Negishi E. 2002 Handbook of organopalladium chemistry for organic synthesis / 1491 152

Br

IV.7 CARBOPALLADATION OF ALLENES

1511

followed by an intramolecular carbopalladation of the allene moiety and finally -hydride elimination to provide the tricyclic compound 128 (Scheme 42).[62]

X

	I or II						I
n					n_1	E	58%			E
						E				E
123 (X = I, Br)	124
						125			126
n = 0−7, 15

I:5 mol % PdCl2(PPh3)2, K2CO3 (5 equiv), EtOH (10 equiv), DMF.

II:5 mol % PdCl2(PPh3)2, K2CO3 (5 equiv), n-Bu4NCl (1 equiv), DMF. E = CO2Et

Scheme 41

				10 mol % Pd(OAc)2		Ph
				20 mol % PPh3
		Ph +		K2CO3, Et4NCl, MeCN, reflux
						H
	I	96%
		Me				H

127

128

Scheme 42

F. INTRAMOLECULAR CARBOPALLADATION OF ALLENES FOLLOWED BY NUCLEOPHILIC TRAPPING

The -allylpalladium intermediate 130, formed by the intramolecular carbopalladation of 129, could be trapped with the enolate of diethyl malonate, with Bu3SnPh, with piperidine, or with phenol to afford a variety of cycloocta-1,3-diene derivatives 131–134

(Scheme 43).[61]

In 1995 Grigg and co-workers reported a similar cascade consisting of an intramolecular carbopalladation and intermolecular nucleophilic trapping (Scheme 44).[63] The regioselectivity of the allylic nucleophilic substitution can be controlled completely by using different bases.

The intermediate -allylpalladium species 138 (Scheme 44) could also be coupled with phenylboronic acid to yield mainly the benzopyridone derivative 139; however, the regioselectivity depends largely on the base used (Scheme 45).[64]

With sodium azide as the trapping reagent, 141 yields cyclic allyl azides, which can immediately undergo an intermolecular 1,3-dipolar cycloaddition with added norbornadiene and the adducts eventually cleave off cyclopentadiene in a retro-Diels–Alder reaction to provide triazoles (Scheme 46).[65] Sodium benzenesulfinate can also be used as a nucleophile.[65]

1512	IV Pd-CATALYZED REACTIONS INVOLVING CARBOPALLADATION

n-Pr

I

E

E

E

n-Pr

129 E

Ph

n-Pr

n-Pr

E

i

ii

E

n-Pr

51%

64%

n-Pr

131

E

PdLnX

132 E

n-Pr

E

OPh

n-Pr

E = COOEt

N

E

130

n-Pr

iii

n-Pr

E

iv

E

54%

56%

n-Pr

E

n-Pr

E

133

E = CO2Et

134

i:I, CH2E2 (3 equiv), 0.05 M, 120 °C, 23 h.

ii:II, PhSn(n-Bu)3 (2.2 equiv), 0.014 M, 120 °C, 11 h.

iii:II, PhOH (5 equiv), 0.013 M, 80 °C, 24 h, 120 °C, 7 h.

iv:II, piperidine (2 equiv), 0.014 M, 80 °C, 9 h.

I = 5% PdCl2(PPh3)2, K2CO3 (5 equiv), EtOH (10 equiv), DMF.

II = 5% PdCl2(PPh3)2, K2CO3 (5 equiv), n-Bu4NCl, DMF.

Scheme 43

K2CO3

N

I

10 mol % Pd(OAc)2

NMe

O 136 91%

20 mol % PPh3

NMe

O

NH

N

135

Ag2CO3

MeCN

NMe

Pd

O 137 77%

NMe

O

138

Scheme 44

I

NMe

O

IV.7		CARBOPALLADATION OF ALLENES									1513
					Ph
5 mol % Pd(OAc)2										Ph
10 mol % PPh3					NMe	+				NMe
toluene, H2O (2:1)
PhB(OH)2
			O				O
		139 (71%)				140 (trace)
Scheme 45
		N
		N N n = 0				56%
					n = 1	54%

O

n

143

MeO2C

CO2Me

N

N3

I

N N

10 mol % Pd(PPh3)4

DMAD

O

O

n = 0

86%

NaN3, DMF

n = 1

57%

n

n

n

n = 0

71%

142

141

n = 1

58%

144

Scheme 46

G. CARBOPALLADATION OF ALLENES FOLLOWED

BY SKELETAL REARRANGEMENT

Under the catalysis of Pd(PPh3)4, 1-propadienyl-2-(Z- -iodo-( -1)-alkenyl)cyclobu- tanol 145 afforded the -allylpalladium intermediate 146 after oxidative addition and intramolecular carbopalladation. Nemoto and co-workers observed that the ring strain of the four-membered ring in 146 was released by ring expansion to afford the bicyclo[6.3.0]undecane derivatives 147 and/or 148 with a cyclopentanone moiety (Scheme 47).[66]

