclic Carbene Complexes

3

Synthesis, Structure and Catalytic Application of Novel Carbene Complexes with Benzothiazolin-2-ylidene

Ni(II), Pd(II) and Pt(II) (1.8-1.15).10(a) Later, they also reported Ir(I), Rh(I), Mn(I),

Cr(0) and Fe(0)-NSHC complexes (1.16-1.23).10(b)

S

N Cl HO

N

N CH3

NH2

1.6

Fig 1.2 Thiamine (vitamin B1), a coenzyme.15-16

Raubenheimer et al reported the synthesis of complexes 1.24 and 1.25 in

1985, ca 10 years after the work of Stone and Lappert.11(a) They explored the

Au(I)-NSHC complexes (1.26-1.32) a few years later.11(b) Some of the thiazolyl and

thiazolinylidene complexes of cyclopentadienyliron(II) (1.33-1.40),11(c) and

molybdenum and tungsten, (1.41-1.44) were prepared and characterized by them.11(d)

A Pd(II)-NSHC (1.45) was reported by Calò et al at 2000 This complex was

studied in the Mizoroki-Heck reaction.12 Hahn and Huynh et al reported Ir(I)

complexes (1.46-1.49) with coordinated and pendant allyl substituent.13 Grubbs et al

also reported Ru(II)-NSHC (1.50-1.56) with applications in olefin metathesis.14

The transition metal complexes of NSHC are less well known than the complexes with NNHC ligands Table 1.1 summarizes the transition metal complexes with NSHC ligands that are currently known in the literature As seen in Table 1.1, only a limited numbers of complexes have been prepared These complexes cover the Group 6 and 8-11 transition metals It clearly suggests that there is much room for the future development of the chemistry of NSHC transition metal complexes

Chapter One: Introduction The Development of N,S-Heterocyclic Carbene Complexes

4

In the following section a comparison between some related NSHC and

NNHC complexes is discussed In the literature, most of the syntheses of these

NSHC-complexes were done under inert condition and judicious handling was needed

In section 1.4, the literature methods for preparation of NSHC- and selected NNHC

metal complexes are reviewed These complexes are the currently known complexes

that are closely related or to a certain extent they are analogous The synthesis of

NNHC forms the background of the synthetic route of NSHC complexes described in

L L Cl

1.8: R = H, L = PMePh2 1.9: R = Me, L = PMePh2

Ir Cl CO

L L Cl

1.10: L = PMePh2

10(a)

Chapter One: Introduction The Development of N,S-Heterocyclic Carbene Complexes

BX4

1.16: M = Ir, R = Me, X=F 1.17: M = Rh, R = Me, X = F 1.18: M = Ir, R = Et, X = Ph

10(a) 10(b)

M PPh3PPh3OC

Mn I CO

CO OC OC

CO OC OC

1.26: X = 2,4-dimethylthiazole 1.27: X = Cl

S N H AuPPh3 PF6

1.29

11(a) 11(b)

S

N Au S N H

S

N Au NBu4

S N

1.32

11(b)

Chapter One: Introduction The Development of N,S-Heterocyclic Carbene Complexes

6

Fe L L

N S

S

N H

L-L

1.33: CNC6H4S-o dppe 1.34: CNC6H4S-o dppm 1.35: CNC(Me)CHS dppm 1.36: CNC(Me)CHS dppe

S N

N H S

S N

Fe

1.39: CNC6H4S-o 1.40: CNC(Me)CHS

N S

11(c)

N

S M(CO)5

1.41: M = Mo 1.42: M = W 1.43: M = Cr

N

S W(CO)5

1.44

11(d)

N

S Pd I

1.46

Ir N Br

S H

1.47

13

Chapter One: Introduction The Development of N,S-Heterocyclic Carbene Complexes

Synthesis, Structure and Catalytic Application of Novel Carbene Complexes with Benzothiazolin-2-ylidene

7

Ir Br S N

1.48

Ir Br

OC OC

S N

Cl Cl

metal complexes are discussed Caló et al managed to isolate and characterize

1,3-di(benzyl)benzimidazolin-2-ylidene had been isolated by the Huynh group in 2005.17

Both X-ray crystal structures of the Pd(II) complexes were characterized as the

trans-isomer (Table 1.2) Huynh et al reported that the yield of trans-1.46 could be increased by using DMSO as solvent Cis-1.45 readily converts to trans-1.45 within

1.5 h upon heating in DMA solvent at 100 C, as observed previously by Caló

Chapter One: Introduction The Comparison of NSHC- and NNHC- Metal Complexes

8

However, there is no report on such trans- to cis- isomerism for the related

Pd(II)-NNHC case with X = I

The 13Ccarbene NMR signals of trans-1.45 were more deshielded ( = 210.5

ppm) than trans-1.46 ( = 181.0 ppm) This is due to the better -acceptor behaviour

of NSHC resulting in a more acidic Pd metal center However, the bond lengths and

angles of both complexes were not significantly different in solid state Although both

complexes were studied in the Mizoroki-Heck reaction, their results could not be

directly compared as the conditions were different However, both were active in

catalysis The details of the catalytic application of Calo’s NSHC will be reviewed in

