Negishi E. 2002 Handbook of organopalladium chemistry for organic synthesis / 0863 942

[116]

[117]−[119]

O

OH

OH

70

O

HN

OH

O

NH

TlOH

O

O

NH

N

O

4

)

3

Pd(PPh

OH

O

OTBS

OTBS

O NH

sameastheacid

OAc OTBS OTBS

OTBS

OTBS

OTBS TBSO

OTBS

HO

2

O

OTBS O

TBSO

MeO

O

I

TBSO O B(OH) TBS

OTBSTBSO

TBSOMe

OTBS

OTBS

TBSO

MeMe

O

O

O

O

O

OCOHN

O

sanglifehrin A

TMS

palytoxin	(cf.[116])	palytoxin carboxylicacid (cf.[119])
123

893

TABLE 4. Heteroaromatics (cf. Sect. III.2.7)

Catalyst Additive Yield (%) Reference

R′X

RM

Name

n C

82 [120]

4 ) 3 Pd(PPh

O

I

ZnBr

15 freelingyne THPO

		[121]			[122]
		98			82
		K			2
						Ba(OH)
		3
		CO
		2
		4			4
		)			)
		3			3
		Pd(PPh				Pd(PPh
							N
N			F	NH				Cl
			I	I				N

B(OH)		NHCOtBu	B(OH)		NHCOtBu
2			2

fascaplysin	amphimedine
18	19

[123]	[123]
19	15

4						4
)						)
3						3
	Pd(PPh					Pd(PPh
	O			O		O		O
						Br
	Br
	ZnCl						ZnCl O
		O		OMe	OTBS			OMe
						TBDPSO
TBDPSO
	egonol					(±machicendiol)-
19						19

O

O

O

OMe

R

HO

O

Me

N

N

O

N

−

Cl

+

N

N H

O

O

O

O

Hegonol	OH(+)-machicendiol
R=	R=

amphimedine

fascaplysin

freelingyne

894

[125]–[128]

III.2.18 SYNTHESIS OF NATURAL PRODUCTS VIA CROSS-COUPLING

895

protocol developed by Negishi[124] with Zn, B, and Sn as well as that involving the use of haloalkynes (Sect. III.2.8.2). Although not yet widely known, it should be noted that the scope of Sonogashira coupling is more limited than the latter. Thus, terminal alkynes cannot be directly and selectively synthesized without protection and deprotection of one of the acetylene carbon atoms. The reaction also is sluggish or it may altogether fail in cases where alkynes contain electron-withdrawing substituents. Despite these limitations, Sonogashira coupling has thus far been the much more widely employed of the two, probably because it is operationally somewhat simpler. It should also be recalled that there are other intricate differences between the two protocols, as discussed in Sect. III.2.8.

In cases where alkynylmetals are generated either in situ or in a separate step as discrete reagents, Mg, Zn, B, and Sn have been the four widely used metals. Comparative studies have shown that Zn is generally the most favorable among them (Sect. III.2.8.2). Here again, however, Sn has been the most frequently used metal. Similar comments on Sn as those made in Sect. D are also applicable to these cases. Particularly noteworthy are examples of the intramolecular cyclization of alkynyltins, as in the synthesis of neocarzinostatin, cyclization via double alkynylation with haloalkynes, as in the synthesis of calicheamicinone[129] and dynemicin A,[130]–[132] and the carbopalladation–cross-coupling tandem cyclization, as in the synthesis of neocarzinostatin.[133],[134]

F. SYNTHESIS OF NATURAL PRODUCTS VIA Pd-CATALYZED CROSS-COUPLING INVOLVING ALLYL, BENZYL,

AND PROPARGYL REAGENTS

Pd-catalyzed cross-coupling has been shown to be particularly well suited for the synthesis of diarylmethanes, allylated arenes, 1,4-dienes, 1,4-enynes, and related derivatives, as discussed in Sect. III.2.9. It should be recalled that this favorable characteristic does not extend to the coupling of two allylic, propargylic, and benzylic reagents to produce 1,5- dienes, 1,5-enynes, bibenzyl, and related compounds (Sect. III.2.10). Also to be recalled is that the use of propargyl reagents often leads to the formation of allenes, and this tendency of Pd is in contrast with that of Cu in dealing with propargyl(allenyl) reagents. As in many other cases of Pd-catalyzed cross-coupling, Zn, B, Al, and Sn have been used most frequently, although it is likely that Cu, Zr, and Si are also satisfactory in some cases.

