Stereoselective synthesis of MeBmt and methyl (4R,5S)-5-isopropyl-2-phenyloxazoline-4-carboxylate by a Pd-catalyzed equilibration

Full text of DOI:10.1021/jo015760m

6818
J . Org. Chem. 2001, 66, 6818-6822
asymmetric dihydroxylation of methyl 4-methyl-2-pen-
Ster eoselective Syn th esis of MeBm t a n d
tenoate with 70% ee, which could be improved to >99%
ee by one recrystallization.9 The Panek group has re-
cently communicated a more direct route from p-bro-
mophenyl (E)-4-methyl-2-pentenoate utilizing an asym-
metric aminohydroxylation reaction.10 Regioselectivity
was 7:1 favoring the R-amino ester with 87% ee. And
more recently, a chiral auxiliary-directed conjugate ad-
dition of O-benzylhydroxylamine (80% de), followed by
aziridine formation, and ring opening, afforded a similar
hydroxyleucine derivative.11
Meth yl (4R,5S)-5-Isop r op yl-2-
p h en yloxa zolin e-4-ca r boxyla te by a
P d -Ca ta lyzed Equ ilibr a tion
Gregory R. Cook* and P. Sathya Shanker
Department of Chemistry, North Dakota State University,
Fargo, North Dakota 58105-5516
Gregory.Cook@ndsu.nodak.edu
Received May 15, 2001
MeBmt (4), another unusual R-amino-â-hydroxy acid,
is an important constituent of cyclosporin.12 The first
synthesis of MeBmt from L-(+)-diethyl tartrate was
reported by Wenger in 1983.13 Since then, a number of
synthetic approaches have appeared relying on asym-
metric aldol reactions,14 opening of chiral epoxides,15 or
beginning with natural chiral building blocks (D-isoascor-
bic acid,16 L-glutamic acid,17 D-2-deoxyribose,18 D-glucose,19
and D-serine20). Most recently, a stereoselective radical
addition to a 2-oxazolone heterocycle was reported.21
In tr od u ction
Lactacystin (1), isolated in 1991,1 has been a target of
intense study recently due to its highly potent and
selective inhibition of the 20 S proteasome.2,3 The first
total synthesis of 1 was reported by the Corey group in
1992, and subsequent evolution of the synthesis and the
preparation of the equally potent lactone analogue 2 have
been described.4 A variety of other synthetic approaches
have appeared utilizing chiral sources such as D-glucose,5
D-glutamic acid,6 and an allylic alcohol derived from a
Sharpless asymmetric epoxidation.7 The 3-hydroxy-
leucine derivative, oxazoline 3, has been employed as a
key intermediate in the total synthesis of lactacystin.
Omura and Smith8 prepared 3 from (E)-4-methyl-3-
penten-1-ol, also via Sharpless epoxidation, in 10 steps
with 41% overall yield. Another route utilized a Sharpless
(1) (a) Omura, S.; Fujimoto, T.; Otoguro, K.; Matsuzaki, K.; Morigu-
chi, R.; Tanaka, H.; Sasaki, Y. J . Antibiot. 1991, 44, 113. (b) Omura,
S.; Matsuzaki, K.; Fujimoto, T.; Kosuge, K.; Furuya, T.; Fujita, S.;
Nakagawa, A. J . Antibiot. 1991, 44, 117.
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E. J .; Schreiber, S. L. Science 1995, 268, 726. (b) Dick, L. R.;
Cruikshank, A. A.; Grenier, L.; Melandri, F. D.; Nunes, S. L.; Stein,
R. L. J . Biol. Chem. 1996, 271, 7273. (c) Tomoda, H.; Omura, S.
Yakugaku Zasshi, 2000, 120, 935. (d) Masse, C. E.; Morgan, A. J .;
Adams, J .; Panek, J . S. Eur. J . Org. Chem. 2000, 2513.
(3) For recent studies on the biology of lactacystin, see: (a) Fenteany,
G.; Schreiber, S. L. J . Biol. Chem. 1998, 273, 8545. (b) McCormack, T.
A.; Cruikshank, A. A.; Grenier, L.; Melandri, F. D.; Nunes, S. L.;
Plamondon, L.; Stein, R. L.; Dick, L. R. Biochemistry 1998, 37, 7792.
(c) Cerundolo, B.; Benham, A.; Braud, V.; Mukherjee, S.; Gould, K.;
Macino, B.; Neefjes, J .; Townsend, A. Eur. J . Immunol. 1997, 27, 336.
(d) Magae, J .; Illenye, S.; Tejima, T.; Chang, Y.-C.; Mitsui, Y.; Tanaka,
K.; Omura, S.; Heintz, N. H. Oncogene 1997, 15, 759. (e) Ostrowska,
H.; Wojcik, C.; Omura, S.; Worowski, K. Biochem. Biophys. Res. Comm.
1997, 234, 729. (f) Bai, A.; Forman, J . J . Immun. 1997, 159, 2142. (g)
Dick, L. R.; Cruikshank, A. A.; Destree, A. T.; Grenier, L.; McCormack,
T. A.; Melandri, F. D.; Nunes, S. L.; Palombella, V. J .; Parent, L. A.;
Plamondon, L.; Stein, R. L. J . Biol. Chem. 1997, 272, 182. (h) Craiu,
A.; Gaczynska, M.; Akopian, T.; Gramm, C. F.; Fenteany, G.; Goldberg,
A. L.; Rock, K. L. J . Biol. Chem. 1997, 272, 13437.
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T. A.; Adams, J .; Plamondon, L. J . Am. Chem. Soc. 1999, 121, 9967.
(10) (a) Panek, J . S.; Masse, C. E. Angew. Chem. 1999, 111, 1161;
Angew. Chem., Int. Ed. Engl. 1999, 38, 1093. (b) Panek, J . S.; Masse,
C. E. J . Org. Chem. 1998, 63, 2382, 5294.
(11) Cardillo, G.; Gentilucci, L.; Gianotti, M.; Tolomelli, A. Tetra-
hedron: Asymmetry 2001, 12, 563.
(12) Wenger, R. M. In Cyclosporin A; White, D. J . G., Ed.; Biomedi-
cal: Amsterdam, 1992.
(13) Wenger, R. M. Helv. Chim. Acta 1983, 66, 2308.
