Rhodium-catalyzed enantio- and diastereoselective intramolecular [2 + 2 + 2] cycloaddition of unsymmetrical dienynes

Article abstract of DOI:10.1039/b804294b

A cationic rhodium(i)/(R)-H₈-BINAP or (R)-Segphos complex catalyzes an intramolecular [2 + 2 + 2] cycloaddition of unsymmetrical dienynes, leading to fused tri- and tetracyclic cyclohexenes bearing two tertiary or quaternary carbon centers in high yields with high enantio- and diastereoselectivity. The Royal Society of Chemistry.

Full text of DOI:10.1039/b804294b

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Rhodium-catalyzed enantio- and diastereoselective intramolecular
[2 + 2 + 2] cycloaddition of unsymmetrical dienynesw
Hiromi Sagae,a Keiichi Noguchi,b Masao Hiranoa and Ken Tanaka*a
Received (in Cambridge, UK) 12th March 2008, Accepted 19th May 2008
First published as an Advance Article on the web 3rd July 2008
DOI: 10.1039/b804294b
A cationic rhodium(I)/(R)-H8-BINAP or (R)-Segphos complex
catalyzes an intramolecular [2 + 2 + 2] cycloaddition of
unsymmetrical dienynes, leading to fused tri- and tetracyclic
cyclohexenes bearing two tertiary or quaternary carbon centers
in high yields with high enantio- and diastereoselectivity.
by the reaction of a more reactive enyne moiety of dienyne A
with rhodium due to the steric repulsion between the Rh–CH2
Transition-metal-catalyzed enantioselective [2 + 2 + 2] cy-
cloadditions involving alkenes are efficient synthetic methods
for the rapid construction of chiral six-membered carbo-
cycles.1,2 Catalytic enantioselective [2 + 2 + 2] cycloadditions
of two monoynes and an alkene,3 1,6-diyne and alkene,4 1,6-
enyne and monoyne,5 and enediyne4b,6 using Ni2 and Rh4–6
complexes have been reported. However, catalytic enantio-
selective [2 + 2 + 2] cycloadditions of one alkyne unit and
two alkene units are scarce.7,8 Sato and co-workers recently
reported the synthesis of cis-fused tricyclic cyclohexenes by a
Ru-catalyzed intramolecular [2 + 2 + 2] cycloaddition of
both symmetrical and unsymmetrical dienynes.9 Indepen-
dently, we have also reported that an intramolecular
[2 + 2 + 2] cycloaddition of a symmetrical dienyne in the
presence of a cationic rhodium(I)/(R)-H8-BINAP complex
proceeded to give the corresponding cis- and trans-fused
tricyclic cyclohexenes in quantitative yield, while the achiral
meso-isomer (cis-fused cyclohexene) was obtained as the major
product.4b,10,11 Thus, we examined a [2 + 2 + 2] cycloaddi-
tion of unsymmetrical dienyne 1a bearing two different tethers,
which would furnish two chiral tricyclic cyclohexenes 2a and
3a possessing two quaternary-substituted carbon centers.12
Although the reaction proceeded in high yield by using the
same rhodium catalyst, and the minor product (+)-3a was
obtained with high ee, the major product (+)-2a was obtained
with low ee (eqn (1)).
ð1Þ
moiety and the equatorial P–Ph group of (R)-H8-BINAP.
Subsequently, the other stereocenter is constructed by the
coordination of another double bond of dienyne A to rhodium
due to the steric repulsion between the tether or R group and
the axial P–Ph group of (R)-H8-BINAP. Although trans-fused
cyclohexene (+)-3a was obtained with high ee, a similar
reactivity of the two enyne moieties of 1a toward rhodium
causes the low ee of cis-fused cyclohexene (+)-2a, presumably
due to the formation of both intermediates E and G. Accord-
ing to the above-mentioned mechanism, a trans-selective co-
ordination mode of the double bond shown in intermediate B
or C would be favorable by employing dienyne A with the
longer tether, which results in increased yield of trans-fused
cyclohexene D. On the other hand, a large difference in the
reactivity between the two enyne moieties of dienyne A toward
rhodium would induce the selective formation of either inter-
mediate E or G, which results in improved ee of cis-fused
cyclohexene F or H, respectively.
