Applications of 5-Endo-trigonal cyclization: Construction of compounds relevant to the synthesis of prostaglandins and methyl epi-Jasmonate

Article abstract of DOI:10.1021/jo982225m

Silane 15, easily constructed by simple methods, undergoes a cascade of radical reactions when treated with a stannane to afford the bicyclic 1,2-oxasiloles 16, with the major isomer having the ester group anti to the O-Si unit. This isomer was elaborated via 19 into 6, a deoxy derivative of the Corey lactone. In a related sequence, ketone 24 was converted into silane 35; this, too, underwent the radical cascade to afford the highly substituted 1,2-oxasiloles 36. Again the major isomer had the ester and O-Si units in an anti relationship. Elaboration of 36 (major isomer) gave the Corey lactone derivative 7. A key intermediate (32) in this second sequence was also prepared in optically pure form by starting with 2-deoxy-D-ribose. Compound 19 was converted into 8, a sequence that constitutes a formal synthesis of methyl (±)-epi-jasmonate. Two examples were found of selective silylation of a propargylic secondary hydroxyl in the presence of an ordinary secondary hydroxyl.

Full text of DOI:10.1021/jo982225m

2776
J . Org. Chem. 1999, 64, 2776-2788
Ap p lica tion s of 5-En d o-tr igon a l Cycliza tion : Con str u ction of
Com p ou n d s Releva n t to th e Syn th esis of P r osta gla n d in s a n d
Meth yl epi-J a sm on a te
Mousumi Sannigrahi, Darrin L. Mayhew, and Derrick L. J . Clive*
Chemistry Department, University of Alberta, Edmonton, Alberta, Canada T6G 2G2
Received November 6, 1998
Silane 15, easily constructed by simple methods, undergoes a cascade of radical reactions when
treated with a stannane to afford the bicyclic 1,2-oxasiloles 16, with the major isomer having the
ester group anti to the O-Si unit. This isomer was elaborated via 19 into 6, a deoxy derivative of
the Corey lactone. In a related sequence, ketone 24 was converted into silane 35; this, too, underwent
the radical cascade to afford the highly substituted 1,2-oxasiloles 36. Again the major isomer had
the ester and O-Si units in an anti relationship. Elaboration of 36 (major isomer) gave the Corey
lactone derivative 7. A key intermediate (32) in this second sequence was also prepared in optically
pure form by starting with 2-deoxy-D-ribose. Compound 19 was converted into 8, a sequence that
constitutes a formal synthesis of methyl (()-epi-jasmonate. Two examples were found of selective
silylation of a propargylic secondary hydroxyl in the presence of an ordinary secondary hydroxyl.
Sch em e 1
Radicals of type 1 (Scheme 1, X ) CH2), when gener-
ated from selenides, cyclize in the expected 5-exo-digonal
manner, but the resulting vinyl radicals (2) undergo
intramolecular hydrogen transfer to produce a silicon-
centered radical (2 f 3) which then closes by a 5-endo-
trigonal pathway (3 f 4).1-3 This unusual last step occurs
easily, as it is not subject to the restrictions embodied in
the Baldwin rules4 against 5-endo-trigonal cyclization,
because of the longer bond lengths involving silicon.5
Only a few cases have been reported of the cyclization of
silicon-centered radicals,3 but there is a growing number
of examples6 involving carbon radicals. The final bicyclic
product (5) of the present reaction has a relative stereo-
chemistry at the three asymmetric centers that is related
in the indicated manner to the stereocenter (see starred
atom in 1) of the starting radical species. We have
previously studied simple cases in which X is carbon1 or
a heteroatom;7 here we describe the use of this sequence
to prepare racemic compounds 6-8. The first two are
derivatives of the Corey lactone,8 and so they are relevant
to the synthesis of prostaglandins,8 while 8 has been
converted9 into the perfume ingredient methyl epi-
jasmonate, and its preparation constitutes a formal
synthesis of the natural product in racemic form. We have
also used a silane derived from 2-deoxy-D-ribose, to show
that optically pure compounds are available by the
method summarized in Scheme 1.
(1) Clive, D. L. J .; Cantin, M. J . Chem. Soc., Chem. Commun. 1995,
319-320.
(2) When radicals of type 1 are generated from iodides, the hydrogen
translocation (2 f 3) does not occur; instead, intermolecular halogen
transfer takes place: Martinez-Grau, A.; Curran, D. P. J . Org. Chem.
1995, 60, 8332-8333.
(3) For other examples involving silicon-centered radicals, see: Cai,
Y.; Roberts, B. P. J . Chem. Soc., Perkin Trans. 1 1998, 467-475.
(4) Baldwin, J . E. J . Chem. Soc., Chem. Commun. 1976, 734-736.
(5) Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.; Orpen,
A. G.; Taylor, R. J . Chem. Soc., Perkin Trans. 2 1987, S1-S19.
(6) For recent examples involving carbon radicals, see: (a) Bogen,
S.; Malacria, M. J . Am. Chem. Soc. 1996, 118, 3992-3993. (b) Baker,
S. R.; Parsons, A. F.; Pons, J .-F.; Wilson, M. Tetrahedron Lett. 1998,
39, 7197-7200. (c) Ikeda, M.; Ohtani, S.; Yamamoto, T.; Sato, T.;
Ishibashi, H. J . Chem. Soc., Perkin Trans 1 1998, 1763-1768. (d)
Ishibashi, H.; Higuchi, M.; Ohba, M.; Ikeda, M. Tetrahedron Lett. 1998,
39, 75-78. (e) Yamamoto, Y.; Ohno, M.; Eguchi, S. J . Org. Chem. 1996,
61, 9264-9271. (f) Schultz, A. G.; Guzzo, P. R.; Nowak, D. M. J . Org.
Chem. 1995, 60, 8044-8050. Cassayre, J .; Quiclet-Sire, B.; Saunier,
J .-B.; Zard, S. Z. Tetrahedron 1998, 54, 1029-1040.
Syn th esis of th e Com m on In ter m ed ia te Lea d in g
to 6 a n d 8. The common radical precursor for the
synthesis of 6 and 8 is the propargyl silane 15 [as a
(8) The designation “Corey lactone” has been used in recent litera-
ture to refer to a variety of hydroxyl-protected derivatives of the
hexahydro-5-hydroxy-4-(hydroxymethyl)-2H-cyclopenta[b]furan-2-
one system. Reviews on prostaglandin synthesis: (a) Mitra, A. The
Synthesis of Prostaglandins; Wiley: New York, 1977. (b) Newton, R.
F.; Roberts, S. M. Prostaglandins and Thromboxanes; Butterworth:
London, 1982.
(7) Clive, D. L. J .; Yang, W. J . Chem. Soc., Chem. Commun. 1996,
1605-1606.
(9) Kitahara, T.; Warita, Y.; Abe, M.; Seya, M.; Takagi, Y.; Mori, K.
Agric. Biol. Chem. 1991, 55, 1013-1017.
10.1021/jo982225m CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/26/1999

Applications of 5-Endo-trigonal Cyclization
J . Org. Chem., Vol. 64, No. 8, 1999 2777
Sch em e 2a
characterization.14 Likewise, the next two steps also gave
products containing small amounts of inseparable im-
purities. Ester reduction (LiAlH4, THF) gave alcohols 17,
and treatment with Bu4NF in warm DMF15 cleaved both
the O-Si and C-Si bonds (17 f 18). Finally, silylation
(t-BuPh2SiCl, imidazole) took the route as far as alcohol
19 (33% over the four steps from 15), which was easily
obtained pure, and fully characterized. The choice of
solvent for the desilylation 17 f 18 is crucial, as use of
THF served only to cleave the O-Si bond, but left the
C-Si bond intact.
Hydrogenolysis of 19 released diol 20 (91%, Scheme
3), and lactone 21 was formed (52%) in a single step by
treatment with KMnO4 and CuSO4‚5H2O16 (20 f 21).
Finally desilylation (Bu4NF; 93%) gave alcohol 6.17,18
Syn th esis of La cton e 7. For synthesis of the Corey
lactone derivative 7, it was necessary to repeat the
sequence of Scheme 2, but with a substrate having an
additional oxygen substituent, and the route to this
species is summarized in Scheme 4. The known hydroxy
ester 2219 was silylated20 (22 f 23; 93%) and converted
(ca. 72%) into the ketone 24 by treatment with the
lithium salt of benzyl propargyl ether in the presence of
BF3‚Et2O. Protection of the hydroxyl, and use of an ethyl
ester is, apparently, necessary20 for efficient reaction with
an acetylide (cf. 23 f 24), but we did not verify this
characteristic of the method for our particular case.
a
(a) C6H11NLiPr-i, -78 °C, THF; (b) 1:1 TFA-water, CH2Cl2;
53% over two steps; (c) BuLi, THF, -78 °C; 81%; (d) (t-Bu)2SiHCl,
THF, imidazole, 65 °C; 95%; (e) Ph3SnH, AIBN, PhH, reflux; (f)
LiAlH4, THF, -78 °C; (g) TBAF, DMF, 60 °C; (h) t-BuPh2SiCl,
imidazole, CH2Cl2; 33% from 15.
mixture of C(2) epimers], and this was constructed as
shown in Scheme 2. Alkylation of 3-iodo-1,1-dimethoxy-
propane (910) with the anion derived11 from methyl
(phenylseleno)acetate12 (10) gave 11, which was best
directly deprotected (TFA, 11 f 12; 53% from 9). The
aldehyde reacted smoothly with the anion derived from
benzyl propargyl ether (13), to afford (81%) a mixture of
diastereoisomeric hydroxy selenides (14). These were
then silylated (t-Bu2SiHCl, imidazole, 65 °C; 95%) to give
the epimeric precursors (15) for radical cyclization, which
were elaborated in two ways: one route led to the deoxy
Corey lactone 6 and the other to nitrile 8. It should be
noted that there are some limitations2 on the nature of
the radical precursor in the present tandem cyclizations,
but a selenide (as in 15) is very suitable.
