Rhodium-catalyzed highly enantio- and diastereoselective cotrimerization of alkenes and dialkyl acetylenedicarboxylates leading to furylcyclopropanes

Article abstract of DOI:10.1021/ol800966f

(Chemical Equation Presented) A cationic rhodium(I)/Segphos or H ₈-BINAP complex catalyzes the unprecedented cotrimerization of commercially available monoenes and dialkyl acetylenedicarboxylates, leading to functionalized furylcyclopropanes with excellent enantioselectivity and perfect diastereoselectivity.

Full text of DOI:10.1021/ol800966f

ORGANIC
LETTERS
2008
Vol. 10, No. 13
2825-2828
Rhodium-Catalyzed Highly Enantio- and
Diastereoselective Cotrimerization of
Alkenes and Dialkyl
Acetylenedicarboxylates Leading to
Furylcyclopropanes
Yu Shibata,† Keiichi Noguchi,‡ Masao Hirano,† and Ken Tanaka*,†
Department of Applied Chemistry, Graduate School of Engineering, and
Instrumentation Analysis Center, Tokyo UniVersity of Agriculture and Technology,
Koganei, Tokyo 184-8588, Japan
tanaka-k@cc.tuat.ac.jp
Received April 26, 2008
ABSTRACT
A cationic rhodium(I)/Segphos or H8-BINAP complex catalyzes the unprecedented cotrimerization of commercially available monoenes and
dialkyl acetylenedicarboxylates, leading to functionalized furylcyclopropanes with excellent enantioselectivity and perfect diastereoselectivity.
The transition-metal-catalyzed intermolecular cotrimerization
of two or three different monoynes leading to substituted
benzenes has been extensively studied because of its highly
atom-economical nature.1 The intermolecular cotrimerization
of two monoynes and one monoene leading to conjugated
cyclohexadienes has also been studied using a number of
transition-metal catalysts.2,3 Enantioselective variants have
been realized by a Ni-catalyzed reaction between cyclic
enones and electron-rich monoynes, but with moderate
enantioselectivity (4-62% ee).4 On the other hand, our
research group demonstrated that a cationic rhodium(I)/
(2) For examples of transition-metal-catalyzed intermolecular cotri-
merizations of one monoene and two monoalkynes leading to cyclohexa-
dienes, see: (a) Yamamoto, Y.; Ohno, T.; Itoh, K. Organometallics 2003,
22, 2267. (b) Ikeda, S.; Mori, N.; Sato, Y. J. Am. Chem. Soc. 1997, 119,
4779. (c) Mori, N.; Ikeda, S.; Sato, Y. J. Am. Chem. Soc. 1999, 121, 2722.
(d) Itoh, K.; Hirai, K.; Sasaki, M. Chem. Lett. 1981, 865. (e) Brown, L. D.;
Itoh, K.; Suzuki, H.; Hirai, K.; Ibers, J. A. J. Am. Chem. Soc. 1978, 100,
8232. (f) Suzuki, H.; Itoh, K.; Ishii, Y.; Simon, K.; Ibers, J. A. J. Am. Chem.
Soc. 1976, 98, 8494. (g) Chark, A. J. J. Am. Chem. Soc. 1972, 94, 5928.
For Ni-catalyzed intermolecular cotrimerizations of ethyl cyclopropylide-
neacetate and two monoalkynes leading to cycloheptadienes, see: (h)
Komagawa, S.; Saito, S. Angew. Chem., Int. Ed. 2006, 45, 2446. (i) Saito,
S.; Masuda, M.; Komagawa, S. J. Am. Chem. Soc. 2004, 126, 10540.
(3) The complete intermolecular cyclohexadiene formation by using the
CpCo system requires prior formation of a stoichiometric amount of a
cobaltacyclopentadiene, see: (a) Wakatsuki, Y.; Aoki, K.; Yamazaki, H.
J. Am. Chem. Soc. 1974, 96, 5284. (b) Macomber, D. W.; Verma, A. G.
Organometallics 1988, 7, 1241.
