Rh-catalyzed triple allene approach to bicyclo[4.4.0]decene derivatives and its application for the stepwise synthesis of steroid-like tetracyclic skeletons

Article abstract of DOI:10.1021/ol702557s

(Chemical Equation Presented) The construction of a new type of bicyclo[4.4.0]decene products with a conjugated exocyclic diene unit was developed using Rh-catalyzed cyclization of 1,5-bisailenes in the presence of monoallenes. The steroid-like tetracycli

Full text of DOI:10.1021/ol702557s

ORGANIC
LETTERS
2007
Vol. 9, No. 25
5319-5321
Rh-Catalyzed Triple Allene Approach to
Bicyclo[4.4.0]decene Derivatives and Its
Application for the Stepwise Synthesis
of Steroid-Like Tetracyclic Skeletons
Ping Lu and Shengming Ma*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, PRC
masm@mail.sioc.ac.cn
Received October 20, 2007
ABSTRACT
The construction of a new type of bicyclo[4.4.0]decene products with a conjugated exocyclic diene unit was developed using Rh-catalyzed
cyclization of 1,5-bisallenes in the presence of monoallenes. The steroid-like tetracyclic products could be obtained by applying an alkylation
−
Diels Alder process.
−
Transition-metal-catalyzed cyclization reactions have shown
their power for the synthesis of complex organic skeletons
in an often highly selective fashion from simple and readily
available starting materials.1 Nowadays, allenes have attracted
extensive attention in these reactions due to their specific
synthetic versatility.2,3 Recently, we reported the bimolecular
cyclometalation of bisallenes for one-step synthesis of
steroid-like tetracyclic skeletons (eq 1).4 Our continuing study
showed that the bimolecular cyclization reaction of two
different bisallenes provided a mixture of four products
leading to the isolation of two “cross” 18,19-norsteroid-like
scaffolds formed from two different bisallenes after chro-
matographic separation.5 Herein, we wish to report a Rh-
catalyzed cyclization of 1,5-bisallenes in the presence of
monoallenes for the efficient synthesis of fused 6,6-bicyclic
(3) For recent examples for cycloisomerizations of allenynes, see: (a)
Brummond, K. M.; Painter, T. O.; Probst, D. A.; Mitasev, B. Org. Lett.
2007, 9, 347. (b) Brummond, K. M.; McCabe, J. M. Tetrahedron
2006, 62, 10541. (c) Lemie`re, G.; Gandon, V.; Agenet, N.; Goddard, J.;
Kozak, A.; Aubert, C.; Fensterbank, L.; Malacria, M. Angew. Chem., Int.
Ed. 2006, 45, 7596. For recent examples for cycloisomerizations of
allenenes, see: (d) Makino, T.; Itoh, K. J. Org. Chem. 2004, 69, 395. (e)
Brummond, K. M.; Chen, H.; Mitasev, B.; Casarez, A. D. Org. Lett.
2004, 6, 2161. For other examples for cyclometalations of allenes, see:
(f) Wender, P. A.; Deschamps, N. M.; Sun, R. Angew. Chem., Int. Ed.
2006, 45, 3957. (g) Wender, P. A.; Croatt, M. P.; Deschamps, N. M.
Angew. Chem., Int. Ed. 2006, 45, 2459. (h) Barluenga, J.; Vicente, R.;
Lopez, L. A.; Tomas, M. J. Am. Chem. Soc. 2006, 128, 7050. (i) Trost, B.
M.; Pinkerton, A. B.; Seidel, M. J. Am. Chem. Soc. 2001, 123, 12466. (j)
Chang, H.-T.; Jayanth, T. T.; Cheng, C.-H. J. Am. Chem. Soc. 2007, 129,
4166.
(1) (a) Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan, R. J. Chem. ReV.
1996, 96, 635. (b) Aubert, C.; Buisine, O.; Malacria, M. Chem. ReV. 2002,
102, 813. (c) Nakamura, I.; Yamamoto, Y. Chem. ReV. 2004, 104, 2127.
