Negishi E. 2002 Handbook of organopalladium chemistry for organic synthesis / 0311 334

III.2.5

PALLADIUM-CATALYZED ARYL–ARYL COUPLING

321

TABLE 5. (Continued )

ArMX PhY

Cat.

Ar−Ph

9:

Entry

Substrates

MX

Y

Catalyst

Yield (%)

Reference

m-Mono

8

MX

Y

SnBu3

Br

Pd(PPh3)4

75

[38]

Me

9

MX

Y

B(OR)2

I

Pd(PPh3)4

95

[66]

O

NH2

10

MX

Y

B(OH)2

Br

Pd(PPh3)4

75

[59]

Me3Si

aArranged according to the following order of substitution pattern in aryl electrophiles: p-monosubstitued arylmetal m-monosubstituted arylmetal. In cases where the substituent pattern is the same, the substituents are arranged according to increasing order of priority determined by the Cahn–Ingold–Prelog rule.

TABLE 6 Pdor Ni-Catalyzed Aryl – Aryl Coupling Using 3,5- Substituted Arylmetals or Aryl Electrophilesa

ArMX Ar Y

Cat.

Ar – Ar

9:

Entry

Substrates

MX

Y

Catalyst

Yield (%)

Reference

F

1

MX

Y

B(OH)2

I

PdCl2

65

[57]

F

2

MX

Y

B(OH)2

Br

Pd(OAc)2

92

[67]

EtO

B(OH)2

Cl

Pd(dba)2 + Ligandb

94

[28]

P O

OEt

3

MX

Y

B(OH)2

Br

Pd(OAc)2, PPh3

86

[68]

O

Ot-Bu

N

t-Bu

N

O

COOMe

4

MX

Y

B(OH)2

Br

Pd(OAc)2

66

[69]

COOMe

Br

5

MX

Y

B(OH)2

Br

Pd(PPh3)4

67

[70]

Br

aAryl electrophiles are arranged according to increasing order of priority determined by the Cahn–Ingold–Prelog rule. bLigand

Cy PO

Cy O

322	III Pd-CATALYZED CROSS-COUPLING

TABLE 7. Pdor Ni-Catalyzed Aryl–Aryl Coupling Using 3,4-Substituted Arylmetals or Aryl Electrophilesa

ArMX Ar Y

Cat.

Ar–Ar

9:

Entry

Substrates

MX

Y

Catalyst

Yield (%)

Reference

1

MX

Y

B(OH)2

Br

Pd(PPh3)4

87

[71]

N

H

2

MX

Y

NH2

B(OH)2

I

Pd(PPh3)4

52

[72]

BuO

MX

B(OH)2

Br

Pd(DIPHOS)2

95

[73]

3

Y

MgBr

OMe

NiCl2(PPh3)2

99

[74]

4

MX

Y

MgBr

Br

Ph2(dba)3 + IPrHClb

98

[27]

OMe

B(OH)2

Br

Pd(OAc)2

99

[75]

Et

B(OH)2

Br

Pd(PPh3)4

95

[76]

MgBr

Br

NiCl2(dppp)

75

[77]

5

MX

Y

N

Y

6

MX

Y

CN

SnBu3

I

Pd2(dba)3. CHCl3

72

[23]

CN

7

MX

Y

OH

MgBr

Br

Cl2Pd(dppf)

87

[43]

COOH

B(OEt)2

Br

Pd(OAc)2

99

[78]

8

MX

Y

S

ZnCl

Br

PdCl2, K2CO3, H2O

100

[79]

B(OH)2

Br

Pd(PPh3)4

98

[80]

N

9

MX

Y

OMe

MgBr

Br

NiCl2(PPh3)2

99

[74]

OMe

aAryl electrophiles are arranged according to increasing order of priority determined by the Cahn–Ingold–Prelog rule. bIPr 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene.