† Department of Applied Chemistry.
‡ Instrumentation Analysis Center.
(1) For recent reviews, see: (a) Agenet, N.; Buisine, O.; Slowinski, F.;
Gandon, V.; Aubert, C.; Malacria, M. In Organic Reactions; Overman, L. E.,
Ed.; John Wiley & Sons: Hoboken, 2007; vol. 68, p 1. (b) Chopade, P. R.;
Louie, J. AdV. Synth. Catal. 2006, 348, 2307. (c) Gandon, V.; Aubert, C.;
Malacria, M. Chem. Commun. 2006, 2209. (d) Kotha, S.; Brahmachary,
E.; Lahiri, K. Eur. J. Org. Chem. 2005, 4741. (e) Yamamoto, Y. Curr.
Org. Chem. 2005, 9, 503. (f) Robinson, J. E. In Modern Rhodium-Catalyzed
Organic Reactions; Evans, P. A., Ed.; Wiley-VCH: Weinheim, 2005; p
129.
(4) Ikeda, S.; Kondo, H.; Arii, T.; Odashima, K. Chem. Commun. 2002,
2422.
10.1021/ol800966f CCC: $40.75
Published on Web 06/11/2008
2008 American Chemical Society

H8-BINAP complex can catalyze highly chemo- and regi-
oselective cotrimerization of two electron-rich terminal
monoynes and one dialkyl acetylenedicarboxylate, leading
to tetrasubstituted benzenes at room temperature.5 In this
paper, we describe unprecedented cotrimerization of one
electron-rich monoene and two dialkyl acetylenedicarboxy-
lates, leading to furylcyclopropanes with excellent enanti-
oselectivity and perfect diastereoselectivity by using a
cationic rhodium(I)/Segphos or H8-BINAP complex as a
catalyst.
Table 1. Screening of Ligands for Rh-Catalyzed Enantio- and
Diastereoselective Cotrimerization of 1a and 2aa
We first investigated the reaction of dimethyl acetylene-
dicarboxylate (2a) with a large excess of 1-octene (1a, 5
equiv) in the presence of a [Rh(cod)2]BF4/(R)-H8-BINAP
catalyst. Surprisingly, the reaction proceeded at room tem-
perature to give an unprecedented cotrimerization product,
chiral furylcyclopropane 3aa, with perfect enantio- and
diastereoselectivity along with conventional cotrimerization
product 4aa (Scheme 1).6 Although chiral cyclohexadiene
% yieldb
of 3aa
(cis/trans, % ee)
% yieldb
of 4aa
(% ee)
entry
ligand
1
2
3
4
5
6
(R)-H8-BINAP
(R)-BINAP
(R)-Segphos
(S)-tol-Segphos
(S)-xyl-Segphos
(R)-DTBM-Segphos
22 (>99:1, >99)
24 (>99:1, >99)
43 (>99:1, 99)
32 (>99:1, 98)
30 (>99:1, >99)
10 (>99:1, >99)
65 (89)
46 (95)
43 (90)
41 (93)
37 (89)
74 (>99)
a Reactions were conducted using [Rh(cod)2]BF4 (0.015 mmol), ligand
(0.015 mmol), 1a (1.50 mmol), 2a (0.300 mmol), and (CH2Cl)2 (3.0 mL)
at rt for 3 h. b Isolated yield.
Scheme 1
dimethyl acetylenedicarboxylate (2a, entry 1). However, di-
tert-butyl acetylenedicarboxylate (2c) failed to react with 1a
(entry 3). Finally, the amount of 1a could be reduced to 1.1
equiv with only slight erosion of the yield of 3ab (entry 4),
but further reduction in the amount of 1a to 0.5 equiv
decreased the yield to 43% (entry 5).
4aa was obtained as a major product with high ee, 4aa was
unstable and gradually decomposed.