(d) Saito, S.; Yamamoto, Y. Chem. ReV. 2000, 100, 2901.
(2) For reviews, see: (a) Mandai, T. Transition Metal-catalyzed Addition/
Cycloaddition of Allenes. In Modern Allene Chemistry; Krause, N., Hashmi,
A. S. K., Eds.; Wiley-VCH: Weinheim, Germany, 2004; Vols. 1 and 2
and references therein. (b) Ma, S. Chem. ReV. 2005, 105, 2829 and
references therein. (c) Wender, P. A.; Baryza, J. L.; Brenner, S. E.; Clarke,
M. O.; Gamber, G. G.; Horan, J. C.; Jessop, T. C.; Kan, C.; Pattabiraman,
K.; Williams, T. J. Pure Appl. Chem. 2003, 75, 143. (d) Trost, B. M. Acc.
Chem. Res. 2002, 35, 695.
(4) Ma, S.; Lu, P.; Lu, L.; Hou, H.; Wei, J.; He, Q.; Gu, Z.; Jiang, X.;
Jin, X. Angew. Chem., Int. Ed. 2005, 44, 5275.
(5) Ma, S.; Lu, L. Chem. Asian J. 2007, 2, 199.
10.1021/ol702557s CCC: $37.00
© 2007 American Chemical Society
Published on Web 11/15/2007

products. In addition, with a sequential alkylation and cyclic
Diels-Alder reaction, the steroid-like skeletons may be
constructed in a stepwise manner diastereoselectively.
Figure 1. ORTEP representations of 4ab (left) and 5ab (right).
We initiated our study with trans-RhCl(CO)(PPh3)2-cata-
lyzed cyclization between 1,5-bisallene 1a and monoallene
3a in toluene. Fortunately, after careful screening of the
reaction conditions, the fused 6,6-bicyclic product 4aa with
two exocyclic carbon-carbon double bonds was isolated in
46% yield when the solution of bisallene 1a in toluene was
added via a syringe pump into the solution of rhodium
catalyst and 2.5 equiv of monoallene 3a in toluene at 80 °C
(condition A) (eq 2).
study (Figure 1, left).6 The reaction of 1a and N-Boc-pro-
tected buta-2,3-dienyl tosylamide 3c provided the 2,4-
dienylamide 4ac in 55% yield (entry 2). Similarly, N-Boc-
protected penta-3,4-dienyl tosylamide 3d could also be used
to afford 4ad in 50% yield (entry 3). Interestingly, the reac-
tion of the unprotected penta-3,4-dien-1-ol 3e with 1a
afforded the alcohol 4ae in good yield (entry 4). The reaction
of buta-2,3-dienyl phthalimide 3f or penta-3,4-dienyl phthal-
imide 3g with 1a both afforded corresponding products 4af
or 4ag in moderate yields, respectively (entries 5 and 6).
Treatment of 4ab with N-phenyl maleimide afforded the
Diels-Alder product 5ab in the yield of 91% (Scheme 1).
Encouraged by the above result, we studied the scope of
this cycloaddition reaction with different monoallenes 3
(Table 1). The reaction of 1a and the freshly prepared
Scheme 1
Table 1. Substrate Scope of Rh-Catalyzed Cyclization of
Bisallene 1a in the Presence of Monoallenesa
The diastereoisomeric ratio should be higher than 6.3:1. The
structure of tetracyclic product 5ab was unambiguously
confirmed by X-ray diffraction study (Figure 1, right).7
Treatment of 4ag and N-ethyl maleimide also afforded the
tetracyclic product 5ag in the yield of 81%. The diastereo-
isomeric ratio is g93.5:6.5.
