Chemoselective transfer of allyl or phenyl group from allyl(phenyl)germanes in Pd-catalyzed reactions with aryl halides

Article abstract of DOI:10.1246/cl.2011.967

Treatment of chloro(phenyl)germanes with allylmagnesium bromide yielded allyl(phenyl)germanes. Coupling of the allyl- (phenyl)germanes with aryl halides in 1,4-dioxane in the presence of aqueous NaOH and Pd catalyst resulted in Heck-type transfer of the allyl group providing the corresponding allylated aryls. On the other hand, reaction of allyl(phenyl)germanes with SbF₅ intercalated in graphite in toluene and subsequent treatment of the resulting germanyl fluorides with TBAF generates reactive hypervalent fluorogermanates that undergo Stille-like Pd-catalyzed cross-coupling with aryl halides in wet toluene to provide biaryls.

Full text of DOI:10.1246/cl.2011.967

doi:10.1246/cl.2011.967
Published on the web September 5, 2011
967
Chemoselective Transfer of Allyl or Phenyl Group from Allyl(phenyl)germanes
in Pd-catalyzed Reactions with Aryl Halides
Jean-Philippe Pitteloud, Yong Liang, and Stanislaw F. Wnuk*
Department of Chemistry and Biochemistry, Florida International University, Miami, Florida 33199, USA
(Received May 27, 2011; CL-110451; E-mail: wnuk@fiu.edu)
Treatment of chloro(phenyl)germanes with allylmagnesium
GeCln
MgBr
(n equiv)
n
Ge
4-n
bromide yielded allyl(phenyl)germanes. Coupling of the allyl-
(phenyl)germanes with aryl halides in 1,4-dioxane in the presence
of aqueous NaOH and Pd catalyst resulted in Heck-type transfer of
the allyl group providing the corresponding allylated aryls. On the
other hand, reaction of allyl(phenyl)germanes with SbF5 interca-
lated in graphite in toluene and subsequent treatment of the
resulting germanyl fluorides with TBAF generates reactive hyper-
valent fluorogermanates that undergo Stille-like Pd-catalyzed
cross-coupling with aryl halides in wet toluene to provide biaryls.
Et2O
0 °C or r.t.
4-n
1 n = 3 (85%)
2 n = 2 (94%)
3 n = 1 (92%)
PhMgBr (5 equiv)
Et2O
GeCl3
3 (44%)
Scheme 1. Synthesis of allyl(phenyl)germanes 1-3.
The application of organogermanes to Pd-catalyzed couplings
has thus far received much less attention1 than the couplings
involving organostannanes and organosilanes.2 This is due to the
lower reactivity of tetracoordinated organogermanium species, the
less developed syntheses of vinyl/aryl germanyl derivatives, and
the higher cost of germanium relative to silicon.3
Based on the available knowledge on the susceptibility of
organogermanes toward coupling, it appears that the coupling is
promoted either by: (i) intramolecular chelation of a pendant
Lewis basic heteroatom which renders the Ge center “permanent-
ly” pentavalent4-7 or (ii) the presence of at least one heteroatom
bound to the Ge center that renders the Ge center more susceptible
to coordination by an external Lewis basic ligand (e.g., fluoride,
hydroxide, etc.), thereby also rendering the Ge center penta-
valent.8-17 Although the effects of fluoride/base activation and Pd-
catalyst/ligand combination on the coupling of organogermanes
are still ambiguous, all but one4 successful example of germane
couplings with aryl/alkenyl halides involved activation with either
base or fluoride.
Recently we reported that trichloro(phenyl)-, dichloro(diphen-
yl)-, and chloro(triphenyl)germanes undergo Pd-catalyzed cross-
couplings with aryl bromides and iodides in the presence of TBAF
in toluene with addition of a measured amount of water. One
chloride ligand on the Ge center is sufficient to allow efficient
activation by fluoride and subsequent transfer of one, two or
three phenyl groups from the organogermane precursors.16,17 We
showed that arylchlorogermanes can render a coupling efficiency
comparable to that of the more established stannane and silane
counterparts and that their coupling efficiency reflected their
ability to generate reactive hypervalent intermediates upon fluoride
activation.17
Hiyama and co-workers utilized tri-, di-, and monoallyl(aryl)-
silanes in Pd-coupling with aryl halides to access biaryls.18 They
suggested that allylsilanes spontaneously cleave upon treatment
with TBAF and an appropriate amount of water to provide an
active silicate species that promotes transmetalation. Although the
chemistry of allylgermanes is well established,19,20 the application
of allyl organogermanes as substrates for the Pd-catalyzed cross-
coupling with aryl halides has not been investigated. Herein, we
report chemoselective application of tri-, di-, and monoallyl-
(phenyl)germanes toward Pd-catalyzed reactions.