Table 2. Rh(I)+/(R)-Segphos-Catalyzed Enantio- and
Diastereoselective Cotrimerization of 1a and 2a-ca
To improve the yield of furylcyclopropane 3aa, various
axially chiral biarylbisphosphine ligands were screened as
shown in Table 1. The study revealed that the yield of 3aa
is dependent on the dihedral angle of the biarylbisphosphine
ligands [dihedral angle: H8-BINAP (entry 1) > BINAP
(entry 2) > Segphos (entry 3),7 yield of 3aa: entry 1 < entry
2 < entry 3]. The use of Segphos that possesses the narrowest
dihedral angle furnished 3aa in the highest yield with
excellent enantioselectivity (entry 3). The effect of the steric
bulk of the aryl group on the phosphorus was also examined,
which revealed that increasing the steric bulk decreases the
yield of 3aa and increases the ratio of 4aa/3aa (entries 3-6).
Next, the effect of alkoxy groups on the dialkyl acety-
lenedicarboxylates was examined as shown in Table 2. The
use of diethyl acetylenedicarboxylate (2b, entry 2) furnished
the cyclopropane product in higher yield than that using
% yieldb
of 3
(cis/trans, % ee)
% yieldb
of 4
(% ee)
2
1a
(equiv)
entry
(R2)
1
2
3
4
5
2a (Me)
2b (Et)
2c (t-Bu)
2b (Et)
2b (Et)
5.0
5.0
5.0
1.1
0.5
43 (>99:1, 99)
58 (>99:1, 98)
0 (-)
54 (>99:1, 98)
43 (>99:1, 98)
43 (90)
32 (90)
0 (-)
33 (90)
27 (90)
a Reactions were conducted using [Rh(cod)2]BF4 (0.015 mmol), (R)-
Segphos (0.015 mmol), 1a (0.150-1.50 mmol), 2a-c (0.300 mmol), and
(CH2Cl)2 (3.0 mL) at rt for 3 h. b Isolated yield.
A variety of monoenes were subjected to the reaction with
2b in the presence of the cationic rhodium(I)/(R)-Segphos
catalyst as shown in Table 3. Not only 1-octene (1a, entry
1) but also a range of primary and secondary alkyl-substituted
1-alkenes (1b-e, entries 3-6) could participate in this
reaction. The reactions involving haloalkyl (1f and 1g, entries
7-9) and oxygen-functionalized alkyl (1h-j, entries 10-12)
substituted 1-alkenes proceeded with excellent ee’s. Impor-
tantly, all reactions shown in Table 3 furnished the trisub-
stituted cyclopropanes with perfect diastereoselectivity.
Furthermore, the catalytic activity of this rhodium catalyst
(5) (a) Tanaka, K.; Shirasaka, K. Org. Lett. 2003, 5, 4697. (b) Tanaka,
K.; Toyoda, K.; Wada, A.; Shirasaka, K.; Hirano, M. Chem.sEur. J. 2005,
11, 1145.
(6) For reviews of the transition-metal-catalyzed cyclopropanation of
olefins with diazo reagents, see: (a) Lebel, H.; Marcoux, J.-F.; Molinaro,
C.; Charette, A. B. Chem. ReV. 2003, 103, 977. (b) Davies, H. M. L.;
Antoulinakis, E. Org. React. 2001, 57, 1. (c) Doyle, M. P.; Forbes, D. C.
Chem. ReV. 1998, 98, 911. (d) Padwa, A.; Krumpe, K. E. Tetrahedron 1992,
48, 5385.
(7) Shimizu, H.; Nagasaki, I.; Saito, T. Tetrahedron 2005, 61, 5405.
