Example Chapter

Title Page

Chapter XX

Recent advances/contributions in the Suzuki-Miyaura reaction

Benjamin R Buckley

Department of Chemistry, Loughborough University, Leicestershire, LE11 3TU, UK

Corresponding Author Email: b.r.buckley@lboro.ac.uk

Abstract

Since the original reports of Suzuki-Miyaura on the coupling of vinyl or aryl boronic

acids with vinyl or aryl halides a remarkable number of publications have either

developed or applied this methodology in both an academic and industrial setting.

This review covers recent developments in the area, focusing on new methodology,

mechanistic implications and applications in medicinal, process and materials

chemistry.

Table of Contents

Chapter X – Recent advances/contributions in the Suzuki-Miyaura reaction

X.1 Introduction

X.2 Recent Methodology

X.3 Alternative Metal Catalysts

X.3.1 NICKEL

X.3.2 RHODIUM

X.3.3 OTHER METAL SYSTEMS

X.4 Recent Applications

X.4.1 IN NATURAL PRODUCT SYNTHESIS

X.4.2 IN MATERIALS CHEMISTRY

X.5 Conclusions

X.6 References

X.1 Introduction

The Suzuki-Miyaura reaction is perhaps one of the most well known coupling

protocols developed to date. A search of the literature reveals over 15000 citations1 to

work employing this coupling protocol that was first developed in 19792 and for

which Akira Suzuki shared the Nobel prize in chemistry in 2010. The two seminal

papers in 1979 coauthored by Suzuki and Miyaura describe the cross-coupling of

vinyl boronic acids with vinyl bromides (Scheme 1)2a or aryl halides (Scheme 2),2b

employing 1 mol% tetrakis(triphenylphosphene)palladium and a base such as sodium

ethoxide. The stereoselectivity of the reactions were excellent with >99% retention of

double bond geometry. The evolution of the various Suzuki coupling partners is

shown in Scheme 3.

Pd(PPh3)4 (1 mol%)NaOEt (1.1 equiv.)

PhH, ∆, 2 h, 81%BrO

B O

Scheme 1.

Br

OMe

OB O

Pd(PPh3)4 (1 mol%)NaOEt (1.1 equiv.)

PhH, ∆, 2 h, 81%OMe

Scheme 2.

Pd cat

BaseX

RB R

Pd cat

Base

RB R

X

Pd cat

Base

Pd cat

Base

RB R

XBR

R

X

Pd cat

Base

RB R

X

Pd cat

Base

RB R

X

Suzuki 1979

Suzuki 1980

Suzuki 1981

Suzuki 1995

Suzuki 1992Fu 2001-2002

Soderquist andFürstner 1995

Scheme 3.

The generally accepted mechanism, employing palladium is shown in scheme 4.

Oxidative addition of palladium (0) to the alkyl halide initially occurs to form an

organopalladium (II) species, which on addition of a base affords intermediate (X),

subsequent reaction with the boron-ate complex provides the organopalladium(II)

species, the coupled product is then obtained through reductive elimination and the

palladium (0) catalyst is restored.

Pd0R1–X

R1–PdII–X

NaOEt

NaXR1–PdII–OEt

BYR2

YB

YR2

YOEtNa

BYEtO

YOEtNa

R1–PdII–R2

R1– R2

Scheme 4.

Lennox and Lloyd-Jones have recently reported a review in which they compare and

contrast mechanistic studies what they term as the “versatile transmetalation” process

“which has allowed the Suzuki–Miyaura reaction to develop into such an important

coupling process in academic and industrial settings”.3 An in depth analysis of this

important transmetallation centres around the propensity for either pathway A or B to

be in operation (Scheme 5). Apparently there is little evidence for significant catalytic

turnover through the boronate pathway A and the authors believe recent work from

Hartwig4 and Amatore and Jutand5 provides “compelling and conclusive evidence”

for the catalytic transit through pathway B, but only with any certainty for coupling of

aryl boronic acids or selected esters, with simple aryl halides.