A possible mechanism for the formation of trans- and
cis-fused tricyclic cyclohexenes using the cationic rhodium(I)/
(R)-H8-BINAP complex as a catalyst is shown in Scheme 1.
We proposed that intermediates B and C furnish the same
enantiomer D of the trans-fused cyclohexene, and intermedi-
ates E and G furnish an enantiomeric pair of cis-fused
cyclohexenes F and H. One of the stereocenters is constructed
Thus, the reaction of unsymmetrical dienyne 1b bearing
different tether lengths was examined in the presence of the
cationic rhodium(I)/(R)-H8-BINAP complex (5 mol%).13 For-
tunately, the reaction proceeded to give the corresponding
chiral tricyclic cyclohexenes 2b and 3b in quantitative yield
(Table 1, entry 1).z In this reaction, trans-isomer 3b was
obtained as the major product with high ee, while cis-isomer
2b was obtained as the minor product with low ee. The
reaction of dienyne 1c bearing an ether-linked 1,6-enyne
moiety proceeded to give trans-isomer (+)-3c as the major
product with high ee and cis-isomer (+)-2c as the minor
product with moderate ee (entry 2). These results might show
that the reactivity of 1,6- and 1,7-enyne moieties toward
a Department of Applied Chemistry, Graduate School of Engineering,
Tokyo University of Agriculture and Technology, Koganei, Tokyo
184-8588, Japan. E-mail: tanaka-k@cc.tuat.ac.jp; Fax: +81 42 388
7037; Tel: +81 42 388 7037
b Instrumentation Analysis Center, Tokyo University of Agriculture
and Technology, Koganei, Tokyo 184-8588, Japan
w Electronic supplementary information (ESI) available: Experimental
details and crystallographic information for 3c and 2e. CCDC
673294–673295. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/b804294b
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Table
1
Rhodium-catalyzed enantio- and diastereoselective
[2 + 2 + 2] cycloaddition of unsymmetrical dienynes 1b–1ja
Product
[2 (cis)/3
(trans)],
yield (%)b
Dienyne
1
{cis : trans},
ee (%)
Entry
Conditions
1
2
1b (Z = NTs)
1c (Z = O)
80 1C, 3 h
2b/3b, 499
{1 : 2.4}, 4/99,
(+)-2c, 24, 45
(3aR,5aS)-(+)-
3c, 75, 499
rt, 16 h
3cd
4ce
5e
1d (R = Me)
1d (R = Me)
1e (R = H)
rt, 64 h
40 1C, 40 h
rt, 16 h
(+)-2d, 98, 94
(+)-2d, 94, 86
(3aR,5aS)-(+)-
2e, 89, 99
6
1e (R = H)
80 1C, 3 h
(3aR,5aS)-(+)-
2e, 82, 98
7e
8
1f [Z = C(CO2Et)2] rt, 16 h
1f [Z = C(CO2Et)2] 80 1C, 3 h
(+)-2f, 87, 97
(+)-2f, 88, 93
(+)-2g, 95, 93
Scheme 1 Possible mechanism for the formation of trans- and cis-
fused tricyclic cyclohexenes.
9
1g (Z = O)
80 1C, 3 h
rhodium is not different enough to allow the selective forma-
tion of intermediate E or G. The absolute configuration of
trans-fused cyclohexene (+)-3c was unambiguously deter-
mined by X-ray crystallographic analysis (Fig. 1), which is
indeed consistent with that derived from our proposed inter-
mediates B and C.
