Suzuki-miyaura coupling of diarylmethyl carbonates with arylboronic acids: A new access to triarylmethanes

Article abstract of DOI:10.1021/ol800078j

Suzuki-Miyaura coupling of diarylmethyl carbonates with arylboronic acids proceeded in the presence of [Pd(n³-C³H ⁵)CI]²-DPPPent (1,5- bis(diphenylphosphino)pentane) catalyst, yielding a variety of triarylmethanes.

Full text of DOI:10.1021/ol800078j

ORGANIC
LETTERS
2008
Vol. 10, No. 5
973-976
Suzuki-Miyaura Coupling of Diarylmethyl
Carbonates with Arylboronic Acids: A
New Access to Triarylmethanes
Jung-Yi Yu and Ryoichi Kuwano*
Department of Chemistry, Graduate School of Sciences, Kyushu UniVersity,
6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
rkuwascc@mbox.nc.kyushu-u.ac.jp
Received January 12, 2008
ABSTRACT
Suzuki-Miyaura coupling of diarylmethyl carbonates with arylboronic acids proceeded in the presence of [Pd(
bis(diphenylphosphino)pentane) catalyst, yielding a variety of triarylmethanes.
η −DPPPent (1,5-
3-C3H5)Cl]2
The triarylmethane framework is often found in various
attractive molecules, for example, leuco dyes1 and some
candidates for molecular magnets.2 The framework appears
in a flavonoid isolated from a cajeput tree, melanervin.3
Recently, it was reported that triarylmethanes containing a
thiophenyl group exhibit antitubercular activity.4 Triaryl-
methanes are typically synthesized by Friedel-Crafts aryl-
ation of diarylmethanols or by reduction of triarylmethanols,
which are prepared by nucleophilic addition of aryl metal
compounds to carbonyl.5,6
diarylmethyl halides, however, have been utilized as elec-
trophilic substrates for the cross-coupling, which will provide
a straightforward approach to triarylmethanes. Recently,
Molander attempted the cross-coupling of bromodiphenyl-
methane with an aryltrifluoroborate but failed to obtain the
desired triarylmethane in pure form.8 This paper discloses
that the cross-coupling of diarylmethyl carbonates with
arylboronic acids proceeded with success in the presence of
a palladium catalyst.
Recently, we and others reported the cross-coupling of
benzylic carbonates8-11 and phosphates12 with organometallic
compounds. The reports stimulated us to develop the cross-
Meanwhile, the Suzuki-Miyaura reaction is widely utilized
for selective C-C bond formation in organic synthesis.7 No
(1) (a) Duxbury, D. F. Chem. ReV. 1993, 93, 381-433. (b) Guinot, S.
G. R.; Hepworth, J. D.; Wainwright, M. J. Chem. Soc., Perkin Trans. 2
1998, 297-303. (c) Lewis, E. S.; Perry, J. M.; Grinstein, R. H. J. Am.
Chem. Soc. 1970, 92, 899-905.
(6) Recently, Yorimitsu and Oshima reported a palladium-catalyzed
synthesis of triarylmethanes containing an azaaryl, see: Niwa, T.; Yorimitsu,
H.; Oshima, K. Org. Lett. 2007, 9, 2373-2375.
(2) (a) Schlenk, W.; Brauns, M. Ber. Deutsch. Chem. Ges. 1915, 48,
661-669. (b) Seitz, G.; Mo¨nnighoff, H. Angew. Chem., Int. Ed. Engl. 1970,
9, 906-907.
(7) Representative reviews: (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995,
95, 2457-2483. (b) Miyaura, N. Top. Curr. Chem. 2002, 219, 11-59. (c)
Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 2419-2440.
(8) Molander, G. A.; Elia, M. D. J. Org. Chem. 2006, 71, 9198-9202.
(9) Kuwano, R.; Yokogi, M. Org. Lett. 2005, 7, 945-947.
(10) Stille coupling of a (4-oxazolyl)methyl carbonate, see: Lindsey,
C. C.; O’Boyle, B. M.; Mercede, S. J.; Pettus, T. R. R. Tetrahedron Lett.
2004, 45, 867-868.
(3) Antus, S.; Schindlbeck, E.; Ahmad, S.; Seligmann, O.; Chari, V. M.;
Wagner, H. Tetrahedron 1982, 38, 133-137.
(4) Parai, M. K.; Panda, G.; Chaturvedi, V.; Manju, Y. K.; Sinha, S.
Bioorg. Med. Chem. Lett. 2008, 18, 289-292.
(5) (a) Nair, V.; Vidya, N.; Abhilash, K. G. Synthesis 2006, 3647-3653.
(b) Katritzky, A. R.; Toader, D. J. Org. Chem. 1997, 62, 4137-4141. (c)
Muthyala, R.; Katritzky, A. R.; Lan, X. Dyes Pigm. 1994, 25, 303-324
and references cited therein.
(11) Hiyama coupling of benzylic carbonates, see: Nakao, Y.; Ebata,
S.; Chen, J.; Imanaka, H.; Hiyama, T. Chem. Lett. 2007, 36, 606-607.
(12) McLaughlin, M. Org. Lett. 2005, 7, 4875-4878.
10.1021/ol800078j CCC: $40.75
© 2008 American Chemical Society
Published on Web 02/06/2008