LPdL

R X

R X(L)nPd

LPdL

R OH

LPdL

R OB

OH

R OH

OH

R B(OH)3

R B(OH)2

transmetallation

LPdL

R R

R R

Pathway B

Pathway A

oxidative addtion reductiveelimination

Scheme 5

This versatile reaction has found application in a wide variety chemical disciplines

from the synthesis of biologically active compounds to materials for electronic

devices (Figure 1). This is perhaps due in part to the wide variety of boronic acid

derivatives that are commercially available or easily prepared. Not surprisingly there

have been many review articles based around this Nobel prize winning methodology.

The present review is by no means comprehensive but serves to update the reader on

recent advances in the area.

NHHN

H2N

OHN

HHO

NH

N

O

NH

Br

Suzuki Miyaura Coupling

Suzuki Miyaura Coupling

Dragamacidin F (antiviral)

O OH

N

O

NNHN

N

Suzuki Miyaura Coupling

Valsartan (hypertension and heart failure treatment)

ClHN O

Cl

Suzuki Miyaura Coupling

Boscalid (fungicide for food crops)

C9H17C9H17

S S

n

Suzuki Miyaura Coupling

PF8T2 (used in the fabrication of photonic devices)

Natural productsBiologically active compounds

Agro chemicals Materials chemistry

Figure 1.

X.2 Recent Methodology

The original cross-coupling reactions of aryl and vinyl halides with boronic acid

coupling partners has been extensively developed since the reactions inception. Over

the past few years several interesting adaptions have expanded the scope of the

original coupling protocol, below are just a few recent examples of systems that have

harnessed the Suzuki-Miyaura protocol to access enantioenriched coupling products.

Morken and coworkers have reported a highly selective desymmeterisation of

germinal bis(pincolboronates) using a catalytic enantioselective Suzuki- Miyaura

coupling (Scheme 6).6 Detailed studies revealed that the transmetalation step is

stereospecific and this step is likely to be stereochemistry determining. They also

believe that the stereoselective transmetalation might occur either by a

desymmetrization if both boronates are equivalent or by a dynamic kinetic resolution

if the geminal boron atoms are not equivalent.

The applicability of the asymmetric cross-coupling reaction for the enantioselective

construction of pharmaceutically relevant benzhydryl derivatives was exemplified

through the construction of (R)-tolterodine (Detrol LA), a therapeutic used for the

treatment of urinary incontinence (Scheme 7).

Ph B(pin)

B(pin) Pd(OAc)2 (5 mol%)Ligand (10 mol%)

KOH (15 equiv.)dioxane/H2O

rt, 12 h

I

MeO

Ph

B(pin)

OMe

>98% yield94:6 er

Ligand =

OP

OO

O

MeMe

NMe2

ArAr

ArAr

Ar = p-Tol

Scheme 6

BnO B(pin)

B(pin) Pd(OAc)2 (5 mol%)Ligand (10 mol%)

KOH (15 equiv.)dioxane/H2O

rt, 12 h

BnO

B(pin)i) Pd(PPh3)4Ag2O, K2CO3

2-iodo-4-methylanisoleTHF

ii) H2, Pd/CBnO

Me

OMe

(iPr)2N

Me

OH

(R)-Tolerodine88% yield88:12 er

Scheme 7

Crudden and coworkers have developed an elegant stratergy to access

enantiomerically enriched triarylmethanes,7 employing a enantiosepcific Suzuki-

Miyaura coupling route (Scheme 8). Enantiomerically enriched dibenzylic boronic

esters were prepared using s-BuLi and a chiral bisoxazoline ligand. These

enantioenriched dibenzylic boronic esters were then cross coupled using Pd(PPh3)4 to

afford the desired triarylmethanes. High levels of stereochemical retention were

observed over a wide range of substrates, with the levelof enantimeric ratio only

governed by the ability to prepare the required dibenzylic boronic esters. The

procedure was amenable to gram scale and was shown to proceed through retention of

configuration.

B(neop)2

MeO

Et

neop = OB

O

Pd(OAc)2 (5 mol%)Ligand (10 mol%)

KOH (15 equiv.)dioxane/H2O

rt, 12 h

Cl

I MeO

Et

Cl

83% yield89:11 er

90:10 er

Scheme 8

An interesting route based on this type of stereochemical retention reaction has been

reported by Ohmura and Suginome. By studying the effects of acidic additives on the

stereochemical course in enantiospecific Suzuki−Miyaura coupling of α-

(acetylamino)benzylboronic esters (Scheme 9). After a range of optimisation studies

they were able to carry out reactions with up to 93% retention of configuration. By

varying the conditions the reaction could be switched to give the product with up to

99% inversion of configuration. The authors propose that the acidic additives can

activate two different pathways leading to either retention of configuration or

inversion (Scheme 10). This likely occurs due to the rotamers derived from the amide

bond, when the amide carbonyl is available for coordination to the acid retention of

configuration is available.

