Extensive studies have been devoted to allylation of carbon pronucleophiles as important methods of C—C bond formation. As described before briefly, reac- tions with allylic carbonates and alkenyloxiranes proceed under neutral conditions due to in situ generation of alkoxides which abstract protons from nucleophiles.
Also allylation with allyl aryl ethers can be carried out without addition of bases.
Reactions of allylic acetates and other allylic compounds are carried out in the presence of bases [5].
Usually presence of two electron-withdrawing groups (EWGs) in carbon pronu- cleophiles are required for facile allylation. Ketones, CHO, CO2R, CN, NO2,SO2
are effective EWGs. Derivatives of malonates and β-keto esters are most exten- sively used. Aryl groups are weakly effective. One NO2and SO2are active enough for the allylation. A number of ligands have been utilized for allylation, showing different activities. Santelli and co-workers reported that tetraphosphine, Tedi- cyp (X-1), combined with (η3-allyl-PdCl)2 generates a very efficient catalyst.
They claimed that TON 10 000 was attained in a typical allylation of β-keto ester 140 with allyl acetate using this catalyst [50]. Uozumi and co-workers pre- pared amphiphilic resin-supported triarylphosphine (PEP) attached to polyethy- lene glycol-polystyrene graft polymer, and they found that Pd complexes of PEP [Pd(PEP) and Pd(PEP)2] are recyclable active catalysts for allylation in water.
Ethyl acetoacetate was allylated with the allyl acetate94in water in the presence of K2CO3at room temperature using Pd(PEP)2(1 mol%) as a catalyst to give rise to the allylated product in 98 % yield [40a].
Intramolecular reaction of the cyclic β-keto ester 141 proceeded with high enantio- and diastereoselectivities. When (R,R)-Trost L-1was used, a mixture of the [2.2.2]bicycles142(99 % ee) and143was obtained in 84 % yield in a ratio of 4.6 : 1. On the other hand, Eu(fod)3as an additive showed a remarkable effect. The diastereoselectivity was reversed when (S,S)-TrostL-1and Eu(fod)3 were used to give a mixture of142 and143 (68 % ee) in a ratio of 1 : 8 in 85 % yield [51].
CO2Me O
OAc
CO2Me O
+
(h3-allyl-PdCl)2, X-1 NaH, THF, rt
48 h, 99% conv.
140
140 : (h3-allyl-PdCl)2
10,000 : 1 TOF = 341 TON = 10,000
N O
CO2Et
OCO2Me
N H
CO2Et O
CH2Cl2, rt, 82%
Pd2(dba)3,Trost L-1
+ N
H CO2Et
O
(R,R)-Trost L-1: 84%, 4.6 : 1, 142 = 99% ee (S,S)-Trost L-1: 85%, 1 : 8, 143 = 68% ee
142 143
141
+ 94
Pd-PEP H2O, K2CO3 rt, 98%
Ph
COMe CO2Et
Ph Ph
EtO2C COMe Ph
OAc
Intramolecular allylation with alkenyloxiranes offers a good method of macro- cyclization. In the total synthesis of roseophilin by F¨urstner, the alkenyloxirane 144 was cyclized smoothly to yield the 13-membered carbocycle 145 in high yield (85 %) in the presence of two ligands DPPE and PPh3. Then Pd-catalyzed reaction of the allylic lactone146with benzylamine afforded the pyrrole carboxylic acid147 cleanly in 70 % yield via regioselective allylation of benzylamine at the electron-deficient terminus of the allylic lactone146 [52].
THF, 70%
THF, 85%
+
Pd(PPh3)4, DPPE steps
TBSO
O
PhO2S MeO2C
OH PhO2S
MeO2C OTBS
O PhO2S
O O
PhO2S O OH
N Bn
144 145
147 146
BnNH2 Pd(PPh3)4
Usually no reaction of alkenyloxiranes bearing a methyl group at the terminus as in149takes place; instead isomerization to enone occurs. The reaction of the epox- ide 149 with the Meldrum’s acid derivative 148 proceeded at room temperature in THF using a precatalyst generated by mixing Pd2(dba)3(1.5 mol%) and cyclic phosphite TMPP (III-2) (20 mol%) to afford150 in 75 % yield, and macrolactam aglycon of fluviricin B1 was synthesized [53].
