Transition metal-mediated stereocontrolled cyclization of urethanes leading to versatile fused piperidines and its application to the synthesis of (+)-prosopinine and (+)-palustrine

Full text of DOI:10.1021/jo961951r

776
J . Org. Chem. 1997, 62, 776-777
Sch em e 1
Tr a n sition Meta l-Med ia ted
Ster eocon tr olled Cycliza tion of Ur eth a n es
Lea d in g to Ver sa tile F u sed P ip er id in es a n d
Its Ap p lica tion to th e Syn th esis of
(+)-P r osop in in e a n d (+)-P a lu str in e
Yoshiro Hirai,* J oshu Watanabe, Tetsuya Nozaki,
Hajime Yokoyama, and Seiji Yamaguchi
Sch em e 2a
Department of Chemistry, Faculty of Science,
Toyama University, 3190 Gofuku, Toyama 930, J apan
Received October 17, 1996
Stereoselective amino cycloaddition1 of alkenylamines
is one of the most important approaches for the stereo-
selective construction of nitrogen heteroalicycles, which
form the skeletons of several biologically active natural
products and related compounds. Palladium(0)-catalyzed
allylic substitution in particular provides efficient ste-
reoselective C-N bond formation.2 Esters and carbam-
ates of allylic alcohols have frequently been used as
substrates in such reactions because of the low reactivity
of the parent alcohol as a leaving group. We recently
developed the intramolecular substitution of an allylic
alcohol by a heteroatom using a palladium(II) catalyst
without activation of the allylic alcohol.3 As a continu-
ation of that work, we have focused on the asymmetric
construction of bicyclic oxazolidinone derivatives (3 and
4, Scheme 1), which provide a path to piperidine alka-
loids.4,5 The stereoselective construction of different
stereoisomers, such as 3 and 4, from similar precursors
by changing transition metals is an especially challenging
problem. We report here the facile preparation of opti-
cally active bicyclic oxazolidinones 3 and 4 by the
stereocontrolled cyclization of urethanes 1 and 2 using
palladium(II) catalyst and silver(I) salt, as well as the
conversion of these bicyclic oxazolidinones to (+)-proso-
pinine and a synthetic intermediate of (+)-palustrine.
First, the substrate 1 for palladium-catalyzed cycliza-
tion was prepared from propargyl alcohol via the Kat-
suki-Sharpless asymmetric epoxidation. 3-[(Methoxy-
methyl)oxy]-2-propyne (5) was reacted with BuLi, BF3‚
OEt2, and oxetane to give an alcohol 6, which was
converted to the allylic alcohol 7 in a four-step process
(catalytic hydrogenation, Swern oxidation, Wittig reac-
tion, DIBALH reduction; overall yield of 56%) (Scheme
2). The asymmetric epoxidation of 7 under Katsuki-
Sharpless conditions6 gave the optically active epoxide
8, [R]D -11.3° (CHCl3), in 80% yield. Treatment of the
epoxide 8 with benzoyl isocyanate, followed by cyclization
with migration of the N-benzoyl group over K2CO3 in
a
Reagents and conditions: (a) n-BuLi, BF3‚OEt2, oxetane, THF,
-78 °C (58%); (b) H2, Lindlar catalyst, AcOEt (84%); (c) (COCl)2,
DMSO, Et3N, CH2Cl2, -78 °C (81%); (d) Ph3PdCHCO2Me, CH2Cl2
(88%); (e) DIBALH, THF (94%); (f) Ti(i-PrO)4, L-DIPT, t-BuOOH,
CH2Cl2, -23 °C (80%); (g) benzoyl isocyanate, THF, rt; (h) K2CO3,
(C8H17)3NMeCl (cat.), CH3CN (96% from 8); (i) PdCl2(CH3CN)2 (20
mol %), THF, rt (77%); (j) K2CO3 (aq), MeOH, rt (95%).
Sch em e 3a
a
Reagents and conditions: (a) concd HCl, MeOH, 60 °C (94%);
(b) MsCl, DMAP, CH2Cl2, rt (75%); (c) AgOCOCF3, NaH, THF, rt
(72%).
acetonitrile, gave the 2-oxazolidinone 1 in 96% yield (94%
ee).7 The intramolecular cyclization of 1 was achieved
by treatment with bis(acetonitrile)palladium(II) chloride
(20 mol %) [PdCl2(CH3CN)2] in THF at room temperature
to give a bicyclic oxazolidinone 3 in 72% yield as a single
diastereoisomer. The structure of 3 was confirmed by
the spectral data and by an NOE experiment that
indicated that the proton at the 1-position and the vinyl
group at the 5-position are in a cis relation.