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6230. (b) Rich, D. H.; Sun, C.-Q.; Guillaume, D.; Dunlap, B.; Evans,
D. A.; Weber, A. E. J . Med. Chem. 1989, 32, 1982. (c) Togni, A.; Pastor,
S. D.; Rihs, G. Helv. Chim. Acta 1989, 72, 1471. (d) Schmidt, U.; Siegel,
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120, 2330. (b) Corey, E. J .; Li, W.; Nagamitsu, T. Angew. Chem. 1998,
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10.1021/jo015760m CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/08/2001

Notes
J . Org. Chem., Vol. 66, No. 20, 2001 6819
Sch em e 1. P r ep a r a tion a n d Isom er iza tion of
palladium-catalyzed oxazoline formation and equilibra-
tion reaction provided oxazolines 8a and 8b with excel-
lent yield and diastereoselectivity (single isomer).24 The
reaction was amenable to scale-up. Thus, the serine
derivative 7a was efficiently transformed into 8a on
greater than a 5 g scale in 4 h utilizing only 0.5 mol %
Pd2(dba)3CHCl3 and 2 mol % bis(diphenylphosphino)-
propane (dppp). Given this success, even lower catalyst
levels should be attainable (vide infra).
2-P r op en yloxa zolin esa
P r ep a r a tion of (4R,5S)-2-P h en yl-4-(m eth oxyca r -
bon yl)-5-isop r op yloxa zolin e (3). The oxazoline 8a was
employed in the synthesis of the hydroxyleucine deriva-
tive 3 (Scheme 1). Hydrogenation using Wilkinson’s
catalyst followed by desilylation with tetrabutylammo-
nium fluoride (TBAF) gave alcohol 9. Subsequent oxida-
tion with catalytic chromium trioxide/periodic acid25 and
treatment with diazomethane afforded the title com-
pound in moderate yield.
Syn th esis of MeBm t. The oxazoline ent-8a , prepared
in an analogous fashion from the D-serine derivative ent-
5a , served as an intermediate for the synthesis of MeBmt.
As shown in Scheme 2, hydroboration with 9-BBN
followed by a Suzuki coupling protocol26 with (E)-1-
bromopropene afforded the chain-extended oxazoline 10
as a 5.5:1 mixture of diastereomers. Deprotection of the
silyl ether gave the alcohol 11 as a solid that could be
recrystallized from ether/hexane to enhance the diaster-
eomeric purity (dr 16:1, 59% yield; 31% isolated from
mother liquor, dr 1.7:1). Hydrolysis of the oxazoline under
acidic conditions yielded the ammonium hydrochloride
benzoate, which, upon neutralization in the presence of
di-tert-butyl dicarbonate, resulted in the formation of the
N-BOC-aminodiol monobenzoate 12 in high yield. Protec-
tion of the primary alcohol to provide 13 was followed
by methylation of the nitrogen and methanolysis of the
benzoate to give 14 via cyclization of the alkoxide onto
the BOC group. Oxidation and esterification afforded the
known ester 15,14a,g which was subsequently hydrolyzed
with KOH13 to afford MeBmt as the free aminohydroxy
acid.
a
Key: (a) DIBAL-H, Tol; (b) 2-propenylmagnesium bromide,
THF; (c) NaH, THF; (d) PhCOCl, NaH, THF; (e) 0.5 mol %
Pd2(dba)3CHCl3, 2 mol % dppp, THF, 45 °C; (f) (PH3P)3RhCl, H2,
PhH; (g) TBAF, THF; (h) cat. CrO3, HIO5, then CH2N2.
As part of our program to synthesize aminohydroxy
acids, we have shown that diastereomeric mixtures of
5-vinyloxazolidinones derived from R-amino acids un-
dergo palladium-catalyzed oxazoline formation by ring
opening, loss of CO2, and subsequent cyclization. Ther-
modynamic equilibration via π-allyl inversion afforded
predominantly trans diastereomers in ratios up to 16:
1.22 We anticipated that the more sterically encumbered
2-propenyl group should present even greater selectivity
and the resulting oxazoline could be utilized as a common
intermediate for the preparation of a variety of novel
aminohydroxy acids. We report herein our investigation
and application of this methodology to the asymmetric
synthesis of the title compounds.
Resu lts a n d Discu ssion
Con clu sion
P r ep a r a tion a n d Isom er iza tion of 2-P r op en ylox-
a zolin es. To study the equilibration of 5-(2-propenyl)-
oxazolines, the oxazolidinones 7a and 7b were prepared
from their respective N-BOC-protected amino esters as
shown in Scheme 1. Diisobutylaluminum hydride reduc-
tion of this ester followed by the addition of 2-propenyl-
magnesium bromide to the crude aldehyde afforded the
alcohols 6a and 6b with modest diastereoselectivity (syn/
anti 4:1 and 2:1, respectively).23 Cyclization of the alcohol
onto the BOC carbonyl was accomplished by stirring with
NaH in THF, and acylation afforded the desired oxazo-
lidinones 7a and 7b. We were gratified to find that the
We have demonstrated that the palladium-mediated
epimerization of 5-(2-propenyl)oxazolines affords com-
plete stereocontrol of vicinal amino and hydroxy func-
tionalities via a thermodynamic equilibration. This pro-
vides a facile and practical route to amino alcohol
derivatives in stereochemically pure form without relying
on intricate chelation controlled additions.23 The oxazo-
line 8a was utilized in an expedient and efficient syn-
thesis of 3, a key intermediate for the synthesis of
lactacystin. MeBmt was synthesized from ent-8a utiliz-
ing a key hydroboration/Suzuki coupling protocol. Con-
sidering the synthetic utility of unnatural amino acids
in organic synthesis, unsaturated oxazolines 8a and 8b
are valuable intermediates for the preparation of novel
amino acids.
(22) (a) Cook, G. R.; Shanker, P. S. Tetrahedron Lett. 1998, 39, 3405.
(b) Cook, G. R.; Shanker, P. S.; Peterson, S. L. Org. Lett. 1999, 1, 615.
(23) Careful chelation controlled addition of vinyllithium reagents
to aminoaldehydes generated in situ from DIBAL/TRIBAL in non-ether
solvents have been reported to proceed with high (>20:1) selectivity.
(a) Sames, D.; Polt, R. J . Org. Chem. 1994, 59, 4596. (b) Sames, D.;
Polt, R. Synlett 1995, 552. (c) Razavi, H.; Polt, R. Tetrahedron Lett.
