Synthesis of unsymmetrical diarylmethanes by cross-coupling between aryl triflates and tetrabutylammonium difluorotribenzylstannate

Article abstract of DOI:10.1021/ol005666c

(Matrix Presented) The benzylation of aryl triflates can be achieved by cross-coupling between aryl triflates and the new hypervalent tin reagent (n-Bu₄N)⁺(Bn₃-SnF₂)^-.

Full text of DOI:10.1021/ol005666c

ORGANIC
LETTERS
2000
Vol. 2, No. 10
1377-1378
Synthesis of Unsymmetrical
Diarylmethanes by Cross-Coupling
between Aryl Triflates and
Tetrabutylammonium
Difluorotribenzylstannate†
Antonio Garc´ıa Mart´ınez,* Jose´ Os´ıo Barcina,
Mar´ıa del Rosario Colorado Heras, and AÄ lvaro de Fresno Cerezo
Departamento de Qu´ımica Orga´nica, Facultad de Ciencias Qu´ımicas, UniVersidad
Complutense de Madrid, Ciudad UniVersitaria, 28040 Madrid, Spain
josio@eucmos.sim.ucm.es
Received February 14, 2000
ABSTRACT
The benzylation of aryl triflates can be achieved by cross-coupling between aryl triflates and the new hypervalent tin reagent (n-Bu4N)+(Bn3-
SnF2)-.
Diarylmethanes are frequently used as subunits in the design
of supramolecular structures such as macrocycles, catenanes,
and rotaxanes.1 Besides this, some diarylmethane derivatives
have been shown to possess interesting biological and
medicinal properties.2,3
The best procedures for the synthesis of the title com-
pounds are the transition metal-catalyzed cross-coupling
between either aryl nucleophiles and benzylic halides3 or aryl
halides and benzylic nucleophiles.4 However, the required
nucleophiles are organomagnesium or organozinc halides,
which are incompatible with a variety of functional groups.
Therefore, the reactions must be carried out using such mild
reaction conditions that global yields obtained are quite low.4
The palladium-catalyzed cross-coupling of organotin re-
agents (Stille reaction) is a widely used method for carbon-
carbon bond formation.5 However, the Stille reaction fails
in the case of cross-coupling between aryl triflates and
substituted benzyltributyltin (highest reported yield: 21%).3,5
Very recently, the Suzuki-Miyaura palladium-catalyzed
cross-coupling reaction has been extended to achieve diaryl-
methanes.6 However, this methodology is also limited by
the availability of boronic acid derivatives.7
Since our preliminary work on the phenylation of alkenyl
triflates with tetrabutylammonium difluorotriphenylstannate,8
a hypervalent tin reagent,9 other hypervalent tin10-12 and
(5) For reviews, see: (a) Stanforth, S. P. Tetrahedron 1998, 54, 263.
(b) Farina, V.; Krishnamurthy, V.; Scott, W. J. Organic Reactions; Wiley:
New York, 1997; Vol. 50. (c) Ritter, K. Synthesis 1993, 735.
(6) Chowdhury, S.; Georghiou, P. E. Tetrahedron Lett. 1999, 40, 7599.
(7) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457.
(8) Garc´ıa Mart´ınez, A.; Os´ıo Barcina, J.; de Fresno Cerezo, A.;
Subramanian, L. R. Synlett 1994, 1047.
† Affectionately dedicated to Prof. Jose´ Luis Soto on the occasion of his
70th birthday.
(1) (a) Ma, J. C.; Dougherty, D. A. Chem. ReV. 1997, 97, 1303. (b) Ja¨fer,
R.; Vo¨gtle, F. Angew. Chem., Int. Ed. Engl. 1997, 36, 930.
(2) (a) Rische, T.; Eilbracht, P. Tetrahedron 1999, 55, 1915. (b) Prat,
L.; Mojovic, L.; Levacher, V.; Dupas, G.; Que´guines, G.; Bourguignon, J.
Tetrahedron: Asymmetry 1998, 9, 2509. (c) Ku, Y.-Y.; Patel, R. P.; Sawick,
D. P. Tetrahedron Lett. 1996, 37, 1949.
(3) de Lang, R.-J.; van Hooijdonk, M. J. C. M.; Brandsma, L.; Kramer,
H.; Seinen, W. Tetrahedron 1998, 54, 2953 and references therein.
(4) Rottla¨nder, M.; Knochel, P. Tetrahedron Lett. 1997, 38, 1749 and
references therein.
(9) Gingras, M. Tetrahedron 1991, 32, 7381.
(10) (a) Fouquet, E.; Pereyre, M.; Rodriguez, A. L. J. Org. Chem. 1997,
62, 5242. (b) Fouquet, E.; Rodriguez, A. L. Synlett 1998, 1323.
(11) Fugami, K.; Ohnuma, S.; Kameyama, M.; Saotome, T.; Kosugi,
M. Synlett 1999, 63.
(12) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1999, 38, 2411.
10.1021/ol005666c CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/27/2000