Following a very satisfactory synthesis of -farnesene via alkenyl–allyl coupling[174] as the first example of natural product syntheses of this class, some other natural products containing 1,4-dienes and allylated arenes have been synthesized, as indicated by the results summarized in Table 7. The synthesis of humulene via intramolecular alkenyl–allyl coupling is noteworthy, even though the cyclization was achieved only in 32% yield.[175] Also noteworthy is the Nior Pd-catalyzed synthesis of allylated quinones, such as menaquinone-3 and coenzymes Qn (n 3 or 10).[176],[177],[194] Both Ni and Pd appear to be highly satisfactory and roughly comparative with each other[194] despite the claim that Ni is superior to Pd.[176] Many additional satisfactory examples may be expected. At present, however, no natural products appear to have been synthesized by using propargylic reagents in Pd-catalyzed crosscoupling.

TABLE 5. Alkyne Synthesis Via Sonogashira Cross-Coupling (cf. Sect. III.2.8.1)

Catalyst Additive Yield (%) Reference

R′X

RC CH

Name

n C

[135]
52
			NH
	CuI		2
			i-Pr
2
)
3
	Pd(PPh
2
	Cl
O			O		OTBS
	I

11 (+)-harveynone

	[136]					[137]
	62					55
	CuI		N			CuI			N	3
			Et						Et	PPh
			3						3
						2
						)
						3
	2					Pd(PPh
	Pd(OAc)					Cl
						2
OMe		O			O			COOH
MeO I								Br

OTBS	OTBS

(±)-harveynone	goniobutenolideA
11	13

[120]
50
CuI	N
	Et
	3
4
)
3
Pd(PPh
	COOH
	I

O

15 freelingyne

[138]

76

2 CuI BuNH -n

2 Pd(OAc)

TMS

Cl

N 18 (−)-calicheamicinone TBSO O

O O

3 PPh

O

NHCO

HO

OH

SSSMe

calicheamicinone-)(−

Me

2

O

O

O

freelingyne

O

O

A

goniobutenolide

OH

OH

OTBS

O

harveynone

O

OH

(+)-

896

[52]

96

2 CuI PrNH -n

2 ) 3 Pd(PPh 2 Cl

OTHP

Br

OH

18 coriolic acid

[135]

54

NH 2 CuI Pr -i

2 ) 3 Pd(PPh 2 Cl

O				O		OTBS
		I

18 (−)-tricholomenyn A

[54]			[139]		[139]
70			98		80
CuI Et		BHT	2		2
				CuI BuNH-n	CuI BuNH-n
	N
3
4			4		4
)			)		)
3			3		3
Pd(PPh				Pd(PPh	Pd(PPh
	COOH			Cl
	I		Cl
					Cl

xerulin	eleostearate	MeOOC
	methyl
18	19

COOMe	7		eleostearate
			methyl
9
H
4
C
			O
	O
			xerulin

					O		OAc
O								tricholomenynA
								−)-
								(
	COOH
						OH		coriolicacid

(Continued )

897

TABLE 5. (Continued )

Catalyst Additive Yield (%) Reference

R′X

RC CH

Name

n C

[140]

CuIpiperidine 85

4 ) 3 Pd(PPh

Cl

Cl

11 H 5 C

HO

(5S,12S)-DiHETE

20

[140]

CuIpiperidine 62

4 ) 3 Pd(PPh

Me 2 CO

OH

I

11 H 5 C

HO

[141]	[141]
82	80
2	2
CuI n-PrNH	CuI n-PrNH
4	4
)	)
3	3
Pd(PPh	Pd(PPh

OTBS	OTBS
Br	Br

				Me
				2
			OH	CO
	TMS
5,15-DiHETE				8,15-DiHETE
20				20

[142]			[142]
70			33
		2		2
CuI		n-BuNH	CuI	n-BuNH
4			4
)			)
3			3
Pd(PPh			Pd(PPh
				17
				H
				8
		Cl	OH	C
Cl
				Cl
		OH	OTBS
17
H
8
C			C
n-			MeO
				2
14,15-dihydro		4
		leukotrieneB
20

	COOH
OH								dihydro
OH								14,15-
17
			H
8
			C
COOH
								8,15-DiHETE
OH							OH
COOH
OH							OH	DiHETE
								5,15-
	COOH
				OH				DiHETE
11								S)-
				C				,12S(5
				H
	5
HO

4 Bleukotriene

898

84-76 [143]