2826
Org. Lett., Vol. 10, No. 13, 2008

Scheme 3
Table 3. Rh(I)+/(R)-Segphos-Catalyzed Enantio- and
Diastereoselective Cotrimerization of 1a-j and 2b Leading to
Furylcyclopropanesa
yield
(%)b
ee
(%)
entry
1 (R)
3
cis/trans
1
1a (n-C6H13
1a (n-C6H13
1b (n-C12H25
1c [(CH2)2Ph]
1d (i-Bu)
1e (Cy)
1f [(CH2)4Cl]
1g [(CH2)3Br]
1g [(CH2)3Br]
1h [(CH2)2Ac]
1i [(CH2)4OAc]
)
)
(+)-3ab
(+)-3ab
(+)-3bb
(+)-3cb
(+)-3db
(+)-3eb
(+)-3fb
(+)-3gb
(+)-3ga
(+)-3hb
(+)-3ib
54
55
56
50
62
58
48
50
34
46
49
53
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
98
98
97
98
99
97
>99
99
>99
98
98
2c
3
)
4d
5
6e
7
8
9f
10d
11d
12
cis configuration.8,9 The reaction of 2 with C furnishes
intermediate D, which subsequently furnishes (1R,2R)-
furylcyclopropane 3. The higher reactivity of dialkyl acety-
lenedicarboxylate 2 than that of monoene 1 to the cationic
rhodium might promote the formation of D.
1j [(CH2)8CO2Me] (+)-3jb
99
a [Rh(cod)2]BF4 (0.015 mmol), (R)-Segphos (0.015 mmol), 1a-j (0.330
mmol), 2b (0.300 mmol), and (CH2Cl)2 (3.0 mL) were used. b Isolated yield.
c Catalyst: 1 mol %. For 16 h. d At 40 °C. e Ligand: (R)-H8-BINAP. f 1g
(1.50 mmol) and 2a (0.300 mmol) were used.
Alternatively, two molecules of 2 react with rhodium to
give rhodacyclopentadiene E (Scheme 4). Insertion of 1 to
E followed by ring contraction or cyclopropanation via
rhodacyclopentatriene G might furnish intermediate H. In
this mechanism, E/Z isomerization of intermediate H to
intermediate I is necessary to form furylcyclopropane 3.
In accordance with the mechanism shown in Scheme 3,
the reaction of 1a and 1e with 2a in the presence of the
cationic rhodium(I)/(R)-Segphos catalyst furnished dienes 6
and 7 as byproducts presumably through ꢀ-hydride elimina-
tion from intermediates A and B, respectively (Scheme 5).
On the other hand, the reaction of sterically demanding
monoene 1k with 2a furnished cyclohexadiene 4ka as a sole
product presumably through intermediate E, thereby sup-
porting the mechanism shown in Scheme 4.10,11
is very high so that the reaction could be carried out even
with 1 mol % of the catalyst (entry 2). The structure of the
cyclopropane product was unambiguously determined by
X-ray crystallographic analysis of (()-3ed prepared by the
reaction of 1e and di-4-bromobenzyl acetylenedicarboxylate
(2d).
The synthetic utility of the furylcyclopropanes is demon-
strated in Scheme 2. A Ru-catalyzed oxidation of furylcy-
Scheme 2
(8) In the intramolecular [2 + 2 + 2] cycloaddition of dienynes with
the Cp*RuCl(cod) catalyst, the formation of tandem cyclopropanation
products was observed. The authors proposed the formation of a ruthenium
carbene complex through ring contraction of an initially formed ruthena-
cyclopentene intermediate; see: (a) Tanaka, D.; Sato, Y.; Mori, M. J. Am.
Chem. Soc. 2007, 129, 7730.
(9) When the carbonyl group is conjugated with the alkyne moiety of
enynes, the Cp*RuCl(cod)-catalyzed cyclopropanation of ethylene with the
enynes proceeded in high yield. The authors proposed that the reaction
proceeds through a ruthenium carbene complex, which is in equilibrium
with oxaruthenacyclobutene; see: (a) Tanaka, D.; Sato, Y.; Mori, M.
Organometallics 2006, 25, 799.
clopropane (+)-3ga furnished ketoester (+)-5 in high yield.
Its absolute configuration was determined to be (1R,2R) by
X-ray crystallographic analysis of the corresponding 2,4-
dinitrophenylhydrazone.