Syn th esis of La cton e 6. Slow addition of Ph3SnH and
AIBN to a refluxing solution of 15, gave the expected
products (16) resulting from sequential 5-exo-digonal
cyclization, intramolecular hydrogen transfer, and 5-endo
cyclization. The stereochemistry of 5-exo-digonal radical
closures (cf. 1 f 2 and 15 f 16) has not received much
attention;13 however, we expected closure to take place
preferentially via conformation A (see eq 1), so as to place
the ester group trans to the O-Si unit (A f B), and, in
the event, the major (75% of the total) product did have
this stereochemical relationship.
(14) The compounds were characterized as follows: Treatment of
crude 16 with BF3‚Et2O (with the intention of breaking the O-Si and
HC-Si bonds) gave i as a colorless oil (52% from 15), which was
characterized fully: FTIR (CHCl3 cast) 1738 cm-1 1H NMR (CDCl3,
;
300 MHz) δ 1.0 (s, 9 H), 1.04 (s, 9 H), 1.79-2.03 (m, 3 H), 2.09-2.27
(m, 1 H), 2.60-2.73 (m, 1 H), 2.84-2.99 (m, 1 H), 3.67 (s, 3 H), 4.51-
4.61 (m, 1 H), 5.00-5.14 (m, 2 H), 5.81-5.99 (m, 1 H); 13C NMR (CDCl3,
50.3 MHz) δ 19.9 (s′) J C-Si-F ) 14.4 Hz, 20.6 (s′) J C-Si-F ) 16.0 Hz,
26.9 (q′), 27.0 (t′), 27.1 (q′), 34.7 (t′), 46.7 (d′), 51.5 (d′), 54.9 (q′), 79.0
(d′), 116.7 (t′), 136.4 (d′), 176.4 (s′); exact mass m/z calcd for C16H28
-
FO2Si (M - OCH3) 299.1843, found 299.1840. In principle, compound
i could have been used for conversion into 6, but this would have
required reintroduction of oxygen. In the event, reduction (LiAlH4) of
the ester and protection (MEMCl, i-Pr2NEt) of the resulting alcohol
gave an olefin that could be hydroborated only in yields of <40%, and
so this approach was abandoned.
(15) Koreeda, M.; Wu, J . Synlett 1995, 850-852, and references
therein.
Compounds 16 were contaminated by chromatographi-
cally inseparable impurities and were used without full
(16) J efford, C. W.; Wang, Y. J . Chem. Soc., Chem. Commun. 1988,
634-635.
(17) (a) Bindra, J . S.; Grodski, A. J . Org. Chem. 1978, 43, 3240-
3241. (b) For spectral data on the C(4) epimer, see: Zanoni, G.; Vidari,
G. J . Org. Chem. 1995, 60, 5319-5323.
(18) Lactone 21 was also made by acetylation of 19 (Ac2O, Et3N,
DMAP, 97%), hydrogenolysis (H2, Pd-C, 92%), oxidation (CH2OH f
CHO, PCC, 4 Å molecular sieves, 93%), further oxidation (CHO f
CO2H, NaClO2, NaH2PO4, t-BuOH, water), and base hydrolysis (K2CO3,
MeOH) of the acetate (spontaneous lactonization occurred; 48% from
the aldehyde).
(10) (a) Wohl, A. Chem. Ber. 1908, 41, 3599-3612. (b) Clive, D. L.
J .; Postema, M. H. D. J . Chem. Soc., Chem. Commun. 1993, 429-430.
(11) Rathke, M. W.; Lindert, A. J . Am. Chem. Soc. 1971, 93, 2318-
2320.
(12) Cf. Ryu, I.; Muraoka, H.; Kambe, N.; Komatsu, M.; Sonoda, N.
J . Org. Chem. 1996, 61, 6396-6403. We generated PhSeNa, using the
PhSeSePh/NaBH4 system.
(13) Cf. (a) Gaudino, J . J .; Wilcox, C. S. J . Am. Chem. Soc. 1990,
112, 4374-4380. (b) Crich, D.; Fortt, S. M. Tetrahedron Lett. 1987,
28, 2895-2898.
(19) Zibuck, R.; Streiber, J . Org. Synth. 1992, 71, 236-241.
(20) Mohr, P. Tetrahedron Lett. 1991, 32, 2219-2222.

2778 J . Org. Chem., Vol. 64, No. 8, 1999
Sannigrahi et al.
Sch em e 3
Sch em e 4a
Desilylation (HF, MeCN; 47% over two steps)21 and
DIBAL-H reduction (90%) of the resulting hydroxy ketone
25 proceeded with high stereoselectivity (ca. 15:1). Ke-
talization of the mixture of diols 26 allowed isolation of
ketal 27 in 88% yield.22 This compound was easily
separated from its C(6) epimer, and the stereochemistry
was assigned by analogy with other reactions of the same
type.20 Acid hydrolysis (CF3CO2H, aqueous THF; 93%)
then released diol 28.23
The next task was to place a t-Bu2SiH group on the
hydroxyl at C(5) of 28, protect the C(3) hydroxyl, and
dihydroxylate the double bond. Initially, we treated diol
28 with t-Bu2SiHCl/imidazole and observed very high
selectivity in favor of the propargylic hydroxyl, the
monosilylated compound C being isolated in 79% yield
(91% based on recovered 28); only a small amount (4%
yield) of doubly silylated material was isolated. NMR
decoupling measurements (see Supplementary Informa-
tion) indicated that the propargylic alcohol had been
silylated preferentially, as required for the intended
radical reaction. We assume that the propargylic alcohol
is more sterically accessible because of the linear geom-
etry of the adjacent alkyne, and the selectivity can be
understood on this basis.
A chemical experiment was also performed to confirm
the structure of C. A sample was treated with PCC, and
the resulting ketone D (56%) was found to have a 1H
NMR spectrum that defined the structure unambigu-
ously. Unfortunately, after protection of the C(3) hydroxyl
of C (as a methoxymethyl ether), it was not possible to
dihydroxylate24 the double bond without unwanted modi-
fication of the t-Bu2Si(O)H group. For this reason, an
indirect route, involving protection and deprotection, was
used as follows.
a
(a) t-BuMe2SiCl, imidazole, CH2Cl2; 93%; (b) BuLi, THF,
BnOCH2CtCH (13), BF3‚Et2O; ca. 72%; (c) HF, aq MeCN; 47%
from 22; (d) DIBAL, THF, -78 °C; 90%; two alcohols (15:1) are
formed; only the major one is shown; (e) 2,2-dimethoxypropane,
TsOH‚pyridine; 88%; (f) CF3CO2H, aq THF; 93%; (g) t-BuMe2SiCl,
imidazole, CH2Cl2; 47% (82% based on conversion); (h) MeOCH2Cl,
i-Pr2NEt, CH2Cl2; 86%; (i) OsO4, NMO, aq THF; 54%; (j) t-BuCOCl,
DMAP, PhMe; 44%; only major isomer of the product is shown;
(k) p-FC6H4OC(S)Cl, pyridine, DMAP; 72%; (l) HF, aq MeCN; 87%;
(m) t-Bu2SiHCl, imidazole, THF; 93%.
Treatment of 28 with t-BuMe2SiCl/imidazole gave the
monoprotected alcohol 29. The selectivity between the
(21) The use of TBAF in this step resulted in complete decomposition
of the starting material.
(22) The isomeric ketal was isolated in 6% yield.
two hydroxyls was lower than with t-Bu2SiHCl, presum-
ably because the dimethyl reagent has a smaller steric
demand, and reaction was best stopped well before
completion.25 Under optimum conditions, the yield of 29
was 47%, or 82% after correction for recovered starting
material. Protection (MeOCH2Cl, i-Pr2NEt; 86%) and
dihydroxylation (OsO4, NMO, aqueous THF; 54%) gave
(23) For other stereocontrolled routes to 1,3-diols, see, for example:
(a) Bartlett, P. A.; Meadows, J . D.; Brown, E. G.; Morimoto, A.;
J ernstedt, K. K. J . Org. Chem. 1982, 47, 4013-4018. (b) Bongini, A.;
Cardillo, G.; Orena, M.; Porzi, G.; Sandri, S. J . Org. Chem. 1982, 47,
4626-4633. (c) Cardillo, G.; Orena, M.; Porzi, G.; Sandri, S. J . Chem.
Soc., Chem. Commun. 1981, 465-466.
(24) Dihydroxylation was attempted using OsO4 under a number
of conditions, but the product did not contain the Si-H unit (absence
of the Si-H band at ca. 2000 cm-1).

Applications of 5-Endo-trigonal Cyclization
J . Org. Chem., Vol. 64, No. 8, 1999 2779
Sch em e 5a
Sch em e 6a
a
(a) Bu3SnH, AIBN, PhMe; 79%; (b) TBAF, DMF-THF, 70 °C;
88%; (c) 10% Pd-C, MeOH, H2; 87%; (d) KMnO4, CuSO4‚5H2O,
CH2Cl2; 63%.
31 as an inseparable mixture of epimers (29 f 30 f 31).
The primary hydroxyl was protected (t-BuCOCl, DMAP;
44%), taking the route as far as alcohols 32 (of which
the major isomer only is shown in Scheme 4). In principle
the formation of two epimers in the dihydroxylation is
inconsequential, as the initial stereochemistry at C(2) is
destroyed when a radical is later generated at that
carbon. Initially, we did not know the stereochemistry
of 32 at C(2); this was established later by comparison
with material obtained by a route in which the stereo-
chemistry at this center is known (see below). The
remaining hydroxyl of 32 was then acylated (32 f 33;
72%) by reaction with p-FC6H4OC(S)Cl/pyridine/DMAP,
and the t-BuMe2Si group was removed (HF, aqueous
MeCN; 87%). In the acylation, the C(2) epimer of 32 was
discarded. Finally, silylation with t-Bu2SiHCl/imidazole)
generated the radical cyclization precursor 35, which was
obtained in 93% yield.
