Polyphenylene as an electron transfer catalyst in lithiation processes

Article abstract of DOI:10.1016/S0040-4020(02)00620-8

The lithiation of different functionalised chlorinated materials (1a-c), dichlorinated compounds (1d-f) and benzofused cyclic ethers (1g,h) with lithium powder in the presence of catalytic amounts of either linear (LPP) or crosslinked (CPP) polyphenylene, in THF at temperatures ranging between -78 and 20°C, leads to the expected organolithium intermediates (Ia-h), which by reaction with electrophiles [Bu^tCHO, PhCHO, Et₂CO, (CH₂)₅CO, PhCOMe, Me₃SiCl] gives, after hydrolysis with water, the expected products 2aa-hf.

Full text of DOI:10.1016/S0040-4020(02)00620-8

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 6207±6210
Polyphenylene as an electron transfer catalyst in
lithiation processes
p
Miguel Yus, Cecilia G o mez and Pablo Candela
Departamento de Qu Âõ mica Org a nica, Facultad de Ciencias, Universidad de Alicante, Apdo. 99, E-03080 Alicante, Spain
Dedicated to Professor Dieter Hoppe on the occasion of his 60th birthday
Received 11 January 2002; revised 28 February 2002; accepted 29 March 2002
AbstractÐThe lithiation of different functionalised chlorinated materials (1a±c), dichlorinated compounds (1d±f) and benzofused cyclic
ethers (1g,h) with lithium powder in the presence of catalytic amounts of either linear (LPP) or crosslinked (CPP) polyphenylene, in THF at
temperatures ranging between 278 and 208C, leads to the expected organolithium intermediates (Ia±h), which by reaction with electrophiles
t
[
Elsevier Science Ltd. All rights reserved.
Bu CHO, PhCHO, Et
2
CO, (CH
2
)
5
CO, PhCOMe, Me
3
SiCl] gives, after hydrolysis with water, the expected products 2aa±hf. q 2002
1
1
1
. Introduction
sary to work under Barbier-type reaction conditions, that
is, in the presence of the electrophile in order to avoid
decomposition of the corresponding organolithium inter-
mediates. One further improvement of the arene-catalysed
lithiation is the use of a naphthalene- or biphenyl-supported
Organolithium intermediates are important reagents in
synthetic organic chemistry as a versatile source of car-
banionic species. Their use, especially in carbon±carbon
1
1
2
formation reactions, has been increased in the last years by
using functionalised organolithium compounds. In this
polymer as a catalyst. In this case, the insoluble electron
transfer agent can be removed at the end of the reaction by
simple ®ltration. In this paper, we report on the use for the
®rst time of oligomers of polyphenylene, very easily avail-
able, as catalysts in lithiation processes. In this case, the
polymeric catalyst contains only aromatic rings without
any spacer between them, being prepared by a polyconden-
2
case, the reaction of these intermediates bearing a function-
ality with electrophilic reagents allows the direct prepara-
tion of polyfunctionalised molecules. Apart from problems
concerning the compatibility between the functional group
and the carbon±lithium bond, one inherent problem asso-
ciated with the preparation of very reactive functionalised
organolithium compounds is the lithiation at low tempera-
tures. In many cases, this process does not work using
1
2
sation method instead of by an ole®n polymerisation.
3
lithium metal and it is necessary to activate the metal in
2. Results and discussion
order to get the desired lithiation. During the last few years,
two methodologies have been developed in order to activate
lithium: (a) the use of a stoichiometric amount of an arene,
4
Linear polyphenylene (LPP) was prepared according to the
1
3
5
procedure described by Yamamoto as a yellow powder by
reaction of 1,4-dibromobenzene with magnesium under
THF re¯ux, followed by treatment with a catalytic amount
what is called lithium-arene or lithium arenide; (b) the use
of a substoichiometric (catalytic) amount of the same
6
,7
0
naphthalene and 4,4 -di-tert-butylbiphenyl
arene,
DTBB) being in both cases the most commonly used
1
4
of NiCl (PPh ) . From its elemental analysis [(C H) ]
2
3 2
1.2
n
(
and its IRdata, this compound seems to be an oligomer of
ca. four aromatic rings per two bromine atoms. In order to
change the properties of this oligomer, we also prepared
another polymer using a 5% of 1,3,5-tribromobenzene as
crosslinking agent, so crosslinked polyphenylene (CPP)
was also isolated as a yellow solid. In this case, the elemen-
arenes. We have extensively applied the second (b) method-
ology in the following areas: (1) to prepare organolithium
reagents from non-halogenated materials; (2) to prepare
8
functionalised organolithium compounds (by halogen±
2
9
lithium exchange or by ring opening of heterocycles );
1
0
(3) to generate polylithiated synthons; and (4) to activate
other metals, especially nickel. In some cases, it is neces-
1
4
3
c
tal analysis [(C H) ] and IRdata correspond to the
1.4 n
existence of ca. 12 aromatic rings per two bromine atoms.