silicon13 reagents have been employed with success in several
coupling reactions. In this paper we report that tetrabuty-
lammonium difluorotribenzylstannate [(n-Bu4N)+(Bn3SnF2)-]
1 can be used as an effective transmetalation reagent14 in
Pd(PPh3)4-catalyzed cross-coupling reactions with aryl tri-
flates 2 (Scheme 1).
Table 1. Reaction of Aryl Triflates with (n-Bu4N)+(Bn3SnF2)-
Scheme 1. Preparation of Unsymmetrical Diarylmethanes (3)
The hypervalent tin reagent 1 was easily prepared from
benzyl chloride according to Scheme 1.9 The coupling
reaction between 1 and aryl triflates 2, prepared from the
corresponding phenols,5c,15 takes place easily in DMF as
solvent at 150 °C. The optimized reaction times for each
triflate are given in Table 1, as well as the yields in isolated
arylphenylmethanes.16 It should be noted that reaction times
in this procedure are very short (1 min-2 h). On the other
hand, no coupling reaction was observed by us when trying
to obtain 3 following the method reported in the literature
based on the use of activated monoorganotins and aryl
triflates.10
by GLC. In entries 2 and 4, a small amount (ca. 10%) of
products proceeding from the arylation of the aryl triflates
was also detected. These compounds are formed in the
reactions by a transmetalation process involving triphenyl-
phosphine.5b
In summary, hypervalent reagent 1 is a highly effective
transmetalation reagent for the Pd(0)-catalyzed cross-
coupling benzylation of aryl triflates. Furthermore, the
hypervalent reagents used do not have the toxicity and
purification drawbacks encountered when using tetraorgan-
otins.17 The scope and limitations of this methodology will
be reported in due course.
As byproducts, small amounts (<10%) of homocoupled
compounds (Ar-Ar and 1,2-diphenylethane) were detected
(13) (a) Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64, 1684. (b)
Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64, 3266.
(14) For the mechanism of the Stille reaction, see: Casado, A. L.; Espinet,
P. J. Am. Chem. Soc. 1998, 120, 8978.
(15) Garc´ıa Mart´ınez, A.; Subramanian, L. R.; Hanack, M. In Encyclo-
pedia of Reagents for Organic Synthesis; Paquette, L. A., Ed.; John Wiley:
Chichester, 1995; Vol. 7.
(16) A solution of 1.3 mmol of aryl triflate 2, 1.31 g (1.95 mmol) of 1,
and 0.13 mmol of Pd(Ph3P)4 in 6 mL of DMF was introduced, under an
argon atmosphere, in an oil bath heated at 150 °C. After the reaction time
indicated in Table 1, the reaction mixture was poured into water (50 mL)
and extracted with Cl2CH2 (3 × 25 mL). The organic solution was washed
with water and a saturated NaHCO3 solution and dried over MgSO4.
Evaporation of the solvent and purification of the residue by flash
chromatography (silica gel, hexane) yielded the corresponding arylphenyl-
Acknowledgment. We thank the DGICYT, Spain (Grant
PB-97-0268-C02), for financial support.
OL005666C
(17) For toxicology of tin reagents, see: Aldridge, W. N. In Chemistry
and Technology of Silicon and Tin; Kurnar Das, V. G., Weng, N. G., Gielen,
M., Eds.; Oxford University Press: New York, 1992; pp 78-92.
1
methanes 3. All compounds were characterized by H and 13C NMR and
MS.
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Org. Lett., Vol. 2, No. 10, 2000