Treatment with Bu3SnH/AIBN (Scheme 5), under the
same conditions used earlier, gave (ca. 79%) the required
product 36, as a mixture of C(4) epimers, with onesthat
corresponding to the type of conformation shown in eq
1sbeing present in great excess (>88%). Protodesilyl-
ation, done earlier (cf. 17 f 18) in DMF, was now carried
out arbitrarily in a 1:1 DMF-THF mixture. From this
experiment, alcohol 37 was isolated as a single isomer
in 88% yield. As in the route to the simpler model 6,
hydrogenolysis served to remove the benzyl protecting
group (37 f 38; 87%), and oxidation with the KMnO4-
CuSO4‚5H2O system gave (63%) the final target (7).
a
(a) DEAD, Ph3P, t-BuCO2H, THF; 58% (83% based on conver-
sion); (b) MeOCH2Cl, i-Pr2NEt, CH2Cl2; 90% for 41â, 92% for 41R;
(c) H2, 5% Pd-C, 50 psi, EtOH; 92% for each epimer; (d)
Ph3PCH3Br, BuLi, PhMe; 72%; (e) t-BuMe2SiCl, imidazole, CH2Cl2;
89%; (f) O3, CH2Cl2, -78 °C; Ph3P; 83%; (g) BnOCH2CtCH (13),
BuLi, -78 °C, THF; 71% (80% based on conversion); 1:1.4 ratio of
isomers; (h) HF, aq MeCN; 86%; (i) t-BuMe2SiCl, imidazole,
CH2Cl2; 94% (major isomer), 92% (minor isomer).
with t-BuCOCl.28 In the latter case, extensive acylation
of the secondary hydroxyl also occurred. Protection of the
C(3) hydroxyl (40R f 41R, 40â f 41â; MeOCH2Cl,
i-Pr2NEt; 90% for 41â, 92% for 41R), and hydrogenolytic
removal of the benzyl group (41R,41â f 42; 92% for each
anomer) proceeded without incident. Homologation of 42
by Wittig reaction with Ph3PdCH2 (72%), and silylation
(43 f 44; t-BuMe2SiCl, imidazole; 89%) of the resulting
alcohol set the stage for introduction of an acetylene unit.
To this end, the double bond of 44 was ozonized (44 f
45; O3, CH2Cl2, -78 °C; Ph3P; 83%), a process best done
using Sudan II red as an internal indicator.29 Reaction
with the anion derived from benzyl propargyl ether (13)
gave a 1:1.4 mixture of chromatographically inseparable
acetylenic alcohols 46 (71%, or 80% based on conversion).
Desilylation (HF, aqueous MeCN; 86%) gave diols 47a
(major isomer) and 47b (minor isomer), which were easily
Use of a Sta r tin g Ma ter ia l fr om th e Ch ir a l P ool.
To establish that the process of Scheme 4 could be applied
to compounds from the chiral pool, we converted 2-deoxy-
D-ribose into optically pure (+)-32 (Scheme 6). For this
purpose, 2-deoxy-D-ribose was first converted into its
benzyl glycosides 39, and the C(5) hydroxyl was pivaloy-
lated by Mitsunobu reaction (39 f 40R,40â)26sa proce-
dure27 that gave much better results than direct acylation
(25) Use of Et3SiCl gave only the bis-silylated product, and t-BuPh2-
SiCl did not react. In retrospect, t-Bu2MeSiCl should have been tested,
as its steric bulk (intermediate between Et3SiCl and t-BuPh2SiCl)
might have made it react with high selectivity.
(26) The anomeric configuration was established by a TROESY
NMR (600 MHz) experiment that established the stereochemistry of
41R.
(27) Cf. (a) Serra, C.; Dewynter, G.; Montero, J .-L.; Imbach, J .-L.
Tetrahedron 1994, 50, 8427-8444. (b) Mitsunobu, O.; Kimura, J .;
Fujisawa, Y. Bull. Chem. Soc. J pn. 1972, 45, 245-247.
(28) Review on selective acylation of carbohydrates: Haines, A. H.
Adv. Carbohydr. Chem. Biochem. 1976, 33, 11-109.
(29) Veysoglu, T.; Mitscher, L. A.; Swayze, J . K. Synthesis 1980,
807-810.

2780 J . Org. Chem., Vol. 64, No. 8, 1999
Sannigrahi et al.
Sch em e 7a
separated. Silylation with t-BuMe2SiCl/imidazole pro-
ceeded with very high regioselectivity, and again the
propargylic secondary hydroxyl reacted preferentially,
giving the required product in over 90% yield for both
the major (47a ) and minor (47b) isomers. The major
product [(+)-32, Scheme 6] was found to be spectroscopi-
cally (1H and 13C NMR) identical to the corresponding
racemic compound obtained by the reactions of Scheme
4. The stereochemistry at C(2) and C(3) in material from
2-deoxy-D-ribose is set by the stereochemistry of the
starting sugar, while the relative stereochemistry at C(3)
and C(5) for material obtained by the method of Scheme
4 is set by the procedure used. As the major products
from the two routes are structurally identical, the relative
stereochemistry of 32 obtained by the method of Scheme
4, and the absolute stereochemistry at C(2), C(3), and
C(5) of (+)-32 obtained from 2-deoxy-D-ribose can be
assigned as shown. The route from the sugar constitutes
a formal synthesis of optically pure 7 (which has the
opposite stereochemistry to that needed, in principle, for
elaboration to a natural prostaglandin).
F or m a l Syn th esis of Meth yl epi-J a sm on a te. Meth-
yl epi-jasmonate (48) is the main component responsible
for the odor of jasmine oil,30 although this fact was long
unrecognized. The substance also has a range of plant
regulatory and pheromonal properties,31 and has at-
tracted attention as a synthetic target.9,31c,32 The radical
sequence of Scheme 1 can also be applied to the synthesis
of 48, as described below.
a
(a) MEMCl, i-Pr2NEt, CH2Cl2; 100%; (b) TBAF, THF; 96%;
(c) o-O2NC6H4SeCN, Bu3P, THF; MCPBA, i-Pr2NEt, CH2Cl2, 40
°C; 80%; (d) BH3‚Me2S, THF, NaOH, H2O2; 85%; (e) TsCl, pyridine,
DMAP; 97%; (f) NaCN, DMSO, 100 °C; 87%; (g) H2, 5% Pd-C,
MeOH; 92%; (h) PCC, CH2Cl2, 4 Å sieves; 78%; (i) (Me3Si)2NK,
PrPPh3Br, PhMe, -78 °C to room temp; 80%.
Alcohol 19 was protected as its methoxyethoxy methyl
ether33 (Scheme 7, 19 f 49; MEMCl, i-Pr2NEt; 100%)
and desilylated (49 f 50; TBAF, THF; 96%). At this
point, attempts to invert the stereochemistry at C(3) by
oxidation of the alcohol and treatment of the resulting
aldehyde with a base were unsuccessful,34 but the
required inversion could be accomplished by dehydration
via an intermediate selenide (50 f 51; o-O2NC6H4SeCN,
Bu3P; MCPBA; i-Pr2NEt, 40 °C; 80%), and rehydration
(51 f 52; BH3‚Me2S, THF, -20 °C; NaOH, H2O2, 0 °C;
85%). The primary hydroxyl of 52 was then replaced by
a cyanide group (52 f 53, TsCl, pyridine, DMAP, 97%;
53 f 54, NaCN, DMSO, 100 °C, 87%). Removal of the
benzyl group by hydrogenolysis (92%) and PCC oxidation
(78%) then gave aldehyde 56. This was treated with the
salt-free Wittig reagent derived from triphenyl(propyl)-
phosphonium bromide, under well-established condi-
tions,32f,h,j to give in high yield (80%) the Z-olefin 8, which
has previously been converted9,35 into methyl epi-jas-
monate.
(30) (a) Chem. Eng. News 1983, 61, 34-36. (b) Acree, T. E.; Nishida,
R.; Fukami, H. J . Agric. Food Chem. 1985, 33, 425-427. (c) Cf.
Montforts, F.-P.; Gesing-Zibulak, I.; Grammenos, W.; Schneider, M.;
Laumen, K. Helv. Chim. Acta 1989, 72, 1852-1859. (d) Occurrence in
lemons: Nishida, R.; Acree, T. E. J . Agric. Food Chem. 1984, 32, 1001-
1003.
(31) (a) For references to plant regulatory activity and comment on
whether the observed effects are due to cis or trans jasmonates, see:
Ward, J . L.; Gaskin, P.; Beale, M. H.; Sessions, R.; Koda, Y.; Waster-
nack, C. Tetrahedron 1997, 53, 8181-8194. (b) See also: Koda, Y.
Physiol. Plant. 1997, 100, 639-646. (c) Potato tuberization: Kitahara,
T.; Nishi, T.; Mori, K. Tetrahedron 1991, 47, 6999-7006. (d) Pheromone
synergist: Baker, T. C.; Nishida, R.; Roelofs, W. L. Science 1981, 214,
1359-1362.
(32) Previous syntheses: (a) Tanaka, H.; Torii, S. J . Org. Chem.
1975, 40, 462-465. (b) Kitahara, T.; Miura, K.; Warita, Y.; Tagaki,
Y.; Mori, K. Agric. Biol. Chem. 1987, 51, 1129-1133. (c) Helmchen,
G.; Goeke, A.; Lauer, G.; Urmann, M.; Fries, J . Angew. Chem., Int.
Ed. Engl. 1990, 29, 1024-1025. (d) Weinges, K.; Lernhardt, U. J ustus
Liebigs Ann. Chem. 1990, 751-754. (e) Seto, H.; Yoshioka, H. Chem.
Lett. 1990, 1797-1800. (f) Crombie, L.; Mistry, K. M. J . Chem. Soc.,
Perkin Trans. 1 1991, 1981-1991. (g) Stork, G.; Ouerfelli, O. New J .
Chem. 1992, 16, 95-98. (h) Sarkar, T. K.; Ghorai, B. K.; Banerji, A.