1998, 39, 3371. (d) Polt, R.; Sames, D.; Chruma, J . J . Org. Chem. 1999,
64, 6147. See also: (e) Angle, S. R.; Henry, R. M. J . Org. Chem. 1997,
62, 8549. (f) McGrane, P. L.; Livinghouse, T. J . Am. Chem. Soc. 1993,
115, 11485. (g) Yong, Y. F.; Lipton, M. A. Bioorg. Med. Chem. Lett.
1993, 3, 2879. (h) Golebiowski, A.; J urczak, J . Synlett 1993, 241. (i)
Ibuka, T.; Habashita, H.; Otaka, A.; Fujii, N.; Oguchi, Y.; Uyehara,
T.; Yamamoto, Y. J . Org. Chem. 1991, 56, 4370.
(24) The diastereoselectivity was determined by careful analysis of
the 400 or 500 MHz 1H NMR spectrum.
(25) Zhao, M.; Li, J .; Song, Z.; Desmond, R.; Tschaen, D. M.;
Grabowski, E. J . J .; Reider, P. J . Tetrahedron Lett. 1998, 39, 5323.
(26) (a) Suzuki, A.; Miyarura, N. Chem. Rev. 1995, 95, 2457. (b) For
recent examples of hydroboration followed by Suzuki coupling, see:
Vice, S.; Bara, T.; Bauer, A.; Evans, C. A.; Ford, J .; J osien, H.;
McCombie, S.; Miller, M.; Nazareno, D.; Palani, A.; Tagat, J . J . Org.
Chem. 2001, 66, 2487 and references therein.

6820 J . Org. Chem., Vol. 66, No. 20, 2001
Sch em e 2. P r ep a r a tion of MeBMTa
Notes
a
Key: (a) 9-BBN, THf; (ii) (E)-1-bromopropene, Pd(PPh3)4 (cat.), THF; (b) TBAF, THF, then recryst; (c) 2 N HCl, THF; (d) NAHCO3,
BOC2O; (e) TBDMSCl, imidazole; (f) NaH, MeI; (g) NaOMe, MeO; (h) PDC, DMF then CH2N2; (i) 2 N KOH.
anti); 1H NMR (400 MHz, CDCl3) δ 7.4-7.1 (m, 10H, syn and
Exp er im en ta l Section
anti), 5.07 (s, 0.33H, anti), 5.02 (s, 0.67H, syn), 4.98 (s, 0.33H,
anti), 4.91 (s, 0.67H, syn), 4.82 (d, J ) 8.1 Hz, 0.67H, syn), 4.71
(d, J ) 6.7 Hz, 0.33H, anti), 4.19 (s, 0.33H, syn), 4.05-3.78 (m,
4H, syn and anti), 2.96-2.52 (m, 4H, syn and anti), 1.80 (s, 1H,
anti), 1.68 (s, 2H, syn), 1.37 (s, 6H, syn), 1.33 (s, 3H, anti); 13C
NMR (100.5 MHz, CDCl3) δ 156.4 (syn), 155.9 (anti), 145.5 (syn),
144.9 (anti), 138.6 (syn and anti), 129.5 (anti), 129.4 (syn), 128.5
(syn), 128.4 (anti), 126.4 (syn), 126.2 (anti), 112.3 (anti), 111.5
(syn), 79.4 (syn and anti), 74.7 (syn and anti), 54.0 (syn), 53.8
(anti), 38.50 (syn), 34.4 (anti), 28.4 (syn and anti), 19.2 (anti),
19.1 (syn); IR (neat film) 3420, 2978, 1691, 1498, 1367, 1170
cm-1. Anal. Calcd for C17H25NO3: C, 70.07; H, 8.65; N, 4.81.
Found: C, 70.09; H, 8.36; N, 4.92.
Gen er a l Meth od s. All reactions were carried out under an
inert atmosphere of dry nitrogen. Reagents were obtained
commercially and used as provided unless otherwise noted. Pd2-
dba3CHCl3 (dba ) dibenzylidineacetone) was prepared as de-
scribed previously.27 Reaction solvents were freshly distilled
under nitrogen from standard drying agents prior to use. NMR
spectra were recorded on J EOL 400, 270 MHz or Varian Inova
500, 400, or 300 MHz instruments. Chemical shifts are reported
in ppm relative to residual solvent as internal standard.
Elemental analyses were obtained from MHW Laboratories.
Optical rotations were recorded on a J ASCO-DIP-370 polarim-
eter. Melting points were uncorrected.
(4S)-4-ter t-Bu toxyca r bon yla m in o-5-ter t-bu tyld im eth yl-
silyloxy-2-m eth ylp en t-1-en -3-ol (6a ). DIBAL-H (35 mL, 1.5
M in toluene, 53 mmol) was added dropwise over a period of 1
h into a solution of ester 5a (7.0 g, 21 mmol) in toluene (100
mL) at -78 °C. The reaction was allowed to stir at -78 °C for 2
h, and methanol (15 mL) was added dropwise at the same
temperature. After warming to 0 °C, the reaction mixture was
poured into a solution of saturated aqueous sodium potassium
tartrate (250 mL) and ethyl acetate (150 mL) and stirred for 30
min. The organic layer was separated, and the aqueous layer
was further extracted with ethyl acetate (2 × 100 mL). The
combined organic extracts were washed with water and brine,
dried over MgSO4, and concentrated to afford the crude alde-
hyde. To the crude aldehyde in THF (100 mL) at 0 °C was added
a solution of 2-propenylmagnesium bromide (prepared freshly
from magnesium (1.53 g, 63 mmol) and 2-bromopropene (5.6 mL,
63 mmol) in THF (75 mL) and the mixture stirred at ambient
temperature for 20 h. The reaction was quenched with saturated
aqueous NH4Cl solution and extracted with ether (3 × 100 mL).
