CU(I)-Catalyzed regioselective synthesis of substituted allyl furans and thiophenes using organostannanes

Article abstract of DOI:10.1055/s-1999-2984

2-Allyl-substituted furans and thiophenes were efficiently synthesized from organostannyl derivatives as starting materials using Cu(I) as catalyst. The effect of DMF and NMP as solvents are discussed, as well as other solvent and temperature effects.

Full text of DOI:10.1055/s-1999-2984

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942
LETTER
Cu(I)-Catalyzed Regioselective Synthesis of Substituted Allyl Furans and
Thiophenes Using Organostannanes
Norma S. Nudelman,* Cecilia Carro
Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pab. II, P.3, C. Universitaria,
1
428 Buenos Aires, Argentina
Received 15 September 1999
Abstract: 2-Allyl-substituted furans and thiophenes were efficient-
ly synthesized from organostannyl derivatives as starting materials
using Cu(I) as catalyst. The effect of DMF and NMP as solvents are
discussed, as well as other solvent and temperature effects.
Key words: furans, thiophenes, copper catalyst, organostannanes
Furans with functionalized C2 substituents are of interest
as intermediates for the synthesis of various natural prod-
ucts and can also serve as pivotal intermediates in synthet-
ic strategy by virtue of their specific chemistry and latent
1
,2
functionality. The Pd-catalyzed cross-coupling of or-
ganic electrophiles such as vinyl halides or triflates with
3
organostannanes (Stille reaction) has become an ex-
tremely powerful tool in organic synthesis and this reac-
tion has been extensively used to the synthesis of
substituted furans and thiophenes. The cross-coupling of
different organic halides with heterocyclic stannanes has
4
been reported.
Recently, the beneficial influence of co-catalytic Cu(I) on
nonproductive or sluggish Stille cross-coupling reaction
5
-9
catalyzed by palladium has been reported as well as the
cross-coupling mediated by stoichiometric amounts of
1
0,11
copper salts.
The use of catalytic amounts of CuX in In a first set of experiments, the copper catalyzed cross-
12
the presence NaCl was recently reported and we have coupling of 2-(tributylstannyl)furan, 1a, with allyl bro-
previously described a Cu(I) catalyzed methodology for mide, 2a, was fully examined to find the best reaction con-
C-C bond formation using α-heteroactivated-aliphatic ditions. Table 1 shows the several solvents and binary
1
3
stannyl derivatives.
mixtures that were tested, changes in reaction times and
temperature were also examined. It can be observed in Ta-
ble 1 the remarkable effect of adding HMPA (entries 1,8)
or NMP (e.g. entries 1, 10; 2, 9; etc.) to the THF.
Nevertheless in spite of the potential utility of the use of
Cu(I) as unique catalyst, this modification to the Stille
reaction have not been examined for the synthesis of al-
1
4
lyl-substituted furans and thiophenes. The present paper Increasing the reaction time from 1 h to 14 h has not a
reports the cross-coupling of 2-(tributyl stannyl)furan and highly convenient effect (see entries 10, 12); in pure NMP
2
-(tributylstannyl)thiophene with allyl halides in the pres- the yield rises up to 82% in only one hour, following the
ence of catalytic amount of CuCl (10 mol%) (without any reaction for more than one hour did not improve the yield.
Pd catalyst) as an efficient method for the synthesis of al- A small increase in yield was observed by increasing the
lyl-substituted furans and thiophenes (Scheme 1).
temperature (entries 13, 14); some recovery of the reagent
was observed after 1 hour but on longer reaction times at
9
0 °C decomposition of both, the reactant and the cou-
pling product, occurs (Table 1, entries 15, 16). Under
these reaction conditions, no homocoupling of stannane
was observed and the only side-products were furan or
thiophene and Bu SnX.
3
It was clear that NMP was the solvent of election and the
reactions of 2-(tributylstannyl)furan, 1a, and 2-(tributyl-
stannyl) thiophene, 1b, with different allyl halides using
Scheme 1
Synlett 1999, No. 12, 1942–1944 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Cu(I)-Catalyzed Regioselective Synthesis of Substituted Allyl Furans and Thiophenes
1943
synthesis, and rapid reactions. This new process provides
allylfurans and thiophenes in good yields under neutral re-
action conditions.
Acknowledgement
C. Carro is a grateful recipient of a National Research Council from
Argentina (CONICET) fellowship. Financial support from the Na-
tional Research Council (CONICET), the Universidad de Buenos
Aires (UBA), the Agency for the Promotion of Science and Tech-
nology and the European Community is gratefully acknowledged.
References and Notes
(
(
(
1) Keay, B. A.; Dibble, P. W. in Comprehensive Heterocyclic
Chemistry, Katritzky, A. R.; Rees, C. W.; Seriven, E. F. Eds.,
Pergamon Press: New York, 1996, Vol 2.
2) Russell, R.; Press, J. B. in Comprehensive Heterocyclic
Chemistry, Katritzky, A. R.; Rees, C. W.; Seriven, E. F. Eds.,
Pergamon Press: New York, 1996, Vol 2.
3) For reviews on Stille reaction see: a) Farina, V.;
Krishnamurphy, V.; Scott, W. J. Organic Reactions 1997, 50,
John Wiley & Sons, New York. b) Mitchel T. Synthesis 1992,
803-815. c) Nudelman, N. S. “The Carbonylation of Main