Treatment of PhGeCl3, Ph2GeCl2, or Ph3GeCl with 3, 2, or 1
equiv of allylmagnesium bromide yielded stable triallyl(phenyl)-
germane (1), diallyl(diphenyl)germane (2), or allyl(triphenyl)ger-
mane (3), respectively (Scheme 1). Moreover, treatment of
allyl(trichloro)germane with phenylmagnesium bromide also
produced allyl(triphenyl)germane (3) (44%).21
Attempted coupling of triallyl(phenyl)germane (1) with aryl
iodides employing conditions used for the reactions of triallyl-
(phenyl)silanes18 (PdCl2/TBAF/PCy3/DMSO/H2O) or vinyltris-
(trimethylsilyl)germanes12 (NaOH/H2O/H2O2/[Pd(PPh3)4]/THF)
with ArX failed to yield biaryl products and resulted in the
recovery of 1. However, treatment of 1 with 1-butyl-4-iodoben-
zene (4a) (18 h, 95 °C), under conditions employed for the
coupling of trichloro(phenyl)germanes9 [NaOH (8 equiv)/H2O/
dioxane/Pd(OAc)2], yielded 1-allyl-4-butylbenzene (5a) resulting
from the transfer of the allyl group (Table 1, Entry 1). The ¡-
methyl vinyl isomer 6a was also formed (5a/6a; 55% total, 87:13).
These unexpected findings prompted us to examine the effect of
reaction parameters on the transfer of allyl group from germane
precursors 1-3.
Thus, treatment of 1 with 4a at higher concentrations of
NaOH afforded a regioisomeric mixture of 5a and 6a in higher
yields (Entries 2 and 3). The combination of NaOH and Pd catalyst
proved to be critical for the transfer of allyl groups from 1, since
reactions with only Pd(OAc)2 yielded product 5a in much lower
yield (Entry 4). The use of different Pd catalysts also gave
coupling products with similar yields and regioselectivity (Entries
5 and 6). Reactions employing Et3N and TBAF afforded 5a in
moderate yields (Entries 7 and 8). The ratio of isomers 5a/6a
seems to be independent of the reaction conditions. For example,
temperature has no effect on regioselectivity of the reaction of
allylgermane 1 with 4a. Thus, increasing the temperature from 50
to 70 to 95 °C increased the reaction rate but the same ratio of the
isomeric products 5a/6a (µ90:10) was observed after 1 h at all
temperatures and remained constant after prolonged heating.
To further investigate the transfer of the allyl group, the
reactions of allylgermanes 1, 2, or 3 with other aryl iodides 4a-4c
(1.05 equiv) were carried out (Table 2). We found that triallyl-
germane 1 gave higher yields of allylated aryl products 5a-5c
than diallylgermane 2, which in turn were more efficient than
Chem. Lett. 2011, 40, 967-969
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

968
Table 1. Effect of the various reaction parameters on the efficiency of
transferring allyl group from triallyl(phenyl)germane (1)a
Table 2. Allylation of aryl iodides with allyl(phenyl)germanes 1-3a
n
Ge
4-n
NaOH, Ar-I (4)
I
Pd, 1,4-dioxane
95 °C, 18 h
Ar
Ar
3
Ge
Base, Pd
1 n = 3
2 n = 2
3 n = 1
1,4-dioxane
95 °C, 18 h
5
6
Series a Ar = 4-BuC6H4
b Ar = 1-naphthyl
Bu
Bu
Bu
c Ar = 4-MeOC6H4
1
4a
6a
5a
Yield
Ratioc
5:6
Entry
Germane
Ar-I
Pd
Ratioc
5a:6a
/%b,c
Base
/equiv
Yield
/%b,c
Entry
Base
Pd
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
4a
4a
4a
4a
4a
4a
4b
4b
4b
4b
4b
4b
4c
4c
4c
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
78
47
32
80
55
33
73
51
29
88
69
40
90
37
15
82:18
82:18
86:14
86:14
85:15
85:15
90:10
90:10
91:9
91:9
92:8
93:7
79:21
76:24
73:27
1
2
3
4
5
6
7
8
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
Et3N
8
10
12
®
12
12
10
10
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)4
Pd2(dba)3
Pd(OAc)2
Pd(PPh3)4
55
60
84
15
78
85
32
42
87:13
89:11
82:18
94:6
84:16
86:14
83:17
82:18
TBAF
aCouplings were performed on 0.16 mmol scale of 1 (0.03 M) with
1.05 equiv of 4a and 0.08 equiv of Pd catalyst in dioxane (5 mL) and
a given stoichiometric amount of NaOH (2 M) or other bases.