C. SYNTHESIS OF BIARYLS CONTAINING ONE OR TWO ORTHO SUBSTITUENTS VIA PdOR Ni-CATALYZED ARYL–ARYL COUPLING

Some representative examples of the synthesis of biaryls containing just one ortho substituent are shown in Table 8. The product yields are generally in the range of 70–100%, and Mg, Zn, B, and Sn are commonly used. Thus, one ortho substituent does not generally exert significant steric effects detrimental to the desired cross-coupling. Somewhat surprisingly, even those substituents that can chelate metals, such as COOMe[81] and CN,[26] have been successfully employed. All in all, the synthesis of biaryls containing only one ortho substituent appears to be closely analogous to those cases discussed in the preceding subsection.

III.2.5 PALLADIUM-CATALYZED ARYL–ARYL COUPLING

323

TABLE 8. Pdor Ni-Catalyzed Aryl–Aryl Coupling Providing Biaryls Containing One Ortho Substituenta

		ArMX Ar′Y				Cat.		Ar−Ar′
					9:
Entry		Substrates				MX	Y	Catalyst	Yield (%)	Reference
1		MX Y				MgBr	Cl	Ni(triphos)ClPF6	53	[82]
						MgCl	Cl	Pd(dppf)Cl2	79	[83]

Cl

2

3

4

5

6

7

8

MX Y

Br

MX Y

NO2

MX YAc

Me

MX YNO2

Me

MX YCOOMe

	MX		Y				Me
CN
	MX		Y				N
		N					N		Me
N N			t-Bu					N
	N						Me

MgBr	Br	Pd(dppb)Cl2	75	[84]
B(OH)2	Br Pd(PPh3)4/Na2CO3		98	[85]
B(OH)2	OTf Pd(PPh3)4		98	[86]
SnMe3	OTf Pd2dba3. CHCl3		93	[87]
B(OH)2	Br	Pd2dba3	98	[87]
ZnCl	Br	PdCl2(PPh3)2/DIBAH	70	[9]
B(OH)2	I	Pd(OAc)2, K2CO3, H2O	98	[87]
ZnBr	Cl	NiCl2(PPh3)2	75	[26]
ZnCl	Br	PdCl2(PPh3)2	78	[88]

9		MX	Y		COOEt	ZnI	Br	Pd(PPh3)4	100	[81]
		COOMe
MeO					CN
10		MX	Y		CN	SnMe3	I	Pd2dba3. CHCl3	75	[23]
		OMe

(Continued )

324	III Pd-CATALYZED CROSS-COUPLING

TABLE 8. (Continued )

ArMX Ar′Y

Cat.

Ar−Ar′

9:

Entry

Substrates

MX

Y

Catalyst

Yield (%)

Reference

11

MX

Cl

ZnCl

Ni(acac)2, dppf

86

[26]

CN

12

MX

Br

Sn(Bu)3

Pd(PPh3)4

95

[47]

COOH

13

MX

Cl

Me

MgBr

Pd(dba)2 + Ligandb

85

[84]

Me

Cl

14

MX

I

TBAF, (allylPdCl) 2/(t-Bu)3P

85

[60]

Si

15

MX

I

ZnBr

Pd(dba)2, tfpc

76

[89]

O

S(O)2(CF2)3CF3

16

MX

Br

MgBr

Ni(acac)2

72

[90]

OMe

17

MX

Br

Br

ZnCl

Pd(PPh3)4

76

[89]

3 : 1

OMe

18

MX

Cl

MgCl

Ni(acac)2, (i-PrO)3P

82

[91]

CN

ZnCl2

aAryl electrophiles are arranged according to increasing order of priority determined by the Cahn–Ingold–Prelog rule. bLigand

Cy PO

Cy O

ctfp tris(o-furyl)phosphine.