O O
O
O
O
N3
O O
O
N3
CO2Bn
OH
CO2Bn
O
O HN
OH + Pd2(dba)3,III-2
THF, rt, 75%
fluviricin B1 aglycon
148 149 150
In the reaction of the activated alkene151with allyl carbonate, Michael attack of an alkoxide to the alkene occurs at first. Then the generated anion152is allylated to afford153. The THF derivative155was obtained in high yield by the coupling of the alkene151 with monocarbonate of 2-buten-1,4-diol 154 in the absence of a base [54].
154
+ Pd(0)
+
155
Ph CN
CN
Pd2(dba)3, DPPE
HO OCO2-i-Pr
THF, rt, 92% O
Ph CN
CN
Ph CN
CN
O O
OR
Ph RO
NC CN
151
Ph RO
NC CN
151
153 152
+Pd CO2
One pot synthesis of tricyclic enone 158 is possible via domino Pd-catalyzed allylation and Co-catalyzed Pauson-Khand reaction. Allylation of the propargylic malonate 156 with 3-acetoxycyclopentene under CO pressure afforded the fused tricyclic compound158via157 in 73 % yield. Bimetallic catalyst PCNS (Pd and Co nanoparticles immobilized on silica) was used as a catalyst [55].
157
+ CO (10 atm), 18 h, 73%
PCNS, NaH, THF, 130°C
158 156
MeO2C Me MeO2C
OAc
MeO2C Me MeO2C
MeO2C MeO2C
Me O
A phosphonate is an activating group. Asymmetric allylation of the chiral race- micα-acetamido-β-keto phosphonate159 with cinnamyl acetate (41) was carried out at−30◦C to affordα-alkyl-α-aminophosphonic acid derivative160with 88 % ee in 78 % yield when (R)-BINAP was used as a chiral ligand [56].
+ [Pd], (R)-BINAP
t-BuOK, toluene
−30°C, 78%, 88% ee
159 160
41 Ph P(OMe)2
O
NHAc O
Ph OAc Ph P(OMe)2
O O
NHAc Ph
Allylation of simple ketone is not possible under usual conditions, but the reac- tion can be carried out under selected conditions. Asymmetric allylation of the chiral racemic α-methylcyclohexanone 161 with allyl carbonate proceeded in the presence of LDA as a base with or without Me3SnCl as a Lewis acid at room tem- perature to provide the allylated ketone162in very high yield with 82 % ee when (S,S)-TrostL-1was used. The choice of base is crucial, and it was claimed that no reaction took place when Na or K bases were used in this reaction [57]. Asymmet- ric allylation of α-aryl and heteroaryl ketones has been carried out. Asymmetric allylation of 2-indolylcyclohexanone 163 took place at 0◦C to give the the allyl ketone in 82 % yield with 84 % ee. In this reaction, NaHMDS was used as a base and Trost L-2 as chiral ligand [58]. Asymmetric allylation of the tetralone 164 with allyl acetate was carried out using Trost L-6 in the presence of Cs2CO3 to provide the allylated ketone with 91 % ee in 90 % yield [59].
163 Ph
O
OCO2Me
Ph
O
NaHMDS, DME 0°C, 82%, 84% ee O
N Me
O
NMe OAc (h3-allyl-PdCl)2,(S,S)-Trost L-2
+ (h3-allyl-PdCl)2,(R,R)-Trost L-5
164
+ (h3-allyl-PdCl)2,(S,S)-Trost L-1 LDA, DME, Me3SnCl
rt, 98%, 82% ee 161
162
+
Cs2CO3, 90%, 91% ee OMe
O Me
OMe
O OAc
Non-stabilized ketone enolates are also allylated. The reaction of Mg enolate of cyclohexanone 165 with 94 afforded the chiral ketone 166 with high diastereo- and enantioselectivities by using (R)-BINAP [60].