d
e
f
bOverall yield of 5a and 6a. Determined by GC-MS of the crude
c
reaction mixture.
aCouplings were performed on 0.16 mmol scale of germanes 1-3
(0.03 M) with 1.05 equiv of aryl halides, 12 equiv of NaOH, and
allylgermane 3 in transferring allyl groups (e.g., Entries 1-3). The
use of Pd2(dba)3 afforded the products 5a-5c in slightly higher
yields, though the 5 to 6 regioselectivity was not improved (e.g.,
Entries 1-3 vs. 4-6). The bulkier 1-iodonaphthalene (4b) showed a
small enhancement in the regioselectivity as compared to 4a (e.g.,
Entry 1 vs. 7). Transfer of the allyl group from allylgermanes also
occurred efficiently with p-MeOC6H4I (4c) (Entries 13-15) but
failed with p-CF3C6H4I.
c
0.08 equiv of Pd catalyst. bOverall yield of 5a and 6a. Based on
GC-MS and 1H NMR of the purified reaction mixture. dWith
[Pd2(dba)3] (56%, 81:19). eWith [Pd2(dba)3] (39%, 79:21). fWith
[Pd2(dba)3] (14%, 80:20).
I
Since triallylgermane 1 could transfer up to three allyl
substituents in the reaction with aryl halides, experiments with 3
equiv of 1-iodonaphthalene (4b) were attempted. Thus, treatment
of 1 with 4b under the optimized conditions [NaOH (12 equiv)]
gave a mixture of 5b/6b (92%, 87:13, Scheme 2). Couplings of
diallylgermane 2 or allylgermane 3 with 3 equiv of 4b provided
isomers 5b/6b in 78% and 38%, respectively, in addition to
unchanged 4b. It is noteworthy that coupling yields increased
proportionally with the number of allyl groups present at the Ge
center (38% ¼ 78% ¼ 92%) while the isomeric ratios 5b/6b
remained similar. Since the overall yield for the couplings with
allylgermanes 1 and 2 never exceeded 100% (based on germanes
as limiting reagents), it seems likely that only one allyl group from
the germane substrates participated in the couplings.
It seems feasible that the formation of products 5 and 6 from
allyl(phenyl)germanes 1-3 in the presence of NaOH might follow
a Heck coupling mechanism. Allylgermatranes5 and allyltri-
methylsilanes22 were reported to undergo Heck reaction with aryl
halides via the initial addition of the aryl-Pd complex to a double
bond of the allyl group. Addition of the aryl group to a less
hindered £-carbon of the allyl substituent on germanes could
account for the observed regioselectivity. Coupling of vinyl-
tributylgermanes with aryl halides has recently been shown to
occur more efficiently under Heck than Stille conditions.7
In our search to find suitable conditions for the cleavage of
Ge-allyl bond and to generate reactive germanate species for
subsequent transmetalation, we found that treatment of allyl-
4b
n
Ge
4-n
(3 equiv)
NaOH/Pd(OAc)2
1,4-dioxane/95 °C/18 h
5b
6b
1 n = 3
2 n = 2
3 n = 1
5b/6b (92%, 87:13) from 1
5b/6b (78%, 89:11) from 2
5b/6b (38%, 92:8) from 3
Scheme 2. Coupling of allyl(phenyl)germanes 1-3 with excess of
1-iodonaphthalene (4b).
(phenyl)germanes 3 or 2 with SbF5 (0.25-0.5 equiv) intercalated in
graphite23 in toluene (0.5-1 h, 50 °C) resulted in disappearance of
the germane substrates (TLC, 1H NMR) and clean formation24,25 of
the fluorogermanes Ph3GeF (s, ¤ ¹202.3, 19F NMR) or Ph2GeF2
(2 © s, ¤ ¹165.2, and ¹167.4), respectively, with spectroscopic
data in agreement with the reported values.15,17 Analogous
treatment of 1 gave cluster of peaks at ¤ ¹140.2 to ¹159.7.
Treatment of the fluorogermane generated in situ from 2/SbF5
with 4b in TBAF/toluene resulted in transfer of phenyl groups
from Ge producing biaryl 7b in addition to the homocoupling by-
product 8b with no formation of the allylated product 5b (or 6b)
(Table 3). We found that addition of at least 3 equiv of TBAF
was required to produce 7b in maximum yield (Entries 1-5).
