Synthesis, resolution, and applications of 2,2′-bis(diphenylphosphino)-3,3′-binaphtho[2,1-d]furan

Article abstract of DOI:10.1021/ol006238+

A short five-step synthesis of (±)-2,2′-bis(diphenylphosphino)-3,3′-binaphtho[2,1-b]furan (BINAPFu, 1) starting from 2-naphthoxyacetic acid is reported. The resolution of BINAPFu 1 was possible using our newly developed resolution procedure for phosphines

Full text of DOI:10.1021/ol006238+

ORGANIC
LETTERS
2000
Vol. 2, No. 18
2817-2820
Synthesis, Resolution, and Applications
of 2,2′-Bis(diphenylphosphino)-3,3′-
binaphtho[2,1-b]furan
Neil G. Andersen, Masood Parvez,† and Brian A. Keay*
Department of Chemistry, UniVersity of Calgary, Calgary, Alberta, Canada T2N 1N4
keay@ucalgary.ca
Received June 21, 2000
ABSTRACT
A short five-step synthesis of (±)-2,2′-bis(diphenylphosphino)-3,3′-binaphtho[2,1-b]furan (BINAPFu, 1) starting from 2-naphthoxyacetic acid is
reported. The resolution of BINAPFu 1 was possible using our newly developed resolution procedure for phosphines wherein (1S)-camphorsulfonyl
azide was used to prepare the bisphosphinimine of BINAPFu via the Staundinger reaction. BINAPFu consistently outperformed BINAP in an
asymmetric Heck reaction between 2,3-dihydrofuran and phenyl triflate.
Optically active bidentate phosphine ligands have, in recent
years, played a vital role in homogeneous transition metal
catalyzed asymmetric synthesis,1 thereby making the design
and synthesis of novel chiral phosphine ligands an active
area of research. Since the initial reports on the axially
dissymmetric ligand BINAP 2 (Scheme 1),2 a wide variety
of new biaryl, bidentate ligands have appeared in the
literature.3 Moreover, many of these ligands have been
applied to a variety transition metal catalyzed asymmetric
† To whom correspondence regarding crystallographic data should be
addressed.
(1) For reviews, see: (a) Noyori, R. Asymmetric Catalysis in Organic
Synthesis; Wiley & Sons: New York, 1994; Chapter 2. (b) Ojima, I.
Catalytic Asymmetric Synthesis; VCH Publishers: Weinheim, 1993; Chapter
1. (c) Morrison, J. D. Asymmetric Synthesis; Academic Press: New York,
1985; Vol. 5, Chapter 1.
Scheme 1
(2) Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi,
T.; Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932. (b) Miyashita, A.;
Takaya, H.; Souchi, T.; Noyori, R. Tetrahedron 1984, 40, 1245. (c) Toriumi,
K.; Ito, T.; Takaya, H.; Souchi, T.; Noyori, R. Acta Crystallogr. Sect B:
Struct. Sci. 1982, B38, 807.
(3) For representative examples, see: (a) Cereghetti, M.; Arnold, W.;
Broger, E.; Rageot, A. Tetrahedron Lett. 1996, 37, 5347. (b) Berens, V.;
Brown, J.; Long, J.; Selke, R. Tetrahedron: Asymmetry 1996, 7, 285. (c)
Benincori, T.; Brenna, E.; Sannicolo`, F.; Trimarco, L.; Antognazza, P.;
Cesarotti, E.; Demartin, F.; Pilati, T. J. Org. Chem. 1996, 61, 6244. (d)
Jendralla, H.; Li, C.; Paulus, E. Tetrahedron: Asymmetry 1994, 5, 1297.
(e) Zhang, X.; Mashima, K.; Koyano, K.; Sayo, N.; Kumobayashi, H.;
Akutagawa, S.; Takaya, H. J. Chem. Soc., Perkin Trans. 1 1994, 2309. (f)
Mashima, K.; Kusano, K.; Sato, N.; Matsumura, Y.; Nozaki, K.; Kumoba-
yashi, H.; Sayo, N.; Hori, Y.; Ishizaki, T.; Akutagawa, S.; Takaya, H. J.