Tetrahedron Lett. 1994, 35, 6907-6908. (i) Stadtmu¨ller, H.; Knochel,
P. Synlett 1995, 463-464. (j) Sarkar, T. K.; Ghorai, B. K.; Nandy, S.
K.; Mukherjee, B.; Banerji, A. J . Org. Chem. 1997, 62, 6006-6011. (k)
Roth, G. J .; Kirschbaum, S.; Bestmann, H. J . Synlett 1997, 618-620.
(l) U, J . S.; Park, H. S.; Gupta, S.; Cha, J . K. Synth. Commun. 1997,
27, 2931-2941. (m) Sarkar, T. K.; Mukherjee, B.; Ghosh, S. K.
Tetrahedron 1998, 54, 3243-3254.
Exp er im en ta l Section
Gen er a l P r oced u r es. Unless stated to the contrary, the
general procedures used previously36 were followed.
(34) We had initially assumed that deprotonation of esters 16,
followed by kinetic reprotonation, would afford an all-syn trisubstituted
cyclopentane system, but we were unable to modify the stereochemistry
in this way, and the task was accomplished by the indirect method
described.
(35) The final oxidation step is best done with PDC (see refs 32c
and 32f) or PCC (see ref 32e).
(33) A methoxymethyl group is unsuitable, as it cannot be removed
in a satisfactory manner in the penultimate step of the synthesis of
methyl epi-jasmonate (cf. ref 9).
(36) Clive, D. L. J .; Wickens, P. L.; Sgarbi, P. W. M. J . Org. Chem.
1996, 61, 7426-7437.

Applications of 5-Endo-trigonal Cyclization
J . Org. Chem., Vol. 64, No. 8, 1999 2781
The designations s′, d′, t′, and q′ for 13C NMR signals
indicate zero, one, two, or three attached hydrogens, respec-
tively. Where the number of signals is less than expected, we
assume that two or more signals are coincident.
EtOAc-hexane), and the combined organic extracts were
washed with brine, dried (MgSO4), and evaporated. Flash
chromatography of the residue over silica gel (3 × 22 cm), using
5:95 EtOAc-hexane, gave 15 as an inseparable mixture (13C
NMR) of diastereoisomers (3.428 g, 95%). The material was a
Meth yl 5,5-Dim eth oxy-2-(ph en ylselen o)pen tan oate (11).
n-BuLi (2.5 M in hexanes, 6.29 mL, 15.73 mmol) was added
dropwise to a stirred and cooled (-78 °C) solution of freshly
distilled N-isopropylcyclohexylamine (2.59 mL, 15.73 mmol)
in dry THF (8 mL). After 15 min, methyl (phenylseleno)acetate
(3.27 g, 14.30 mmol) in dry THF (4 mL plus 2 mL as a rinse)
was added dropwise at -78 °C. After 30 min, the cold bath
was removed, and the solution was allowed to warm to room
temperature (over ca. 40 min). The enolate solution was added
quickly (ca. 2 min) to a room-temperature solution of 3-iodo-
1,1-dimethoxypropane10 (4.93 g, 21.44 mmol) in dry DMSO (20
mL), and stirring was continued for 3 h. Water (200 mL) was
added, and the aqueous solution was extracted with EtOAc
until extraction was complete (TLC control, silica, 1:4 EtOAc-
hexane). The combined organic extracts were washed with
brine, dried (MgSO4), and evaporated. The crude product was
used in the next step without characterization.
Meth yl 5-F or m yl-2-(p h en ylselen o)p en ta n oa te (12). An
aqueous solution of TFA (50%v/v, 30 mL) was added dropwise
to a stirred solution of 11 (crude material from previous
reaction) in CH2Cl2 (70 mL), and the resulting heterogeneous
mixture was stirred vigorously for 14 h at room temperature.
The mixture was cooled (0 °C), titrated with saturated aqueous
NaHCO3 until basic (pH paper), and extracted with CH2Cl2
until extraction was complete (TLC control, silica, 1:4 EtOAc-
hexane). The combined organic extracts were washed with
saturated aqueous NaHCO3 and brine, dried (MgSO4), and
evaporated. Flash chromatography of the residue over silica
gel (4.5 × 28 cm), using 15:85 EtOAc-hexane, gave 12 (2.15
g, 53% over two steps) as a pale yellow oil: FTIR (CH2Cl2 cast)
1728 cm-1; 1H NMR (CD2Cl2, 300 MHz) δ 1.95-2.20 (m, 2 H),
2.60 (dt, J ) 1.2, 7.3 Hz, 2 H), 3.55-3.70 (m, 4 H), 7.25-7.40
(m, 3 H), 7.52-7.65 (m, 2 H), 9.71 (t, J ) 1.3 Hz, 1 H); 13C
NMR (CDCl3, 50.3 MHz) δ 24.2 (t′), 42.0 (t′), 42.4 (d′), 52.2
(q′), 127.3 (s′), 128.8 (d′), 129.2 (d′), 135.8 (d′), 172.9 (s′), 200.6
(d′); exact mass m/z calcd for C12H14O3Se 286.0108, found
286.0100. Anal. Calcd for C12H14O3Se: C, 50.54; H, 4.95.
Found: C, 50.57; H, 4.95.
colorless oil: FTIR (CH2Cl2 cast) 1733, 2094 cm-1 1H NMR
;
(CD2Cl2, 300 MHz) δ 0.85-1.10 (m, 18 H), 1.67-2.21 (m, 4
H), 3.50-3.75 (m, 4 H), 4.10 (s, 1 H), 4.12-4.22 (m, 2 H), 4.48-
4.62 (m, 3 H), 7.20-7.42 (m, 8 H), 7.52-7.65 (m, 2 H); 13C NMR
(CDCl3, 50.3 MHz) δ 19.7 (s′), 20.0 (s′), 27.2 (q′), 27.4 (t′), 36.4
(t′), 36.5 (t′), 43.1 (d′), 43.2 (d′), 51.9 (q′), 57.2 (t′), 65.6 (d′),
71.3 (t′), 81.1 (s′), 81.2 (s′), 86.8 (s′), 127.6 (s′), 127.8 (d′), 128.1
(d′), 128.4 (d′), 128.5 (d′), 129.0 (d′), 135.6 (d′), 135.7 (d′), 137.5
(s′), 173.1 (s′); exact mass m/z calcd for C30H42O4SeSi 574.2018,
found 574.2020. Anal. Calcd for C30H42O4SeSi: C, 62.81; H,
7.38. Found: C, 62.98; H, 7.42.
Meth yl (3r,3a â,4r,6a â)- a n d (3r,3a â,4â,6a â)-(()-2,2-Bis-
(1,1-d im eth yleth yl)h exa h yd r o-3-[(p h en ylm eth oxy)m eth -
yl]-2H-cyclop en t[d ]-[1,2]oxa silole-4-ca r boxyla te (16). A
solution of Ph3SnH (629.0 mg, 1.79 mmol) and AIBN (33.9 mg,
0.21 mmol) in dry PhH (20 mL) was added over 7 h by syringe
pump to a refluxing solution of 15 (790.0 mg, 1.38 mmol) in
dry PhH (100 mL). Refluxing was continued for 1 h after the
addition, and the mixture was then allowed to cool to room
temperature. Evaporation of the solvent and flash chroma-
tography of the residue over silica gel (4 × 20 cm), using 5:95
EtOAc-hexane, gave crude 16, contaminated with tin resi-
dues. It was used directly in the next step, without full
characterization. The 1H NMR spectrum (300 MHz) showed
the presence of two isomers in a 3:1 ratio.
(3r,3a â,4r,6a â)- a n d (3r,3a â,4â,6a â)-(()-2,2-Bis(1,1-d i-
m eth yleth yl)h exa h yd r o-3-[(p h en ylm eth oxy)m eth yl]-2H-
cyclop en t[d ]-[1,2]oxa silol-4-yl]m eth a n ol (17). A solution
of crude 16 (from the previous reaction) in dry THF (5 mL
plus 2 mL as a rinse) was added dropwise to a stirred and
cooled (-78 °C) suspension of LiAlH4 (52.31 mg, 1.38 mmol)
in dry THF (20 mL). After 5 min, the resulting mixture was
allowed to cool to room temperature and was then poured into
ice-water (50 mL). The aqueous solution was extracted with
EtOAc until extraction was complete (TLC control, silica, 1:4
EtOAc-hexane), and the combined organic extracts were
washed with brine, dried (MgSO4), and evaporated. Flash
chromatography of the residue over silica gel (3 × 21 cm), using
1:4 EtOAc-hexane, gave 17, which was contaminated (1H
NMR) with some impurities that were not separable by flash
chromatography. Alcohols 17 were used in the next step
without full characterization. We depict 17 arbitrarily as a
mixture of isomers, but we do not know for a fact whether one
of the impurities is the isomer, or a totally different compound.
(1r,2r,3â)- a n d (1r,2r,3r)-(()-3-(Hyd r oxym eth yl)-2-[2-
(p h en ylm eth oxy)eth yl]cyclop en ta n ol (18). TBAF (1.0 M
in THF, 30 mL, 30 mmol) was added dropwise to a stirred
solution of impure 17 in DMF (25 mL). The resulting solution
was heated at 60 °C for 3 h, cooled to room temperature, and
poured into water (100 mL). The mixture was extracted with
EtOAc until extraction was complete (TLC control, silica, 3:1
EtOAc-hexane), and the combined organic extracts were
washed with brine, dried (MgSO4), and evaporated. Flash
chromatography of the residue over silica gel (3 × 18 cm), using
3:1 EtOAc-hexane, gave 18, which was contaminated (1H
NMR) with some impurities not separable by flash chroma-
tography. Diols 18 were used in the next step without full
characterization. We arbitrarily depict 18 as a mixture of
isomers, but we do not know for a fact whether one of the
impurities is the isomer, or a totally different compound.
(1r,2r,3â)-(()-3-[[[(1,1-dim eth yleth yl)diph en ylsilyl]oxy]-
m eth yl]-2-[2-(p h en ylm eth oxy)eth yl]cyclop en ta n ol (19).
