In Sect. B, the intermolecular carbopalladations of allenes are followed by a -hydride elimi- nation to afford a 1,3-diene. However, in the presence of a nucleophile, a Tsuji–Trost-type nucleophilic substitution of the intermediate -allylpalladium species[19]–[21]has been fully established (Scheme 6).
Shimizu and Tsuji[16] and Cazes, Goré, and co-workers[22]–[25]reported the first exam- ples of such transformations in 1984. The Pd(0)-catalyzed reactions of either an aryl halide (bromide or iodide) or an alkenyl bromide with a 1,2-diene in the presence of sodium diethyl malonate afforded styrene derivatives 24 and 1,3-diene derivatives 25, respectively (Scheme 10).[22]–[25]
In these kinds of transformations, the configuration of the newly formed carbon–carbon double bond in either 24or 25depends on the relative stabilities of the two -allylpalladium species anti-26and syn-26(Scheme 11).[25],[26]
R1
R2 Nu R2X
cat. Pd(0)
R1 R2
Pd+
L L
anti-26
R2
Pd+
L L
syn-26 R1
Nu−
R1 E-27
R2 Nu Z-27 Z and E refer to R1 and R2
R1
Nu−
Scheme 11
Using trimethylsilyl-substituted vinyl bromides, the carbopalladation – intermolecular trapping protocol afforded trimethylsilyl-substituted 1,3-dienes 30/31and 2-alkenyl-allyl silane 32, which could be used for further elaboration (Scheme 13).[27]
Under the catalysis of Pd(dba)2 and PPh3, the reaction of 1-hexynyl bromide with deca- 1,2-diene and nucleophiles afforded enyne derivatives such as 35and 36(Scheme 14).[28]
n-C7H15 n-C7H15
n-C7H15
NaCH(CO2Et)2
Br R
I
CO2Et CO2Et
CO2Et CO2Et R
29 66 °C , 14 h
28 E / Z = 85:15
R = Me, E / Z = 100:0, 85%
R = H, E / Z = 50:50, 75%
71%
+
4 mol % Pd(dba)2-dppe
, as above
Scheme 12
Br Me3Si
Br Me3Si
SiMe3
Br
Na DMSO
Me
CO2Et CO2Me
CHZZ Me3Si
CHZZ′
′ SiMe3
TiCl4 Me3Si
Me CO2Me
CO2Et
OH CO2Et +
4 mol % Pd(dba)2, dppe THF, NaCHZZ′
30 75%
+
31 69%
+ 85%
CH2Cl2, 78 °C, 2 h
33 49%
32
as above, but
as above THF,
_
Scheme 13
In these cases the interactions between R1and R2play the major role to determine the stereochemical outcome of the sequence of an intermolecular carbopalladation and an in- termolecular nucleophilic trapping. Some typical results are listed in Scheme 12. In the case of 29, the methyl group at the 2-position of the alkenyl bromide clearly shifts the equilibrium between anti-26and syn-26exclusively to anti-26(Scheme 12).[23]
Na+−CH(COOMe)2 DMF n-C7H15
n-C4H9 Br
n-C7H15
Bu-n
CO2Me CO2Me
n-C7H15
Bu-n
n-C7H15
Bu-n
MeO2C CO2Me Pd +
cat. Pd(dba)2, PPh3
a b
37% +
34
35 36
82 : 18 E/Z = 0:100 Scheme 14
The following points should be noted.[28](i) The yield is usually low in this reaction, mainly due to a homocoupling reaction of the 1-alkynyl bromide and polymerization.
(ii) The configuration of the carbon–carbon double bond in 35is exclusively Z(not E), indicating that the effect of the interaction between R1and R2in 26(Scheme 11) on the stereochemical outcome is replaced by that between R and the Pd residue[26]; that is, due to the linear spatial arrangement of R2, syn-26is exclusively formed in the reaction mix- ture. (iii) The regioselectivity is somewhat lower; however, with a less reactive nucle- ophile, the regioselectivity is 100% (Scheme 15).