This second compound seems to be more similar than poly-
phenylene of high molecular weight.
1
4
Keywords: catalysis; electron transfer; lithiation; lithium; polyphenylene.
Corresponding author. Tel.: 134-9-6590-3548; fax: 134-9-6590-3549;
e-mail: yus@ua.es
p
With these two polymers in hand we studied their use as
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00620-8

6208
M. Yus et al. / Tetrahedron 58 (2002) 6207±6210
electron transfer catalysts in the following three lithiation
reactions:
hydrolysis, the expected hydroxyacetals 2aa±bc (Chart 3
and Table 1, entries 1±4) and hydroxyethers 2cc,cd (Chart
3
and Table 1, entries 5 and 6).
Preparation of functionalised organolithium compounds by
chlorine±lithium exchange catalysed by LPP or CPP,
starting from chloroacetals 1a and 1b or the chloroether
In situ generation of dilithiated synthons by LPP- or CPP-
catalysed lithiation of dichlorinated materials 1d±f (Chart
1) under Barbier-type reaction conditions, in the presence of
the corresponding electrophiles [Et CO, (CH ) CO,
1
c (Chart 1) in THF at 2788C. The corresponding inter-
mediates Ia±c (Chart 2) reacted with carbonyl compounds
Et CO, (CH ) CO, PhCHO, PhCOMe] to give, after
2
2 5
[
Me SiCl] in THF at 2788C, so the expected products
3
2
2 5
Chart 1. Starting materials used in the LPP- and CPP-catalysed lithiation.
Chart 2. Intermediates involved in the lithiation of compounds 1.
Chart 3. Compounds 2 prepared from starting materials 1.

M. Yus et al. / Tetrahedron 58 (2002) 6207±6210
6209
Table 1. Preparation of compounds 2
a
b
c
d
Entry
Starting material
Catalyst
Intermediate
Electrophile
Product 2
e
f
No.
Yield (%)
Reference
1
2
3
4
5
6
7
8
9
1a
1a
1b
1b
1c
1c
1d
1d
1e
1f
1g
1g
1g
1g
1g
1h
1h
LPP
CPP
CPP
CPP
CPP
CPP
LPP
LPP
CPP
CPP
CPP
CPP
CPP
CPP
CPP
CPP
CPP
Ia
Ia
Ib
Ib
Ic
Ic
Id
Id
Ie
If
Ig
Ig
Ig
Ig
Ig
Ih
Ih
Et
(CH
(CH
PhCHO
PhCHO
PhCOMe
2
CO
2aa
2ab
2bb
2bc
2cc
2cd
2da
2db
2ee
2fe
2ga
2gb
2gc
2gd
2gf
64 [46]
65 [70±79]
46 [61]
64 [51]
91 [84]
75 [91]
66 [72]
15
15
16
16
17
17
18
18
19
19
20
20
20
20
20
21
21
2
)
)
5
CO
CO
2
5
Et
2
CO
g
(CH
Me
Me
2
)
5
CO
92, 79 [67]
3
SiCl
SiCl
44 [78]
65 [83]
60 [74]
66 [51]
61 [68]
56 [63]
66 [56]
49 [53]
53 [59]
10
11
12
13
14
15
16
17
3
Et
2
CO
) CO
2 5
(CH
PhCHO
PhCOMe
t
Bu CHO
(CH
2
)
5
CO
2hb
2hf
t
Bu CHO
a
b
c
d
e
See Chart 1.