I

Pd(OAc) 2

N

S Pd I

I NS

I

Pd(OAc) 2

N

N Pd I

I NN

Chapter One: Introduction The Comparison of NSHC- and NNHC- Metal Complexes

9

Synthesis, Structure and Catalytic Application of Novel Carbene Complexes with Benzothiazolin-2-ylidene

Another relevant comparison is of Ir(I)-NSHC13 and Ir(I)-NNHC18 complexes Reaction of [Ir(-OMe)(cod)]2 with 3-(2-propenyl)benzothiazolium bromide or 1,3-di(2-propenyl)benzimidazolium bromide under similar conditions gave different complexes

acetone

Ir N N

BF4AgBF4

Scheme 1.1 Formation of Ir(I)-NNHC complexes 1.46-1.47.20

For the Ir(I)-NNHC, the synthetic pathway was straightforward (Scheme 1.1)

where the five-coordinated and n2-C coordinated mode of Ir(I)-NNHC (1.46) was

obtained.18 The cationic derivative [Ir(cod)(n2:n2-C-NNHC)]BF4, (1.47) was obtained

by treatment of 1.46 with AgBF4.18 Instead of the target complex of the

five-coordinated Ir(I) for NSHC complex (1.48) (Scheme 1.2),13 similar reaction gives the

unexpected complex, N-coordinated unsubstituted benzothiazole ligand complex, 1.49

The difference can be explained by the radical [1,3]-sigmatropic rearrangement of

N-allyl dibenzotetraazafalvalene In order to obtain complex 1.48, a different synthetic

pathway was designed [Ir(-Cl)(cod)]2 is used as the substrate to react with AgBF4

in CH3CN to help replace chloride by CH3CN The benzothiazolium salt was added followed by KOtBu as an external base Using this procedure, the five-coordinated

Ir(I)-NSHC (1.48) was obtained

1,3-di(2-propenyl)-benzimidazolium bromide in ethanol with excess of NaOEt gives the four-coordinate

complex 1.52 (Scheme 1.3).13 The excess presence of NaOEt leads to slow

Chapter One: Introduction The Comparison of NSHC- and NNHC- Metal Complexes

10

hydrogenation of the carbene ligand allyl substituents Ir(I)-NSHC 1.50 with the

N-propylbenzothiazolin-2-ylidene ligand was obtained by using the excess of NaH

Bubbling CO into the solution of 1.50 affords complex 1.51.13

Br + 2

BF4

N

S H Br

Ir Br N S

BF4

Ir Br S N

1.48

Ir NBr

S H

1.49

Ir Br S N

1.50

Ir Br OC OC S N

Ir N

Br N N

1.52

Br +

NaOEt EtOH

Scheme 1.3 Formation of Ir(I)-NNHC complex 1.52.13

The two examples given above suggest that there are times when different formation pathways could be needed for the analogous NSHC and NNHC complexes Their catalytic properties have not been studied yet

Table 1.3 shows the comparison of 13Ccarbene NMR signals and selected Ir-C bonds for analogous NSHC and NNHC complexes All the chemical shifts for the

Chapter One: Introduction The Comparison of NSHC- and NNHC- Metal Complexes

Synthesis, Structure and Catalytic Application of Novel Carbene Complexes with Benzothiazolin-2-ylidene

11

carbon resonances of Ir(I)-NSHC complexes are shifted downfield ( = 202.1 - 218.9

ppm) compared to the analogous complex with NNHC ( = 172.3 – 191.2 ppm) The

Ir-Ccarbene distances in complexes with NSHC ligands are comparable with the

analogous benzimidazolin-2-ylidene complexes, which indicates that both the N,N-

and N,S-stabilized carbene ligands have -donor properties.13, 18

Table 1.3 Comparison of the 13C carbene NMR signals and selected Ir-C carbene bond data of

analogous NSHC and NNHC complexes

1.3 Preparative Methods for NSHC- and NNHC- Metal

Complexes

In this section, the literature of synthetic methods of metal-carbene complexes

will be reviewed Some of the NNHC metal complexes are discussed in comparison

with NSHC metal complexes

Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

12

1.3.1 Preparation of N,S- and N,N-heterocyclic Carbenes

A variety of methods for the generation of free carbenes are known (Scheme 1.4) The most commonly used method is based on deprotonation at the C2-position

of the azolium salts with bases such as, Li(NiPr2) (LDA) and K[N(SiMe3)2] (Scheme 1.4 (a)) to yield the corresponding free carbenes.19

The stable carbene 3-(2, 6-diisopropylphenyl) thiazole-2-ylidene is formed from the reaction of 3-(2, 6-diisopropylphenyl)-4,5-dimethylthiazolium chloride with potassium hydride in tetrahydrofuran (THF) at room temperature (Scheme 1.4 (b)) In the presence of a protic acid, the dimerization reaction would proceeds smoothly Both monomer and dimer of 3-(2,6-diisopropylphenyl) thiazole-2-ylidenes have been isolated.8

R' X

N N R

R'