The organic layer was washed with water and brine, dried over
MgSO4, concentrated, and purified by column chromatography
over silica gel (1:16 ethyl acetate/hexane) to afford the alcohol
6a (5.67 g, 78%) as a colorless oil in a 4:1 mixture of syn and
anti isomers, respectively: 1H NMR (270 MHz, CDCl3) δ 5.10
(bs, 0.2H, anti), 5.05 (bs, 0.8H, syn), 5.02 (bs, 0.2H, anti), 4.98
(m, 0.8H, syn), 4.91 (bs, 0.8H, syn), 4.90 (m, 0.2H, anti), 4.32
(bs, 0.8H, syn), 4.25-4.14 (m, 2H, syn and anti), 3.92-3.60 (m,
6H, syn and anti), 3.47 (bs, 2H, syn and anti), 1.73 (s, 0.6H, anti),
1.72 (s, 2.4H, syn), 1.43 (s, 1.8H, anti), 1.41 (s, 7.2H, syn), 0.88
(s, 7.2H, syn), 0.875 (s, 1.8H, anti), 0.06 (s, 4.8H, syn), 0.05 (s,
0.6H, anti), 0.04 (s, 0.6H, anti); 13C NMR (100.5 MHz, CDCl3) δ
156.4 (syn), 155.9 (anti), 144.8 (anti), 144.0 (syn), 111.8 (syn and
anti), 79.4 (syn), 77.7 (anti), 75.5 (syn and anti), 65.3 (syn), 63.3
(anti), 52.5 (syn), 51.5 (anti), 28.5 (syn), 28.4 (anti), 25.9 (syn),
25.7 (anti), 19.1 (syn and anti), 18.2 (anti), 18.1 (syn), -5.5 (syn),
-5.6 (anti); IR (neat film) 3446, 1710, 1502 cm-1. Anal. Calcd
for C17H35NO4Si: C, 59.09; H, 10.21; N, 4.05. Found: C, 58.81;
H, 10.10; N, 4.17.
(4S)-3-Ben zoyl-4-ter t-bu tyld im eth ylsilyloxym eth yl-5-(2-
p r op en yl)oxa zolid in -2-on e (7a ). To a suspension of NaH (1.32
g, 60% in mineral oil, 33 mmol) in THF (30 mL) at 0 °C was
added a solution of the alcohol 6a (5.67 g, 16 mmol) in THF (90
mL), and the mixture was allowed to stir at room temperature
for 12 h. It was cooled to 0 °C, and benzoyl chloride (2.3 mL, 20
mmol) was added dropwise. After being stirred for 1 h at room
temperature, the reaction mixture was carefully quenched with
water and extracted with ether (3 × 100 mL). The combined
organic extracts were washed with water and brine, dried over
MgSO4, concentrated, and purified by column chromatography
over silica gel (graduated from 1:12 to 1:7, ethyl acetate/hexane)
to yield the oxazolidinone 7a (5.45 g, 88%) as a colorless oil in a
4:1 mixture of trans and cis isomers, respectively: 1H NMR (400
MHz, CDCl3) δ 7.65-7.59 (m, 4H, cis and trans), 7.56-7.5 (m,
2H, cis and trans), 7.46-7.39 (m, 4H, cis and trans), 5.29 (bs,
1H, cis), 5.17 (bs, 2H, cis and trans), 5.07 (bs, 0.8H, trans), 5.06
(d, J ) 6.5 Hz, 0.2H, cis), 4.96 (d, J ) 4.8 Hz, 0.8H, trans), 4.61
(m, 0.2H, cis), 4.37 (dt, J ) 4.3, 2.2 Hz, 0.8H, trans), 4.16 (dd, J
) 10.5, 4.3 Hz, 0.2H, cis), 4.12 (dd, J ) 10.8, 4.3 Hz; 0.8H, trans),
3.78 (dd, J ) 10.8, 2.5 Hz, 0.8H, trans), 3.74 (dd, J ) 10.5, 1.6
Hz, 0.2H, cis), 1.86 (s, 0.6H, cis), 1.83 (s, 2.4H, trans), 0.9 (s,
7.2H, trans), 0.83 (s, 1.8H, cis), 0.08 (s, 2.4H, trans), 0.04 (s,
2.4H, trans), 0.01 (s, 0.6H, cis), 0.0 (s, 0.6H, cis); 13C NMR (100.5
MHz, CDCl3) δ 170.0 (trans), 169.8 (cis), 153.1 (trans), 153.0 (cis),
140.4 (trans), 136.2 (cis), 133.5 (cis), 133.3 (trans), 132.4 (trans),
132.1 (cis), 129.0 (trans), 128.8 (cis), 128.0 (trans), 127.9 (cis),
114.8 (trans), 114.5 (cis), 79.7 (cis), 79.0 (trans), 60.5 (trans),
60.1 (trans), 59.4 (cis), 58.7 (cis), 25.9 (trans), 25.8 (cis), 19.5
(cis), 18.2 (trans), 18.1 (cis), 17.0 (trans), -5.4 (trans), -5.5
(trans), -5.6 (cis); IR (neat film) 2930, 2858, 1790, 1680, 1469,
1325, 1112 cm-1. Anal. Calcd for C20H29NO4Si: C, 63.97; H, 3.73;
N. 7.78. Found: C, 63.89; H, 3.73; N, 7.59.
(4S )-3-Be n zoyl-4-b e n zyl-5-(2-p r op e n yl)oxa zolid in -2-
on e (7b): colorless oil (yield 81%) (2.4:1 mixture of trans and
cis); 1H NMR (400 MHz, CDCl3) δ 7.67-7.17 (m, 20H, trans and
cis), 5.34 (s, 0.3H, cis), 5.20 (s, 0.3H, cis), 5.07-4.95 (m, 0.6H,
cis), 4.99 (s, 0.7H, trans), 4.97 (s, 0.7H, trans), 4.74 (d, J ) 4.5
Hz, 0.7H, trans), 4.60 (ddd, J ) 8.1, 4.6, 3.5 Hz, 0.7H, trans),
3.37 (dd, J ) 13.7, 3.2 Hz, 0.7H, trans), 3.14 (dd, J ) 13.7, 4.3
Hz, 0.3H, cis), 3.08 (dd, J ) 13.7, 8.6 Hz, 0.7H, trans), 2.94 (dd,
J ) 13.7, 7.7 Hz, 0.3H, cis), 1.57 (s, 2.1H, trans), 1.53 (s, 0.9H,
(4S)-4-ter t-Bu toxycar bon ylam in o-2-m eth yl-5-ph en ylpen t-
1-en -3-ol (6b): colorless oil (yield 87%) (2:1 mixture of syn and
(27) Ukai, T.; Kawazura, H.; Ishii, Y.; Bonnet, J . J .; Ibers, J . A. J .
Organomet. Chem. 1974, 65, 253.

