Pd-catalyzed reactions of various allylic compounds via the formation of π- allylpalladium complexes offer many synthetically useful methods. The following allylic compounds are known to form π-allylpalladium complexes by oxidative addition.
Allylic compounds used for Pd-catalyzed reactions
OAc OCO2R OCONHR O
OPh OH
OP(O)(OR)2
NR2
SO2Ph NO2
Cl
EWG EWG NR3X SR2X
NR
In addition, π-allylpalladium complexes 1 and 2 are formed as intermediates in the reactions of organic halides with 1,3- and 1,2-dienes. Usually these π- allylpalladium complexes, without isolation, undergo a variety of transformations as summarized in Scheme 4.1, offering many useful synthetic methods.
Reaction of π-allylpalladium chloride with malonate and acetoacetate was re- ported in 1965, showing that π-allylpalladium complexes are electrophilic [1].
Most importantly, electrophilic π-allylpalladium complexes react with various kinds of pronucleophiles of carbon, oxygen, and nitrogen. Then Pd(0) is regener- ated after the reactions. The generation of Pd(0) offers the possibility of a catalytic process. This is the characteristic feature ofπ-allylpalladium chemistry.
π-Allyl complexes of other transition metals, typicallyπ-allylnickel complexes are either nucleophilic or electrophilic depending on the nature of the reactants,
Palladium Reagents and Catalysts—New Perspectives for the 21st Century J. Tsuji
2004 John Wiley & Sons, Ltd ISBNs: 0-470-85032-9 (HB); 0-470-85033-7 (PB)
+ Ar-X Pd(0)
+ Ar-X Pd(0)
1
2 Pd-X
Ar Ar
Pd X Ar
X-Pd
Ar
Pd-X
•
1
hydrogenolysis
b-elimination transmetallation transmetallation
carbonylation
metallation transmetallation
M′R′
M′Ar
R′M′M′R′ Pd(0)
C, O, N nucleophile (NuH)
Nu
Pd-X R
M'
CO2R R
R M′R′
R
R R
R
R′ X
X R
R
R R′
R′
Ar R
CO, ROH
R H
Scheme 4.1 Pd-catalyzed reactions of allylic compounds.
+ Pd(0)+ HX−
Pd(0) NuH
R X R
Pd X
Nu R
and generate either Ni(II) or Ni(0) after the reaction. When Ni(II) is regenerated, the reaction is stoichiometric.
+ M(II)XY E+
R X M(0) R
M X
E R
Although it is not a common reaction, some nucleophiles, particularly ester enolates, are known to attack the central sp2carbon ofπ-allyl group in the presence of σ-donor ligands to generate palladacyclobutane 3, which is converted to the substituted cyclopropanes 4 by reductive elimination [2,3]. Satakeet al. reported thatπ-allylpalladium-pyridinylimidazole complex7is a very effective catalyst for the cyclopropanation [4]. Ethylα-cyclopropylisobutyrate (6) was obtained in high yield with high chemoselectivity by the reaction of the ketene silyl acetal5 with cinnamyl acetate using7as a catalyst.
3 4
Pd X
Pd X Pd
R R R
R
Nu Nu
Nu
+ Pd(0)
+ 6 22 : 1
7 5
AcONa, DMSO 87%
Pd cat
Ph OAc + OEt
OSiMe3
CO2Et CO2Et
N N
N Me
Pd Ph
Ph
As shown above many allylic compounds can be used for catalytic reactions with different reactivity. Allylic esters such as carbonates, acetates, and phosphates are widely used. Allylic acetates and phosphates react in the presence of bases such as Et3N and AcONa. However, Giambastiani and Poli reported that allylation of β-keto esters, but not malonates, with allylic acetates can be carried out under neutral conditions, although the reaction is slower [5].
+ Pd(PPh3)4 , PPh3
CH2Cl2, 69%
OAc CO2Me
O
Ph CO2Et
O
Ph
Allylic carbonates are more reactive than acetates. In addition, reaction of car- bonates proceeds in the absence of bases [6]. Formation of π-allylpalladium 9 from allyl methyl carbonates8proceeds by oxidative addition, followed by decar- boxylation, andπ-allylpalladium methoxide9is generated at the same time, which abstracts a proton from a pronucleophile to form10.In situ formation of methox- ide is a key in the allylation under neutral conditions. Allylation under neutral conditions is useful for the reaction of base-sensitive compounds. For example, exclusive chemoselective reaction of the carbonate group in 4-acetoxy-2-butenyl methyl carbonate (11) occurred in the absence of a base to yield 12. Similar chemoselective reaction of the allyl carbonate group in the chiral cyclopentenyl methyl carbonate13 with theβ-keto ester14without attacking the allylic acetate group to give15was observed even in the presence of NaH. As expected, retention of stereochemistry (see Chapter 4.2.1) was observed in this substitution [7].
Nu NuH
9
+ Pd2(dba)3 , PPh3
11
12
8 OMe 10
_ _
THF, 77%
R O OMe
R Pd+
R
O
Pd+ R
Nu
AcO
OCO2Me
CO2Me
AcO
O
CO2Me
O
MeOH Pd
CO2
13
15
14
+ Pd2(dba)3 , PPh3
NaH, 91%
AcO OCO2Me
t-Bu-O CO2Et
AcO
H CO2Et
O
O-t-Bu O
Alkenyloxirans 16are reactive allylating agents used under neutral conditions.