Next, we examined the silver(I) salt-promoted cycliza-
tion8 of the chloride (2), which was easily obtained from
1. Cyclization of 2 using silver trifluoroacetate9 in the
presence of NaH in THF gave a bicyclic oxazolidinone
10 in 72% yield as a single diastereoisomer (Scheme 3).
The structure of 10 was confirmed by comparison of its
spectral data to those of the alcohol (9), which was
(1) (a) Saitoh, Y.; Moriyama, Y.; Hirota, H.; Takahashi, T.; Khuong-
Huu, Q. Bull. Chem. Soc. J pn. 1981, 54, 488. (b) Hirama, M.;
Shigemoto, T.; Yamazaki, Y.; Ito, S. J . Am. Chem. Soc. 1985, 107, 1797.
(c) Knapp, S.; Rodriques, K. E.; Levorse, A. T.; Ornaf, R. M. Tetrahe-
dron Lett. 1985, 26, 1803. (d) Tamaru, Y.; Hojo, M.; Yoshida, Z. J . Org.
Chem. 1988, 53, 5731 and references cited therein.
(2) (a) Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96, 395.
(b) Bando, T.; Harayama, H.; Fukazawa, Y.; Shiro, M.; Fugami, K.;
Tanaka, S.; Tamaru, Y. J . Org. Chem. 1994, 59, 1465. (c) Takao, K.,
Nigawara, Y.; Nishio, E.; Takagi, I., Maeda, K.; Tadano, K.; Ogawa,
S. Tetrahedron 1994, 50, 5681.
(3) (a) Hirai, Y.; Terada, T.; Momose, T. Tetrahedron Lett. 1992, 33,
7893. (b) Hirai, Y.; Nagatsu, M. Chem. Lett. 1994, 21.
(4) Fodor, G. B.; Colasanti, B. In Alkaloids: Chemical and Biological
Perspectives; Pelletier, S. W., Ed.; Wiley; New York, 1985; Vol. 3, pp
1-90.
(7) The optical purity of the 2-oxazolidinone 1, [R]D -31.2° (CHCl3),
was determined by HPLC using a chiral column (Daicel AS, Daicel
Chemical Industries, Ltd.).
(8) Kimura, M.; Tanaka, S.; Tamaru, Y. Bull. Chem. Soc. J pn. 1995,
68, 1689.
(9) Though the cyclization reaction using other silver salts was
examined, silver trifluoroacetate provided the best results.
(5) Some of these alkaloids possess local anesthetic activity: Bour-
rinet, P.; Quevauviller, A. Comput. Rend. Soc. Biol. 1968, 162, 1138;
Ann. Pharm, Fr. 1968, 26, 787.
(6) Katsuki, T.; Sharpless, K. B. J . Am. Chem. Soc. 1980, 102, 5974.
S0022-3263(96)01951-2 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 4, 1997 777
Sch em e 4
Sch em e 5a
a
Reagents and conditions: (a) BnBr, NaH, Bu4NI, THF (97%);
(b) O3, Me2S, CH2Cl2 (70%); (c) NaH, DMSO, Ph3P+(CH2)9OAc Br-,
THF (65%); (d) satd NaHCO3 (aq), MeOH (70%); (e) (COCl)2,
DMSO, Et3N, CH2Cl2 (72%); (f) EtMgBr, THF (65%); (g) PCC,
CH2Cl2 (91%); (h) ethylene glycol, p-TsOH, benzene (73%); (i) H2,
10% Pd-C, MeOH (89%); (j) 8 N KOH, MeOH (45%); (k) 10%
aqueous HCl, 2 h (80%).
obtained from 3 by alkaline hydrolysis of the benzoate
(Scheme 2).10
Sch em e 6a
This high stereoselectivity of the palladium(II)-cata-
lyzed allylic substitution reaction can be explained by
assuming the involvement of a transition state A, which
minimizes nonbonding interaction between the oxa-π-
allylpalladium complex and the oxazolidinone ring
(Scheme 4). The initial formation of an oxa-π-allylpal-
ladium intermediate A, followed by backside N-nucleo-
philic attack upon the remote Pd-coordinated alkene,
usually results in palladium-oxygen elimination to give
the trans-2,6-disubstituted piperidine system 3 stereo-
selectively. On the other hand, the high stereoselectivity
of silver(I)-promoted cyclization can be explained by
assuming a transition state B, which gives the cis-2,6-
disubstituted piperidine system 10 via 4.