Notes
J . Org. Chem., Vol. 66, No. 20, 2001 6821
cis); 13C NMR (100.5 MHz, CDCl3) δ 170.0 (trans), 169.4 (cis),
152.9 (trans), 152.7 (cis), 140.1 (trans), 136.7 (cis), 136.6 (cis),
135.1 (trans), 133.4 (trans), 133.3 (cis), 132.5 (trans), 132.4 (cis),
130.1 (trans), 129.9 (cis), 129.2 (cis), 129.1 (cis), 129.0 (trans),
128.6 (cis), 128.1 (trans), 128.0 (cis), 127.6 (trans), 127.0 (cis),
115.6 (cis), 114.6 (trans), 80.5 (cis), 80.0 (trans), 59.7 (trans),
59.1 (cis), 37.6 (trans), 34.4 (cis), 19.3 (cis), 17.0 (trans); IR (neat
film) 1788, 1680, 1448, 1309 cm-1. Anal. Calcd for C20H19NO3:
C, 74.75; H, 5.96; N, 4.36. Found: C, 75.00; H, 6.02; N, 4.47.
(4S,5S)-4-ter t-Bu tyld im eth ylsilyloxym eth yl-2-p h en yl-5-
(2-p r op en yl)oxa zolin e (8a ). Pd2(dba)3CHCl3 (75 mg, 0.07
mmol) and dppp (120 mg, 0.29 mmol) were taken in a Schlenk
tube, evacuated, and flushed with nitrogen. THF (10 mL) was
added, and the mixture was stirred at ambient temperature until
the deep red solution turned yellow (15 min). A solution of the
oxazolidinone 7a (5.45 g, 14.5 mmol) in THF (50 mL) was added,
and the reaction was stirred at 50 °C. After 4 h, the reaction
was concentrated and purified by column chromatography over
silica gel (1:19, ethyl acetate/hexane) to afford the oxazoline 8a
layer was washed with brine, dried over MgSO4, and concen-
trated. The residue was treated with a solution of diazomethane
in ether (freshly prepared from N-methyl-N-nitrosourea28) to
afford the methyl ester. The product was purified by column
chromatography over silica gel (1:4, ethyl acetate/hexane) to yield
the ester 3 (382 mg, 50%) as a pale yellow oil: [R]25 ) -111.3
D
(c ) 0.68, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.0-7.95 (m,
2H), 7.5-7.35 (m, 3H), 4.67 (t, J ) 6.8 Hz, 1H), 4.56 (d, J ) 7.3
Hz, 1H), 3.80 (s, 3H), 1.95 (m, 1H), 1.02 (d, J ) 6.7 Hz, 3H),
0.99 (d, J ) 6.7 Hz, 3H); 13C NMR (100.5 MHz, CDCl3) δ 172.2,
165.8, 131.9, 128.6, 128.4, 127.2, 87.2, 71.4, 52.8, 32.5, 17.5, 17.4;
IR (neat film) 2962, 1743, 1643, 696 cm-1. Anal. Calcd for C14H17
-
NO3: C, 68.00; H, 6.93; N, 5.66. Found: C, 67.84; H, 6.99; N,
5.60.
(4R,5R)-4-ter t-Bu tyld im eth ylsilyloxym eth yl-5-((E,1R)-1-
m eth yl-3-p en ten yl)-2-p h en yloxa zolin e (10). To a solution of
oxazoline ent-8a (1.67 g, 5.1 mmol) in THF (5 mL) at 0 °C was
added 9-BBN (20.2 mL, 0.5 M solution in THF), and the mixture
was stirred at room temperature. After 3 h, 2 N NaOH (10 mL)
followed by a THF (3 mL) solution of Pd(PPh3)4 (58 mg, 0.05
mmol) and 1-bromopropene (0.52 mL, 6.1 mmol) was added. The
mixture was heated at 55-60 °C for 4 h. The reaction mixture
was cooled to room temperature and extracted with ether (3 ×
50 mL). The combined organic layer was washed with water and
brine, dried over MgSO4, concentrated, and purified by column
chromatography over silica gel (1:19 ethyl acetate:hexane). The
product was further purified by bulb-to-bulb distillation to yield
pure oxazoline 10 (1.53 g, 81%) as a 5.5:1 mixture of diastere-
(4.69 g, 97%) as a colorless oil: [R]25 ) +2.2 (c ) 1.18, CHCl3);
D
1H NMR (400 MHz, CDCl3) δ 8.01-7.95 (m, 2H), 7.51-7.38 (m,
3H), 5.04 (t, J ) 0.7 Hz, 1H), 4.97 (d, J ) 5.9 Hz, 1H), 4.88 (t, J
) 1.4 Hz, 1H), 4.05 (dt, J ) 6.4, 3.8 Hz, 1H), 3.89 (dd, J ) 10.2,
3.8 Hz, 1H), 3.66 (J ) 10.2, 6.7 Hz, 1H), 1.74 (s, 3H), 0.85 (s,
9H), 0.07 (s, 3H), 0.03 (s, 3H); 13C NMR (100.5 MHz, CDCl3) δ
164.1, 143.6, 131.4, 128.4, 128.4, 127.8, 111.7, 85.0, 73.2, 65.0,
25.9, 18.3, 17.1, -5.2, -5.3; IR (neat film) 2930, 1649, 1450, 1221
cm-1. Anal. Calcd for C19H29NO2Si: C, 68.84; H, 8.82; N, 4.22.
Found: C, 69.05; H, 8.82; N, 4.21.