Ph B

HN O

Me

O

O

Br

Me

Pd(dba)2 (5 mol%)XPhos (10 mol%)K2CO3 (3 equiv.)

Zr(OiPr)4.iPrOH (0.5 equiv.)PhH, 80 ºC, 18 h

Pd(dba)2 (5 mol%)XPhos (10 mol%)K2CO3 (3 equiv.)

PhOHPhH, 80 ºC, 12 h

Ph

HN O

Me

Me

Ph

HN O

Me

Me

71% yield85% es

51% yield99% es

Scheme 9

Ar1 B

HN

O

OAr1 B

HN O

Me

O

O

Ar1 B

HN O

Me

O

O

[acid]

Me

O

Ar1 B

HN

O

O

Me

O[acid]

baseL(Ar2)Pd–Y

NBO

Me

OO(Ar2)LPd

HAr1

Y

‡

(Ar2)LPd YBOO

NH

Ar1HMe

O ‡

Ar1 Ar2

HN O

Me

Ar1 Ar2

HN O

Me

inversion retention

Scheme 10

Takeda and Minakata have reported a Pd-catalyzed enantiospecific and regioselective

cross-coupling of 2-arylaziridines with arylboronic acids (Scheme 11).8 The reaction

was found to work well with an NHC-ligated Palladium complex, which was able to

out compete β-hydride elimination (Scheme 12). This coupling process allowed the

preparation of configurationally defined 2-arylphenethylamine derivatives that are

otherwise difficult to access in a simple operation by current conventional routes.

Ph

H NTs B(OH)2

OMe

Catalyst (4 mol%)

Na2CO3 (1.1 equiv.)PhH/H2O (5:1)

rt, 4 h

PhNHTs

H

OMe(99.5:0.5 er)

74% yield99.5:0.5 er

N N

PdCl

Ph

iPr

iPr iPr

iPr

Catalyst =

Scheme 11

PdCl

Ph

SIPrArB(OH)2base, H2O Ph Ar

Pd(SIPr)Ph

H NTs

PhHNHTs

PdSIPr

or Pd NTs

HPh

SIPrPhHNHTs

PdSIPr Ar

ArB(OH)2base, H2O

Ph

ArNHTs

H

Scheme 12

Several reports have emerged utilising an allylic C−H functionalisation strategy.

Zhang and coworkers have reported the Suzuki–Miyaura coupling reaction of

unsymmetric 1,3-disubstituted secondary allylic carbonates with arylboronic acids

(Scheme 13).9 The coupling products were afforded with high yields and high regio-

and E/Z selectivities and good to excellent chemoselectivities. The stereochemical

course of the coupling reaction, afforded the products with inversion of the original

carbonate stereochemistry. The authors then applied this coupling method to the

synthesis of (S)-naproxen.

Ph

OBOC

Me

97.5:2.5 erMeO

B(OH)2 Pd(OAc)2 (2 mol%)rac-BINAP (2 mol%)

THF (1 M), 50 ºCH2O (500 mol%)

24 h Ph Me

OMe

82% yield97.5:2.5 er

KMnO4

NaIO4K2CO3

O

Me

MeO

OH

78% yield>99.5:0.5 er

(after recrystallisation)

Scheme 13

Sigman and coworkers have developed a novel coupling strategy that capitialised on

the slow oxidative addition to the metal centre for alkyl electrophiles and the

subsequent competing β-hydride elimination prior to the cross-coupling event.10 The

main challenge was in the identification of a catalytic system that could avoid the

formation of the formal Suzuki−Miyaura product and instead afford a diene

intermediate through oxidative addition and rapid β-hydride elimination. In addition,

the catalyst would have to be able to reinsert the 1,3-diene intermediate in order to

subsequently access the desired cross-coupled product (the relay Suzuki−Miyaura

product). After a range of optimization experiments using phosphine and N,N-

substituted ligands and various bases excellent yields of the desired products were

obtained (optimized route sown in scheme 14). The reaction was ameable to a range

of aryl boronic acid derivatives and even secondary tosylates could be effectively

coupled with high yields and regiocontrol.