Imidazole (96.7 mg, 1.42 mmol) and t-BuPh2SiCl (0.259 mL,
0.995 mmol) were added successively to a room-temperature
solution of crude 18 (obtained from the previous reaction) in
dry CH2Cl2 (20 mL). After 1 h, water (30 mL) was added, and
the mixture was extracted with CH2Cl2 until extraction was
complete (TLC control, silica, 15:85 EtOAc-hexane). The
combined organic extracts were washed with brine, dried
(MgSO4), and evaporated. Flash chromatography of the residue
Meth yl (2R*,5R*)- an d (2R*,5S*)-(()-5-Hydr oxy-8-(ph en -
ylm eth oxy)-2-(p h en ylselen o)-6-octyn oa te (14). n-BuLi (1.6
M in hexanes, 21.0 mL, 33.7 mmol) was added dropwise to a
stirred and cooled (-78 °C) solution of benzyl propargyl ether
(1337) (4.92 g, 33.7 mmol) in dry THF (50 mL). After 15 min,
aldehyde 12 (3.84 g, 13.5 mmol) in dry THF (20 mL plus 10
mL as a rinse) was added dropwise at -78 °C. After 2 h
(stirring), the cold reaction mixture was poured into water (150
mL) and extracted with EtOAc. The combined organic extracts
were washed with brine, dried (MgSO4), and evaporated. Flash
chromatography of the residue over silica gel (4.5 × 22 cm),
using 1:3 EtOAc-hexane, gave 14 (4.74 g, 81%) as a pale
yellow oil: FTIR (CH2Cl2 cast) 1728, 3435 cm-1 1H NMR
;
(CD2Cl2, 200 MHz) δ 1.61-2.20 (m, 5 H), 3.55-3.75 (m, 4 H),
4.20 (s, 2 H), 4.32-4.50 (m, 1 H), 4.55 (s, 2 H), 7.21-7.45 (m,
8 H), 7.51-7.65 (m, 2 H); 13C NMR (CDCl3, 50.3 MHz) δ 27.4
(t′), 35.7 (t′), 42.9 (d′), 52.0 (q′), 57.3 (t′), 61.6 (d′), 71.6 (t′),
81.0 (s′), 87.0 (s′), 127.5 (s′), 127.8 (d′), 128.0 (d′), 128.4 (d′),
128.6 (d′), 129.0 (d′), 135.7 (d′), 137.2 (s′), 173.2 (s′). Anal. Calcd
for C22H24O4Se: C, 61.25; H, 5.61. Found: C, 61.42; H, 5.47.
Meth yl (2R*,5R*)- a n d (2R*,5S*)-(()-5-[[Bis(1,1-d i-
m et h ylet h yl)silyl]oxy]-8-(p h en ylm et h oxy)-2-(p h en ylse-
len o)-6-octyn oa te (15). Imidazole (860.3 mg, 12.64 mmol)
and t-Bu2SiHCl (1.60 mL, 7.90 mmol) were added consecutively
to a stirred solution of 14 (2.723 g, 6.32 mmol) in dry THF (50
mL), and the resulting white suspension was stirred and
refluxed for 12 h, cooled to room temperature, and then poured
into water (100 mL). The aqueous mixture was extracted with
EtOAc until extraction was complete (TLC control, silica, 5:95
(37) Kwart, H.; Sarner, S. F.; Slutsky, J . J . Am. Chem. Soc. 1973,
96, 5234-5242.

2782 J . Org. Chem., Vol. 64, No. 8, 1999
Sannigrahi et al.
over silica gel (3 × 20 cm), using 15:85 EtOAc-hexane, gave
19 (222.8 mg, 33% over four steps) as a colorless oil: FTIR
(q′), 14.1 (q′), 18.0 (s′), 25.6 (q′), 43.7 (t′), 60.3 (t′), 70.8 (d′),
114.5 (t′), 140.3 (d′), 171.0 (s′). Anal. Calcd for C13H26O3Si: C,
60.42; H, 10.14. Found: C, 60.28; H, 10.17.
1
(CH2Cl2 cast) 3450 cm-1; H NMR (CD2Cl2, 200 MHz) δ 1.05
(s, 9 H), 1.40-2.08 (m, 8 H), 2.68 (s, 1 H), 3.32-3.73 (m, 4 H)
4.23 (s, 1 H), 4.48 (s, 2 H), 7.21-7.50 (m, 11 H), 7.58-7.75 (m,
4 H); 13C NMR (CDCl3, 50.3 MHz) δ 19.3 (s′), 26.3 (t′), 26.9
(q′), 28.8 (t′), 33.0 (t′), 45.1 (d′), 47.6 (d′), 66.4 (t′), 70.5 (t′),
73.5 (t′), 74.6 (d′), 127.6 (d′), 127.7 (d′), 128.5 (d′), 129.6 (d′),
134.0 (s′), 135.7 (d′), 137.9 (s′). Anal. Calcd for C31H40O3Si: C,
76.18; H, 8.25. Found: C, 76.28; H, 8.29.
(()-6-[[(1,1-Dim eth yleth yl)silyl]oxy]-1-(ph en ylm eth oxy)-
7-octen -2-yn -4-on e (24). n-BuLi (2.5 M in hexanes, 10.05 mL,
25 mmol) was added dropwise to a stirred and cooled (-78
°C) solution of benzyl propargyl ether (1337) (3.67 g, 25.1 mmol)
in dry THF (20 mL). After 30 min, the cold bath was removed,
and the solution was allowed to warm to room temperature.
In a separate round-bottomed flask, BF3‚Et2O (2.76 mL, 22.5
mmol) was added dropwise to a stirred and cooled (-78 °C)
solution of 23 (5.27 g, 20.4 mmol) in dry THF (30 mL). The
lithium acetylide solution (now at room temperature) was
added dropwise to the stirred and cooled solution of 23.
Stirring at -78 °C was continued for 2 h, and the mixture was
poured into water (150 mL). The aqueous layer was extracted
with EtOAc until extraction was complete (TLC control, silica,
1:9 EtOAc-hexane). The combined organic extracts were
washed with brine, dried (MgSO4), and evaporated. During
flash chromatography, crude 24 coeluted with benzyl propargyl
ether, and so 24 was not characterized, but used directly in
the next step.
(1r,2r,3â)-(()-3-[[[(1,1-Dim et h ylet h yl)d ip h en ylsilyl]-
oxy]m eth yl]-2-[2-h yd r oxyeth yl]cyclop en ta n ol (20). Pd/C
(10%, ca. 8 mg) was added to a solution of 19 (75.8 mg, 0.16
mmol) in bench MeOH (10 mL). The mixture was stirred under
a H2 atmosphere (balloon) for 7 h and then filtered through a
short pad (0.5 × 1 cm) of Celite. Evaporation of the filtrate,
and flash chromatography of the residue over silica gel (1 ×
18 cm), using EtOAc, gave 20 (56.3 mg, 91%) as a colorless
oil: FTIR (CH2Cl2 cast) 3334 cm-1; 1H NMR (CD2Cl2, 200 MHz)
δ 1.07 (s, 9 H), 1.38-2.10 (m, 8 H), 2.74 (br s, 2 H), 3.49-3.82
(m, 4 H), 4.19-4.35 (m, 1 H), 7.29-7.52 (m, 6 H), 7.58-7.81
(m, 4 H); 13C NMR (CDCl3, 50.3 MHz) δ 19.3 (s′), 26.0 (t′), 26.9
(q′), 30.9 (t′), 33.4 (t′), 44.8 (d′), 46.6 (d′), 62.1 (t′), 66.3 (t′),
74.8 (d′), 127.6 (d′), 129.6 (d′), 133.8 (s′), 135.6 (d′); exact mass
m/z calcd for C24H34NaO3Si (M + Na) 421.2175, found 421.2181.
(3a r,4r,6a r)-(()-4-[[[(1,1-Dim eth yleth yl)d ip h en ylsilyl]-
oxy]m et h yl]h exa h yd r ocyclop en t a [b]fu r a n -2-on e (21).
KMnO4 (0.2 g, 1.27 mmol) and CuSO4‚5H2O (0.02 g, 0.08
mmol) were added consecutively to a stirred solution of 20
(31.9 mg, 0.080 mmol) in dry CH2Cl2 (5 mL). After 16 h, the
heterogeneous mixture was filtered through a short pad (0.5
× 0.5 cm) of Celite and evaporated. Flash chromatography of
the residue over silica gel (1 × 16 cm), using 3:7 EtOAc-
hexane, gave 21 (16.5 mg, 52%) as a colorless oil: FTIR
(()-6-Hyd r oxy-1-(p h en ylm eth oxy)-7-octen -2-yn -4-on e
(25). HF (48% in water, 1.41 mL, 41 mmol) was added in one
lot to a solution of crude 24 (from the previous experiment) in
MeCN (100 mL). After 5 h, saturated aqueous NaHCO3 (100
mL) was added dropwise from a separatory funnel. EtOAc (50
mL) was added, and the aqueous layer was extracted with
EtOAc until extraction was complete (TLC control, silica, 2:3
EtOAc-hexane). The combined organic extracts were washed
with brine, dried (MgSO4), and evaporated. Flash chromatog-
raphy of the residue over silica gel (4.5 × 17 cm), using 2:3
EtOAc-hexane, gave 25 (2.33 g, 47% over two steps) as a
colorless oil: FTIR (CH2Cl2 cast) 1675, 3447 cm-1 1H NMR
;
1
(CH2Cl2 cast) 1766 cm-1; H NMR (CDCl3, 400 MHz) δ 1.05
(CDCl3, 200 MHz) δ 2.51 (br s, 1 H), 2.81 (d, J ) 6.1 Hz, 2 H),
4.31 (s, 2 H), 4.52-4.75 (m, 3 H), 5.15 (dt, J ) 10.5, 1.3 Hz, 1
H), 5.29 (dt, J ) 17.2, 1.4 Hz, 1 H) 5.85 (ddd, J ) 17.2, 10.5,
5.5 Hz, 1 H), 7.22-7.44 (m, 5 H); 13C NMR (CDCl3, 50.3 MHz)
δ 51.8 (t′), 56.9 (t′), 68.4 (d′), 72.2 (t′), 85.2 (s′), 89.0 (s′), 115.6
(t′), 128.1 (d′), 128.2 (d′), 128.5 (d′), 136.6 (s′), 138.5 (d′), 185.7
(s′). Anal. Calcd for C15H16O3: C, 73.75; H, 6.60. Found: C,
73.55; H, 6.63.
