In contrast to facile Pd(0)-catalyzed reactions of allyl esters with soft carbon nucleophiles via π-allylpalladium intermediate, propargyl esters such as acetate are less reactive toward soft carbon nucleophiles. However, β-keto esters and malonates react under neutral conditions with propargyl carbonates using DPPE as a ligand [37]. Acetoacetate reacts with methyl propargyl carbonate (119) in THF at room temperature to afford 4-(methoxycarbonyl)-5-methyl-3-methylene- 2,3-dihydrofuran (120) in 88 % yield. The furan121was obtained by isomerization of the methylenefuran 120under slightly acidic conditions.
+ OCO2Me
COMe
CO2Me O
O
CO2Me CO2Me
120 121
119
Pd2(dba)3
DPPE, 25 °C, 88%
H+
The furan123was obtained by intramolecular reaction of the propargyl benzoate with an enolate of theβ-keto ester in122using DPPF as a ligand, and the reaction was applied to the synthesis of the C(1)-C(18) segment of lophotoxin [38].
MeCN, 84 °C, 72%
122 123
Pd(OAc)2, DPPF, K2CO3
O O
CO2Me CO2Me
BzO OPMB
TMS TMS OPMB
Propargyl carbonate124which has a hydroxy group at C-5 undergoes cyclization by attack of the hydroxy group at the central carbon of the allenyl system 125.
The intermediary σ-allylpalladium complex 126 undergoes β-H elimination to give the diene 127, which is converted to the more stable furan 128 in 80 %
yield using DPPP and DBU [1a, p. 2608]. Similarly, the unsaturated dihydropyran 131 was obtained from 1-phenyl-6-hydroxy-2-hexynyl carbonate (129) via the π-allylpalladium intermediate130 [39].
R= C10H21
Pd(OAc)2, DPPP DBU, 90 °C dioxane, 80%
131
Pd2(dba)3, DPPB
129
130 127 128
124
THF, 50 °C, 40%
126
125 OH C8H17
Pd-OMe
C8H17
R
C8H17
O R R O C9H19
C8H17
O OCO2Me
Pd OMe
OCO2Me Ph HO
R
R
OH O
Ph
O Ph
Pd-OMe
•
The asymmetric three-component reaction of the carbonate 132 with o- methoxyphenol under CO2 atmosphere afforded the cyclic carbonate 135 in 83 % yield with 91 % ee using (S)-BINAP as a chiral ligand. In this reaction, the π-allylpalladium intermediate 133, formed by the attack of phenol to the allenylpalladium intermediate, reacts with CO2 to generate the carbonate 134.
Then intramolecular attack of the carbonate anion to theπ-allylpalladium terminus provides the cyclic carbonate135 [40].
+ ArOH + CO2
132 133
134 CO2
dioxane, 83%, 91% ee
= Pd2(dba)3, (S)-BINAP
HO OCO2Me
OAr X-Pd
HO
O O
O
ArO
Pd O O
Cy Cy Cy
Cy Cy
Cy
Cy Cy
OAr O
OH ArOH OMe
135
2,3-Dihydro-1,4-benzodioxines 139 and 140 are prepared by the reaction of propargyl carbonates 136 with catechol (137) by attacking either terminus of the π-allylpalladium intermediate138.
PdLn
136
a b
137
138
b
139
140 a
R1
R3 OCO2Me
R2
OH
OH R3
R2 L2Pd
R1
O O
R3
R1 R2
O O
R1 R2
R3
O O
R2 R3
R1 H Pd
•
The reaction of propargyl carbonate (141) with catechol (137) using DPPB gave 2-methylenebenzodioxin142. The reaction of methyl-substituted alkynyl carbonate 143 with 137 afforded 3-methylbenzodioxin 144, and a mixture of 146 and 147 was obtained from145 in a ratio of 22 : 78 [41].
143
22 : 78 Pd2(dba)3, DPPB
98%
+
145
Et3N, THF, rt 141
81%
137
137 C5H11
H OCO2Me
Ph
O O
Ph
O O
C5H11 C5H11
Ph OH
OH
Et3N, THF, rt
Pd2(dba)3, DPPB +
Me
H OCO2Me
H
O O
Me OH
OH H
OCO2Me OH
OH H
H O
O
144
146 142
93%
+ Et3N, THF, rt
137
147 Pd2(dba)3, DPPB
The reaction of propargylic mesylate148with aniline proceeded without a catalyst to afford the propargylamine150with inversion of configuration. On the other hand, the Pd-catalyzed reaction of148gave149with retention of configuration [42].
150 149 + PhNH2
63%
Me C7H15
C7H15
Me OMs
NHPh
C7H15
Me
NHPh 148
THF, 78%
MeCN Pd(PPh3)4
In some intramolecular reactions, the amino group attacks either the sp2 or sp carbon of σ-allenylpalladium intermediates depending on the monodentate or bidentate ligand being used. Carbapenam skeletons are prepared by intramolecular attack of 6-aminopropargyl compounds. Treatment of the propargyl phosphate151 having a β-lactam moiety with Pd2(dba)3 and bidentate ligand (DPPF) afforded the carbapenam skeletons 154 and 155. In this reaction, the lactam nitrogen attacked the central sp carbon of the σ-allenylpalladium 152 as expected and theπ-allylpalladium intermediate153 was generated.
152
154 155
153
Pd2(dba)3, DPPF
+
22% 44%
151
PhCO2Na, THF NH
O R3SiO
H H
OPO(OEt)2
NH O R3SiO
H H
PdX
N O R3SiO
H H
N O R3SiO
H H
OCOPh N
O R3SiO
H H
Pd
R3SiO = TBDMSO
In the reaction of the propargyl benzoate 156, attack of the lactam nitrogen occurred in two ways as shown by 157 depending on the ligands used. The car- bapenam 159 was formed by attack of the amino nitrogen to Pd-X to form the palladacycle158, followed by reductive elimination by using monodentate ligand P(o-Tol)3and Cs2CO3. On the other hand, the carbacepham161was obtained via the formation ofπ-allylpalladium160 when DPPF was used [43].
Treatment of the propargyl benzoate 162 with Pd2(dba)3 and DPPF in the presence of N-alkyltosylamide generated the allenylpalladium 163, and the π- allylpalladium intermediate164 was generated by the attack of the amino group.
158 Pd(0) NH
OCOPh O
R3SiO
H H
NH O R3SiO
H H
N O R3SiO
H H
N O R3SiO
H H
Pd-X
N O R3SiO
H H
N O R3SiO
H H
Pd Pd2(dba)3
P(o-Tol)3
b
a
b
a
Pd2(dba)3
DPPF Cs2CO3 toluene, 56%
156
159 Cs2CO3
toluene, 57%
160 161
157
Pd-X
41% 19%
164 R = CH2OBn
162 163
165
+
167 166
Pd2(dba)3, P(o-Tol)3
Cs2CO3, toluene, TsNHMe (2 equiv.)
95%
Cs2CO3, toluene R
R
NHTs
OCOPh
N R R
Ts NTs R
R
NHTs PdX Pd(0)
N R R
Ts
Pd Pd2(dba)3, DPPF Cl
N
R R
Ts
N
R R
Ts
Me TsNHMe
Finally the azepine derivative 165 was obtained in 95 % yield by the attack of N-alkyltosylamide to the π-allylpalladium intermediate 164. On the other hand, the 2-allenyl- and 2-vinylpiperidines166 and 167 were obtained from 162 when P(o-Tol)3 was used [44].