The epoxy ring is opened by Pd(0) to form π-allylpalladium with generation of an alkoxide anion, which abstracts a proton from a pronucleophile to produce the α-hydroxy-π-allylpalladium 17. Reductive elimination of 17 affords either 1,4-adducts18or 1,2-adducts19[8,9]. The 1,4-adducts are mainly obtained under usual conditions due to the electronic effect of the epoxide oxygen. The 1,4-adducts 18are allylic alcohols, and can be used again for the allylation after esterification to yield19a.
Nu− NuH
1,4-addition
1,2-addition 16
17
18
19
18
NuH
19a Pd(0)
R
R′
O O−
R′
R R
R′ OH
OH R′ R
R
R′ OH
Nu Nu
Pd Ln Pd
Ln
R
R′ OH
Nu
R
R′ OCO2Me
Nu
R
R′ Nu
Nu
Reaction of isoprene monoepoxide (20) with acetoacetate afforded the allylic alcohol21. The pheromone24was synthesized after second allylation of acetoac- etate with22 to provide23[8]. The regioselectivity is controlled by ligands. The 1,4-adducts such as21are formed when achiral ligands are used. Interestingly, the same reaction of20afforded the 1,2-adduct25(64 % yield) and the 1,4-adduct26 in a ratio of 79 : 16 when TrostL-1 as a bulky chiral ligand (even racemic) was used [10].
THF, rt, 62%
+
20 21
22
O COMe
CO2Me
HO COMe
CO2Me
AcO COMe
Pd(PPh3)4
NaH, 91%
steps 23
24 COMe
CO2Me
COMe COMe
MeO2C
MeO2C CO2Me
Pd(PPh3)4
25 Pd2(dba)3, Trost L-1
CH2Cl2, rt 20
26
79 : 16 64%
O COMe
CO2Me
O O Me MeO O
Me H
HO COMe
CO2Me
+ +
Trost designed chiral diamides of 2-diphenylphosphinobenzoic acid (DPPBA) and 2-diphenylphosphinoaniline (DPPA), and their derivatives (abbreviated as Trost L-1, L-2, L-3, L-4, andL-5), which are remarkably effective ligands in asymmetric allylations as described later.
Trost L-1 (XIII-1)
Trost L-2 (XIII-2)
Trost L-3 (XIII-3)
Trost L-4 (XIII-4)
Trost L-5 (XIII-5) HN
NH Ph2P PPh2
O O
HN NH
Ph2P PPh2
O O
HN NH
Ph2P PPh2
O O
HN NH
Ph2P PPh2
O O
PPh2
NH O
HN O Ph2P
Less reactive allylic alcohols can be used in the presence of some activators.
Lewis acids are used for this purpose. Allylation of amines and malonates with allyl alcohols was carried out by Ozawa using a sp2-hybridized bidentate phosphine-Pd
in the presence of pyridine [10a]. Et3B is one of them, and allyl alcohols behave as good electrophiles in the presence of the borane. Amination ofcis-5-methoxycar- bonylcyclohexen-3-ol (27) withN-methylaniline proceeded at 50◦C in the presence of 2 equivalents of Et3B to yield a mixture of cis- and trans-cyclohexenylamines 28. The hydroxy group is activated by coordination of Et3B as shown by29[11].
Also Ti(O-i-Pr)4is used for allylation with allylic alcohols in benzene [12]. CO2
activates allylic alcohols presumably by forming monoallyl carbonate, and amina- tion proceeds under 1 atm of CO2. Allylation of α-methylacetoacetate with allyl alcohol occurred at room temperature under 30 atm of CO2[13].
50°C, 73%
27 28
+ Pd(PPh3)4, CO2 (30 atm)
29
rt, 77%
+ OH
MeO2C MeO2C
MeNPh
OH CO2Me
O
CO2Me O
O
MeO2C
H BEt3
Pd(PPh3)4, Et3B PhNHMe
Allylamines are less reactive allylating agents. Bricoutet al. reported that C and N-allylations with allyldiethylamine occurred using Pd(OAc)2 and DPPB, but Ni catalysts were found to be better [14].
The nitro group is a good leaving group, and allyl nitro compounds are used conveniently for allylation because they can be prepared easily by the reaction of nitromethane with aldehydes and ketones, and used for Pd-catalyzed reactions [15].
As an interesting application, the alkenyl triflate30was converted to the allyl nitro derivative31, which was, without isolation, subjected to the Pd-catalyzed amina- tion with32in the presence of tetramethylguanidine (TMG) as a strong amine base to afford theanti-MRS carbapenem intermediate33 in 34 % overall yield [16].
33
32 TMG, MeOH, 34%
30
OTf CO2PNB O
TBSO H H
31
CO2PNB O
TBSO H H
NO2
N S O2
OH
CO2PNB O
TBSO H H
HN S O2
OH
Pd(OAc)2,P(OEt)3 CH3NO2
Intramolecular amination of the allyl sulfone 34 proceeded regioselectively in MeCN in the presence of TMG to give cephalotaxine intermediate35in 98 % yield.
The use of TMG is important. When Et3N was used, the yield was 64 % [17].
Pd(PPh3)4, MeCN TMG, 98%
34 35
O O
PhSO2
OMOM
S S
NHPMB
O
O OMOM
S S
N PMB