An analogous ring expansion was observed upon an intermolecular carbopalladation of the 1-propadienylcyclobutanol 149 with PhPdX formed from phenyl iodide or phenyl triflate (Scheme 48).[66]

Recently, Jeong and Nagao observed a similar ring enlargement of a nitrogen-containing five-membered ring (Scheme 49).[67]

1514

IV Pd-CATALYZED REACTIONS INVOLVING CARBOPALLADATION

XLnPd

HO

10 mol % Pd(PPh3)4

H

O

I

Ag2CO3 (1 equiv)

n

toluene, 80 °C

n

145

O H

146

O

147

n −1

148

n −1

n = 1

α-hydroxy

67%

n = 1

β-hydroxy

63%

n = 2

α-hydroxy 24%

n = 2

α-hydroxy

34% (reflux)

Scheme 47

10% Pd(PPh3)4

O Ph

O Ph

O

HO

K2CO3 (5 equiv)

Me +

Me +

Ph

+

PhX

DMF, 80 °C

n-C7H15

n-C7H15

n-C

H

15

n-C

H

15

H

7

7

149

150

151

152

X = I

β-hydroxy

12 h

33% ( 76:24:0 )

X = I

β-hydroxy

20 h

76% ( 52:0:48 )

X = OTf

β-hydroxy

6 h

27% ( 62:38:0 )

Scheme 48

Me

5 mol % Pd(PPh3)4

O Me

HO

K2CO3 (1.2 equiv)

N

I

THF, reflux, 16 h

72%

N

O 154

153

O

5 mol % Pd(PPh3)4

Me

ArI (3 equiv)

O

HO

K2CO3 (1.2 equiv)

Me

NR

THF, reflux, 16 h

Ar

68−92%

NR

155

O 156

O

R = alkyl, benzyl

Ar = phenyl, p-methylphenyl, p-methoxyphenyl

Scheme 49

IV.7 CARBOPALLADATION OF ALLENES

1515

H. POLYMERIZATION REACTIONS INVOLVING

CARBOPALLADATIONS OF ALLENES

The Pd(0)-catalyzed reaction of bis(allene)s, dihaloarenes, and nucleophiles can be applied toward the synthesis of polymers (Scheme 50).[68] The carbon chain between the two allene units ends up as the linker group in the polymer 158.

Aryl halides containing an alkoxy-tethered malonate unit have also been reported to react with allenes yielding a class of polymers 160, which, due to the two regioisomeric modes of the nucleophilic trapping reaction, contained two kinds of repeating units (Scheme 51).[69]

An alternating copolymerization of allene and CO initiated by an acylor methylpalladium complex was developed by Kacker and Sen (Scheme 52).[70]

6

157

+

(CH2)6

X

Ar

X

Ar

m

Ar

(CH2)6

n

+

2 Na+ Nu

Nu

Nu

Nu

Nu

Nu = CH(CO2Et)2

158

Scheme 50

CO2Et

1.5 mol % Pd(OAc)2

R1

O

3 mol % dppe

CO2

2

+

+ NaH

1,4-dioxane

R2

159

I

R2

CO2

3O

R1

3 O

n

m

CO2

CO2Et

p

CO

Et

R

2

1

R

2

160

Scheme 51

O

Pd(MeCN)4(BF4)2 +

2 PPh3

500 psi of CO

m

3.8 10

−2

mmol

7.6

10

−2

mmol

MeNO2/MeOH (2:1)

1.0 g

161

O

5 mol % Pd/C

m

162

Scheme 52

1516	IV Pd-CATALYZED REACTIONS INVOLVING CARBOPALLADATION

I. CARBOPALLADATION REACTION FORMING Csp2—Pd SPECIES

In all of the reactions discussed above, the carbopalladation of the allene occurred regioselectively in such a way that the substituent of the first formed organopalladium intermediate would be attached to the central carbon atom of the allene moiety to form a - allylpalladium intermediate. However, Grigg et al.[71] and later Oppolzer et al.[72] observed that the intramolecular carbopalladation of the first formed allene 165 proceeded in a completely different manner (Scheme 53). Instead of the formation of a - allylpalladium complex, a reverse regioselectivity to form a Csp2—Pd intermediate was observed.