We anticipated that the reaction of phenol-linked dienyne
1d would selectively provide cis-fused cyclohexene 2d with
high ee through intermediate E (W = NTs). The phenol-
linked 1,7-enyne moiety may be much less reactive to rhodium
than the 1,6-enyne moiety, the double bond of which may not
coordinate to rhodium with trans-selectivity due to the rigid
structure of the phenol-linked tether. As expected, 1d cleanly
cyclized at room temperature to give (+)-2d as a sole product
in high yield with high ee, although a high catalyst loading
(20 mol%) was required (entry 3).14 By conducting the reac-
tion at elevated temperature (40 1C), the catalyst loading could
be reduced to 10 mol% with slight erosion of the yield and ee
10
1h
80 1C, 3 h
4, 70
{E/Z =
1 : 3.3}
11
1i
80 1C, 3 h
2i/3i, 57
{14 : 1}, 96/499
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Table 1 (continued )
Notes and references
Product
[2 (cis)/3
(trans)],
z General procedure: under an Ar atmosphere, a CH2Cl2 (1.0 mL)
solution of (R)-H8-BINAP or (R)-Segphos (0.010–0.040 mmol) was
added to a CH2Cl2 (1.0 mL) solution of [Rh(cod)2]BF4 (0.010–
0.040 mmol, 5–20 mol% Rh), and the solution was stirred at room
temperature for 5 min. H2 (1 atm) was introduced to the resulting
solution in a Schlenk tube. After stirring at room temperature for
0.5 h, the resulting solution was concentrated to dryness and the
residue was dissolved in CH2Cl2 (rt–40 1C) or (CH2Cl)2 (80 1C) (0.5
mL). To this solution was added a CH2Cl2 or (CH2Cl)2 (1.5 mL)
solution of 1 (0.200 mmol). The solution was stirred at rt–80 1C for
3–64 h. The resulting solution was concentrated and purified by
preparative TLC, which furnished 2 and/or 3.
yield (%)b
{cis : trans},
ee (%)
Dienyne
1
Entry
Conditions
1 For recent reviews of transition-metal-catalyzed [2 + 2 + 2]
cycloadditions, see: (a) N. Agenet, O. Buisine, F. Slowinski, V.
Gandon, C. Aubert and M. Malacria, Org. React., 2007, 68, 1;
(b) P. R. Chopade and J. Louie, Adv. Synth. Catal., 2006, 348,
2307; (c) V. Gandon, C. Aubert and M. Malacria, Chem. Com-
mun., 2006, 2209; (d) S. Kotha, E. Brahmachary and K. Lahiri,
Eur. J. Org. Chem., 2005, 4741; (e) Y. Yamamoto, Curr. Org.
Chem., 2005, 9, 503.
12e
1j
80 1C, 16 h
(+)-2j 81, 98
a
[Rh(cod)2]BF4 (0.010 mmol), (R)-H8-BINAP (0.010 mmol), 1b–1j
(0.20 mmol), and CH2Cl2 (rt–40 1C) or (CH2Cl)2 (80 1C) (2.0 mL) were
used. Isolated yield. Ligand: (R)-Segphos. Catalyst: 20 mol%.
b
c
d
e
Catalyst: 10 mol%.
2 For pioneering works on transition-metal-catalyzed enantioselec-
tive [2 + 2 + 2] cyclizations, see: (a) Y. Sato, T. Nishimata and M.
Mori, J. Org. Chem., 1994, 59, 6133; (b) I. G. Stara, I. Stary, A.
Kollarovic, F. Teply, S. Vyskocil and D. Saman, Tetrahedron Lett.,
1999, 40, 1993.
3 S. Ikeda, H. Kondo, T. Arii and K. Odashima, Chem. Commun.,
2002, 2422.
4 (a) K. Tsuchikama, Y. Kuwata and T. Shibata, J. Am. Chem. Soc.,
2006, 128, 13686; (b) K. Tanaka, G. Nishida, H. Sagae and M.
Hirano, Synlett, 2007, 1426; (c) T. Shibata, A. Kawachi, M.
Ogawa, Y. Kuwata, K. Tsuchikama and K. Endo, Tetrahedron,
2007, 63, 12853.
Fig. 1 ORTEP drawings of trans-cyclohexene (3aR,5aS)-3c (left) and
cis-cyclohexene (3aR,5aS)-2e (right).
5 (a) P. A. Evans, K. W. Lai and J. R. Sawyer, J. Am. Chem. Soc.,
2005, 127, 12466; (b) T. Shibata, Y. Arai and Y. Tahara, Org. Lett.,
2005, 7, 4955.