III.2.5 PALLADIUM-CATALYZED ARYL–ARYL COUPLING

325

The Pdor Ni-catalyzed reaction of 2,6-disubstituted arylmetals or aryl electrophiles appears to represent a point of deviation in that low product yields of 50% have been frequently reported, as indicated by the results shown in Table 9. Despite this unmistakable trend, the currently available data on this class of reactions are still limited and seemingly erratic or inconsistent. Consequently, they do not lend themselves to providing a reliable and useful set of generalizations. With the understanding that these cases share some critical features with the synthesis of biaryls containing three or four ortho substituents, it is recommended one consult the following subsection (Sect. D) for probing critical factors, such as metal countercations, leaving groups, and catalysts.

TABLE 9. Pdor Ni-Catalyzed Aryl – Aryl Coupling Providing Biaryls Containing Two Ortho Substituentsa

	ArMX Ar′Y	Cat.	Ar −Ar′
		9:
Entry	Substrates	MX	Catalyst	Yield (%) Reference
	2,4-Di-

1					MX	Br
2					MX	Cl
3					MX	MsO					CN
					OMe
4					MX	Br					Br
					OMe	1:1
	2,4,6-Tri-
5					MX	I
											Cl
6					MX	Br
7					MX	Br					CHO
8											O
					MX	Cl
											Me
9					MX	Cl					OMe

B(OH)2	Pd(OAc)2, K3PO4	97	[92]
B(OH)2	NiCl2(PPh2Et)2/	94	[29]
	zinc metal
B(OH)2	NiCl2(dppf)	56	[93]
B(OH)2	Pd(PPh3)4, Cs2CO3	50	[94]
B(OH)2	Pd(PPh3)4	92	[95]
MgBr	Ni complex	41	[96]
B(OH)2	Pd(PPh3)4	45	[40]
B(OH)2	NiCl2(dppf)	78	[25]
MgBr	Pd2(dba)3 . HCl	95	[27]

(Continued )

326		III Pd-CATALYZED CROSS-COUPLING
TABLE 9. (Continued )
				ArMX Ar′Y			Cat.	Ar −Ar′
							9:
	Entry			Substrates			MX	Catalyst	Yield (%)	Reference
		2,4,5,6-Tetra-
						CHO
10				MX Br			SnBu3	Pd(PPh3)2Cl2	62	[97]

Br

11

12

13

14

15

16

17

18

Ph		OMOM
		MX	Br
							N
Ph		OMOM

MX I

MX Cl

MX TfO

MX TfO

O

N(i-Pr)2

			MeOOC
Me3Si			I
N		MX
Me3Si			MeOOC

ZnCl Ni(PPh3)Cl2 49 [98]

B(OH)2	Pd(OAc)2, PPh3	92	[92]
MgBr	Pd2(dba)3 . CHCl3	87	[27]
MgBr	Cl2Pd(dppp)	94	[99]
MgBr	Ni(acac)	47	[53]
ZnCl	Ni(PPh3)4	20	[100]

		MX	Br			SnBu3	Pd(PPh3)4	58	[38]
Cl
			MeO		O
		MX	I		O	B(OH)2	Pd(OAc)2, K2CO3	100	[101]
			O
				Ph

III.2.5

PALLADIUM-CATALYZED ARYL–ARYL COUPLING

327

TABLE 9. (Continued )

ArMX Ar′Y

Cat.

Ar −Ar′

9:

Entry

Substrates

MX

Catalyst

Yield (%)

Reference

OEt

19

MX

TfO

B(OH)2

Pd(PPh3)4

96

[102]

H

N

Cl

TBAF,

[103]

20

MX

I

Si

(allylPdCl)2/(t-Bu)3P 70

Me

O2N

21

MX

Br

MgBr

NiCl2

49

[104]

Me

Cl

22

MX

Br

SnBu3

PdBnCl(PPh3)2

95

[105]

NHC(O)Ot-Bu OHC

23

MX

Br

SnBu3

Pd(PPh3)Cl2

74

[106]

NHC(O)Ot-Bu

Cl

O

24

MX

Br

O SnBu3

Pd(OAc)2

63

[107]

MeO

N

C(O)Ot-Bu

OHC

MX

SnMe3

Pd(PPh3)4, CuBr

70

[103]

25

MeO

Br

NO2

OHC

26

MX

I

MgBr

Pd(PPh3)4

66

[108]

OMe

Me

N

SiMe3

aAryl electrophiles are arranged according to increasing order of priority determined by the Cahn–Ingold–Prelog rule.