+ Pd2(dba)3, (R)-BINAP 0°C, 67%, 99% ee
O OMgCl O
Ph Ph
Ph OAc Ph
165 94 166
MeMgCl (i-Pr)2NH
Direct allylation of esters is difficult, but their enolates are allylated. Expected 1,4-addition of Li enolate of ethyl isobutyrate to the isoprene monoxide 20 took place to give167at room temperature by using DPPE as a ligand [61].
20
THF, rt, 90%
+ E : Z= 8 : 2
Pd(OAc)2, DPPE
167
O OLi
OEt
CO2Et OH
Tamaru reported that Pd-catalyzed α-allylation of aldehydes to afford 168 can be carried out even with allyl alcohols in the presence of a stoichiometric amount of Et3B, NEt3, and LiCl. Although the mechanism is not clear, activation of allyl alcohol by Et3B occurs by coordination to generate π-allylpalladium. In addition, boron enolates are formed by the reaction of aldehydes with Et3B and Et3N, and attacked by π-allylpalladium [62]. Similarly allylation of malonates and ketones with allylic alcohols169and 169awere carried out [63].
+ Et3B, Pd(OAc)2, PPh3 THF, NEt3, LiCl, rt
92% 4%
Pd(0)
BEt2
168
CHO OHC HO
Ph Ph
Ph OH
R OH R O
H
R Pd
R Cl Pd O
R H
O R
H H
R Cl Pd
O R
H
R OH
Et3B LiCl
BEt3
Et3B NEt3
Et3B
+
Et3B, Pd(OAc)2, PPh3 THF, NaH, rt, 81%
+
+ Et3B, Pd(OAc)2, PPh3 THF, NaH, rt, 74%
169
OH
OH CH(CO2Et)2
OH O OH O
CH2(CO2Et)2
169a
Nitroalkanes are smoothly allylated. Asymmetric allylation of nitromethane with the carbonate 169b at room temperature afforded 170 in 90 % yield with 98.5 % ee. PHOX derivativeVII-3 was used as a chiral ligand [64].
+ THF, rt, 90%, 98.5% ee
Pd2(dba)3,VII-3
Ph Ph
OCO2Me
Ph
Ph NO2
170 CH3NO2
169b
N-(Diphenylmethylene)glycine t-butyl ester (t-butyl glycinate-benzophenone Schiff base) (171) is a reactive prochiral nucleophile and α-allyl-α-amino acids can be prepared by allylation and hydrolysis of the allylated product. Asym- metric allylation of 171 with cinnamyl acetate (41) afforded 172 regioselec- tively with high % ee when the reaction was carried out in presence of achiral phosphite P(OPh)3, and a chiral phase-transfer catalyst of alkaloid [O-allyl-(9- anthracenylmethyl)cinchonidinium iodide] [65,66].
172 171
+
(h3-allyl-PdCl)2, P(OPh)3
Ph N CO2-t-Bu Ph
chiral PTC, KOH toluene, 89%,
96% ee OAc
Ph N CO2-t-Bu Ph
PTC=O-methyl cinchonidinium iodide 41
Ph
Ph
As a different type C-allylation, Trost reported asymmetric ring expansion involving Wagner–Meerwein shift of the allyl carbonate 173 bearing a cyclo- propanol group to give the 2-vinylcyclobutanone175 as shown by174in quanti- tative yield with 92 % ee, when Trost L-2 as a chiral ligand and TMG as a base were used. Efficient differentiation of the prochiral face of the alkene occurred [67].
Pd2(dba)3, Trost L-2 TMG, toluene 100%, 92% ee
173 174 175
MeO2CO Me
OH
Me O H
X-Pd
O Me