R

R

K THF,

H

S N

Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

13 Synthesis, Structure and Catalytic Application of Novel Carbene Complexes with Benzothiazolin-2-ylidene

A different route to generate free NHCs involves the reductive desulfurisation

of imidazolin-2-thiones with potassium in refluxing THF (Scheme 1.4 (c)) This reaction gives the corresponding imidazolin-2-ylidenes in high yield.22

Thermal elimination of methanol from a 5-methoxytriazole allowed the isolation of the first triazole based free NHC (Scheme 1.4 (d)) This carbene was the first commercially available free carbene.23 This method is also used for preparation the NHC’s from imidazolidines 23-26 and benzimidazolines.27

(a) N

N N N

N

N 2

S

N

S N

S

N

S N

Scheme 1.5 Chemical reactivities of selected azolium salts 8, 21-31

Equilibrium mixtures of tetraaminoethylene and free NHC have been studied

for some benzimidazolin-2-ylidenes (R=iso-butyl) (Scheme 1.5 a).28 This equilibrium known as the Wanzlick Equilibrium is postulated more than 30 years ago.29-30 However, this is not observed for benzothiazolin-2-ylidene

A [1,3]-sigmatropic rearrangement of the electron-rich olefin occurs when the ethylene dimer is heated to 90 C for 2 hours (Scheme 1.5 b).31

These ethylene dimers

Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

14

are highly sensitive to oxygen Baldwin et al reported that exposure of a

dichloromethane solution of 3-methylbenzothiazole-2-ylidene dimer to oxygen at 0

C gave the amide compound in high yield (Scheme 1.5 c).32

1.3.2 Preparative methods based on NNHC’s

The NNHC carbene complexes were previously prepared by the coordination

of the free NNHC ligand to a metal precursor Free NNHCs are strong -donor ligands that can displace other donor ligands such as phosphines from both Pd(0)33-36and Pd(II)37-40 phosphine complexes

N N Pd

O

O O

O

Scheme 1.6 Synthesis of dinuclear Pd(II) complex from the coordination of the free NNHC

ligand to [(COD)Pd(NQ)] 1.57.42

Scheme 1.6 shows the reaction of the free NNHC IMes and [(COD)Pd(NQ)]

to yield a Pd(0) complex 1.57 The NNHC can also displace the 1,5-cyclooctadiene

ligand in the Pd(II) precursors [MCl2(COD)] to form Pd(II) dinuclear complexes

PdIIX2(NNHC)(PR3),44 Pd0(NNHC)(PR3),33,45 Pd0(NNHC)(NNHC’),45 and

PdII(hydrocarby)(NNHC) 38,46-47 complexes can be obtained by this synthetic route

Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

15 Synthesis, Structure and Catalytic Application of Novel Carbene Complexes with Benzothiazolin-2-ylidene

Other metal carbene complexes synthesized by the coordination of the free NNHC ligands include Cr, 48 Mn,49, Co,51 Re,50 Ru,51-53 Rh,54 Pt,55 Cu,56 Ge,57 Ga58complexes Extra precaution is needed to handle the air- and moisture-sensitive free NNHC ligands when this method is employed This method is still rare in synthesizing NSHC-metal complexes This is probably because the [1,3]-sigmatropic rearrangement can occur

1.3.3 Preparative methods based on bond cleavage of electron rich olefins

Another approach to generate heterocyclic carbene complexes involves the bond cleavage of the “carbene dimer” (an electron-rich olefin (ERO)) in the presence

of appropriate metal precursors This method was employed extensively and has been reviewed by Lappert and co-workers.59-62

S

N N

1.7

Scheme 1.7 Synthesis of Rh(I) by bond cleavage of an electron rich olefins.59

Scheme 1.7 shows the synthesis of a Rh(I) complex 1.7 using the ERO

approach Mono-, di- or tri-carbene complexes of Cr, Mo, W, Mn, Fe, Ru, Ir, Os, Co,

Ni and Au in various oxidation states were obtained by using this preparative method.45-46,63 Other complexes with benzimidazolin-2-ylidene ligands have been synthesized by cleaving of ERO by PdI2,64-65 [{RhCl(cod)}2]66 or [Mo(nor)(CO)4]28 (nor = norbornadiene) A limitation of this ERO-based synthesis approach is that the

Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

or imidazolium salts of other coordinating counterions gives products PdX2(NNHC)2

(X = anion of imidazolium salt) The first report of this method involved the reaction

of Hg(OAc)2 and 1,3-diphenylimidazolium perchlorate.68 The advantages of the deprotonation method are simplicity, relative stability toward oxygen and moisture, with the reaction normally involving only one step without the need to isolate free carbene

N

S H

I

Pd(OAc)2

N

S Pd I

S THF

+

Reflux

1.45

Scheme 1.8 Synthesis of a Pd(II) carbene complex 1.45 from Pd(OAc)2 12

The Pd(II) carbene complex with 3-methylbenzothiazolin-2-ylidene 1.45 was

synthesized by using the method as shown in Scheme 1.8.12 However, this method has successfully applied mainly to Pd(II) carbene complexes