coupling of arylboronic acids with diarylmethyl carbonates,
which are a type of benzylic carbonates. Thus, the reaction
of diphenylmethyl methyl carbonate (1a) with phenylboronic
acid (2a) was attempted under the conditions optimized in
the previous work, that is, using [Pd(η3-C3H5)Cl]2-
DPPPent13 catalyst in DMF at 80 °C, but resulted in no
formation of triphenylmethane 3a. Elevating the reaction
temperature led to the production of 3a but in low yield
(Table 1,14 entry 1). Solvent strongly affected the reaction
Table 2. Reactions of Diarylmethyl Carbonates 1 with 2aa
Table 1. Effect of Ligand and Solvent on the Cross-Coupling
of Diphenylmethyl Carbonate (1a) with Phenylboronic Acid
(2a)a
entry
ligand
solvent
DMF
Toluene
1,4-dioxane
tert-amyl alcohol
tert-amyl alcohol
tert-amyl alcohol
tert-amyl alcohol
tert-amyl alcohol
tert-amyl alcohol
tert-amyl alcohol
tert-amyl alcohol
yield, %b,c
1
2
3
4
5
6
7
8
9
DPPPent
DPPPent
DPPPent
DPPPent
15
35
36
76 (87)d
14
1
87 (90)e
16
1
1
c
PPh3
DPPE
DPPF
DPEphos
Xantphos
Cy-Xantphos
DPPPent
10
11f
1
a Reactions were conducted on a 0.2 mmol scale in 1.0 mL of solvent at
100 °C for 3 h. The ratio of 1a:2a:K2CO3:[Pd(η3-C3H5)Cl]2:ligand was 20:
30:60:0.5:1.1. b GC yield (average of two runs). c The yields in parentheses
were isolated yields in a 1 mmol scale with 1.0 mol % palladium. d The
reaction was conducted for 48 h. e The reaction was conducted for 27 h.
f Diphenylmethyl acetate was used in place of 1a.
a Reactions were conducted on a 1.0 mmol scale in tert-amyl alcohol
(1.0 mL) at 100 °C. The ratio of 1:2a:K2CO3:[Pd(η3-C3H5)Cl]2:DPPPent
was 100:110:220:0.5:1.1. b Isolated yield. c The reaction was conducted with
5 mol % palladium.
rate (entries 2-4). The desired cross-coupling product 3a
was obtained in high yield when tert-amyl alcohol was used
as a solvent. As with other palladium-catalyzed reactions
involved with benzylic C-O bond cleavage, the choice of
phosphine ligand was crucial for the palladium catalysis
(entries 5-10). In this case, DPPF was comparable to
DPPPent.15 However, employment of other phosphine ligands,
including monophosphines, caused a significant decrease in
the catalytic activity. To our surprise, the formation of 3a
was scarcely observed in the reaction using Cy-Xantphos
(13) DPPPent ) 1,5-bis(diphenylphosphino)pentane: Sacconi, L.; Gel-
somini, J. Inorg. Chem. 1968, 7, 291-294.
(14) Bidentate phosphine ligands in Table 1 were abbreviated as
follows: (a) DPPE ) 1,2-bis(diphenylphosphino)ethane: Issleib, K.; Mu¨ller,
D.-W. Chem. Ber. 1959, 92, 3175-3182. (b) DPPF ) 1,1′-bis(diphenyl-
phosphino)ferrocene: Bishop, J. J.; Davison, A.; Katcher, M. L.; Lichten-
berg, D. W.; Merrill, R. E.; Smart, J. C. J. Organomet. Chem. 1971, 27,
241-249. (c) DPEphos ) bis[2-(diphenylphosphino)phenyl]ether, Xantphos
) 9,9-dimethyl-4,6-bis(diphenylphosphino)xanthene: Kranenburg, M.; van
der Burgt, Y. E. M.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Goubitz,
K.; Fraanje, J. Organometallics 1995, 14, 3081-3089. (d) Cy-Xantphos )
4,5-bis(dicyclohexylphosphino)-9,9-dimethylxanthene: Kuwano, R.; Ku-
sano, H. Chem. Lett. 2007, 36, 528-529.
(15) As with the Suzuki-Miyaura reaction of benzylic carbonate, the
production of triphenylmethane might significantly be affected by the bite
angle of the chelate bisphosphine. Our speculation about the effect was
mentioned in ref 9.
974
Org. Lett., Vol. 10, No. 5, 2008

