Novel asymmetric route to carbanucleoside and prostanoid intermediates: Efficient preparation of both optical antipodes of chiral cyclopentenone

Full text of DOI:10.1021/jo970616f

3806
J . Org. Chem. 1997, 62, 3806-3807
Earlier work in our laboratories established the fea-
Novel Asym m etr ic Rou te to
Ca r ba n u cleosid e a n d P r osta n oid
In ter m ed ia tes: Efficien t P r ep a r a tion of
Both Op tica l An tip od es of Ch ir a l
Cyclop en ten on e
sibility of the camphor skeleton as a chiral source to effect
asymmetric additions with excellent stereoselectivity,6
and we aimed at employing camphor-based acylnitroso
to prepare enantiomerically pure dihydrooxazine. The
requisite camphor-derived hydroxamic acid was synthe-
sized according to eq 2. Reaction of ketopinic acid 1 with
Chun-Chieh Lin, Ying-Chuan Wang, J ung-Lang Hsu,
Chao-Cheng Chiang, Dah-Wei Su, and Tu-Hsin Yan*
Department of Chemistry, National Chung-Hsing
University, Taichung, Taiwan 400, Republic of China
Received April 4, 1997
Acylnitroso compounds constitute useful building blocks
for synthesis via asymmetric hetero-Diels-Alder reac-
tions because of their potential for further structural
elaboration.1 Extensive research in the chemistry of
dihydrooxazine educts derived from cyclohexadienes has
led to the development of numerous synthetically impor-
tant organic transformations;2 nevertheless, the struc-
tural elaboration of the cycloadducts from cyclopentadi-
ene remains far less developed, and its utilization in
organic synthesis has therefore been fairly limited.3 The
development of a general approach for the construction
of unusual chiral cyclopentenoids would serve to enhance
the utility of this cycloaddition reaction. In particular,
changing the reaction profile whereby the same dihy-
drooxazine intermediate could be channeled into both
antipodes of cyclopentenone greatly expands synthetic
flexibility (eq 1). We wish to record such a chemoselec-
2.2 equiv of phenylmagnesium bromide and CeCl3 (2.2
equiv) in THF at -50 °C for 1 h and 25 °C for 3 h afforded
the corresponding tertiary alcohol 2 in 92% isolated yield,
which upon treatment with SOCl2 at 0 °C for 3 h followed
by concentration and immediate treatment with a solu-
tion of HONH2‚HCl (1.2 equiv) and Me3SiCl (3 equiv) in
CH3CN initially at 0 °C and then at 25 °C for 6 h provided
the desired hydroxamic acid 3 (95% yield). The acylni-
troso 4 was generated by in situ oxidation of 3 with the
salts of periodate (eq 3).7 Reactions were carried out
employing the hydroxamic acid 3 as the limiting reagent
in the presence of 2.5 equiv of cyclopentadiene. In the
preliminary study, we chose to assay cycloaddition dias-
tereoselection as a function of temperature and solvent.
As the data in Table 1 show, increasing the reaction
temperature from -78 to 0 °C exerts no influence on the
reaction stereocontrol (entry 1 vs 3, 2 vs 4).8a Switching
the solvent from CH2Cl2 to MeOH makes virtually no
difference in the selectivity and yield of the cycloaddition
(entry 1 vs 2, 3 vs 4). Consideration of Dreiding models
and molecular modeling9 suggested that the s-trans
conformation was the most stable one for acylnitroso 4,
tivity switch in the construction of chiral cyclopentenone,
a key intermediate toward several classes of important
biologically active compounds ranging from prostaglan-
din4 to antiviral carbanucleosides such as neplanocin A
and aristeromycin.5
(1) (a) Weinreb, S. M. In Comprehensive Organic Synthesis; Perga-
mon Press: Oxford, 1991; Vol. 5, p 419. (b) Watanabe, Y.; Iida, H.;
Kibayashi, C. J . Org. Chem. 1989, 54, 4088. (c) Kresze G. In Organic
Synthesis in USSR; Chizhov, O., Ed.; Moscow, 1986; p 169. (d) Iida,
H.; Watanabe, Y.; Kibayashi, C. J . Am. Chem. Soc. 1985, 107, 5534.