Ph

HOTs

Ph–B(OH)2 (1.5 equiv.)Pd(quinox)Cl2 (2.5 mol%)

KF.2H2Oi-PrOH

Ph Me

Ph

PhPh

92% yield>20:1

Scheme 14

The ability to carry out the reaction with secondary tosylates opened up the possibility

for chirality transfer from the tosylate starting material to the desired products.

However, a substantial erosion in enantiomeric ratio was observed when the methyl

tosylate shown in scheme 15 was employed 96:4 er, was eroded to just 60:40 er. This

loss in er was explained using conformational analysis with the hypothesis that the β-

hydride elimination step would be responsible for the loss of stereochemical integrity

as a result of the existence of an equilibrium between two Pd−alkyl conformational

isomers (Figure 2). This was substantiated by replacing the methyl group in the

substrate with a bulky isopropyl group, thus increasing the steric penalty of the

gauche interaction, resulting in a selective β-hydride elimination (Scheme 16). No

erosion of er was observed when employing this bulky substrate.

Ph

H

OTs

Me

96:4 er

Ph–B(OH)2 (1.5 equiv.)Pd(quinox)Cl2 (10 mol%)

KF.2H2O (3.0 equiv.)i-PrOH (0.1 M), rt, 16 h

Ph Me

Ph

62% yield(60:40 er)

Scheme 15

H HR

PdLnH

Ph

H HPdLn

HR

Ph

singleregiosiomer

mixture of regiosiomers

favoured if R is bulky

Figure 2

Ph

H

OTs

98:2 er

Ph–B(OH)2 (1.5 equiv.)Pd(quinox)Cl2 (15 mol%)

KF.2H2O (3.0 equiv.)i-PrOH (0.1 M), rt, 16 h

Ph

Ph

52% yield(98:2 er)

Me

MeMe

Me

Scheme 16

X.3 Alternative Metal Catalysts

The Suzuki-Miyaura coupling has traditionally been carried out using palladium as

the metal catalyst, however, there have been several reports that employ alternative

metals as catalysts for the coupling reaction. In fact a rather controversial report even

disclosed the use of no metal catalyst,11 however, on careful examination of the

reaction conditions it was found that palladium contaminants down to a level of 50

ppb found in commercially available sodium carbonate were responsible for the

generation of the biaryl rather than an alternative non-palladium-mediated reaction.12

X.3.1 NICKEL

The use of nickel catalysts as a replacement for palladium is attractive since it would

be far more cost-effective as it much cheaper and more earth abundant than

palladium. But because nickel usually displays Ni(0)/Ni(II) as well as Ni(I)/Ni(III)

oxidation states and is more nucleophilic than palladium, nickel cannot be simply

considered as a direct substitute for palladium, it possesses distinctive catalytic

properties that palladium does not have. One particular advantage to using nickel is its

propensity to insert into C–Cl bonds more readily than palladium, this is

advantageous since aryl chlorides are generally much cheaper than the corresponding

aryl bromides or iodides.

In 1996, Miyaura and co-workers reported the first nickel catalysed cross-coupling of

aryl chlorides with boronic acids (Scheme 17).13 Various aryl chlorides with electron-

withdrawing or electron-donating groups were tolerated when using between 3–10

mol% of Ni(0), prepared in situ by reduction of NiCl2(dppf) with four equivalents of

butyllithium or Dibal-H. This initial report spurned a range of new reports employing

various nickel catalysts for cross-coupling reactions.14

B(OH)2 NiCl2(dppf) 3-10 mol%BuLi (4 equiv.), K3PO4

solvent, 70-80 ºC

RR Cl

CN

74%

Me

69%

OMe

83%

MeO

Me

O

90%Me

Me

Me

Me

O

78%

Me

90%

ON

Me

Scheme 17

Han has comprehensively reviewed the use of nickel catalysts for the Suzuki-Miyaura

cross-coupling reaction,15 and found that the nickel mediated process can tolerate a

broad range of aryl electrophiles, for example, sulfamates, carbamates, carboxylates,

ethers, carbonates, phosphoramides, phosphonium salts, phosphates, phenols, and

broad range of alkyl substrates including both secondary and primary alkyl iodides,

bromides, and chlorides. Many of these electrophiles have been found to be

uncompatible with traditional palladium catalysed processes.