Apparently, selective cleavage of the Ge-allyl bond with SbF5 and
subsequent treatment of the resulting germanyl fluorides with
TBAF generates reactive hypervalent fluorogermanates that pro-
Chem. Lett. 2011, 40, 967-969
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

969
Table 3. SbF5-promoted coupling of diallyl(diphenyl)germane (2) with
1-iodonaphthalene (4b): Transfer of the phenyl groups from Gea
Table 4. SbF5-promoted coupling of germanes 1-3 with aryl halidesa
1. SbF5/C
toluene/50 °C/1 h
n
Ge
4-n
1. SbF5/C
toluene/50 °C/1 h
2. 1-iodonaphthalene (4b, 2 equiv)
[Pd2(dba)3]/TBAF/100 °C/18 h
m
Ar
Ar
m ArX
+
Ph
2. Pd/TBAF/100 °C
2
Ge
18 h/(H2O)
Ph
Ar
m = 1 (for 1)
m = 2 (for 2)
m = 3 (for 3)
1 n = 3
2 n = 2
3 n = 1
7b-d
8b-d
2
Yield Ratioc
7/%b,c
7:8
52 (45) 10:1
42 15:1
82 (71) 20:1
46 (41) 1.9:1
72 (62) 5.6:1
7b
8b
Ratiod
7b:8b
Entry Germane Ar-X
Product
TBAFb
/equiv
Yield
7b/%c,d
Entry
Germane
1
2
3
4
5
6
7
8
9
1
1
1
1
2
2
2
2
3
3
3
3
1-Iodonaphthalene
1-Bromonaphthalene
4-CH3OC6H4I
7b
7b
7c
7d
7b
7b
7c
7d
7b
7b
7c
7d
1
2
3
4
5
6
7
8
2
2
2
2
2
2
2
2
1
2
3
4
43
53
60 (54)
47
44
67 (59)
72 (62)
68
4.4:1
3.9:1
3.8:1
2.0:1
1.3:1
5.2:1
5.6:1
6.1:1
4-CF3C6H4I
1-Iodonaphthalene
1-Bromonaphthalene
4-CH3OC6H4I
34
45
33
2.3:1
2.8:1
1:1
5
3e
3f
3g
4-CF3C6H4I
1-Iodonaphthalene
1-Bromonaphthalene
4-CH3OC6H4I
71 (63)
14
32
4:1
3.3:1
1.6:1
10
11
12
aCouplings were performed on 0.14 mmol scale of germanes 2
(0.04 M) with 2 eqiuv of 4b and 0.05 equiv of Pd catalyst.
bCommercial 1 M THF solution containing 5% H2O. cBased upon
transferring of two phenyl groups from 2. Isolated yield in
parenthesis. Based on GC-MS of the crude reaction mixture. With
25 ¯L of H2O added. With 50 ¯L H2O. With 75 ¯L H2O.
4-CF3C6H4I
22
1:1.5
aCouplings were performed on 0.14 mmol scale of germanes (1-3;
0.04 M) with 0.05 equiv of Pd2(dba)3 catalyst and 1.0 (for 1), 2.0 (for
2), or 3.0 (for 3) equiv of halides and TBAF/(1 M/THF, 3 equiv)/
water (50 ¯L). bBased upon transferring of one, two, or three phenyl
groups from 1, 2, or 3, respectively. Isolated yield in parenthesis.
cDetermined by GC-MS of the crude reaction mixture.
d
e
f
g
mote transmetalation via a Stille-like mechanism. Treatment of 2
with SbF5/C alone, as a fluoride source, failed to produce cross-
coupling product 7b. The yield increased when couplings were
performed with addition of a measured amount of water (µ10-30
equiv; Entries 6-8), as observed before for couplings with
chloro(phenyl)germanes.16,17 The SbF5/TBAF combination in
moist toluene allowed transfer of two phenyl groups from germane
2, as expected based on the couplings of Ph2GeCl2 with aryl
halides promoted by TBAF.17
One-pot treatment of germanes 1, 2, or 3 with SbF5/C
followed by Pd-catalyzed (TBAF/moist toluene) reactions with 1,
2, or 3 equiv of aryl halides, respectively afforded various biaryls
7b-7d in good yields and regioselectivity (Table 4). Couplings
with 1-bromonaphthalene also afforded 7b although in lower
yields than with iodonaphthalene.