(e) Sabuni, M.; Kresze, G. Tetrahedron Lett. 1984, 25, 5377. (f) Keck,
G. E.; Nickell, D. G. J . Am. Chem. Soc. 1980, 102, 3632. (g) Keck, G.
E. Tetrahedron Lett. 1978, 19, 4767.
(2) (a) Martin, S. F.; Tso, H.-H. Heterocycles 1993, 35, 85. (b) Defoin,
A.; Poichet, A. B.; Streith, J . Helv. Chim. Acta 1991, 74, 103. (c)
Werbitzky, O.; Klier, K.; Felber, H. Liebigs Ann. Chem. 1990, 267. (d)
Beier, B.; Schurrle, K.; Werbitzky, O.; Piepersberg, W. J . Chem. Soc.,
Perkin Trans. 1 1990, 2255. (e) Miller, A.; Procter, G. Tetrahedron Lett.
1990, 31, 1041. (f) Kirby, G. W.; Nazeer, M. Tetrahedron Lett. 1988,
29, 6173. (g) Defoin, A.; Schmidlin, C.; Streith, J . Tetrahedron Lett.
1984, 25, 4515. (h) Felber, H.; Kresze, G.; Braun, H.; Vasella, A.
Tetrahedron Lett. 1984, 25, 5381. (i) Kresze, G.; Kysela, E.; Dittel, W.
Liebigs Ann. Chem. 1981, 202. (j) Kresze, G.; Kysela, E. Liebigs Ann.
Chem. 1981, 210. (k) Kresze, G.; Dittel, W.; Melzer, H. Liebigs Ann.
Chem. 1981, 224. (l) Kresze, G.; Dittel, W. Liebigs Ann. Chem. 1981,
610. (m) Keck, G. E.; Fleming, S. A. Tetrahedron Lett. 1978, 19, 4763.
(3) (a) King, S. B.; Ganem, B. J . Am. Chem. Soc. 1991, 113, 5089.
(b) Miller, A.; Procter, G. Tetrahedron Lett. 1990, 31, 1043.
(5) (a) Medich, J . R.; Kunnen, K. B.; J ohnson, C. R. Tetrahedron
Lett. 1987, 28, 4131. (b) Borcherding, D. R.; Scholtz, S. A.; Borchardt,
R. T. J . Org. Chem. 1987, 52, 5457. (c) Wolfe, M. S.; Borcherding, D.
R.; Borchardt, R. T. Tetrahedron Lett. 1989, 30, 1453. (d) Wolfe, M.
S.; Anderson, B. L.; Borcherding, D. R.; Borchardt, R. T. J . Org. Chem.
1990, 55, 4712.
(6) (a) Yan, T.-H.; Tan, C.-W.; Lee, H.-C.; Lo, H.-C.; Huang, T.-Y. J .
Am. Chem. Soc. 1993, 115, 2613. (b) Yan, T.-H.; Hung, A.-W.; Lee,
H.-C.; Chang, C.-S. J . Org. Chem. 1994, 59, 8187. (c) Yan, T.-H.; Hung,
A.-W.; Lee, H.-C.; Chang, C.-S.; Liu, W.-H. J . Org. Chem. 1995, 60,
3301. (d) Wang, Y.-C.; Hung, A.-W.; Chang, C.-S.; Yan, T.-H. J . Org.
Chem. 1996, 61, 2038.
(7) For in situ oxidation of acylnitroso with R4NIO4, see refs 1-3.
(8) (a) Proof that 5 had in fact been formed exclusively was gained
by conversion to 8, which upon treatment with D-(+)-camphorsulfonyl
chloride and Et3N at 0-25 °C afforded the corresponding sulfonamide,
which showed only a single set of absorptions for the methylene protons
(H2CSO2-) at δ 3.60 and 3.15 in the 300-MHz NMR spectrum
suggestive of complete asymmetric induction. For similar examples of
the use of this method, see ref 1e. (b) Belanger, P.; Prasit, P.