(entry 4). Interestingly, the reactions of dienynes 1e–1g bearing
monosubstituted 1,6-enyne moieties proceeded to give the
desired cyclohexenes (+)-2e–2g in high yields with high ees
(entries 5–9). Furthermore, these reactions could be conducted
with lower catalyst loadings than those for dienyne 1d bearing
a geminally disubstituted 1,6-enyne moiety. However, the
reaction of dienyne 1h bearing a monosubstituted 1,7-enyne
moiety furnished an E/Z mixture of diene 4 presumably
through b-hydride elimination of the rhodacycle intermediate
(entry 10). Finally, ester-linked cyclohexene 2i and cyclohex-
ene (+)-2j containing a seven-membered ring were also ob-
tained with high ees from the corresponding dienynes 1i and
1j, respectively (entries 11 and 12). The absolute configuration
of cis-fused cyclohexene (+)-2e was unambiguously deter-
mined by X-ray crystallographic analysis (Fig. 1), which is
again consistent with that derived from our proposed inter-
mediate E (W = NTs).
6 T. Shibata, H. Kurokawa and K. Kanda, J. Org. Chem., 2007, 72,
6521.
7 For a Rh(I)+/modified-BINAP-catalyzed enantioselective [2 + 2 + 2]
cycloaddition of 1,4-diene-ynes, see: T. Shibata and Y. Tahara, J. Am.
Chem. Soc., 2006, 128, 11767.
8 For a Ni-catalyzed non-asymmetric [2 + 2 + 2] cycloaddition
of 1,6-enynes with alkenes, see: J. Seo, H. M. P. Chui, M. J.
Heeg and J. Montgomery, J. Am. Chem. Soc., 1999, 121
476.
9 D. Tanaka, Y. Sato and M. Mori, J. Am. Chem. Soc., 2007, 129,
7730.
10 For our first discovery of the cationic Rh(I)/BINAP-type bis-
phosphine complex-catalyzed [2 + 2 + 2] cycloadditions, see: K.
Tanaka and K. Shirasaka, Org. Lett., 2003, 5, 4697.
11 For our accounts of cationic Rh(I)/BINAP-type bis-phosphine
complex-catalyzed [2 + 2 + 2] cycloadditions, see: (a) K. Tanaka,
Synlett, 2007, 1977; (b) K. Tanaka, G. Nishida and T. Suda, J.
Synth. Org. Chem., Jpn., 2007, 65, 862.
12 For recent reviews of catalytic asymmetric methods that
generate quaternary-substituted carbon centers, see: (a) B. M.
Trost and C. Jiang, Synthesis, 2006, 369; (b) C. J.
Douglas and L. E. Overman, Proc. Natl. Acad. Sci. U. S. A.,
2004, 101, 5363; (c) I. Denissova and L. Barriault, Tetrahedron,
2003, 59, 10105.
13 In favor of this approach, the cationic Rh(I)/H8-BINAP complex
can catalyze an intramolecular [2 + 2 + 2] cycloaddition of triynes
bearing a long tether to give enantioenriched [n]metacyclophanes
with high enantioselectivity, see: (a) K. Tanaka, H. Sagae, K.
Toyoda, K. Noguchi and M. Hirano, J. Am. Chem. Soc., 2007,
129, 1522; (b) K. Tanaka, H. Sagae, K. Toyoda and M. Hirano,
Tetrahedron, 2008, 64, 831.
14 In this case, the use of (R)-Segphos as a ligand furnished the
cycloaddition product with higher ee than that using (R)-H8-
BINAP.
In conclusion, we have determined that a cationic rhodium(I)/
(R)-H8-BINAP or (R)-Segphos complex catalyzes an intra-
molecular [2 + 2 + 2] cycloaddition of rationally designed
unsymmetrical dienynes, leading to fused tricyclic and tetracyclic
cyclohexenes possessing two tertiary or quaternary carbon
centers in high yields with high enantio- and diastereoselectivity.
This work was supported partly by a Grant-in-Aid for
Scientific Research (No. 19350046 and 20675002) from the
Ministry of Education, Culture, Sports, Science and Technol-
ogy, Japan. We thank Takasago International Corporation
for the gift of modified-BINAP ligands.
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This journal is The Royal Society of Chemistry 2008
3806 | Chem. Commun., 2008, 3804–3806