Encouraged by this highly selective intermolecular Diels-
Alder reaction, the intramolecular reaction of the 1,3-diene
unit in 4aa with an activated alkene, e.g., R,â-unsaturated
conditions/
time (h)
entry
R
yield of 4 (%)
1
2
3
4
5
6
Ph (3b)
Bb/22
Ad/21
A/24
A/22
A/24
A/24
55 (4ab)c
55 (4ac)c
50 (4ad)c
54 (4ae)e
56 (4af)e
50 (4ag)c
CH2NTsBoc (3c)
CH2CH2NTsBoc (3d)
CH2CH2OH (3e)
CH2NX (3f)f
CH2CH2NX (3g)f
a
The reaction was carried out using 1a (0.25 mmol), 3 (0.625 mmol),
(6) Crystal data for 4ab: C30H28O4S2, MW ) 516.64, monoclinic,
P2(1)/c. a ) 13.4994(15) Å, b ) 21.855(2) Å, c ) 8.6424(10) Å, V )
2548.7(5) Å3, T ) 293(2) K, Z ) 4. R indices (all data), R1 ) 0.0844,
wR2 ) 0.1379. Final R indices [I > 2σ(I)], R1 ) 0.0557, wR2 ) 0.1269.
Reflections collected/unique: 14929/5553 (Rint ) 0.1088), number of
observations [>2σ(I)] 3583; parameters, 329. Supplementary crystal-
lographic data have been deposited at the Cambridge Crystallographic Data
Center, CCDC 651338.
(7) Crystal data for 5ab: C40H35NO6S2, MW ) 689.81, monoclinic,
P2(1)/c. a ) 16.4936(14) Å, b ) 9.1500(8) Å, c ) 23.709(2) Å, V ) 3371.1-
(5) Å3, T ) 293(2) K, Z ) 4. R indices (all data), R1 ) 0.0754, wR2 )
0.1276. Final R indices [I > 2σ(I)], R1 ) 0.0529, wR2 ) 0.1190,
Reflections collected/unique: 17938/6631 (Rint ) 0.0940), number of
observations [>2σ(I)] 4701; parameters, 442. Supplementary crystal-
lographic data have been deposited at the Cambridge Crystallographic Data
Center, CCDC 651339.
b
and 5 mol % of trans-RhCl(CO)(PPh3)2 in toluene (12 mL) at 80 °C.
Conditions B: a solution of 1a and 3 in toluene (10 mL) was added to a
solution of trans-RhCl(CO)(PPh3)2 in toluene (2 mL) via a syringe pump
c
over ∼10 h at 80 °C. The byproduct 2a was contaminated with other
uncharacterized mixtures. d Conditions A: a solution of 1a was added to a
solution of trans-RhCl(CO)(PPh3)2 and 3 in toluene (2 mL) via a syringe
pump over ∼10 h at 80 °C. e The yield of byproduct 2a was less than 18%.
f
NX ) phthalimide.
phenylallene 3b efficiently afforded the cyclization product
4ab in 55% yield under condition B (entry 1). The structure
of 4ab was unambiguously confirmed by X-ray diffraction
5320
Org. Lett., Vol. 9, No. 25, 2007

enoate, was also studied. It was a surprise for us to observe
that when product 4aa was treated with ethyl 4-bromo-
crotonate, K2CO3, and TBAB in DMF at 35 °C, the cyclic
Diels-Alder reaction followed the allylation reaction im-
mediately to afford the steroid-like tetracyclic product 6 in
the yield of 85% (Scheme 2).8 The diastereoisomeric ratio
Scheme 3
Scheme 2
of trans-RhCl(CO)(PPh3)2 provided the Diels-Alder product
8 as a mixture of diastereoisomeric products. Aromatization
of 8 with DDQ in toluene under reflux afforded the
tetracyclic product 9 with two aromatic six-membered rings
in 55-85% yield,10 indicating a desulfonylation reaction took
place together with the dehydrogenation reaction.11 The
structure of aromatic product 9 was unambiguously con-
firmed by X-ray diffraction study (Figure 2, right).12
In conclusion, we have developed a Rh-catalyzed cycliza-
tion of a 1,5-bisallene in the presence of a monoallene
affording a new type of fused 6,6-bicyclic products with a
conjugated exocyclic diene unit, which may be applied as
precursors for synthesis of tetracyclic skeletons with high
diastereoselectivity efficiently via the alkylation and the
subsequent cyclic Diels-Alder reaction. Further study in this
area is being pursued in our laboratory.