Org. Chem. 1994, 59, 3064. (g) Yamamoto, N.; Murata, M.; Morimoto, T.
Achiwa, K. Chem. Pharm. Bull. 1991, 39, 1085.
10.1021/ol006238+ CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/08/2000

transformations with a remarkable degree of success. For
example, superior catalytic activity and enantioselectivity
have been observed in hydrogenations utilizing diphosphine
ligands bearing aromatic rings with electron-donating meth-
oxy and methyl substituents.3g As a result, the great majority
of homochiral phosphine ligands reported to date are
electron-rich with respect to triphenylphosphine.3d However,
evidence has been reported to suggest that less electron rich
phosphines are or would be advantageous for some transition
metal mediated organic reactions. For example, Farina and
co-workers reported significant rate accelerations for the
Stille reaction when tri-2-furylphosphine (TFP) or triphen-
ylarsine was employed as ligands.4 Moreover, Shibasaki has
reported superior results in a tandem Suzuki-Heck process
when either TFP or triphenylarsine was utilized to complex
palladium.5 The later results subsequently lead to the
development of 2,2′-bis(diphenylarsino)-1,1′-binaphthyl (3,
BINAs, Scheme 1) as an effective ligand for the asymmetric
Heck reaction.6 Finally, the oxidative addition of phenyl
iodide has been studied with in situ generated Pd(0)
complexes of triphenylphosphine and TFP showing that in
DMF {Pd(dba)2 + nTFP} is always more reactive than {Pd-
(dba)2 + nPPh3} for n g 2.7 These results in conjunction
with our interests in the asymmetric palladium-catalyzed
polyene cyclizations8 led us to develop 2,2′-bis(diphen-
ylphosphino)-3,3′-binaphtho[2,1-b]furan (1) (BINAPFu,
Scheme 1) as a new bidentate phosphine ligand. We herein
report a short, highly efficient synthesis of the title com-
pound, its resolution using (S)-camphorsulfonyl azide, and
the use of BINAPFu 1 in the Heck arylation of 2,3-
dihdrofuran.
Our design of BINAPFu 1 was based on previous studies
reported with other 2,2′-bis(diphenylphosphino)-3,3′-bihet-
eroaryl systems 4-8 (Scheme 1). In 1996, bisbenzofuran 4
was prepared and found to be configurationally unstable at
room temperature.9 Interestingly, compound 5 was mentioned
in a patent,10 but it has not been reported as a ligand in any
organic reaction. Similarly, bisindole 6 has been prepared
and resolved but not used in any reactions.11 Bisben-
zothiophenes 7 and 8 have been prepared, resolved, and
found to be configurationally stable.9 Both compounds 7
(bitinap) and 8 provided good ee’s in Ru(II)-catalyzed
hydrogenations,9 while 8 has recently been used in asym-
metric Heck reactions.12 We wanted to design a 3,3′-bifuryl
ligand that would have the diphenylphosphino groups at-
tached to the C-2 position and be configurationally stable
under a variety of reaction conditions (>150 °C). Semiem-
pirical calculations (PM3) indicated that BINAPFu 1 should
be configurationally stable; thus a synthesis and resolution
of (()-3 was undertaken.
We envisaged that the biaryl bond in BINAPFu could be
formed via a low-valent titanium-mediated dimerization of
naphthoketone 10. Hence, commercially available and in-
expensive 2-naphthoxyacetic acid (9) was converted to
ketone 10 using a simple, high-yielding two-step procedure
(Scheme 2). McMurry coupling of 10 in DME and subse-
Scheme 2a
quent DDQ oxidation of the resulting olefin cleanly afforded
the desired biaryl precursor 11. Dilithiation of binaphthofuran
11 with 2 equiv of t-BuLi in diethyl ether followed by
treatment with chlorodiphenylphosphine furnished (()-
BINAPFu 3 in 91% yield. The product can be easily isolated
from the reaction mixture by crystallization, and in contrast
to BINAP 1,3d we have found it to be remarkably resistant
to air oxidation in both solution and crystalline forms.