Tetrahedron Lett. 1988, 29, 5521.
(9) Energy-optimized acylnitroso structures were determined using
Cerius2 (Version 2.0) software (Molecular Simulation, Inc.) with the
Dreiding force field: Mayo, S. L.; Olafson, B. D.; Goddard, W. A., III.
J . Phys. Chem. 1990, 94, 8897.
(4) (a) J ohnson, C. R.; Penning, T. D. J . Am. Chem. Soc. 1988, 113,
4726. (b) Babiak, K. A.; Behling, J . R; Dygos, J . H.; McLaughlin, K.
T.; Ng, J . S.; Kalish, V. J .; Kramer, S. W.; Shone, R. L. J . Am. Chem.
Soc. 1990, 113, 7441. (c) Kolb, M.; Hijfte, L. V.; Ireland, R. E.
Tetrahedron Lett. 1988, 29, 6769. (d) Hudlicky, T.; Luna, H.; Barbieri,
G.; Kwart, L. D. J . Am. Chem. Soc. 1988, 113, 4726.
S0022-3263(97)00616-6 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 12, 1997 3807
Ta ble 1. Heter o-Diels-Ald er Rea ction of Acyln itr oso 4
with pyridinium dichromate in CH2Cl2 at 25 °C for 6 h
resulted in efficient oxidation of the hydroxyl group and
spontaneous elimination of (NO)2 to produce unsaturated
ketone 11, [R]23D +71.4° (c ) 3.5, CHCl3) [lit.4a [R]D +71.8°
(c ) 0.91, CHCl3)] in a single step (80% for the two steps).
To redirect a reactivity switch for 8 to lead to the antipode
of 11, we devised an alternative route, in which the N-O
bond was subjected to reductive cleavage in order to
permit the chemoselective oxidation of the amino group.
Following trial experiments that served to indicate the
need to append a phenyl group to nitrogen, treatment of
the electrophilic amination reagent10 8 with 3 equiv of
phenylmagnesium bromide in THF at -78 to 0 °C for 1
h resulted in reductive cleavage of the N-O bond and
w ith Cyclop en ta d ien e
entry
oxidant
T (°C)
solvent
ratioa 5:6
1
2
3
4
Et4IO4
Et4IO4
Et4IO4
Et4IO4
-78 to -30
CH2Cl2
MeOH
CH2Cl2
MeOH
99:1
99:1
99:1
99:1
-78 to -30
0
0
a
Ratios determined by 300 MHz 1H NMR; see ref 8a.
Sch em e 1
N-phenyl formation to furnish 12, mp 107-108 °C, [R]23
D
+14.7° (c ) 1.3, CHCl3), in almost quantitative yield.
Exposure of 12 to dimethyldioxirane (as acetone solu-
tion11) at 0 °C for 3 h smoothly effected the desired
chemoselective oxidation to give keto alcohol 13, mp
84.5-85 °C, [R]23 -295° (c ) 1.8, CHCl3) [lit.8b mp 83-
D
85 °C, [R]D -237° (c ) 1, CHCl3)], in 81% yield. Subse-
quent dehydration with NH4Cl in aqueous acetone at 25
°C for 6 h gave enone 14, [R]23 -69.9° (c ) 0.95, CHCl3)
D
[lit.4a [R]D -70.8° (c ) 0.925, CHCl3)], in 97% yield.
The results reported herein clearly indicate that the
chiral bicyclo[2.2.1]oxazine derivative is a valuable build-
ing block. Employing the same chiral precursor, this
face-selectivity-switch-like method provides an unprec-
edented entry to both enantiomers of cyclopentenone.