Han’s group have also developed the use of what they believe is a much more

effective and readily available nickel catalyst [NiCl2(dppp)].16 This catalyst allowed

for very general and efficient cross-coupling of a large range of aryl bromides as well

as the less reactive aryl chlorides with a catalyst loadings down to 1 mol% or below

(Scheme 18).

B(OH)2 NiCl2(dppp) (1 mol%) K3PO4 (4 equiv.),

dioxane, 100 ºC

R2

R2 X

X = Br 91%X = Cl 96%

CNMeO

R1

R1

MeO

X = Br 90%X = Cl 96%

NH2

X = Br 92%X = Cl 98%

MeO2C

X = Br 89%X = Cl 90%

N

X = Cl 95%

MeO

N

X = Cl 98%

MeO

Scheme 18

Gandelman and coworkers have reported the synthesis of secondary alkyl fluorides

using a Suzuki-Miyaura cross-coupling of 1-halo-1-fluoroalkanes (Scheme 19).17

Geminal dihaloalkanes were used as starting materials and the report demonstrated

that these simple 1-fluoro-1-haloalkanes with no adjacent functional groups could be

used as electrophiles for the cross-coupling reaction. Their optimized system

employed NiCl2.glyme and the alkylated 1,2-diaminocyclohexane ligand, which

afforded a wide variety of fluorinated alkanes, as well as site-selective fluorinated

analogs of bioactive molecules and known C-F containing compounds with

interesting biomedical properties. A wide range of alkyl boranes were compatible but

Gandelman and coworkers found that 9-BBN-based alkyl nucleophiles bearing

functional groups such as aryls, ethers, esters, and amines reacted particularly well to

give the desired cross-coupling products in high yields.

Br

F-B9BN Ph

NiCl2.glyme (10 mol%)Ligand (11 mmol)

KOtBu, iBuOH,dioxane, rt

FPh

85% yield

Ligand =

NHMe

NHMe

Scheme 19

The direct asymmetric catalytic stereoconvergent synthesis of enantioenriched

secondary alkyl fluorides from a racemic mixture of 1-fluoro-1-haloalkanes also

proved feasible. For example, the cross-coupling of racemic sulfonamides and

organoboranes using NiCl2.glyme as a catalyst and the chiral bisamine ligand X

occurred with high levels of enantiocontrol (95.5:4.5 er). However, the yield of the

process requires some further optimization (Scheme 20).

N Br

F

SO2PhMeO

-B9BN

NiCl2.glyme (12 mol%)Ligand (16 mmol)

KOtBu, iBuOH,iPr2O, rt

NH

NH

N

F

SO2Ph OMe

Ligand =

40% yield95.5:4.5 er

Scheme 20

X.3.2 RHODIUM

Rhodium has been successfully used in a range of Suzuki-Miyaura type reactions.

Satoh and Miura have reported the Suzuki−Miyaura-type cross-coupling of arylboron

compounds with aryl halides in the presence of a rhodium-based catalyst system to

produce the corresponding biaryls (Scheme 21).18 They also found, unexpectedly, that

when employing benzonitrile as substrate under similar reaction conditions a multiple

arylation is observed, in which nucleophilic arylation on the cyano group and

subsequent ortho arylation via C−H bond cleavage is involved.