omers. [R]25 ) +58.5 (c ) 1.44, CHCl3); 1H NMR (500 MHz,
D
(4S,5S)-4-Ben zyl-2-p h en yl-5-(2-p r op en yl)oxa zolin e (8b):
CDCl3) (major isomer) δ 7.96-7.86 (m, 2H), 7.48-7.32 (m, 3H),
5.52-5.34 (m, 2H), 4.40 (dd, J ) 6.7, 5.6 Hz, 1H), 4.02 (m, 1H),
3.81 (dd, J ) 10.1, 3.7 Hz, 1H), 3.58 (dd, J ) 10.1, 6.7 Hz, 1H),
2.23 (m, 1H), 1.90 (m, 1H), 1.78 (m, 1H), 1.63 (d, J ) 6.5 Hz,
3H), 0.88 (d, J ) 7 Hz, 3H), 0.83 (s, 9H), 0.04 (s, 3H), 0.00 (s,
3H); (minor isomer, characteristic peaks) δ 4.50 (t, J ) 5.2 Hz,
1H), 3.86 (dd, J ) 10.1, 4 Hz, 1H), 3.54 (dd, J ) 10.1, 7.4 Hz,
1H), 2.19 (m, 1H), 1.66 (m, 1H), 0.84 (s, 9H), 0.05 (s, 3H), 0.01
(s, 3H); 13C NMR (125 MHz, CDCl3) (major isomer) δ 164.30,
131.42, 128.94, 128.47, 128.44, 127.14, 86.25, 70.72, 65.54, 37.80,
35.25, 26.06, 26.05, 18.47, 18.23, 14.42, -5.09, -5.11,; (minor
isomer, characteristic peaks) δ 164.60, 129.30, 128.25, 85.90,
71.06, 65.65, 38.21, 36.11, 18.44, 18.21, 13.95, -5.13. IR (neat
film) 1649, 1604, 1462, 1282 cm-1. Anal. Calcd for C22H35NO2-
Si: C, 70.73; H, 9.44; N, 3.75. Found: C, 70.93; H, 9.35; N, 3.81.
colorless oil (yield 93%); [R]25 ) +38.6 (c ) 2.32, CHCl3); 1H
D
NMR (400 MHz, CDCl3) δ 8.05-7.95 (m, 2H), 7.5-7.18 (m, 8H),
4.73 (s, 2H), 4.72 (d, J ) 5.9 Hz, 1H), 4.24 (dt, J ) 8.3, 5.9 Hz,
1H), 3.23 (dd, J ) 13.8, 5.4 Hz, 1H), 2.76 (dd, J ) 13.7, 8.3 Hz,
1H), 1.51 (s, 3H); 13C NMR (100.5 MHz, CDCl3) δ 163.3, 143.1,
137.7, 131.5, 129.8, 128.6, 128.5, 128.4, 127.8, 126.7, 112.0, 86.6,
73.0, 42.3, 16.7; IR (neat film) 1649, 1494, 1450, 696. cm-1. Anal.
Calcd for C19H19NO: C, 82.28; H, 6.90; N, 5.05. Found: C, 81.98;
H, 6.99; N, 5.04.
(4S,5S)-5-isop r op yl-4-H yd r oxym et h yl-2-p h en yloxa zo-
lin e (9). To a solution of the oxazoline 8a (1.16 g, 3.5 mmol) in
benzene (15 mL) was added (PPh3)3RhCl (33 mg, 0.04 mmol).
The mixture was shaken under H2 at 55 psi. After 12 h, one
more portion of the catalyst (PPh3)3RhCl (33 mg, 0.04 mmol)
was added and shaking continued under H2 for 24 h. The
reaction mixture was filtered through Florisil and concentrated
to afford the saturated oxazoline in quantitative yield as a
colorless oil: 1H NMR (270 MHz, CDCl3) δ 7.95-7.85 (m, 2H),
7.5-7.32 (m, 3H), 4.34 (t, J ) 5.9 Hz, 1H), 4.0 (m, 1H), 3.84 (dd,
J ) 10, 4 Hz, 1H), 3.57 (dd, J ) 10, 7.1 Hz, 1H), 1.85 (m, 1H),
0.98 (d, J ) 6.7 Hz, 3H), 0.95 (d, J ) 6.7 Hz, 3H), 0.84 (s, 9H),
0.05 (s, 3H), 0.02 (s, 3H); 13C NMR (100.5 MHz, CDCl3) δ 164.2,
131.3, 128.3, 128.3, 128.1, 87.5, 70.6, 65.5, 32.5, 25.9, 18.3, 17.6,
17.4, -5.2. The hydrogenated oxazoline was dissolved in dry
THF (10 mL) and treated with tetrabutylammonium fluoride
(TBAF) (3.85 mL, 1 M in THF) at ambient temperature. After 1
h, the reaction mixture was diluted with water (20 mL) and
extracted with ethyl acetate (3 × 25 mL). The combined organic
layer was washed with brine, dried over MgSO4, concentrated,
and recrystallized from ether/hexane (1:2) to afford alcohol 9 as
(4R,5R)-4-Hydr oxym eth yl-5-((E,1R)-1-m eth yl-3-pen ten yl)-
2-p h en yloxa zolin e (11). To a solution of oxazoline 10 (689 mg,
1.85 mmol) in THF (5 mL) was added TBAF (2.2 mL, 1 M in
THF). After being stirred at room temperature for 30 min, the
reaction mixture was diluted with water and extracted ethyl
acetate (3 × 25 mL). The combined organic layer was washed
with brine, dried over MgSO4, and concentrated. The residue
was recrystallized from ether (3 mL) and hexane (12 mL) to
afford the alcohol 11 (280 mg, 59%) as 16:1 mixture of diaster-
eomers: mp 128 °C; [R]25D ) +118.6 (c ) 1.16, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 7.92-7.78 (m, 2H), 7.48-7.3 (m, 3H), 5.54-
5.36 (m, 2H), 4.38 (t, J ) 7 Hz, 1H), 4.06 (dt, J ) 7, 4 Hz, 1H),
3.96 (dd, J ) 11.5, 3.5 Hz, 1H), 3.57 (dd, J ) 11.5, 5 Hz, 1H),
3.14 (bs, 1H), 2.3-2.22 (m, 1H), 2.0-1.79 (m, 2H), 1.67 (dd, J )
6, 1 Hz, 3H), 0.9 (d, J ) 7 Hz, 3H); 13C NMR (125 MHz, CDCl3)
δ 165.03, 131.56, 128.50, 128.47, 128.41, 127.53, 85.0, 71.04,
64.92, 37.73, 35.51, 18.26, 14.18; IR (neat film) 3194, 1651, 1465,
1375 cm-1. Anal. Calcd for C16H21NO2: C, 74.10; H, 8.16; N, 5.40.