(s, 9 H), 1.41-1.55 (m, 1 H), 1.75-2.06 (m, 4 H), 2.30-2.45
(m, 1 H), 2.51-2.63 (m, 1 H), 2.66-2.80 (m, 1 H), 3.45-3.65
(m, 2 H), 4.85-4.95 (m, 1 H), 7.30-7.46 (m, 6 H), 7.55-7.65
(m, 4 H); 13C NMR (CDCl3, 50.3 MHz) δ 19.2 (s′), 26.8 (q′),
27.1 (t′), 31.9 (t′), 35.5 (t′), 42.0 (d′), 48.6 (d′), 65.9 (t′), 86.5
(d′), 127.7 (d′), 129.8 (d′), 133.4 (s′), 135.5 (d′), 177.4 (s′); exact
mass m/z calcd for C24H30NaO3Si (M + Na) 417.1862, found
417.1862.
(3R*,5S*)- a n d (3R*,5R*)-(()-8-(P h en ylm et h oxy)-1-
octen -6-yn e-3,5-d iol (26). DIBAL (1.0 M in PhMe, 15.3 mL,
15.3 mmol) was added dropwise to a stirred and cooled (-78
°C) solution of 25 (1.488 g, 6.10 mmol) in dry THF (80 mL).
After 40 min, MeOH (4 mL), Na2SO4‚10H2O (4 g), Celite (6.3
g), and water (2 mL) were added sequentially to the cold (-78
°C) mixture. The cold bath was removed, and stirring was
continued for an additional 30 min. The mixture was then
filtered through a pad (7 × 4 cm) of Celite, EtOAc being used
to elute all of the product (TLC control, silica, 1:1 EtOAc-
hexane). Evaporation of the filtrate and flash chromatography
of the residue over silica gel (2.5 × 17 cm), using 1:1 EtOAc-
hexane, gave 26 (1.346 g, 90%) as an inseparable mixture of
diastereoisomers. The ratio of the two diols could not be
calculated from the 1H NMR spectrum, and both isomers were
used directly in the next step (from which the isomer ratio of
the diols could be estimated as ca. 15:1). The major isomer
was fully characterized, as described below (see compound 28).
tr a n s-(()- an d cis-(()-4-Eth en yl-2,2-dim eth yl-6-[3-(ph en -
ylm eth oxy)-1-p r op yn yl]-1,3-d ioxa n e (27). 2,2-Dimethoxy-
propane (6.73 mL, 54.7 mmol) and PPTS (ca. 10 mg) were
added consecutively to a stirred solution of 26 (all the material
from the above experiment) in dry CH2Cl2 (15 mL). After 6 h,
the solution was poured into saturated aqueous NaHCO3 (50
mL) and extracted with CH2Cl2 until extraction was complete
(TLC control, silica, 1:9 EtOAc-hexane). The combined organic
extracts were washed with brine, dried (MgSO4), and evapo-
rated. Flash chromatography of the residue over silica gel (2.5
× 22 cm), using first 1:19 EtOAc-hexane and then 1:9 EtOAc-
hexane, gave 27 (1.370 g, 88%) as a colorless oil, and the minor
(trans) diastereoisomer (92.6 mg, 6%), which was discarded.
(3a r,4r,6a r)-(()-Hexa h yd r o-4-(h yd r oxym eth yl)cyclo-
p en ta [b]fu r a n -2-on e (6). TBAF (1.0 M in THF, 0.18 mL, 0.18
mmol) was added dropwise to a stirred solution of 21 (35.2
mg, 0.089 mmol) in dry THF (5 mL). After 48 h, water (5 mL)
was added and the aqueous solution was extracted with EtOAc
until extraction was complete (TLC control, silica, EtOAc), and
the combined organic extracts were washed with brine, dried
(MgSO4), and evaporated. Flash chromatography of the residue
over silica gel (1.0 × 15 cm), using EtOAc, gave 617 (13.0 mg,
1H NMR (CDCl3, 400 MHz) δ 1.41-1.58 (m, 1 H), 1.72 (s, 1
H), 1.80-2.05 (m, 4 H), 2.32-2.45 (m, 1 H), 2.52-2.65 (m, 1
H), 2.70-2.85 (m, 1 H), 3.45-3.63 (m, 2 H), 4.90-5.00 (m, 1
H); 13C NMR (CDCl3, 50.3 MHz) δ 27.0 (t′), 31.9 (t′), 35.6 (t′),
41.9 (d′), 48.6 (d′), 64.9 (t′), 86.6 (d′), 177.6 (s′); exact mass m/z
calcd for C8H12O3 156.0786, found 156.0788.
Eth yl (()-3-[[(1,1-Dim eth yleth yl)silyl]oxy]-4-pen ten oate
(23). Imidazole (2.982 g, 43.8 mmol) and t-BuMe2SiCl (3.961
g, 26.3 mmol) were added consecutively to a stirred solution
of 22 (2.891 g, 21.9 mmol) in dry CH2Cl2 (150 mL). After 3 h,
water (75 mL) was added, and the aqueous layer was extracted
with CH2Cl2 until extraction was complete (TLC control, silica,
1:9 EtOAc-hexane). The combined organic extracts were
washed with brine, dried (MgSO4), and evaporated. Flash
chromatography of the residue over silica gel (4.5 × 20 cm),
using 1:9 EtOAc-hexane, gave 23 (5.27 g, 93%) as a colorless
oil: FTIR (CH2Cl2 cast) 1739 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 0.02 (s, 3 H), 0.04 (s, 3 H), 0.85 (s, 9 H), 1.25 (t, J ) 7.2 Hz,
3 H), 2.42 (dd, J ) 14.5, 5.2 Hz, 1 H), 2.50 (dd, J ) 14.5, 8.1
Hz, 1 H), 4.02-4.18 (m, 2 H), 4.50-4.60 (m, 1 H), 5.05 (dt, J
) 10.3, 1.3 Hz, 1 H), 5.20 (dt, J ) 17.1, 1.5 Hz, 1 H), 5.75-
5.90 (m, 1 H); 13C NMR (CDCl3, 50.3 MHz) δ -5.2 (q′), -4.5
93%) as a colorless oil: FTIR (CH2Cl2 cast) 1767, 3427 cm-1
;
Compound 27: FTIR (CH2Cl2 cast) 1200 cm-1
;
1H NMR
(CDCl3, 400 MHz) δ 1.46 (s, 3 H), 1.50 (s, 3 H), 1.68-1.83 (m,

Applications of 5-Endo-trigonal Cyclization
J . Org. Chem., Vol. 64, No. 8, 1999 2783
2 H), 4.20 (s, 2 H), 4.30-4.39 (m, 1 H), 4.58 (s, 2 H), 4.72-
4.79 (m, 1 H), 5.12-5.18 (m, 1 H), 5.22-5.30 (m, 1 H), 5.73-
5.86 (m, 1 H), 7.23-7.38 (m, 5 H); 13C NMR (CDCl3, 50.3 MHz)
δ 19.3 (q′), 30.0 (q′), 36.9 (t′), 57.4 (t′), 60.1 (d′), 69.6 (d′), 71.6
(t′), 80.7 (s′), 84.9 (s′), 99.3 (s′), 115.9 (t′), 127.8 (d′), 127.9 (d′),
128.4 (d′), 137.3 (s′) 137.7 (d′); exact mass m/z calcd for
128.3 (d′), 137.4 (s′), 137.5 (d′). Anal. Calcd for C23H36O4Si: C,
68.27; H, 8.97. Found: C, 67.93; H, 9.21.
(2R*,3R*,5S*)- a n d (2R*,3S*,5R*)-(()-5-[[(1,1-Dim eth -
yleth yl)d im eth ylsilyl]oxy]-3-(m eth oxym eth oxy)-8-(p h en -
ylm eth oxy)-6-octyn e-1,2-d iol (31). 4-Methylmorpholine N-
oxide (644.9 mg, 5.50 mmol) and OsO4 (2.5% in t-BuOH, 1.86
g, 0.18 mmol) were added consecutively to a stirred solution
of 30 (741.5 mg, 1.83 mmol) in THF (90 mL) and water (10
mL). After 20 h, Na2S2O3 (1.0 M, 30 mL) was added, the
mixture was stirred for 15 min, and the aqueous layer was
extracted with EtOAc until extraction was complete (TLC
control, silica, 3:1 EtOAc-hexane). The combined organic
extracts were washed with brine, dried (MgSO4), and evapo-
rated. Flash chromatography of the residue over silica gel (2
× 20 cm), using 3:1 EtOAc-hexane, gave 31 (429.6 mg, 54%)
as an inseparable mixture of diastereoisomers: FTIR (CH2Cl2
C
18H22O3 286.1569, found 286.1531. Anal. Calcd for C18H22O3:
C, 75.50; H, 7.74. Found: C, 75.82; H, 7.57.