Examples of the synthesis of biaryls containing two aryl groups, each of which contains one ortho substituent, seem to be rather rare. In the synthesis of magnolol and ( )-monoterpenylmagnolol shown in Scheme 3,[18] Zn was reported to be more satisfactory than Sn. The latter reaction was reported to be accompanied by double bond migration to significant extents.

328	III Pd-CATALYZED CROSS-COUPLING

D. SYNTHESIS OF BIARYLS CONTAINING THREE

OR FOUR ORTHO SUBSTITUENTS

Biaryls containing three or four ortho substituents are discrete from the others in that they can exist as persistent atropisomers that are chiral. There are even a number of natural products containing such chiral biaryl moieties including michellamines A and B [109],[110] and vancomycin.[111] These compounds provide some of the ultimately challenging synthetic tasks. Specifically, two synthetic issues separate them from most of the other biaryls. One is dealing with three or four ortho substituents that exert strong steric hindrance to cross-coupling. Their electronic effects may also be significant in some cases. The other is controlling the absolute and relative stereochemistry of the atropisomers. Some noteworthy progress have been made recently along these lines. In recent synthesis of michellamines A and B,[17] Zn, B, and Sn were compared by using some model compounds. As the results shown in Scheme 2 indicate, both 1-iodo and 1- bromo derivatives of 2,4,6-tris(methoxy)benzenes are satisfactory cross-coupling partners in the Pd-catalyzed reaction with the 1-naphthylboronic acid derivative, whereas only the iodo derivative is satisfactory in the reaction of the 1-naphthylzinc derivative. Noteworthy is the complete failure observed with the 1-naphthyltin derivative.[17] Although these results represent just one study, the inferior reactivity of Sn as compared with Zn and/or B has been recorded in a growing number of more demanding cases of the Pd-catalyzed cross-coupling reactions, as discussed also in the following dozen or so sections in this part.

As indicated by the results shown in Tables 10 and 11, successful syntheses of biaryls containing three or four ortho substituents have indeed been reported by the use of Zn, B, and Mg. Although it is still premature to draw firm conclusions, areneboronic acids appear to lead to at least comparable and possibly even higher yields of the desired biaryls than arylmetals containing Zn or Mg, despite their significantly lower intrinsic reactivity. If true, this might stem from the facts that biaryls generally unassociated with delicate regioand/or stereochemical issues are thermally stable compounds and that areneboronic acids are much more thermally stable than the corresponding arylmetals containing Zn or Mg. These stability features must permit the formation of sterically hindered biaryls under forcing conditions with minimal complications arising from competitive side reactions including reagent decomposition.

In view of the significance of chiral biaryls, it may be predicted that many additional investigations along this line will be reported in the near future, and they should help provide a more definitive discussion of this topic.

The other important issue of enantioselective synthesis of chiral biaryls is discussed in Sect. III.2.16, and it is therefore not duplicated here.

E. SYNTHETIC APPLICATIONS OF THE PdOR Ni-CATALYZED

ARYL–ARYL COUPLING

Synthesis of biaryls via Pdor Ni-catalyzed aryl–aryl coupling has found many attractive applications in the synthesis of oligoand polyaryls and natural products containing biaryls. The former topic is discussed in Sect. III.2.17.2, and the latter is further supplemented in Table 1 of Sect. III.2.18.