With (()-BINAPFu 1 in hand, attention was then focused
on resolution of the two optical isomers. Unfortunately, a
number of reported methods for phosphine resolution13-16
failed to resolve the BINAPFu ligand. However, a minor
variation of our novel phosphine resolution procedure,17 using
(1S)-camphorsulfonyl azide as the resolving agent, efficiently
(12) Tietze, L. F.; Thede, K.; Sannicolo`, F. J. Chem. Soc., Chem.
Commun. 1999, 1811. Tietze, L. F.; Thede, K.; Schimpf, R.; Sannicolo`, F.
J. Chem. Soc., Chem. Commun. 2000, 583.
(13) Pietrusiewicz, K. M.; Zablocka, M. Chem. ReV. 1994, 94, 1375.
(14) Treatment of (()-1 with homochiral ortho-palladated resolving
agents 13 or 14 efficiently provided the desired diastereomeric complexes
in a 1:1 ratio as evidenced by 31P NMR analysis.15 Unfortunately, numerous
attempts to separate the above complexes by crystallization from a variety
of solvent systems failed. Alternatively, protonation of the weakly basic
phosphoryl oxygens of bisphosphine oxide 12 was explored as a possible
resolution procedure. However, treatment of (()-12 with either (-)-
dibenzoyltartaric acid or (1S)-(+)-camphorsulfonic acid under a wide variety
of conditions failed to furnish the desired diastereomeric complexes.16
(4) (a) Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585. (b)
Farina, V.; Krishnamurthy, V.; Scott, W. The Stille Reaction; John Wiley
& Sons: New York, 1998.
(5) Kojima, A.; Honzawa, S.; Boden, C.; Shibasaki, M. Tetrahedron Lett.
1997, 38, 3455.
(6) Kojima, A.; Boden, C.; Shibasaki, M. Tetrahedron Lett. 1997, 38,
3459.
(7) Amatore, C.; Jutand, A.; Meyer, G.; Atmani, H.; Khalil, F.; Chahdi,
F. Organometallics 1998, 17, 2958.
(8) (a) Lau, S. Y. W.; Keay, B. A. Synlett 1999, 605. (b) Maddaford, S.
P.; Andersen, N. G.; Cristofoli, W. A.; Keay, B. A. J. Am. Chem. Soc.
1996, 118, 10766. (c) Cristofoli, W. A.; Keay, B. A. Synlett 1994, 625.
(9) Benincori, T.; Brenna, E.; Sannicolo`, F.; Trimarco, L.; Antognazza,
P.; Cesarotti, E.; Demartin, F.; Pilati, T. J. Org. Chem. 1996, 61, 6244.
(10) Antognazza, P.; Benincori, T.; Brenna, Cesarotti, E.; Sannicolo`, F.;
Trimarco, L. Int. Pat. WO 9601831 A1.
(11) Berens, U.; Brown, J. M.; Long, J.; Selke, R. Tetrahedron:
Asymmetry 1996, 7, 285.