Found: C, 73.78; H, 8.44; N, 5.40. The mother liqour was
concentrated and purified by column chromatography over silica
gel (3:2 ethyl acetate/hexane) to yield more alcohol 11 (150 mg,
31%, dr ) 1.7:1).
white crystalline solid: mp 146 °C; [R]25 ) -115.5 (c ) 0.64,
D
CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.92-7.88 (m, 2H), 7.49-
7.41 (m, 1H), 7.40-7.31 (m, 2H), 4.29 (t, J ) 6.7 Hz, 1H), 4.03
(m, 1H), 3.95 (dd, J ) 11.5, 3.1 Hz, 1H), 3.57 (dd, J ) 11, 3.5
Hz, 1H), 1.90 (m, 1H), 1.74 (bs, 1H), 1.01 (d, J ) 6.7 Hz, 3H),
0.96 (d, J ) 7 Hz, 3H); 13C NMR (100.5 MHz, CDCl3) δ 164.9,
131.3, 128.3, 128.2, 127.3, 86.2, 71.0, 64.6, 32.3, 17.65, 17.4; IR
(neat film) 3192, 2957, 2870, 1649, 1450, 1371, 1344 cm-1. Anal.
Calcd for C13H15NO2: C, 71.87; H, 6.96; N, 6.45. Found: C, 71.70;
H, 7.15; N, 6.32
(2R,3R,4R)-2-ter t-Bu t oxyca r b on yla m in o-3-b en zoyloxy-
4-m eth yloct-6-en ol (12). The alcohol 11 (217 mg, 0.84 mmol)
was dissolved in THF (5 mL) and 2 N HCl (3 mL) and stirred at
room temperature for 16 h. The reaction mixture was cooled in
an ice bath, and solid NaHCO3 (4 g) was added. Water (15 mL)
was added followed by a solution of Boc2O (365 mg, 1.68 mmol)
in THF (3 mL). After being stirred at room temperature for 2 h,
Meth yl (4R,5S)-5-Isop r op yl-2-p h en yloxa zolin e-4-ca r box-
yla te (3). To a solution of the alcohol 9 (686 mg, 3.13 mmol) in
CH3CN (10 mL) at room temperature was added a solution of
H5IO6 (2.14 g, 9.40 mmol) and CrO3 (16 mg, 0.16 mmol) in CH3-
CN (20 mL) over a period of 15 min, and the mixture was allowed
to stir for 30 min. It was diluted with water (20 mL) and
extracted with ethyl acetate (3 × 30 mL). The combined organic
(28) Arndt, R. Organic Syntheses; Blatt, A. H., Ed.; Wiley: New
York, 1943; Collect. Vol. II, p 165.

6822 J . Org. Chem., Vol. 66, No. 20, 2001
Notes
the solution was extracted with CHCl3 (3 × 25 mL). The
combined organic layers were washed with brine, dried over
MgSO4, concentrated, and purified by column chromatography
(m, 1H), 4.19 (dd, J ) 6.8, 5.4 Hz, 1H), 3.83 (dd, J ) 11.8, 3.4
Hz, 1H), 3.59 (dd, J ) 11.9, 3.5 Hz, 1H), 3.43 (dt, J ) 5.4, 3.4
Hz, 1H), 2.89 (s, 3H), 2.40 (bs, 1H), 2.24-2.16 (m, 1H), 1.94-
1.74 (m, 2H), 1.65 (dd, J ) 6.4, 1.2 Hz, 3H), 0.9 (d, J ) 6.7 Hz,
3H); 13C NMR (125 MHz, CDCl3) δ 158.87, 128.02, 127.92, 79.25,
61.55, 61.50, 37.61, 34.68, 29.39, 18.21, 14.07; IR (neat film)
3445, 1757, 1728, 1483 cm-1. Anal. Calcd for C11H19NO3: C,
61.95; H, 8.98; N, 6.57. Found: C, 61.85; H, 9.02; N, 6.60.
Meth yl (4S,5R)-3-Meth yl-5-((E,1R)-1-m eth yl-3-p en ten yl)-
oxa zolid in -2-on e-4-ca r boxyla te (15). Oxazolidinone 14 (108
mg, 0.51 mmol) and PDC (954 mg, 2.54 mmol) were dissolved
in DMF (1.5 mL) and stirred at room temperature for 17 h. The
reaction mixture was cooled, diluted with ether (10 mL), and
acidified with 2 N HCl. The organic layer was separated, and
the aqueous layer was further extracted with ether (2 × 15 mL).
The combined organic extract was washed with brine, dried over
MgSO4, and concentrated. The residue was esterified with
ethereal CH2N2 and purified by column chromatography over
silica gel (2:3 ethyl acetate/hexane) to yield the ester 15 (70 mg,
over silica gel (3:7 ethyl acetate/hexane) to afford 12 (271 mg,
1
85%) as a viscous liquid: [R]25 ) +75.1 (c ) 2.14, CHCl3); H
D
NMR (500 MHz, CDCl3) δ 8.1-8.0 (m, 2H), 7.65-7.55 (m, 1H),
7.5-7.4 (m, 2H), 5.5-5.25 (m, 2H), 5.15 (dd, J ) 9, 2.5 Hz, 1H),
4.65 (d, J ) 10 Hz, 0.8H), 4.41 (d, J ) 8.5 Hz, 0.2H, rotamer),
4.15 (m, 0.8 H), 4.03 (m, 0.2H, rotamer), 3.60 (dd, J ) 12, 6 Hz,
1H), 3.33(dd, J ) 12, 8 Hz, 1H), 2.93 (br, 1H), 2.24-1.9 (m, 3H),
1.57 (br, 3H), 1.48 (s, 0.2 × 9H), 1.42 (s, 0.8 × 9H), 1.01 (d, J )
7 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 167.39, 155.94, 133.75,
130.09, 128.80, 128.23, 127.69, 80.07, 76.9, 62.52, 52.52, 35.98,
34.36, 28.51, 18.15, 15.99; IR (neat film) 3450, 3406, 1707, 1504,
1273 cm-1. Anal. Calcd for C21H31NO5: C, 66.82; H, 8.28; N, 3.71.
Found: C, 66.68; H, 8.10; N, 3.78.