III.2.5 PALLADIUM-CATALYZED ARYL–ARYL COUPLING

329

TABLE 10. Pdor Ni-Catalyzed Aryl–Aryl Coupling Providing Biaryls Containing Three

Ortho Substituents

ArMX Ar'Y

Cat.

Ar−Ar'

9:

Entry

Substrates

MX

Catalyst

Yield (%)

Reference

Me

OHC

1

MX

Br

B(OH)2

Pd(PPh3)4

82

[112]

B(OH)2

Pd(PPh3)4

80

[113]

Cr(CO)3

MeO

CHO

2		MX
		OMe
3		MX
		OMe
4		MX

5 MOMOMX

6 OMX

7	O	MX
	O	CHO

8 MX

9 MX

10 MX

I

MeO

TfO

MeO

MeO

TfO

MeO2C

Me

Y OMe

MeO

Me Bn

N

Me

BrOBn

BnO

HOH2C

BrOMe

Cr(CO)3

MeO OMe

Y

Cl

I

Cl

Br

	B(OH)2
	B(OH)2
	B(OH)2
	ZnCl		Y = I
	B(OH)2		Y = I
	SnBu3		Y = I
	ZnCl		Y = Br
	B(OH)2		Y = Br
	SnBu3		Y = Br
	SnBu3
	SnBu3
	B(OH)2
ZnCl		Y = I
B(OH)2		Y = Br
B(OH)2		Y = Cl

Pd(PPh3)4	73	[114]
Pd(PPh3)2Cl2	74	[115]
Pd(PPh3)2Cl2	0	[116]
Pd(PPh3)4	50	[17]
Pd(PPh3)4	79	[17]
Pd(PPh3)4	0	[17]
Pd(PPh3)4	16	[17]
Pd(PPh3)4	56	[17]
Pd(PPh3)4	0	[17]
Cl2Pd(PPh3)2	15	[117]
Cl2Pd(PPh3)2	21	[118]
Pd(PPh3)4	67	[119]
Ni(PPh3)4	93	[11]
Pd2(dba)3, P(t-Bu)3	97	[87]
Pd2(dba)3, P(t-Bu)3	93	[87]

B(OH)2	Pd(PPh3)4, Ba(OH)2	94	[114]
B(OH)2	Pd(PPh3)4, Ba(OH)2	56	[114]

(Continued )

330

III

Pd-CATALYZED CROSS-COUPLING

TABLE 10. (Continued )

ArMX Ar'Y

Cat.

9: Ar−Ar'

Entry

Substrates

MX

Catalyst

Yield (%)

Reference

11

Br

MX

Br

MgBr

NiBr2, (S)-PPFOMeb 89

[120]

Me

Me

MeO

MeO

12

BnO

MX

Br

OMe

B(OH)2

Pd(PPh3)4

90

[121]

O

O

OMe

MeO

13

MX

Br

B(OH)2

Pd(PPh3)4

86

[122]

Cr(CO)3

MOMO

aAryl electrophiles are arranged according to increasing order of priority determined by the Cahn–Ingold–Prelog rule.

b PPFOMe		PPh2
	Fe
		C	OMe
	H		Me

TABLE 11. Pdor Ni-Catalyzed Aryl–Aryl Coupling Providing Biaryls Containing Four Ortho Substituents

			ArMX Ar Y			Cat.		Ar – Ar
						9:
Entry			Substrates				MX	Catalyst	Yield (%)	Reference
1						R = H	MgBr	Ni(PPh3)Cl2	55–79	[123]
		MX	Br			Me
			R			OMe
							ZnCl	Ni(PPh3)Cl2	36	[124]
2		MX	I				ZnCl	(CH3CN)2PdCl2	35	[124]
							B(OH)2	Pd(PPh3)4	39	[124]
		OEt	MeO
		MX	Br
3		OMe	N		O		B(OH)2	Pd(PPh3)4, Na2CO3	73	[125]

N