NaBPh4

[RhCl(cod)2](dppp) (1 mol%)

o-xylene

RR X

X = Br 72%X = Cl 73%

CO2Et

X = Br 74%

Cl OMe

X = Br 82%

N

X = Cl 71%

N

X = Cl 82% X = Cl 51%

CF3

Scheme 21

Fürstner and coworkers have shown that rhodium-catalysts decorated with either

phosphines or N-heterocyclic carbenes can be useful mediators for the addition of

aryl- and alkenylboronic acids to aldehydes.19 Frost and co-workers have also

reported the addition of arylboronic acids to aldehydes using [RhCl(ethylene)]2

RuCl3·3H2O and [RhCl(cod)]2 catalysts in the presence of the nitrogen-containing

ligand.20

Hayashi has reported a wide range of reactions employing rhodium with chiral

binaphthylphosphine ligands, for example in the asymmetric 1,4-addition of boronic

acids and triarylboranes to a variety of unsaturated starting materials; α,β-unsaturated

ketones, esters, 1-alkenylphosphonates, nitroalkenes and 5,6-dihydro-2(1H)-

pyridinones.21

The Miyaura and Batey have also independently reported the use of rhodium catalysts

for addition to aldehydes in the presence of phosphine ligands.22 Lautens has shown

that [Rh(cod)Cl]2 catalysed reactions of heterocyclic alkynes with arylboronic acids in

the presence of water-soluble ligands such and sodium dodecylsulphate (SDS) and

sodium carbonate as bases affords trisubstituted alkenes in high regio-selectivity.23

Supported rhodium(0) catalysts have also been reported to catalyse a range of cross-

coupling reactions. For example, a layered double hydroxide (LDH) supported

catalyst has been successfully used in the traditional Suzuki-Miyaura reaction to

afford biaryl compounds in excellent yield.24 The catalyst could be quantitatively

recovered from the reaction mixture by simple filtration and reused for a number of

runs with consistent activity in all the reactions. The catalyst was also simply prepared

by treating LDH-CO3 (Mg:Al = 3:1) with treated with RhCl3.H2O in doubly

deionized water.

X.3.3 OTHER METAL SYSTEMS

Rhodium and nickel have been by far the most common metals aside from palladium

employed in Suzuki-Miyura carbon-carbon bond forming reactions. Platinum has

been used on several occasions, for example, Bedford and Hazelwood showed that

platinum complexes with π-acidic, ortho-metalated triaryl phosphite and phosphinite

ligands showed what they termed as “unexpectedly good activity” in Suzuki biaryl

coupling reactions with aryl bromide substrates (Scheme 22). Application to aryl

chlorides resulted in low conversion to the desired biaryl products.

X B(OH)2

cat. (0.1-0.5 mol%)

K3PO4, 1,4-dioxane100 ºC, 18 h

O

Pt

POAr2

Cl2

Ar =

O

cat.

Me

OMe

O

X = Br or Cl Br = 100% conv.Cl = 29% conv.

Scheme 22

Copper has also found wide use, however, it has generally only been found to be

applicable to heteroatom-carbon coupling reactions when employing boronic acids as

coupling partners, now known as the Chan-Lam Coupling.25

X.4 Recent Applications:

X.4.1 IN NATURAL PRODUCT SYNTHESIS

The use of the Suzuki-Miyaura reaction in the synthesis of natural products has been

wide spread over the years and well reviewed. The intramolecular Suzuki-Miyaura

reaction macrocyclisation to form macrocyclic natural products has been well

reviewed by Fairlamb.26 Interestingly the first report employing this type of approach

for macrocyclic formation came from the group of Miyaura and Suzuki in their

synthesis of humulene (Scheme 23).27

X B2

X = Br or Cl

Pd(PPh3)4 (20 mol%)NaOH

PhH, ∆, 32%

Humulene

Scheme 23

Below are a number of representative routes employing the Suzuki-Miyaura reaction

from the past few years. Yamaguchi, Itami and Davies have reported the synthesis of

the dictyodendrins A and F, which are active for cancer chemotherapy by telomerase

inhibition, using C-H functionalization and a Suzuki-Miyaura coupling (Scheme

24).28

N

OMe

CO2Me

MeO2C

OMe

OMe

Br

MeO

NBOC

B(pin)

OBn

Pd[P(t-Bu)3]2

K3PO4

N

OMe

CO2Me

MeO2C

OMe

OMe

MeO NBOC

N

OH

MeO2C

OH

HO

OH

OH

NH

OSO3Na

dictyodendrins A

N

OH

HO

OH

O

NH

OH

O

dictyodendrin F47%

Scheme 24

Shea and coworkers have reported an elegant rout towards N-methylwelwitindolinone

B isothiocyanate, employing a as a key step in coupling the aryl unit with the carbon

unit in order to build up the core of the bicyclic natural product framework (Scheme