LPP: linear polyphenylene; CPP: crosslinked polyphenylene.
See Chart 2.
See Chart 3.
Isolated crude yield (.90% pure from 300 MHz H NMRand/or GLC) for entries 1±10 and isolated yield ( .95% pure from 300 MHz H NMRand/or GLC)
after column chromatography (silica gel, hexane/ethyl acetate) for entries 11±17, based on the starting material 1; in square brackets, isolated yields
corresponding to the reaction performed with the arene (naphthalene or DTBB) in solution.
1
1
f
Literature reference for the same reaction using the arene catalyst in solution.
Yield after reusing the same polymeric catalyst.
g
2
da±fe were obtained after hydrolysis (Chart 3 and Table 1,
3. Conclusion
entries 7±10). In this case we really do not know if
dilithiated species Id±f are involved in the process (the
process can also take place following a double sequence
From the results included in this paper we conclude than
polyphenylene, either in a linear (LPP) or crosslinked (CPP)
form, is an adequate electron transfer catalyst in lithiation
reactions, both by chlorine±lithium exchange or by ring
opening of oxygen-containing heterocycles, its ef®ciency
being comparable to the reaction using an arene in catalytic
amount but in solution or other polymer supported arene
catalysts.
of lithiation±S -reaction), but at the end we can introduce
E
as many electrophilic fragments as chlorine atoms are
present in the starting material, giving the corresponding
products 2da±fe.
Ring opening of benzofused cyclic ethers such as phthalan
(
1g) and isochroman (1h) (Chart 1). The CPP-catalysed
lithiation of these systems in THF at 08C (for 1g) or room
temperature (for 1h) give the corresponding intermediates
Ig,h (Chart 2), which upon treatment with different electro-
philic reagents [Et CO, (CH ) CO, PhCHO, PhCOMe,
4. Experimental
4.1. General
2
2 5
t
Bu CHO] and ®nal hydrolysis gave the expected compounds
ga±hf (Chart 3 and Table 1, entries 11±17).
2
For general information, see Ref. 23.
Some general comments can be done from the results shown
in Table 1. First of all, yields using LPP or CPP are com-
parable to the reaction carried out in solution (Table 1,
footnotes e and f). Secondly, both catalysts (LPP and
CPP) work with similar yields, being possible to reuse
then in a second catalysed lithiation (Table 1, footnote g).
One possible reason for the slight loose of catalyst activity
can be attributed to the presence of the bromine atoms in the
catalyst structure, which can give undesirable by-reactions
4.2. Preparation of linear (LPP) and crosslinked (CPP)
polyphenylene13
To a suspension of magnesium (0.29 g, 12 mmol) in THF
(2 mL) was added 1,2-dibromoethane (50 mL). Then, a
solution of 1,4-dibromobenzene (2.95 g, 12 mmol) in THF
(5 mL) was added and the resulting mixture was re¯uxed for
2 h. A solution of NiCl (PPh ) (10 mg) in THF (5 mL) was
2
3 2
added dropwise and the polymerisation was completed after
re¯uxing 1 h. The reaction mixture was hydrolysed with
2 M HCl (10 mL) and the precipitated polymer was
collected over a glass ®lter and dried in vacuo to yield linear
polyphenylene (LPP, 0.94 g) as a yellow powder.
2
2
(
general advantage of the procedure described here, common
lithiation followed by S or condensation reactions). One
E
1
2
to the use of other insoluble polymer supported catalysts,
is that the catalyst can be easily removed at the end of the
reaction by simple ®ltration. Finally, this is the ®rst time
wherein a polymeric electron transfer catalyst is used in the
reductive opening of heterocyclic precursors.
Crosslinked polyphenylene (CPP, 1.07 g) was prepared as
described above for LPP but adding 1,3,5-tribromobenzene

6210
M. Yus et al. / Tetrahedron 58 (2002) 6207±6210
(0.193 g, 0.6 mmol) as crosslinking agent together with 1,4-
dibromobenzene.
Spanish Ministerio de Educaci o n y Cultura (MEC) (project
no. PB-97-0133). P. C. thanks the University of Alicante for
®
nancial support.