is g10:1. The structure of the major diastereoisomer,
obtained easily by recrystallization from CH2Cl2 and petro-
leum ether, was unambiguously confirmed by X-ray diffrac-
tion study of 6 (Figure 2, left).9 The C/D ring junction here
Acknowledgment. Financial support from the Major
State Basic Research Development Program (2006CB806105),
National Natural Science Foundation of China (20423001,
20121202, and 20332060), and the Shanghai Municipal
Committee of Science and Technology is greatly appreciated.
We thank Mr. Xuefeng Jiang in our research group for
reproducing the results presented in eq 1, Scheme 2, and
Scheme 3.
Figure 2. ORTEP representations of 6 (left) and 9 (right).
is trans, which is opposite to what was observed in our
previous report.4
Supporting Information Available: Experimental pro-
cedures and characterization data of all new products (PDF).
This material is available free of charge via the Internet at
http://pubs.acs.org.
Furthermore, the intramolecular Diels-Alder reaction of
the 1,3-diene unit in 4aa and a terminal alkyne was also
explored (Scheme 3). However, the reaction of 4aa, the
propargyl bromide, K2CO3, and TBAB in DMF afforded the
alkylation product 7 in almost quantitative yield without
further Diels-Alder reaction. Treament of 7 with 5 mol %
OL702557S
(10) The ring C in compound 8 may be somewhat aromatized in the
solvent if exposed to air.
(8) Crystal data for 6: C36.5H41ClO10S2, MW ) 739.26, triclinic, P-1. a
) 14.74(1) Å, b ) 16.01(1) Å, c ) 16.60(1) Å, V ) 3550(5) Å3, T )
293(2) K, Z ) 4. R indices (all data), R1 ) 0.1107, wR2 ) 0.2031. Final
R indices [I > 2σ(I)], R1 ) 0.0688, wR2 ) 0.1791. Reflections collected/
unique: 18526/12890 (Rint ) 0.0813), number of observations [>2σ(I)]
7256; parameters, 898. Supplementary crystallographic data have been
deposited at the Cambridge Crystallographic Data Center, CCDC 651340.
(9) For recent examples for synthesis of steroid from an intramolecular
Diels-Alder procedure, see: (a) Bear, B. R.; Parnes, J. S.; Shea, K. J.
Org. Lett. 2003, 5, 1613. (b) No¨rret, M.; Sherburn, M. S. Angew. Chem.,
Int. Ed. 2001, 40, 4074.
(11) (a) Adeva, M.; Sahagun, H.; Caballero, E.; Pelaez-Lamamie de
Clairac, R.; Medarde, M.; Tome, F. J. Org. Chem. 2000, 65, 3387. (b)
Donaldson, R. E.; Fuchs, P. L. J. Am. Chem. Soc. 1981, 103, 2108.
(12) Crystal data for 9: C27H24O6S, MW ) 476.52, monoclinic, P2(1)/
c. a ) 9.3539(11) Å, b ) 8.0181(9) Å, c ) 31.277(4) Å, V ) 2326.9(5)
Å3, T ) 293(2) K, Z ) 4. R indices (all data), R1 ) 0.1305, wR2 ) 0.1621.
Final R indices [I > 2σ(I)], R1 ) 0.0578, wR2 ) 0.1198. Reflections
collected/unique: 13686/9561 (Rint ) 0.0973), number of observations
[>2σ(I)] 4103; parameters, 618. Supplementary crystallographic data have
been deposited at the Cambridge Crystallographic Data Center, CCDC
651337.
Org. Lett., Vol. 9, No. 25, 2007
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