Group Organometallic Compounds”, in The Chemistry of
Double-Bonded Funcional Groups, Patai, S. Ed., Wiley:
Chichester 1989.
4) a) Roth, G.; Farina, V. Tetrahedron Lett. 1995, 36, 2191-2194.
b) Yang, Y.; Wong, H. Tetrahedron. 1994, 50, 9583-9608. c)
Clough, J. M.; Mann, I. S.; Widdowson, D. A. Tetrahedron
Lett. 1987, 28, 2645. d) Katsumura, S.; Fumiwara, S.; Isoe, S.
Tetrahedron Lett. 1988, 29, 1173.
CuCl as catalyst were studied, the results are summarized
in Table 2. High yields of the coupling product, 3a-f, are
1
5
obtained by the general procedure, similar results were
found by using either allyl chloride or bromide. On the
contrary, in the absence of CuCl, the reaction between 1a
and 2a did not proceed at all, and 99% of 1a was recov-
ered after 7.5 hs (in NMP, at 90 °C). It can be observed
that the use of DMF gives similar results (Table 2). The
reaction mixtures were carefully examined looking for
isomeric product. For the allylic systems tested, the reac-
tion is highly regioselective and coupling only occurs in
the α position, products arising via an allylic rearrange-
ment were never observed. Considering E/Z selectivity,
for cases were two isomeric products are likely (eg. 2b
and 2c) only the E isomers were obtained. The reaction of
Z-1-bromo-2-pentene with 1b gave the coupling product
in 83% and only the Z-isomer was observed.
(
(
(
5) Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebeskind,
L. S. J. Org. Chem. 1994, 59, 5905-5911.
6) a) Liebeskind, L. S.; Riesinger, S. W. J. Org. Chem. 1993, 58,
408-413. b) Liebeskind, L. S.; Fengl, R. W. Ibid. 1990, 55,
5359-5364.
(
7) Ye, J.H.; Bhatt, R. K.; Falk, J. R. J. Am. Chem. Soc. 1994, 116,
1-5.
(
(
8) Saa, J. M.; Martorell, G. J. Org. Chem. 1993, 58, 1963-1966.
9) Hinkle, R. J.; Poulter, G. T.; Stang, P. J. J. Am. Chem. Soc.
1993, 115, 11626-11627.
6
b
In the original disclosure of the copper effect, it was sug-
gested that transmetallation of the R group from RSnBu3
to copper salts could be the responsible for the catalysis
and recent studies support the tin to copper transmetalla-
(
(
(
(
(
10) Piers, E.; Romero, M. A. J. Am. Chem. Soc. 1996, 118, 1215-
216.
11) Allred, G. D.; Liebeskind, L. S. J. Am. Chem. Soc. 1996, 118,
748-2749.
12) Kang, S-K.; Kim, J-S.; Choi, S-C. J. Org. Chem. 1997, 62,
4208-4209.
1
2
5
tion. The remarkable effect of NMP might be to facilitate
the Sn/Cu transmetallation (perhaps by coordination at Sn
in the transition state) and/or stabilize the intermediate or-
13) Nudelman, N. S.; Carro, C. Anales Asoc. Quím. Arg. 1998, 86,
1
7
119
171-179.
ganocopper. Thus, while the Sn NMR chemical shift
14) For an excellent discussion of New perspectives in the cross-
coupling reactions of organostannanes, see Farina, V. Pure
Appl. Chem. 1996, 68, 73.
(15) General Procedure: A vial containing CuCl (10% mol) and a
Teflon-coated stir bar was capped with a non-air stopper,
evacuated and filled with dry nitrogen alternatively, several
times. Anhydrous NMP or DMF (2 ml) and the organo-
of 1a and 1b are almost insensitive to the solvent change,
that of Bu SnCl is shifted 60 ppm upfield in Cl CD:NMP
3
3
1
8
9
:1 relative to Cl CD.
3
It is also interesting to note that in THF, the cross-cou-
pling product was obtained in low yield (32%) (Table 1,
entry 2) and the 2-(tributylstannyl)furan, 1a, was recov-
ered only in 3% yield, whereas in NMP yield and recovery
were much better (Table 1, entries 14, 15).
16
stannane (0.65 mmol) were added by a syringe and the vial
was put in a bath at 90 °C. The allyl halide (1.2 equiv.) was
added and the reaction mixture stirred for 1h. Quantitative
analyses were carried out by gas chromatography. Isolation of
the compounds: the reaction mixture was cooled to rt, and 0.1
ml of satd. KF soln. was added. After filtration, the reaction
mixture was extracted with ether, the organic layer dried over
This CuCl-mediated cross-coupling protocol is highly ef-
ficient for the synthesis of α-allyl-substituted furans and
thiophenes, and it is economical in terms of cost and time.
Under these conditions, the coupled product was obtained
as the only product in excellent yield. CuCl possesses a
good spectrum of properties: inexpensive, easy and rapid
anhydrous MgSO and evaporated in vacuo. The crude
4
product was separated by neutral alumina column
chromatography using CH Cl as eluant. Satisfactory spectra
2
2
Synlett 1999, No. 12, 1942–1944 ISSN 0936-5214 © Thieme Stuttgart · New York

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N. S. Nudelman, C. Carro
LETTER
(18) By studying the reaction mixture of 1a and 2a or 2b in the
1
data ( H NMR, 13C NMR and mass spectra) were obtained for
all the compounds. Isolated yields were slighly lower (5-7%)
than those obtained by GC.
1
19
13
presence of CuCl, by Sn- and C- NMR evidences for the
presence of a (furil-Cu) intermediate and Bu SnX species
n
3
(
(
16) The organostannanes were prepared similarly to other
organotin derivatives as described in: Nudelman, N. S.; Carro
C. J. Organometal. Chem. 1998, 563, 31-36.
17) We thank one of the referees for this suggestion about the role
of NMP.
were gathered. (to be published elsewhere)
Article Identifier:
1437-2096,E;1999,0,12,1942,1944,ftx,en;S01199ST.pdf
Synlett 1999, No. 12, 1942–1944 ISSN 0936-5214 © Thieme Stuttgart · New York