In summary, we have developed two chemoselective Pd-
catalyzed reactions with allyl(phenyl)germanes. One reaction
allows for the selective transfer of the allyl group in the reaction
with aryl halides mediated by NaOH providing allylaryls, while
the second reaction allows for the selective transfer of the phenyl
group from Ge center yielding biaryls upon treatment with SbF5/C
and TBAF.
Rappoport, John Wiley & Sons, Chichester, 2002, Vol. 2.
M. Kosugi, T. Tanji, Y. Tanaka, A. Yoshida, K. Fugami, M. Kameyama,
T. Migita, J. Organomet. Chem. 1996, 508, 255.
J. W. Faller, R. G. Kultyshev, Organometallics 2002, 21, 5911.
J. W. Faller, R. G. Kultyshev, J. Parr, Tetrahedron Lett. 2003, 44, 451.
N. M. Torres, J. M. Lavis, R. E. Maleczka, Jr., Tetrahedron Lett. 2009,
50, 4407.
T. Nakamura, H. Kinoshita, H. Shinokubo, K. Oshima, Org. Lett. 2002,
4, 3165.
T. Enokido, K. Fugami, M. Endo, M. Kameyama, M. Kosugi, Adv.
Synth. Catal. 2004, 346, 1685.
4
5
6
7
8
9
10 M. Endo, K. Fugami, T. Enokido, H. Sano, M. Kosugi, Adv. Synth.
Catal. 2007, 349, 1025.
11 S. F. Wnuk, P. I. Garcia, Jr., Z. Wang, Org. Lett. 2004, 6, 2047.
12 Z. Wang, S. F. Wnuk, J. Org. Chem. 2005, 70, 3281.
13 Z. Wang, A. Gonzalez, S. F. Wnuk, Tetrahedron Lett. 2005, 46, 5313.
14 A. C. Spivey, C.-C. Tseng, J. P. Hannah, C. J. G. Gripton, P. de Fraine,
N. J. Parr, J. J. Scicinski, Chem. Commun. 2007, 2926.
15 A. C. Spivey, C. J. G. Gripton, J. P. Hannah, C.-C. Tseng, P. de Fraine,
N. J. Parr, J. J. Scicinski, Appl. Organomet. Chem. 2007, 21, 572.
16 Z.-T. Zhang, J.-P. Pitteloud, L. Cabrera, Y. Liang, M. Toribio, S. F.
Wnuk, Org. Lett. 2010, 12, 816.
17 J.-P. Pitteloud, Z.-T. Zhang, Y. Liang, L. Cabrera, S. F. Wnuk, J. Org.
Chem. 2010, 75, 8199.
18 A. K. Sahoo, T. Oda, Y. Nakao, T. Hiyama, Adv. Synth. Catal. 2004,
346, 1715.
19 A. C. Spivey, C. M. Diaper, Sci. Synth. 2003, 5, 181.
20 T. Akiyama, in Main Group Metals in Organic Synthesis, ed. by H.
Yamamoto, K. Oshima, Wiley-VCH, Weinheim, 2004, Vol. 2, pp. 593-
619.
21 Supporting Information is available electronically on the CSJ-Journal
Web site, http://www.csj.jp/journals/chem-lett/index.html.
22 K. Karabelas, C. Westerlund, A. Hallberg, J. Org. Chem. 1985, 50,
3896.
This work was supported by an award from NIH/NCI
(5SC1CA138176) and FIU University Graduate School Dis-
sertation Year Fellowship to JPP.
This paper is in celebration of the 2010 Nobel Prize awarded
to Professors Richard F. Heck, Akira Suzuki, and Ei-ichi Negishi.
References and Notes
1
2
3
A. C. Spivey, C. J. G. Gripton, J. P. Hannah, Curr. Org. Synth. 2004, 1,
211.
Metal-Catalyzed Cross-Coupling Reactions, ed. by A. de Meijere, F.
Diederich, Wiley-VCH, Weinheim, Germany, 2004.
The Chemistry of Organic Germanium, Tin and Lead Compounds, ed.
by S. Patai, John Wiley & Sons, Chichester, 1995, Vol. 1; The
Chemistry of Organic Germanium, Tin and Lead Compounds, ed. by Z.
23 R. J. P. Corriu, J. M. Fernandez, C. Guerin, J. Organomet. Chem. 1980,
192, 347.
24 Activated C(sp3)-Ge bonds in allylgermanes can be cleaved in the
presence of Lewis acids.20,23
25 Treatment of 115 or 2 with TBAF did not affect cleavage of Ge-allyl
1
bond(s) since formation of fluorogermane(s) was not observed on H or
19F NMRs.
Chem. Lett. 2011, 40, 967-969
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/