n-C7H15
n-C4H9 Br
SO2Ph CO2Et
N 2 CO2Me
n-C7H15
Bu-n
+ Nu
cat. Pd (dba)2,PPh3
37 Nu =
THF, 65 °C, 24 h 36%
THF, 65 °C, 50 h 31%
NaNu
CPh
−
−
Scheme 15
Enol triflates, which can easily be prepared by trapping regiospecifically generated enolates with triflic anhydride or N-phenyl triflimide,[29],[30]have also been applied in car- bopalladation reactions of allenes (Scheme 16).[31],[32]
The Pd(0)-catalyzed reaction of the enol triflate of -tetralone with 1,2-propadiene in the presence of the enolate of 1,3-cyclopentadione afforded bicyclic precursors to the steroid skeleton 39. Under the catalysis of 10 mol % of Me3SiOTf at different tempera- tures, 39(R1H, R2Me) could be highly selectively converted into compounds 40or 41(Scheme 17).[33]–[35]
R
OTf Na
CO2Me CO2Me
CO2Me R
CO2Me +
cat. Pd(dba)2, PPh3, LiCl DMSO, 65 °C
38 R = H 85%
R = n-C7H15 80% (E/Z = 90:10)
−
Scheme 16 OTf
R1
O
O R2
O
O R2
O O
R1
+ +
cat. Pd(dba)2, PPh3
39
R1 = H, R2= H 50%
R1 = H, R2 = Me 76%
R1 = OMe, R2 = Me 94%
R2 = Me
40
41 +
10 mol % Me3SiOTf, CH2Cl2, 0 °C, 5 h 40 (54%) : 41 (2%) the same, but 25 °C 40 (0) : 41 (90%)
−
Scheme 17
Functional groups in allenes such as phenyl, Me3SiCH2, and methoxy are tolerated to afford the correspondingly functionalized 1,3-dienes in the Pd(0)-catalyzed reactions of the respective allenes with alkenyl bromides (Scheme 18).[36]
Using the enolate of the glycine equivalent methyl diphenylmethyleneaminoacetate 46 or of diethyl acetamidomalonate 49as nucleophiles, novel amino acid derivatives have been prepared from allenes (Scheme 19).[24],[25],[37]
Amines have also been applied as nucleophiles.[6],[38]Under the catalysis of the palla- dium, the o-iodobenzyl homopropargyl ether 52formed the seven-membered ring vinyl- palladium intermediate 53, which subsequently reacted with 1,2-propadiene in the pres- ence of a secondary amine to eventually afford 54(Scheme 20).[38]
Ph Br
Ph
CO2Et CO2Et
Me3Si
CO2Et CO2Et
EtO2C MeO
CO2Et H3C
EtOOC CO2Et Ph
Me3Si Br
+
44 as above
21%
MeO Br
+
45 as above, but DMSO
40 °C, 20 h 94%
+ cat. Pd(dba)2, dppe 65 °C, THF
+ +
42 43
E/Z = 35:65 91 : 9 Na+−CH(COOMe)2
Scheme 18
Br
CO2Me Ph N LiHC
Ph
I
CO2Et NHAc NaC CO2Et
I Br DMSO
DMSO
N
CO2Me Ph Ph
CO2Et NHAc
CO2Et
CO2Et NHAc
CO2Et CO2Me
Ph N
Ph 47 56%
+
46
THF, 65−70 °C
48 35%
THF, 65−70 °C
50 50%
+
49
51 40%
catalyst = 4 mol % Pd(dba)2 + 4 mol % dppe , cat.
, cat.
, cat.
, cat.
Scheme 19
O
I K
2CO3
O XPd
N HN OH
HNR2
O NR2 10 mol %
Pd(OAc)2 20 mol % PPh3
52 53 54
NR2 =
68%
71%
Scheme 20
O
I cat. Pd(0)toluene, 70 °C 20 h
55 56
N H
O
57 N +
43% 1 : 1.4 O N
Scheme 21
X Y I
N
H N
H
X Y
NR2
58 59
n
+ + HNR2
Et4NCl, K2CO3
n
X = NMe, Y = CO; X = NTs, Y = CH2; X = O, Y = CH2; X = CO, Y = NBu; X = CH2, Y = O.
NR2 = or n = 1,2
10 mol % Pd(OAc)2
mol % PPh3
20
Scheme 22
In a similar way, even the benzooxacyclooctene derivative 56with an eight-membered ring could be prepared, albeit in low yield along with the premature trapping product 57 (Scheme 21).[38]
Similar results involving o-(-alkenyl)phenyl iodides have also been reported to afford benzolactams and benzoannelated cyclic amines or ethers (Scheme 22).[39]
Sodium benzenesulfinate is also a nucleophile of choice (Scheme 23). The reaction provided an efficient route to allyl phenylsulfones 60, which are of synthetic impor- tance.[40]
Acylpalladium species formed in situvia the insertion of CO can also react inter- molecularly with an allene to form the corresponding -allylpalladium intermediate, which could be trapped with NaSO2Ph or N-phenyltosylamide to afford the ,- unsaturated ketones 61 and 62 with an allylsulfone and an allylamine moiety, respec- tively (Scheme 24).[41]
A five-component cascade reaction in which the last step is the trapping of a -allyl- palladium species with a nucleophile such as piperidine, pyrrolidine, morpholine, and NaBPh4afforded benzocyclopentenone derivatives 68(Scheme 25).[42]
DMSO
Br
S Br
Br
N OTf
Boc RX
SO2Ph R
RX + + PhSO2Na
cat. Pd(PPh3)4
60
75
20
75 65
70
72
59
69 Temperature ( °C) yield (%)
Scheme 23
S I
OMe I
N Ts
OMe O
Ph SO2Ph O
S 5% Pd(PPh3)4
+ CO 95%
61 (1 atm)
+
+ CO + PhNHTs as above 98%
62 Et4NCl,
NaSO2Ph, DMF
Scheme 24
I
PdX O
PdX O O
O O
PdX
NaBPh4
NaBPh4
O
Ph O
PdI CO
68 50%
67
66 63 64
10% Pd(OAc)2 20% PPh3, K2CO3, Et4NCl + CO +
65
Scheme 25
Ph
H H
Me
DMSO Ph
H Ph
CO2Me CO2Me Me H
+ PhI + Na CH(CO2Me)2
Pd(dba)2
Ligand Yield (ee) %
69
(S)-BINAP 42 (96)
(+)-MOD-DIOP 89 (90)
(R)-(S)-BPPFOAc 77 (95)
Scheme 26
Using 4 mol % of Pd(dba)2plus 4 mol % of a chiral phosphine ligand such as BINAP, DIOP, MOD-DIOP, and ferrocenyl phosphines, the reaction of PhI, ( )-1-phenyl-1,2- butadiene, and sodium dimethyl malonate afforded chiral nonracemic (S)-dimethyl 1- methyl-2,3-diphenylallyl malonate 69with up to 96% ee (Scheme 26).[43]