a
Reagents and conditions: (a) BnBr, NaH, Bu4NI, THF (93%);
The resulting oxazolidinones 9 and 10 are useful chiral
building blocks for the preparation of nitrogen-containing
natural products, and their versatility has been demon-
strated by their transformation into (+)-prosopinine11,12
and a synthetic intermediate of (+)-palustrine,13,14 re-
spectively. Benzylation of 9 followed by ozonolysis gave
the aldehyde 11, which was subjected to a Wittig reac-
tion, hydrolysis of the acetate moiety, and Swern oxida-
tion to give the aldehyde 12 in 22% overall yield (Scheme
5). Grignard reaction of 12 with ethylmagnesium bro-
mide in THF and the subsequent treatment of the
resulting alcohol with PCC gave the ketone, which was
converted to the ketal 13. Finally, the conversion of 13
to 14 was achieved in three steps: debenzylation and
hydrogenation of the olefin moiety, cleavage of the
oxazolidinone ring, and deketalization. The physical data
for the synthetic product, including the specific rotation,
were identical to those reported for natural (+)-prosopi-
nine.10
(b) OsO4, NMO, 1,4-dioxane; (c) NaIO4 (aq) (two steps 82%); (d)
EtMgBr, MgBr2, THF, -20 °C (57%); (e) MOMCl, Et2NMe, CH2Cl2,
rt (75%); (f) 8 N KOH, MeOH and then (Boc)2O (40%).
was subjected to a Grignard reaction with ethylmagne-
sium bromide in the presence of MgBr2 to give the alcohol
16 stereoselectively in 57% yield. Protection of the
alcohol moiety and cleavage of the oxazolidinone ring of
16 furnished 17, which is a prospective intermediate for
the synthesis of (+)-palustrine.14
In conclusion, a highly efficient method was established
for constructing both the trans-2,6-disubstituted and the
cis-2,6-disubstituted piperidine ring from the same pre-
cursor via transition metal-catalyzed intramolecular N-
alkylation. Further application of the approach described
here to the synthesis of other natural products is in
progress.
Ack n ow led gm en t. We are grateful to Professor Qui
Khuong-Huu, Centre National de la Recherche Scien-
tifique, for his kind gift of the natural prosopinine. This
work was supported in part by a Grant-in-Aid for
Scientific Research (C) from the Ministry of Education,
Science, Sports, and Culture of J apan and by the First
Bank of Toyama Student Loan Foundation.
Furthermore, the conversion of 10 to a synthetic
intermediate of (+)-palustrine (18) was also examined
(Scheme 6). Benzylation of 9 followed by oxidative
cleavage of the olefin moiety gave the aldehyde 15, which
(10) The signal of an allylic methine proton of 10, which was situated
in an equatorial position in PMR, was observed at a lower field (4.40-
4.47 ppm, m) than that of 9, and no NOE was observed between the
proton at the 1-position and the vinyl proton at the 11-position of 10.
(11) (a) Ratle, G.; Monseur, X.; Das, B. C.; Yassi, J .; Khuong-Huu,
Q., Goutarel, R. Bull. Soc. Chim. Fr. 1966, 2945. (b) Khuong-Huu, Q.,
Ratle, G.; Monseur, X.; Goutarel, R. Bull. Soc. Chim. Belges 1972, 81,
425; (c) 1972, 81, 443.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures, characterization data, and 1H NMR spectra for new
compounds (42 pages).
J O961951R
(12) Cook, G. R.; Beholz, L. G.; Stille, J . R. J . Org. Chem. 1994, 59,
3575.
(13) (a) Eugster, C. H.; Griot, R.: Karrer, P. Helv. Chim. Acta 1953,
36, 1387. (b) Mayer, C.; Green, C. L.; Trueb, W.; Walchli, P. C.; Eugster,
C. H. Helv. Chim. Acta 1978, 61, 905. (c) Walchli, P. C.; Mukherjee-
Muller, G.; Eugster, C. H. Helv. Chim. Acta 1978, 61, 9221.
(14) (a) Natsume, M; Ogawa, M. Chem. Pharm. Bull. 1984, 32, 3789.
(b) Wasserman, H. H.; Leadbetter, M. R.; Kopka, I. E. Tetrahedron
Lett. 1984, 25, 2391.