4
.2.1. Linear polyphenylene (LPP). n (KBr) 3026, 1585,
1
2
479, 810 (CvC±H), 1072 cm (C±Br). HRMS (EI),
1
Found: 76.0323 (1%), C H requires 76.0313; 152.0618
(7%), C H
8
C H Br requires 230.9808; 304.1247 (8%), C H16
1
4
6
References
1
requires 152.0626; 230.9856 (15%),
1
1
2
1
1
2
8
24
1 (a) Wake®eld, B. J. Organolithium Methods; Academic:
London, 1988. (b) Lithium Chemistry: A Theoretical and
Experimental Overview; Sapse, A.-M., von Ragu e Schleyer,
P., Eds.; Wiley: Chichester, 1995. (c) Bartsab, R.; Drost, C.;
Klingebiel, U. Synthetic Methods of Organometallic and
Inorganic Chemistry; Herrmann, W. A., Ed.; George Thieme:
Stuttgart, 1996; Vol. 2, pp 1±23.
2. (a) N a jera, C.; Yus, M. Trends Org. Chem. 1991, 2, 155.
(b) N a jera, C.; Yus, M. Recent Res. Devel. Org. Chem.
1997, 1, 67.
3. (a) F uÈ rstner, A. Angew. Chem. Int. Ed. Engl. 1993, 32, 164.
(b) Cintas, P. Activated Metals in Organic Synthesis; CRC:
Boca Rat o n, 1993. (c) Active Metals; F uÈ rstner, A., Ed.; VCH:
Weinheim, 1996. (d) Guijarro, A.; G o mez, C.; Yus, M. Trends
Org. Chem. 2000, 8, 65.
requires 304.1252. Anal. found: C, 60.60; H, 4.23; calcd
for (C H Br ) : C, 62.10; H, 3.45.
2
4
16 2 n
4
1
.2.2. Crosslinked polyphenylene (CPP). n (KBr) 3027,
1
2
592, 1479, 807 (CvC±H), 1074 cm (C±Br). HRMS
1
(
EI), Found: 152.0601 (45%), C H requires 152.0626;
12 8
1
2
26.0804 (42%), C H
requires 226.0783; 228.0956
requires 228.0939; 230.9856 (34%),
1
8
10
1
(34%), C H
18 12
C H Br requires 230.9808; 300.0912 (33%), C H
requires 300.0939; 380.1599 (7%), C H
0
3
4
1
1
1
2
8
24 12
1
20
1
requires
requires
3
80.1565; 461.9640 (100%), C H Br
2
2
4
16
61.9619. Anal. found: C, 80.77; H, 4.84; calcd for
(
C H Br ) : C, 80.61; H, 4.48.
72 48 2 n
4.3. LPP- or CPP-catalysed lithiation of starting
materials 1. Isolation of compounds 2
4. Holy, N. L. Chem. Rev. 1974, 74, 243.
5. Cohen, T.; Bhupathy, M. Acc. Chem. Res. 1989, 22, 152.
6
. (a) Yus, M. Chem. Soc. Rev. 1996, 155. (b) Ram o n, D. J.; Yus,
M. Eur. J. Org. Chem. 2000, 225 (Microreview). (c) Yus, M.
Synlett 2001, 1197 (Account). (d) Yus, M.; Ram o n, D. J. Latv.
J. Chem. 2002, 79.
Two-step preparation of compounds 2aa±cd,2ga±
gf,2hb,hf: general procedure. To a suspension of lithium
powder (0.125 g, 18 mmol) and the corresponding polymer,
LPP or CPP (30 mg), in THF (4 mL) was added 2 mmol of
the corresponding starting material at different temperatures
7. Mechanistic study: (a) Yus, M.; Herrera, R. P.; Guijarro, A.
Tetrahedron Lett. 2001, 42, 3455. (b) Yus, M.; Herrera, R. P.;
Guijarro, A. Chem. Eur. J., 2002, 8, 2574.