(2R,3R,4R)-2-ter t-Bu t oxyca r b on yla m in o-3-b en zoyloxy-
1-ter t-bu tyld im eth ylsiloxy-4-m eth yloct-6-en e (13). Com-
pound 12 (750 mg, 1.99 mmol), TBDMSCl (360 mg, 2.39 mmol),
and imidazole (163 mg, 2.39 mmol) were charged in a flask and
kept under N2. Dichloromethane (10 mL) was added, and the
mixture was stirred at 10 °C for 2 h. The mixture was diluted
with additional dichloromethane, washed with water and brine,
dried over MgSO4, concentrated, and purified by column chro-
matograpy over silica gel (1:24 ethyl acetate/hexane) to yield 13
(881 mg, 90%) as a colorless oil: [R]25D ) +12.6 (c ) 0.88, CHCl3);
1H NMR (500 MHz, CDCl3) δ 8.09-8.01 (m, 2H), 7.61-7.54 (m,
1H), 7.5-7.44 (m, 2H), 5.48-5.34 (m, 2H), 5.28 (dd, J ) 6.3, 4.8
Hz, 1H), 4.86 (d, J ) 10.5 Hz, 1H), 4.1 (m, 1H), 3.65 (dd, J )
10.5, 4.5 Hz, 1H), 3.6 (dd, J ) 10, 5.5 Hz, 1H), 2.28-2.2 (m,
1H), 2.06-1.9 (m, 2H), 1.63 (d, J ) 5.5 Hz, 3H), 1.38 (s, 9H),
57%) as a colorless liquid: [R]25 ) +39.2 (c ) 1.67, CH2Cl2)
D
[lit.14g [R]D ) +37.1 (c ) 1.51, CH2Cl2)]; 1H NMR (500 MHz,
CDCl3) δ 5.52-5.44 (m, 1H), 5.38-5.3 (m, 1H), 4.27 (dd, J )
6.4, 4.7 Hz, 1H), 3.96 (d, J ) 5 Hz, 1H), 3.81 (s, 3H), 2.90 (s,
3H), 2.23-2.15 (m, 1H), 1.98-1.82 (m, 2H), 1.65 (dd, J ) 6.4,
1.3 Hz, 3H), 0.93 (d, J ) 6.7 Hz, 3H); 13C NMR (125 MHz, CDCl3)
δ 170.51, 157.58, 128.37, 127.51, 79.50, 61.96, 53.14, 37.81, 34.48,
30.32, 18.23, 14.06; IR (neat film) 1764, 1437, 1398, 1217, 1045
cm-1. Anal. Calcd for C12H19NO4: C, 59.74; H, 7.94; N, 5.81.
Found: C, 59.70; H, 7.82; N, 5.72.
(E ,2S,3R ,4R )-2-Me t h y la m in o -3-h y d r o x y -4-m e t h y l-6-
octen oic Acid (MeBm t) (4). The hydrolysis of the oxazolidi-
none ester was carried out in a manner similar to that reported
by Wenger.13 A solution of oxazolidinone 15 (87 mg) in 2 N KOH
(1.5 mL) was heated at 80-95 °C for 10 h, cooled to room
temperature, and acidified with 1 N HCl to pH 5. The solution
was concentrated to 1 mL, and the precipitate was filtered. The
solid was recrystallized by first dissolving in hot ethanol/water
(2 mL/1 mL respectively), filtered while hot, and then concen-
trated to 1 mL. The precipitated amino acid was filtered, washed
with ethanol, and dried under vacuum to yield MeBmt (4) (58
mg, 80%) as a white solid (mp 234-236 °C) (lit.13 mp 240-241
°C; lit.20 mp 233 °C)): δ ) +7.1 (c ) 0.45, 0.4 N HCl) (lit.13 δ )
+13.0 (c ) 0.46, H2O pH 7 phosphate Tritisol buffer) [lit.20 δ )
+12.2 (c ) 0.55, H2O pH 7 phosphate Tritisol buffer)]. Spectro-
scopic analysis was consistent with previous literature reports:
1.00 (d, J ) 7 Hz, 3H), 0.87 (s, 9H), 0.01(s, 3H), 0.0 (s, 3H); 13
C
NMR (125 MHz, CDCl3) δ 166.30, 155.79, 133.16, 130.42, 129.98,
129.13, 128.58, 127.13, 79.57, 77.10, 63.46, 52.53, 35.15, 34.76,
28.51, 26.02, 18.41, 18.17, 16.37, -5.38; IR (neat film) 1722,
1496, 1269 cm-1. Anal. Calcd for C27H45NO5Si: C, 65.95; H, 9.22;
N, 2.85. Found: C, 66.16; H, 9.21; N, 2.98.
(4R,5R)-4-Hyd r oxym eth yl-3-m eth yl-5-((E,1R)-1-m eth yl-
3-p en t en yl)oxa zolid in -2-on e (14). To a suspension of NaH
(147 mg, 3.67 mmol) in THF (3 mL) at 0 °C was added a solution
of 13 (300 mg, 0.61 mmol) in THF (3 mL). After 15 min, methyl
iodide (0.38 mL, 6.1 mmol) was added, and the mixture was
stirred at room temperature for 2 days. The reaction was cooled,
quenched with water, and extracted with ethyl acetate (3 × 25
mL). The combined organic layer was washed with water and
brine, dried over MgSO4, and concentrated. The residue was
dissolved in methanol (3 mL), and NaOMe (0.25 mL, 1.24 M in
MeOH) was added. The mixture was heated at 55-60 °C for 24
h. The solution was cooled, concentrated, dissolved in 2 N HCl
(6 mL) and THF (3 mL), and stirred at room temperature for 3
h. The solution was diluted with water and extracted with ethyl
acetate (3 × 10 mL). The combined organic layer was washed
with water and brine, dried over MgSO4, concentrated, and
purified by column chromatography over silica gel (1:19 methanol/
ethyl acetate) to yield oxazolidinone 14 (108 mg, 83%) as a white
14f,15a
1H NMR (500 MHz, D2O) δ 5.37 (dq, J ) 15.1, 6.4 Hz, 1
H), 5.28 (dtq, J ) 15.1, 7.8, 1.5 Hz, 1 H), 3.57 (dd, J ) 5.9, 6.4
Hz, 1H), 3.45 (d, J ) 6.4 Hz, 1 H), 2.53 (s, 3H), 2.08 (m, 1 H),
1.68 (dt, J ) 13.7, 8.3 Hz, 1 H), 1.50 (m, 1 H), 1.45 (d, J ) 5.9
Hz, 3 H), 0.74 (d, 6.8 Hz, 3 H).
Ack n ow led gm en t . We are grateful to NIH
(GM58470-01), NSF (OSR-9452892, CHE-9875013), and
North Dakota State University for support of our
programs.
crystalline solid (mp 83-84 °C): [R]25 ) +76.9 (c ) 0.92, CH2-
D
Cl2); 1H NMR (500 MHz, CDCl3) δ 5.52-5.43 (m, 1H), 5.4-5.31
J O015760M