(3R*,5S*)-(()-8-(P h en ylm et h oxy)-1-oct en -6-yn -3,5-d i-
ol (28). CF3CO2H (1.0 mL, 13 mmol) was added to a stirred
solution of 27 (2.27 g, 7.94 mmol) in THF (45 mL) and water
(5 mL). After 4 h, the solution was titrated with saturated
aqueous NaHCO3 until basic (pH paper). The aqueous layer
was extracted with EtOAc until extraction was complete (TLC
control, silica, 3:2 EtOAc-hexane), and the combined organic
extracts were washed with brine, dried (MgSO4), and evapo-
rated. Flash chromatography of the residue over silica gel (2
× 16 cm), using 3:2 EtOAc-hexane, gave 28 (1.82 g, 93%) as
a colorless oil: FTIR (CH2Cl2 cast) 3374 cm-1; 1H NMR (CDCl3,
400 MHz) δ 1.88-2.03 (m, 2 H), 2.49 (br s, 2 H), 4.20 (s, 2 H),
4.35-4.43 (m, 1 H), 4.58 (s, 2 H), 4.66-4.72 (m, 1 H), 5.13 (dt,
J ) 10.4, 1.3 Hz, 1 H), 5.27 (dt, J ) 17.1, 1.4 Hz, 1 H), 5.88
(ddd, J ) 16.9, 7.1, 6.0 Hz, 1 H), 7.25-7.39 (m, 5 H); 13C NMR
(CDCl3, 50.3 MHz) δ 43.7 (t′), 57.2 (t′), 61.2 (d′), 71.5 (t′), 71.6
(d′), 80.6 (s′), 87.1 (s′), 114.8 (t′), 127.8 (d′), 128.0 (d′), 128.3
(d′), 137.0 (s′), 139.9 (d′); exact mass m/z calcd for C15H18O3
246.1256, found 246.1241.
(3R*,5S*)-(()-5-[[(1,1-Dim eth yleth yl)dim eth ylsilyl]oxy]-
8-(p h en ylm eth oxy)-1-octen -6-yn -3-ol (29) a n d (3R*,5S*)-
(()-[(1,1-Dim eth yleth yl)dim eth yl][[5-[[(1,1-dim eth yleth yl)-
d im et h ylsilyl]oxy]-8-(p h en ylm et h oxy)-1-oct en -6-yn -3-
yl]oxy]silan e. Imidazole (2.247 g, 33.0 mmol) and t-BuMe2SiCl
(2.736 g, 18.2 mmol) were added consecutively to a stirred
solution of 28 (4.06 g, 16.5 mmol) in dry CH2Cl2 (200 mL). After
20 min, the reaction was quenched by addition of water (100
mL) (the reaction time represents the point at which formation
of disilylated product becomes a competing reaction). The
aqueous layer was extracted with CH2Cl2 until extraction was
complete (TLC control, silica, 3:2 EtOAc-hexane), and the
combined organic extracts were washed with brine, dried
(MgSO4), and evaporated. Flash chromatography of the residue
over silica gel (4 × 19 cm), using first 1:9 EtOAc-hexane and
then 3:2 EtOAc-hexane, gave 29 (2.81 g, 47%, 82% based on
recovered starting material) as a colorless oil, starting diol 28
(1.710 g), and the disilylated product (410.6 mg). Compound
29: FTIR (CH2Cl2 cast) 3432 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 0.18 (s, 3 H), 0.20 (s, 3 H), 0.91 (s, 9 H), 1.86-2.05 (m, 2 H),
2.69 (br s, 1 H), 4.19 (d, J ) 1.5 Hz, 2 H), 4.30-4.39 (m, 1 H),
4.58 (s, 2 H), 4.63-4.70 (m, 1 H), 5.11 (dt, J ) 10.4, 1.4 Hz, 1
H), 5.28 (dt, J ) 17.3, 1.5 Hz, 1 H), 5.87 (ddd, J ) 17.1, 10.5,
5.8 Hz, 1 H), 7.24-7.38 (m, 5 H); 13C NMR (CDCl3, 50.3 MHz)
δ -5.0 (q′), -4.3 (q′), 18.1 (s′), 25.7 (q′), 45.1 (t′), 57.3 (t′), 62.3
(d′), 71.2 (d′), 71.5 (t′), 81.1 (s′), 87.4 (s′), 114.6 (t′), 127.9 (d′),
128.0 (d′), 128.4 (d′), 137.4 (s′), 140.2 (d′); exact mass m/z calcd
for C17H23O3Si (M - C4H9) 303.1417, found 303.1423.
1
cast) 3432 cm-1; H NMR (CDCl3, 400 MHz) δ 0.13 (s, 3 H),
0.17 (s, 3 H), 0.89 (s, 9 H), 1.86-2.10 (m, 4 H), 3.40 (s, 3 H),
3.58-3.95 (m, 4 H), 4.20 (s, 2 H), 4.58 (s, 2 H), 4.60-4.72 (m,
3 H), 7.23-7.39 (m, 5 H); 13C NMR (CDCl3, 50.3 MHz) (only
the signals for the major isomer are given) δ -5.0 (q′), -4.5
(q′), 18.1 (s′), 25.7 (q′), 40.4 (t′), 56.0 (q′), 57.3 (t′), 60.4 (d′),
63.2 (t′), 71.5 (t′), 73.2 (d′), 78.8 (d′), 81.4 (s′), 87.1 (s′), 97.5
(t′), 127.9 (d′), 128.0 (d′), 128.4 (d′), 137.4 (s′); exact mass m/z
calcd for C22H35O5Si (M - OCH3) 407.2254, found 407.2258.
(2R*,3S*,5R*)- a n d (2R*,3R*,5S*)-(()-5-[[(1,1-Dim eth -
ylet h yl)d im et h ylsilyl]oxy]-2-h yd r oxy-3-(m et h oxym et h -
oxy)-6-octyn -1-yl 2,2-Dim eth ylp r op ion a te (32). DMAP
(406.7 mg, 3.33 mmol) and t-BuCOCl (0.21 mL, 1.66 mmol)
were added consecutively to a stirred and cooled (0 °C) solution
of 31 (662.8 mg, 1.51 mmol) in dry PhMe (25 mL). The ice bath
was removed and, after 1 h, water (25 mL) was added. The
aqueous layer was extracted with EtOAc until extraction was
complete (TLC control, silica, 1:4 EtOAc-hexane), and the
combined organic extracts were washed with brine, dried
(MgSO4), and evaporated. Flash chromatography of the residue
over silica gel (2 × 17 cm), using 1:9 EtOAc-hexane, gave
diastereoisomeric alcohols 32 (only the major isomer is shown
in Scheme 4) (348.2 mg, 44%) as an inseparable mixture: FTIR
1
(CH2Cl2 cast) 1730, 3445 cm-1; H NMR (CDCl3, 400 MHz) δ
0.14 (s, 3 H), 0.18 (s, 3 H), 0.90 (s, 9 H), 1.20 (s, 9 H), 1.88-
1.95 (m, 1 H), 2.05-2.13 (m, 1 H), 3.30-3.42 [m, 4 H, including
a singlet at δ 3.39, (3 H)], 3.76-3.91 (m, 2 H), 4.09-4.23 (m,
4 H), 4.58 (s, 2 H), 4.60-4.72 (m, 3 H), 7.24-7.37 (m, 5 H);
13C NMR (CDCl3, 50.3 MHz) (signals indicated are for the
major diastereoisomer only) δ -5.0 (q′), -4.4 (q′), 18.1 (s′), 25.7
(q′), 27.2 (q′), 38.8 (s′), 40.08 (t′), 56.0 (q′), 57.3 (d′), 60.4 (t′),
65.1 (t′), 71.4 (d′), 71.5 (t′), 78.7 (d′), 81.3 (s′), 87.2 (s′), 97.4
(t′), 127.9 (d′), 128.0 (d′), 128.4 (d′), 137.4 (s′), 178.7 (s′).
(2R*,3S*,5R*)-(()-5-[[(1,1-Dim eth yleth yl)d im eth ylsilyl]-
oxy]-2-[(4-flu or op h e n oxy)t h ioca r b on yloxy]-3-(m e t h -
oxym eth oxy)-6-octyn -1-yl 2,2-Dim eth ylp r op ion a te (33).
Dry pyridine (0.081 mL, 1.00 mmol), DMAP (40.7 mg, 0.33
mmol), and p-FC6H4OC(S)Cl (0.28 mL, 2.0 mmol) were added
consecutively to a stirred solution of 32 (348.2 mg, 0.67 mmol)
in dry CH2Cl2 (12 mL). After 18 h, saturated aqueous NH4Cl
(20 mL) was added, and the aqueous layer was extracted with
CH2Cl2 until extraction was complete (TLC control, silica, 1:9
EtOAc-hexane). The combined organic extracts were washed
with brine, dried (MgSO4), and evaporated. Flash chromatog-
raphy of the residue over silica gel (2 × 18 cm), using 1:9
EtOAc hexane, gave 33 (324.6 mg, 72%) as a colorless oil,
whose relative stereochemistry was later assigned, as de-
(4R*,6S*)-(()-[(1,1-Dim eth yleth yl)d im eth yl][[6-(m eth -
oxym eth oxy)-1-(p h en ylm eth oxy)-7-octen -2-yn -4-yl]oxy]-
sila n e (30). i-Pr2NEt (2.34 mL, 13.4 mmol) and MeOCH2Cl
(1.02 mL, 13.4 mmol) were added consecutively to a stirred
and cooled (0 °C) solution of 29 (1.612 g, 4.48 mmol) in dry
CH2Cl2 (50 mL). After 1 h, the ice bath was removed, and
stirring was continued for an additional 9 h. Water (50 mL)
was added, and the aqueous layer was extracted with CH2Cl2
until extraction was complete (TLC control, silica, 1:9 EtOAc-
hexane). The combined organic extracts were washed with
brine, dried (MgSO4), and evaporated. Flash chromatography
of the residue over silica gel (2.5 × 16 cm), using 1:9 EtOAc-
hexane, gave 30 (1.563 g, 86%) as a colorless oil: FTIR (CH2Cl2
1
scribed in the text: FTIR (CH2Cl2 cast) 1735 cm-1; H NMR
(CDCl3, 400 MHz) δ 0.12 (s, 3 H), 0.17 (s, 3 H), 0.90 (s, 9 H),
1.20 (s, 9 H), 1.94-2.12 (m, 2 H), 3.42 (s, 3 H), 4.21 (s, 2 H),
4.22-4.32 (m, 1 H), 4.32-4.51 (m, 2 H), 4.57 (s, 2 H), 4.60-
4.68 (m, 1 H), 4.71 (s, 2 H), 5.71-5.80 (m, 1 H), 6.95-7.08 (m,
4 H), 7.24-7.37 (m, 5 H); 13C NMR (CDCl3, 50.3 MHz) δ -5.0
(q′), -4.5 (q′), 18.1 (s′), 25.8 (q′), 27.1 (q′), 38.8 (s′), 40.5 (t′),
56.1 (q′), 57.3 (t′), 60.3 (d′), 61.6 (t′), 71.5 (t′), 73.3 (d′), 81.5
(s′), 83.7 (d′), 86.8 (s′), 96.5 (t′), 116.2 (d′) J C-C-F ) 23.5 Hz,
123.4 (d′) J C-C-C-F ) 8.3 Hz, 127.8 (d′), 128.1 (d′), 128.4 (d′),
1
cast) 1318 cm-1; H NMR (CDCl3, 200 MHz) δ 0.12 (s, 3 H),
0.18 (s, 3 H), 0.91 (s, 9 H), 1.75-1.92 (m, 1 H), 1.96-2.14 (m,
1 H), 3.38 (s, 3 H), 4.14-4.33 (m, 3 H), 4.47-4.74 (m, 5 H),
5.12-5.30 (m, 2 H), 5.55-5.79 (m, 1 H), 7.25-7.43 (m, 5 H);
13C NMR (CDCl3, 50.3 MHz) δ -5.0 (q′), -4.4 (q′), 18.1 (s′),
25.7 (q′), 44.4 (t′), 55.3 (q′), 57.2 (t′), 60.2 (d′), 71.2 (t′), 74.1
(d′), 80.6 (s′), 87.6 (s′), 93.6 (t′), 117.8 (t′), 127.7 (d′), 127.9 (d′),

2784 J . Org. Chem., Vol. 64, No. 8, 1999
Sannigrahi et al.