2818
Org. Lett., Vol. 2, No. 18, 2000

afforded a 1:1 mixture of diastereomeric phosphinimines 15a
and 15b which were separable by column chromatography
(Scheme 3). The diastereomerically pure phosphinimines 15a
indicates an increase in the s-character of the phosphorus
lone pair orbital (i.e., less basic phosphine). A comparison
1
of the J(31P-77Se) coupling values for 16 with selenium
derivatives 17-19 (Scheme 4) shows that the phosphorus
Scheme 3
Scheme 4
atoms in 1 are less basic than those in bitinap 7 and BINAP
2 (Scheme 1) but are more basic than the phosphorus atom
in tri-2-furylphosphine.19
With (+)-1 and (-)-1 in hand, we compared the efficacy
of BINAPFu in the asymmetric Heck arylation of 2,3-
dihydrofuran and compared the results to those obtained with
BINAP 1 (Table 1). In our hands, Hiyashi’s reaction
conditions reported with BINAP20 and Proton Sponge
and 15b were subsequently converted to their respective
phosphine oxides (-)-12 and (+)-12 by treatment with 3 M
H2SO4 in dioxane (100 °C). Trichlorosilane reduction of (+)-
12 and (-)-12 in xylenes provided enantiopure (+)-1 and
(-)-1, respectively (Scheme 3). The absolute stereochemistry
of BINAPFu 1 was unequivocally established by obtaining
a single-crystal X-ray structure analysis on diselenide 16,
prepared from enantiopure (-)-1 (Figure 1).18
Table 1. Asymmetric Heck Results with BINAPFu and
BINAP
% yield of products
ligand
solvent
°C
% sm 22 (% ee)
23
24 (ee %)
1. (R)-2 C6H6a
2. (R)-1 C6H6a
3. (R)-2 C6H6a
4. (R)-1 C6H6a
5. (R)-2 dioxanea
6. (R)-1 dioxanea
7. (R)-2 dioxanea 100d
8. (R)-1 dioxanea 100d
9. (R)-2 DMEb
10. (R)-1 DMEb
11. (R)-2 dioxaneb 100d
12. (R)-1 dioxaneb 100d
13. (R)-2 DMFb
14. (R)-1 DMFb
15. (R)-2 dioxaneb 100c
16. (R)-1 dioxaneb 100c
30c
30c
30d
30d
30d
30d
99
83
70
67
54
29
0
0
0
0
0
0.7 (s)
1.2 (s)
27 (86)
21 (>97)
43 (73)
61 (>97)
90 (57)
94 (74)
55 (48)
95 (73)
73 (41)
90 (77)
55 (35)
94 (71)
93 (54)
66 (79)
3
13 (93)
3 (51)
11 (75)
2 (46)
9 (57)
10 (64)
5 (69)
32 (72)
4 (64)
17 (26)
10 (40)
41 (47)
3 (39)
0.1
0.5
2
2
2
Figure 1. ORTEP diagram of selenide 16 drawn with 30%
probability ellipsoids. Hydrogens are represented as spheres of
arbitrary size.
1
13
85d
85d
1
9
1
5
2
4
2
Allen and Taylor have reported19 that an increase in the
1J(31P-77Se) coupling constant of phosphorus selenides
0
0
0
0
90d
90d
(15) (a) Otsuka, S.; Nakamura, A.; Kano, T.; Tani, K. J. Am. Chem.
Soc. 1971, 93, 4301. (b) Tani, K.; Brown, L. D.; Ahmed, J.; Ibers, J. A.;
Yokota, M.; Nakamura, A.; Otsuka, S. J. Am. Chem. Soc. 1977, 99, 7876.
(c) Roberts, N. K.; Wild, S. B. J. Am. Chem. Soc. 1979, 101, 6254. (d)
Mayashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.;
Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932. (e) Jendralla, H.; Li, C. H.;
Paulus, E. Tetrahedron: Asymmetry 1994, 5, 1297.
3 (23)
33 (44)
0
a 3 mol % Pd(OAc)2 for 9 d. b 1.5 mol % Pd2dba3 for 7 d. c Proton sponge
used as base. d (i-Pr)2NEt used as base.
Org. Lett., Vol. 2, No. 18, 2000
2819

afforded low product conversion. BINAPFu gave similar
results under otherwise identical conditions (entry 2). Hunig’s
base was found to increase the conversion in benzene (entries
3 and 4). Changing the solvent to 1,4-dioxane further
increased the amount of product obtained (entries 5 and 6).