OCO2Me

XPd

10 mol % Pd(OAc)2

PdX

20 mol % PPh3

5-exo insertion

toluene, 85 °C, 16

h

N

N

N

Ref. [72]

SO2Ph

SO2Ph

SO2Ph

165

163

164

CO2Me

PdX

CO

MeOH

N

SO2Ph

3-exo insertion

167

N

R

SO2Ph

RSnBu3

166

or NaBR4

N

SO2Ph

X

168

X

2.5 mol % Pd2(dba)3 .CHCl3

O

MeO

R

10% PPh3, CO (1 atm)

MeOCO2

MeOH

R

R

R

Ref. [73]

R = Me or H

170

169

X = NTs, C(SO2Ph)2, CHSO2Ph

Scheme 53

Obviously, in this case the normal regiochemical preference cannot be achieved due to the geometrical constraints exerted by the attachment of both reacting units to the fivemembered ring. Instead, 3-exo-dig carbopalladation prevails, and the thus formed alkenylpalladium intermediate 166 is trapped by CO and MeOH to yield a bicyclic - cyclopropylacrylate 167 and 170. Other trapping reagents for the intermediate 166 can be applied as well (Scheme 53). In addition to the same type of product 172, the reaction of the propargyl carbonate 171 with two methyl groups adjacent to the carbonate moiety gave

IV.7 CARBOPALLADATION OF ALLENES

1517

a bicyclo[4.3.0]nonenone derivative 173, which must have been formed by CO insertion after the first intramolecular carbapalladation step affording 174, followed by intramolecular acylpalladation to give 175 and reductive elimination, that is, by cyclization of the intermediate acylpalladium intermediate 175 (Scheme 54).[72]

PhO2S

SO2Ph

PhO2S

SO2Ph

PhO2S

SO2Ph

2.5 mol % Pd2(dba)3

10 mol % AsPh3

CO, HOAc, 45 °C

+

MeO2C

AcO

MeOCO2

O

171

172

31%

173

45%

reductive

elimination

PhO2S

SO2Ph

PhO2S SO2Ph

O

AcOLnPd II

PdOAc

O

175

174

Scheme 54

This reaction was utilized to synthesize ( )- -thujone (Scheme 55).[72] The two centers of chirality in the cyclopropane ring were controlled in a highly diastereoselective manner by the center of chirality originally present in the starting aldehyde 176.

PhO2S

SO2Ph

PhO2S SO2Ph

CHO 4 steps

Pd2(dba)3, Me2Zn

OTHP

Et2O, reflux, 91%

H

176

MeOCO2

177

178

PhO2S SO2Ph

O

1. Al-Hg, THF, H2O

PtO2, H2, MeCO2Et

2. LDA, MoOPh

HOAc, 50 °C, 96%

H

60%

H

179

-α-thujone

180

Scheme 55

1518	IV Pd-CATALYZED REACTIONS INVOLVING CARBOPALLADATION

In all of the stoichiometric intermolecular reactions of a -allylpalladium complex with an allene to form a new -allylpalladium intermediate, the type of insertion reaction was established by 1H NMR spectroscopy as well as X-ray single crystal structure analy- sis.[1]–[15] However, it is interesting to note that the corresponding intramolecular carbopalladations of allenes displayed two different modes to form either a Csp2 —Pd species or a new -allylpalladium intermediate highly selectively depending largely on the length of the tether between the two moieties (Scheme 56).[73]–[75]

This abnormal insertion mode was applied in a total synthesis of the natural product ( )-isoiridomyrmecin 197 in seven steps starting from 2,3-butadienyl bromide (Scheme 57).[73]

Pd OAc

	n = 2			n = 3	R		PdOAc
R
	R		PdOAc
181		182				183
R = (CH2)n
							PdOAc
	10 mol % Pd(PPh3)4		PdOAc
	HOAc, CO
	75 °C, 22%
OAc
184			185			186
				O		H	O
	O		H
CO
	PdOAc						O
				O
				PdOAc
	187		188			189
	Pd(PPh3)4	Me	H		Me	H
	HOAc						CO3H
	OAC CO, 60 °C			PdX
	28%					H
			H
190			191			192

Scheme 56

IV.7 CARBOPALLADATION OF ALLENES

1519

Br

O

3 steps

5 mol % Pd2(dba)3.CHCl3

+

OAc

NMe2

193

30 mol % P(2-furyl)3

HOAc, 58%

H

H

194

H

Me

CO2H

+

CO2H

3 steps

O

O

isomer separation

Me H

Me H

Me H

197

	195	196
		Isoiridomyrmecin
		Scheme 57

J.SUMMARY

1.The intermolecular carbopalladation of allenes has been shown to form -allyl- palladium intermediates.

2.The intramolecular carbopalladations of allenes has been shown to afford either -

allylpalladium intermediates or Csp2—Pd species, depending on the structure of the substrates.

3.-Allylpalladium intermediates described in this section can undergo either a -H elimination or a nucleophilic substitution reaction. Enantioselective nucleophilic substitution can afford the corresponding chiral compounds with high enantiomeric excesses.

In conclusion, with subtle design, carbopalladation of allenes will provide efficient access to dienes, alkenes, monocycles, and oligocycles with functional groups and will show its utility in the synthesis of specific target molecules.

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