(10) Importantly, ee values of cyclohexadiene 4 are lower than those of
furylcyclopropane 3 (Scheme 5). We anticipated that cyclohexadienes 4
generated through intermediate E possess the absolute configurations
opposite to those generated through intermediates A and B. Sterically less
demanding monoene 1a reacts with 2a to give (-)-4aa through intermediates
A and B, which might result in the high ee value of (-)-4aa. On the other
hand, sterically demanding monoene 1e reacts with 2a to give (-)-4ea
through not only intermediates A and B but also intermediate E, which
might result in the low ee value of (-)-4ea. In the reaction of sterically
more demanding monoene 1k with 2a, intermediate E might be formed
predominantly to give cyclohexadiene (+)-4ka as a sole product with high
ee. The opposite optical rotations, (-)-4aa/(-)-4ea vs (+)-4ka, might be
Although the precise mechanism cannot be determined at
the present stage, our proposed mechanism for the formation
of furylcyclopropane 3 is shown in Scheme 3. Monoene 1
and dialkyl acetylenedicarboxylate 2 react with rhodium to
give rhodacyclopentene A or B depending on the steric
interaction between the substituent (R1) of monoene or the
Rh-CH2 moiety and the equatorial P-Ph group of (R)-
Segphos. Ring contraction of A or B occurs to form rhodium
carbene C bearing a cyclopropane ring with R1 and E in a
correlated with the opposite absolute configurations
.
Org. Lett., Vol. 10, No. 13, 2008
2827

Scheme 4
Scheme 6
Yamamoto, and co-workers reported the Ru(II)-catalyzed
cotrimerization of norbornene and 1,6-diynes leading to
tandem cyclopropanation products via a ruthenacyclopen-
tatriene intermediate.12 Therefore, the reaction of norbornene
1l with 2a was also investigated, which revealed that
cyclohexadiene 4la was obtained as a sole product and 3, 8,
and 9 were not obtained at all (Scheme 6). According to
these results, the mechanism shown in Scheme 3 is more
likely than that shown in Scheme 4 at the present stage.
In conclusion, we have demonstrated that a cationic
rhodium(I)/Segphos or H8-BINAP complex catalyzes the
unprecedented cotrimerization of commercially available
monoenes and dialkyl acetylenedicarboxylates, leading to
functionalized furylcyclopropanes with excellent enantiose-
lectivity and perfect diastereoselectivity. Mechanistic studies
revealed that furylcyclopropanes might be generated through
rhodacyclopentene intermediates. Future studies will focus
on expanding the scope and elucidation of the precise
mechanism.
To gain more mechanistic insights, the reaction of ethoxy-
carbonyl-substituted 1,6-diyne 10 with 1a was investigated
(Scheme 6). As E/Z isomerization of intermediate H to
intermediate I is impossible in this case, tandem cyclopro-
panation product 8 or furan 9 shown in Scheme 4 might be
Scheme 5
Acknowledgment. This work was supported in part by a
Grant-in-Aid for Scientific Research [Nos. 20675002 and
19028015 (Chemistry of Concerto Catalysis)] from the
Ministry of Education, Culture, Sports, Science and Technol-
ogy, Japan. We thank Takasago International Corp. for the
gift of modified-BINAP ligands.
Supporting Information Available: Experimental pro-
cedures, compound characterization data, and X-ray crystal-
lographic information files (CIF). This material is available
free of charge via the Internet at http://pubs.acs.org.
generated. However, cyclohexadiene 11 was obtained as a
sole product, and 8 and 9 were not obtained at all. Itoh,
OL800966F
(11) In this reaction, no conversion of 1k was observed using (R)-
(12) Yamamoto, Y.; Kitahara, H.; Ogawa, R.; Kawaguchi, H.; Tatsumi,
K.; Itoh, K. J. Am. Chem. Soc. 2000, 122, 4310.
Segphos as a ligand
.
2828
Org. Lett., Vol. 10, No. 13, 2008