25).29

N-methylwelwitindolinone B isothiocyanate

NMe

OH

Me

Me

O

ClMe

SCNBnO

BrCO2Me

NO

Me

B(pin)

NO

Me

CO2MeBnOPd(dppf)Cl2(10 mol%)CsF, TBAB

THF:H2O120 ºC, MW

89%

Scheme 25

Tang and coworkers have used an asymmetric Suzuki-Miyaura coupling reaction in

their syntheses of the atropoisomeric natural products Korupensamines A, B and

Michellamine B (Figure 3).30 In their key enantioselective biaryl coupling step the

presence of a polar-π interaction between the highly polarized BOP group and the

extended π system of the arylboronic acid coupling partner was believed to be

essential for high selectivity (Scheme 26). Synthesis of the heterodimer was also

accomplished using this novel methodology.

HN

NH

OMeOH

OHOMe

OH

OH

NH

OMeOH

HO

OH

OH

HO NH

OMeOH

HO

OH

Michellamine B Korupensamine A Korupensamine B

Figure 3

BrCHOBOPO

OTBSP NO

N

O

O

O

O

BOP =

B(OH)2

OBn OMe

Pd(OAc)2Ligand

K3PO4, PhH/H2O (5:1)96%, 93% ee

OBn OMe

CHOBOPO

OTBS

Ligand =

NiPr

tBuOMeMeO

Scheme 26

X.4.2 IN MATERIALS CHEMISTRY

The Suzuki-Miyaura coupling has found widespread applications in materials

chemistry, below are a few recent examples that harness the coupling protocol to

produce novel materials.

Deep-blue organic light-emitting diodes have been produced that are based on

multibranched oligofluorenes with a phosphine oxide centre.31 A series of these

compounds were produced (Scheme 27) and the compounds showed excellent thermal

stabilities, pronounced photoluminescence efficiencies, and good solution

processability. Double-layered nondoped OLEDs based on these materials exhibited

highly efficient deep-blue electroluminescence.

H

B(OH)2

C6H13 C6H13

n

PO

Br

BrRPO

R

C6H13C6H13 C6H13

C6H13

HH

n n

R = H or

HC6H13 C6H13

nPd(PPh3)4, K2CO3, PhH, EtOH

Scheme 27

Using a similar approach a range of stable emulsions of spherical and rod-like

conjugated polymer nanoparticles were synthesized by Suzuki−Miyaura cross-

coupling of 9,9-dioctylfluorene-2,7-diboronic acid bis(1,3-propanediol) ester with a

range of different dibromoarene monomers.32 Using this protocol the direct synthesis

of conjugated polymer nanoparticles at room temperature was possible, to afford high

concentrations of conjugated polymers dispersed in water. These concentrations are

within the range of organic solutions employed for organic electronic device

fabrication. This room temperature emulsion polymerisation can be applied to a

variety of suitably functionalised monomers. These novel materials (Figure 4) are to

be used in the fabrication of OFET, OPV, and photonic devices.

C8H17C8H17

S S

nC8H17C8H17 n

C8H17C8H17 n

NSN

C8H17C8H17

n

N

PF8 PF8T2

PF8BT PF8TAA

Figure 4

X.5 Conclusion

As can be seen from the above reports the Suzuki-Miayura reaction has had and

continues to have broad applicability across a wide manner of scientific disciplines,

with a diverse series of applications spanning pharma and materials chemistry. There

have been some fascinating developments of this process form its inception some 35

years ago. Suzuki and Miayura have significantly added to their original report, with

the ability to catalyse the coupling reaction with a variety of metals. Undoubtedly

there have been significant advances in asymmetric catalysis since the Suzuki-

Miayura reaction was initially reported and groups from around the globe have

harnessed tis reaction to prepare enantioenriched compounds that would previously

have been difficult or impossible to prepare without the original coupling protocol.

Not surprisingly this has led to the synthesis of several natural products and

biologically active compounds. Applications in materials chemistry are perhaps some

of the most exciting as one would anticipate that Suzuki and Miayura would not have

drempt of such applications for their work.

The application, modification and development of this cross-coupling methodology is

surely set to continue apace and we look forward to the next step change

developments in this area.

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