[
2788C (1a±c), 08C (1g) and 208C (1h)] and the mixture
was stirred for 1 h at the same temperature. Then, the corre-
sponding electrophile (2.2 mmol) was added at 2788C, the
mixture was stirred 1 h at the same temperature and hydro-
lysed with water (5 mL). The polymer was ®ltered off and
the solution neutralised with 2 M HCl and extracted with
ethyl acetate (3£10 mL). The organic layer was dried over
anhydrous Na SO and evaporated at reduced pressure
8. Guijarro, D.; Yus, M. Recent Res. Dev. Org. Chem. 1998, 2,
713.
9. Yus, M.; Foubelo, F. Rev. Heteroatom. Chem. 1997, 17, 73.
10. Foubelo, F.; Yus, M. Trends Org. Chem. 1998, 7, 1.
11. Alonso, F.; Yus, M. Recent Res. Dev. Org. Chem. 1997, 1,
397.
12. (a) G o mez, C.; Ruiz, S.; Yus, M. Tetrahedron Lett. 1998, 39,
397. (b) G o mez, C.; Ruiz, S.; Yus, M. Tetrahedron 1999, 55,
7017.
2
4
(
indicated in Table 1. Compounds 2aa,ab, 2bb,bc,
2
15 Torr) to obtain the expected products with the yields
1
5
16
1
cc,cd, 2ga±gf, and 2hb,hf, previously prepared in
7
20
21
13. Yamamoto, T.; Yamamoto, A. Chem. Lett. 1977, 353.
14. Theoretical ®gures for polyphenylene [±(C H ) ±] would be
our laboratory, were identi®ed by comparison of their
spectroscopic data with authentic samples.
6
4 n
C1.5H.
5. Gil, J. F.; Ram o n, D. J.; Yus, M. Tetrahedron 1993, 49, 4923.
1
Preparation of compounds 2da±fe under Barbier-type
reaction conditions: general procedure. To a suspension
of lithium powder (0.125 g, 18 mmol) and the correspond-
ing polymer, LPP or CPP (30 mg), in THF (4 mL) was
added a solution of the corresponding electrophile
16. (a) Ram o n, D. J.; Yus, M. Tetrahedron Lett. 1990, 31, 3763.
(b) Ram o n, D. J.; Yus, M. J. Org. Chem. 1991, 56, 3825.
17. (a) Guijarro, A.; Yus, M. Tetrahedron Lett. 1993, 34, 3487.
(b) Guijarro, A.; Manche nÄ o, B.; Ortiz, J.; Yus, M. Tetrahedron
1996, 52, 1643.
(
(
2.2 mmol) and the dichlorinated starting material 1d±f
1 mmol) at 2788C and the resulting mixture was stirred
18. (a) Ram o n, D. J.; Yus, M. Tetrahedron Lett. 1992, 33, 2217.
(b) G o mez, C.; Ram o n, D. J.; Yus, M. Tetrahedron 1993, 49,
4117. (c) Alonso, F.; Lorenzo, E.; Yus, M. Tetrahedron Lett.
1997, 38, 2187.
19. (a) G o mez, C.; Huerta, F. F.; Yus, M. Tetrahedron Lett. 1997,
38, 687. (b) G o mez, C.; Huerta, F. F.; Yus, M. Tetrahedron
1998, 54, 1853.
allowing the temperature to rise to 208C. Then, it was hydro-
lysed and worked up, as it was described above for the two-
step procedure, to obtain the expected products with the
1
8
yields indicated in Table 1. Compounds 2da,db, and
1
9
2
ee,fe, previously prepared in our laboratory, were identi-
ed by comparison of their spectroscopic data with
authentic samples.
®
20. Almena, J.; Foubelo, F.; Yus, M. Tetrahedron 1995, 51, 3351.
21. Almena, J.; Foubelo, F.; Yus, M. Tetrahedron 1995, 51, 3365.
2
2. We thank one of the referees for calling our attention to this
possible explanation for the loose of activity of the catalyst.
Acknowledgements
This work was ®nancially supported by the DGES from the
23. (a) Prieto, O.; Ram o n, D. J.; Yus, M. Tetrahedron: Asymmetry
000, 11, 1629. (b) Yus, M.; Mart Âõ nez, P.; Guijarro, D.
Tetrahedron 2001, 57, 10119.
2