2 CuI PrNH -n

4 ) 3 Pd(PPh

	OMe
	O
OTf	t-Bu

O

O

O

Me

20 (+)-ginkgolide B

[60]	[69]
94	100
2
CuI n-PrNH		above
4		as
		same
Pd(PPh
)
3
Me
2
CO
OTBS		Br

TMS

4		4
leukotrieneB	(cf.Table3)	leukotrieneB	(cf.Table3)
20		20

[144]	[61]
96	70
2	2
CuI n-PrNH	CuI n-PrNH
4	4
)	)
3	3
Pd(PPh	Pd(PPh

	OTBS	OH	OH
	Br
		Cl
OTBS	OTBS	OTBS
		C
	MeOOC	2
		MeO	)
	lipoxinA	lipoxinB	(cf.Table3
	20	20

	COOMe							OH		B
										4
	OH							HO		lipoxin
	COOMe					C				HETE
							11
						H
							5
	OH									(S)-
										5-
						COOH
	OH									15-(S)-HETE
	COOH
	OH									A
	HO							OH		lipoxin
	H tBu							H		B
H HO HO			O						O	ginkgolide-(+)
							H Me
O	O			O				O
			O					OH

(Continued )

899

TABLE 5. (Continued )

Catalyst Additive Yield (%) Reference

R′X

RC CH

Name

n C

[145]

92

2 CuI PrNH -n

4 ) 3 Pd(PPh

OTBS

Br

Me 2 CO

15-(S)-HETE	(cf.above)
20

[146]	[147]	[148]	[148]	[148]	[148]
83	75	70	54	54	50
CuI piperidine	CuI piperidine	CuI Et	CuI Et	CuI Et	CuI Et
		N	N	N	N
		3	3	3	3

3

2

Pd(PPh

Pd(PPh

Pd(PPh

Pd(PhCN)

2

2

2

)

)

)

4

3

3

3

)

Pd(PPh

Cl

Cl

Cl

Cl

2

2

2

2

Me

TMS

Cl

Br

COOH

I

COOH I

Br

COOH I

OTBS CO

2

I

AcO

Br

AcO

Br

AcO

11

H

5

C

OH

OH

Br

Br

Br

Br

C

AcO

AcO

AcO

11

H

5

-)S(-5HETE above)(cf.

lipoxinB

above)(cf.

rubrolideA

below)(cf.

rubrolideC

below)(cf.

rubrolideD

below)(cf.

4

21

21

21

2 ) 3 Pd(PPh 2 Cl

I

COOH

AcO

rubrolide E AcO (cf. below)

900

[149]

[150]

98
CuI			NH	3
			Et	PPh
		2
2
Pd(OAc)
OBn		3		OCH
			OCH
				3
I
		C
		2
		MeO
OH
			TBSO

81

CuIpiperidine

2 Pd(PhCN) 2 Cl

I	N
	Boc

OH

furaquinoneA	furaquinoneB	furaquinoneH	himbacine
22	22	22	22

HO	O	Me	Me	himbacine
H		H	H
		H	N

R

OH H OH

3

R

H OH OH

2

3

R

R

OH OH OH

R

2

1

R OH

A B H

1

O O

O

furaquinone

MeO

Z

H H H H

Y

Br H Br H

X

Br Br H H

R

Ac Ac Ac Ac

Rubrolides diacetates

A C D E

O

Z

Y

O

X

RO

Y

X

RO

(Continued )

901

TABLE 5. (Continued )

Catalyst Additive Yield (%) Reference

R′X

RC CH

Name

n C

[151]			[152]
88			86
2			2
		CuI PrNH-n PPh	CuI BuNH-n
3
2			2
		Pd(OAc)	Pd(OAc)
TMS
		Cl

O

O

O 30 dynemicin A models PhO N

	[153]
	25
3
PPh	CuI
	4
	)
	3
	Pd(PPh

				OMe
O
	N
MeO H						Me
			O
						O
			Br
	dynemicinA	related
30

[86]

91

2 CuI PrNH -n

4 ) 3 Pd(PPh

I

TBSO

31 (−)-pateamine A HO

12 [154]

	CuI
4
)
3
	Pd(PPh
Me
2
CO
			Br
				OH
O
		N
CO
3
H
	A				CO
	dynemicin				H
			3
	tri-O-methyl		methylester
32

2 NMe

S	N			O Me	pateamine- A
	O
	O
				O	−)
					(
	Me	N
		H
		2

	COOH				OMe
Me									OOH	A
	HNO									dynemicin
		O
	OH								OH

902