Subsequently, the Suzuki-Miyaura coupling was applied to
a series of ortho-substituted diarylmethyl carbonates 1f-j.
The reactivity of mono-methylated substrate 1f was com-
parable to that of the para-isomer 1e (entry 5). However, a
second ortho-methyl substituent caused significant obstruc-
tion of the cross-coupling with 2a. As a matter of fact, the
reactions of diarylmethyl carbonates 1g and 1h failed to react
with 2a in good yields (entries 6 and 7). The additional
methyl may sterically obstruct the attack of DPPPent-
palladium on the diarylmethyl substrates. More congested
triarylmethanes 3i and 3j could be obtained by means of
DPPPent-palladium catalysis but in low yield (entries 8 and
9). The low yields of 3g-j were hardly improved when the
catalyst loading increased to 5%.
Table 3. Cross-Couplings of 1a with Arylboronic Acids 2a
A range of arylboronic acids worked as coupling partners
of diphenylmethyl carbonate 1a as shown in Table 3. The
catalytic cross-coupling was scarcely affected by the elec-
tronic property of the para-substituent of the arylboronic acid
(entries 1, 2). An interesting discrepancy has been ob-
served: triarylmethane 3c was obtained in high yield from
the reaction of 2c, whereas the cross-coupling of 1c with 2a
was shown to be less effective. Whereas the ortho-substit-
uents of 2d and 2e slightly hindered the catalytic reaction,
coupling products 3f and 3k were obtained in good yields
(entries 3, 4). The Suzuki-Miyaura coupling of diphenyl-
methyl carbonate was compatible with chloro, aldehyde, and
Boc-protected amino groups (entries 5-7). However, nitro
and hydroxyl groups obstructed the conversion of the starting
materials. The DPPPent-palladium did not work well for
the reaction of 2-phenylethenylboronic acid, giving the cross-
coupling product in only 15% yield.
a Reactions were conducted on a 1.0 mmol scale in tert-amyl alcohol
(1.0 mL) at 100 °C for 24 h. The ratio of 1a:2:K2CO3:[Pd(η3-C3H5)Cl]2:
DPPPent was 100:110:220:0.5:1.1. b Isolated yield.
The Suzuki-Miyaura reaction of diarylmethyl carbonates
1 would proceed like that of benzylic carbonates (Scheme
1).9 DPPPent-palladium(0) cleaves the benzylic C-O bond
ligand, which was the most effective for the palladium-
catalyzed nucleophilic substitution of 1a with malonate
carbanions.14d The reaction using acetate in place of carbonate
resulted in a trace yield of 3a (entry 11).16 The loading of
the DPPPent- or DPPF-palladium catalyst was reduced to
1% without a significant loss of yield of 3a (entries 4 and
7). DPPF was slightly superior to DPPPent for the reaction
of 1a with 2a.
Scheme 1. Probable Pathway of the Suzuki-Miyaura Coupling
of Diphenylmethyl Carbonates 1
The effect of the substituent on the aromatic ring of the
diarylmethyl carbonate was investigated for the cross-
coupling with phenylboronic acid (Table 2). The reaction
of electron-deficient 1b gave the desired product 3b in good
yield (entry 1). In contrast, the electron-donating methoxy
group of 1c caused significant deterioration of the yield of
triarylmethane 3c (13%) due to formation of R-methoxy-R-
(p-methoxylphenyl)toluene through palladium-catalyzed de-
carboxylative etherification. Efficient production of 3c
required an increase of the catalyst loading (entry 2). In the
above two reactions, DPPPent ligand was preferable to
DPPF. Electrophilic substrate 1d bearing both electron-rich
and -poor aryl groups was converted into 3d in 77% yield
(entry 3). The electron-withdrawing trifluoromethyl group
might cancel the undesirable effect of methoxy group.
of 1 to form (diarylmethyl)palladium intermediate 4. The
alkoxo ligand on 4 undergoes transmetalation with an
arylboronic acid. Reductive elimination of the resulting
(aryl)(diarylmethyl)palladium(II) 5 yields the desired tri-
arylmethane 3 and regenerates palladium(0).
We developed the Suzuki-Miyaura coupling of diaryl-
methyl carbonates. The reaction proceeds well by using
[Pd(η3-C3H5)Cl]2-DPPPent or -DPPF as catalyst. The
former catalyst was applied to the synthesis of a wide range
(16) Kuwano, R.; Yokogi, M. Chem. Commun. 2005, 5899-5901.
Org. Lett., Vol. 10, No. 5, 2008
975

of triarylmethanes. The method disclosed here will be useful
for constructing various triarylmethane frameworks in or-
ganic synthesis.
MEXT. This paper is dedicated to the memory of Professor
Yoshihiro Matsumura.
Supporting Information Available: Experimental pro-
cedures and characterization data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. This work was supported by
Tokuyama Science Foundation, Iketani Science and
Technology Foundation, KAKENHI (No. 16685011 and
19020051), and a Grant-in-Aid for the Global COE
Program, “Science for Future Molecular Systems” from
OL800078J
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Org. Lett., Vol. 10, No. 5, 2008