In accordance with Hayashi’s findings, use of Pd(OAc)2 as
the precatalyst was essential for achieving product of high
enantiomeric excess. At low temperature (30 °C), in dioxane
using Hunig’s base, BINAPFu provided a 61% yield of 22
in >97% ee (entry 6) while BINAP only provided 22 in 43%
yield with a 73% ee (entry 5). To increase the conversion to
product, we turned our attention to trying the reaction at
higher temperatures. Repeating the reaction at 100 °C in
dioxane for 9 d21 provided a 94% yield of 22 in 74% ee
with BINAPFu (entry 8). BINAP under otherwise identical
conditions gave a 90% yield of 22 but a much lower ee of
57% (entry 7). Unlike the low-temperature reactions, we
found that changing the Pd source from Pd(OAc)2 to Pd2-
dba3 did not significantly change the enantioselectivity of
the reaction (entries 9-14). At high temperatures (85-100
°C) in a variety of solvents, the BINAPFu ligand provided
the major product 22 with significantly improved optical
purity relative to the reactions performed with BINAP.
Hence, the Heck arylation of 2,3-dihydrofuran may be
performed over 9 d with BINAPFu at 30 °C to ensure a high
% ee of 22 (>97%) with a diminished yield of 61% (entry
6) or refluxed in dioxane to provide 22 with a 74% ee in
94% yield (entry 8). It is interesting to note that in all the
reactions performed to date, the conjugated product 23 was
always observed with BINAP and BINAPFu. Compound 23
has not been reported as a product of this reaction, and we
are now examining the mechanism of its formation.
In conclusion, we have shown that enantiopure BINAPFu
can be easily prepared and outperforms BINAP in the Heck
reaction between phenyl triflate and 2,3-dihydrofuran. Further
structural modifications of BINAPFu are currently underway
in order to improve the enantioselectivity of the high-
temperature Heck arylation reaction.
Acknowledgment. We thank the Natural Sciences and
Engineering Research Council of Canada (NSERC) for
financial support. N.G.A. gratefully acknowledges receipt
of a Ralph Steinhauer Award of Distinction from the Alberta
Heritage Foundation and an Honorary Killam Fellowship.
(16) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi,
H.; Taketomi, T.; Akutagawa, S.; Noyori, R. J. Org. Chem. 1986, 51, 629.
(17) Andersen, N. G.; Ramsden, P. D.; Che, D.; Parvez, M.; Keay, B.
A. Org. Lett. 1999, 1, 2009.
(18) Compound 14: monoclinic P21 (No. 4); a ) 9.842(4) Å, b )
21.045(5) Å, c ) 10.347(3) Å, â ) 108.64(3)°, V ) 2031(1) Å3; Z ) 2;
R ) 0.0406; Rw ) 0.0915; Flack parameter ) 0.006(19). Bijvoet analysis
was performed. A refinement of the inverted structure was carried out which
converged with R ) 0.0465, Rw ) 0.1043; Flack parameter ) 0.20(2) and
was therefore rejected as the absolute configuration present in the crystal.
(19) Allen, D. W.; Taylor, B. F. J. Chem. Soc., Dalton Trans. 1982, 51.
(20) Ozawa, F.; Kubo, A.; Matsumoto, Y.; Hayashi, T. Organometallics
1993, 12, 4188. (b) Ozawa, F.; Kubo, A.; Hayashi, T. J. Am. Chem. Soc.
1991, 113, 1417.
Supporting Information Available: Experimental pro-
cedures for the preparation of (+)-1 and (-)-1, a general
experimental procedure for the Heck reaction, and charac-
terization data for compounds 1, 10-12, 15a, and 15b. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(21) All reactions were performed in a sealed vial for the time shown.
OL006238+
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Org. Lett., Vol. 2, No. 18, 2000