This technology represents an attractive synthetic strat-
egy to various structurally related natural products. In
addition, this work demonstrates the importance of an
appropriately oriented proximal phenyl ring for achieving
the exceptionally high levels of asymmetric induction12
without the aid of a Lewis acid or intramolecular
hydrogen bonding.2e We believe the above represents a
useful working model for designing asymmetric partners
in the cycloaddition reaction.
and the aromatic ring then served as a steric steering
group to direct the incoming diene to the re face to give
adduct 5. This assignment was confirmed by the suc-
cessful conversion of 5 into the cyclopentenone 11 and
14 of known absolute configuration (vide infra). Having
established that excellent diastereoselectivity was pos-
sible with camphor-based chiral auxiliary, we turned our
attention to the structural elaboration of 5 (Scheme 1).
Dihydroxylation of 5 with catalytic OsO4 in the presence
of trimethylamine N-oxide or 4-methylmorpholine N-
oxide (50 wt % solution in water) at 25 °C for 20 h to
give the corresponding diol proceeded from the less
hindered R-face. Subsequent conventional acetonide
formation afforded the functionalized oxazine 7 in good
overall yield (96% for the two steps). Partial reduction
of the N-acyloxazine 7 with LiAlH4 in THF at 0 °C for 5
Ack n ow led gm en t. Support from the National Sci-
ence Council of the Republic of China (NSC 85-2113-
M-005-003) is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Full experimental
details and analytical data for all compounds (except 10) (7
pages).
J O970616F
(10) (a) Beak, P.; Kokko, B. J . J . Org. Chem. 1982, 47, 2822. (b)
Kokko, B. J .; Beak, P. Tetrahedron Lett. 1983, 24, 561. (c) Beak, P.;
Basha, A.; Kokko, B. J . J . Am. Chem. Soc. 1984, 106, 1511. (d) Boche,
G.; Wagner, H.-U. J . Chem. Soc., Chem. Commun. 1984, 1591.
(11) (a) Murray, R. W.; J eyaraman, R. J . Org. Chem. 1985, 50, 2847.
(b) Adam, W.; Chan, Y.-Y.; Cremer, D.; Gauss, J .; Scheutzow, D.;
Schindler, M. J . Org. Chem. 1987, 52, 2800. (c) Eaton, P. E.; Wicks,
G. E. J . Org. Chem. 1988, 53, 5353.
(12) For examples of the requirement of a proximal phenyl ring for
highly diastereoselective reactions, see: (a) Trost, B. M.; O’Krongly,
D.; Belletire, J . L. J . Am. Chem. Soc. 1980, 102, 7595. (b) Ito, Y.; Amino,
Y.; Nakatsuka, M.; Saegusa, T. J . Am. Chem. Soc. 1983, 105, 1586. (c)
Masamune, S.; Choy, W.; Petersen, J . S.; Sita, L. R. Angew. Chem.,
Int. Ed. Engl. 1985, 24, 1. (d) Smith, A. B.; Liverton, N. J .; Hrib, N. J .;
Sivaramakrishnan, H.; Winzenberg, K. J . Am. Chem. Soc. 1986, 108,
3040. (e) Evans, D. A.; Chapman, K. T.; Bisaha, J . J . Am. Chem. Soc.
1988, 110, 1238. (f) Whitesell, J . K. Acc. Chem. Soc. 1985, 18, 280. (g)
Oppolzer, W. Pure Appl. Chem. 1981, 53, 1181.
h gave the dihydrooxazine 8 (85% yield), [R]23 +67.4° (c
D
) 0.9, CHCl3), along with aldehyde 9, which could be
easily converted to the starting hydroxamic acid 3. To
control the reaction profile in cyclopentenone construction
from 3, cleavage of the N-O bond and then chemoselec-
tive oxidation of an amino versus an alcohol were
required. We first addressed the oxidative cleavage
methodology. Of various oxidizing agents examined,
m-CPBA proved optimum in precluding ketal ring open-
ing and allowing the N-H bond to be easily oxidized,
with concomitant cleavage of the N-O bond. Exposure
of 8 to 1.2 equiv of m-CPBA in CH2Cl2 at 25 °C for 1 h
provided dimeric bisnitroso 10, which upon treatment