137.4 (s′), 149.2 (s′), 160.6 (s′) J C-F ) 245.7 Hz, 178.1 (s′), 194.7
(s′); exact mass m/z calcd for C35H49FO8SSi 676.2902, found
676.2892.
(t′), 69.6 (t′), 72.9 (t′), 80.7 (d′), 81.2 (d′), 96.0 (t′), 127.9 (d′),
128.0 (d′), 128.5 (d′), 137.4 (s′).
(1r,2â,3â,5â)-(()-3-Hyd r oxy-5-(m eth oxym eth oxy)-2-[2-
(p h en ylm eth oxy)eth yl]cyclop en tylm eth yl 2,2-Dim eth yl-
p r op ion a te (37). TBAF (1.0 M in THF, 1.42 mL, 1.42 mmol)
was added dropwise to a stirred solution of 36 (76.1 mg, 0.14
mmol) in THF (3 mL) and DMF (3 mL), and the mixture was
heated at 70 °C for 2 h and then cooled to room temperature.
Water (10 mL) was added, and the aqueous layer was
extracted with EtOAc until extraction was complete (TLC
control, silica, 1:1 EtOAc-hexane). The combined organic
extracts were washed with brine, dried (MgSO4), and evapo-
rated, residual DMF being removed under oil pump vacuum
(ca. 0.1 mmHg). Flash chromatography of the residue over
silica gel (1 × 14 cm), using 2:3 EtOAc-hexane, gave 37 (49.3
mg, 88%) as a colorless oil: FTIR (CH2Cl2 cast) 1727, 3507
(2R*,3S*,5R*)-(()-2-[(4-F lu or op h en oxy)t h ioca r b on yl-
oxy]-5-h yd r oxy-3-(m eth oxym eth oxy)-6-octyn -1-yl 2,2-Di-
m eth ylp r op ion a te (34). HF (48% in water, 0.5 mL, 14.5
mmol) was added to a solution of 33 [R ) p-FC6H4OC(S)] (297.3
mg, 0.44 mmol) in MeCN (10 mL). After 2 h, saturated aqueous
NaHCO3 (20 mL) was added, and the aqueous layer was
extracted with EtOAc until extraction was complete (TLC
control, silica, 3:7 EtOAc-hexane). The combined organic
extracts were washed with brine, dried (MgSO4), and evapo-
rated. Flash chromatography of the residue over silica gel (2
× 14 cm), using 3:7 EtOAc-hexane, gave 34 (216.1 mg, 87%),
which was not characterized but used directly in the next step.
(2R *,3S *,5R *)-(()-5-[[B is (1,1-d im e t h y l)e t h y ls ily l]-
oxy]-2-[(4-fluorophenoxy)thiocarbonyloxy]-3-(methoxymeth-
oxy)-6-octyn -1-yl 2,2-Dim eth ylp r op ion a te (35). Imidazole
(52.4 mg, 0.77 mmol) and t-Bu2SiHCl (0.10 mL, 0.50 mmol)
were added consecutively to a stirred solution of 34 (216.1 mg,
0.38 mmol) in dry THF (20 mL). After 10 h, water (15 mL)
was added, and the aqueous layer was extracted with EtOAc
until extraction was complete (TLC control, silica, 1:9 EtOAc-
hexane). The combined organic extracts were washed with
brine, dried (MgSO4), and evaporated. Flash chromatography
of the residue over silica gel (2 × 14 cm), using 1:9 EtOAc-
hexane, gave 35 (251.7 mg, 93%) as a colorless oil: FTIR
1
cm-1; H NMR (CD2Cl2, 400 MHz) δ 1.19 (s, 9 H), 1.60-1.70
(m, 1 H), 1.74-1.98 (m, 3 H), 2.00-2.12 (m, 2 H), 2.75 (d, J )
6.0 Hz, 1 H), 3.32 (s, 3 H), 3.49-3.58 (m, 1 H), 3.60-3.69 (m,
1 H), 3.92-4.08 (m, 2 H), 4.08-4.19 (m, 2 H), 4.51 (s, 2 H),
4.63 (s, 2 H), 7.24-7.40 (m, 5 H); 13C NMR (CD2Cl2, 50.3 MHz)
δ 27.3 (q′), 28.9 (t′), 39.1 (s′), 40.2 (t′), 45.3 (d′), 49.7 (d′), 55.5
(d′), 64.3 (t′), 70.2 (t′), 73.3 (q′), 73.5 (t′), 79.8 (d′), 95.8 (t′),
128.0 (d′), 128.1 (d′), 128.7 (d′), 138.8 (s′), 178.6 (s′); exact mass
m/z calcd for C22H34NaO6 (M + Na) 417.2253, found 417.2258.
(1r,2â,3â,5â)-(()-3-Hydr oxy-2-(2-h ydr oxyeth yl)-5-(m eth -
oxym eth oxy)cyclop en tylm eth yl 2,2-Dim eth ylp r op ion a te
(38). Pd/C (10%, ca. 3 mg) was added to a solution of 37 (35.2
mg, 0.089 mmol) in bench MeOH (4 mL). The mixture was
stirred under a H2 atmosphere (balloon) for 1 h and filtered
through a pad (1 × 1 cm) of Celite, using EtOAc. Evaporation
of the solvent and flash chromatography of the residue over
silica gel (1 × 10 cm), using EtOAc, gave 38 (23.6 mg, 87%) as
a colorless oil: FTIR (CH2Cl2 cast) 1729, 3425 cm-1; 1H NMR
(CD2Cl2, 400 MHz) δ 1.18 (s, 9 H), 1.61-1.71 (m, 1 H), 1.71-
1.82 (m, 1 H), 1.82-1.94 (m, 2 H), 1.97-2.07 (m, 1 H), 2.11
(ddd, J ) 9.9, 9.8, 4.4 Hz, 1 H), 2.19 (br s, 1 H), 2.79 (br s, 1
H), 3.35 (s, 3 H), 3.61-3.80 (m, 2 H), 3.92-4.05 [m, 2 H,
including a dd at δ 3.99 (J ) 11.3, 6.1 Hz, 1 H)], 4.11 (dd, J )
11.3, 4.6 Hz, 1 H), 4.20 (br s, 1 H), 4.62 (s, 2 H); 13C NMR
(CD2Cl2, 50.3 MHz) δ 27.3 (q′), 31.8 (t′), 39.1 (s′), 40.5 (t′), 45.4
(d′), 50.0 (d′), 55.6 (d′), 62.1 (t′), 64.6 (t′), 74.1 (q′), 80.1 (d′),
95.6 (t′), 178.7 (s′); exact mass m/z calcd for C15H27O5 (M -
OH) 287.1859, found 287.1857.
1
(CH2Cl2 cast) 1736, 2095 cm-1; H NMR (CDCl3, 200 MHz) δ
0.99 (s, 9 H), 1.04 (s, 9 H), 1.18 (s, 9 H), 1.92-2.23 (m, 2 H),
3.41 (s, 3 H), 4.12 (s, 1 H), 4.22 (d, J ) 1.3 Hz, 2 H), 4.25-4.34
(m, 1 H), 4.38 (dd, J ) 12.3, 7.7 Hz, 1 H), 4.49 (dd, J ) 12.2,
3.3 Hz, 1 H), 4.56 (s, 2 H), 4.61-4.70 (m, 1 H), 4.71 (s, 2 H),
5.65-5.79 (m, 1 H), 6.89-7.06 (m, 4 H), 7.19-7.35 (m, 5 H);
13C NMR (CDCl3, 50.3 MHz) δ 19.7 (s′), 20.0 (s′), 27.1 (q′), 27.2
(q′), 38.8 (s′), 40.2 (t′), 56.1 (q′), 57.3 (t′), 61.6 (t′), 63.8 (d′),
71.4 (t′), 73.4 (d′), 82.3 (s′), 83.6 (d′), 86.1 (s′), 96.7 (t′), 116.2
(d′) J C-C-F ) 23.9 Hz, 123.3 (d′) J C-C-C-F ) 8.5 Hz, 127.8 (d′),
128.1 (d′), 128.4 (d′), 137.4 (s′), 149.2 (s′), 160.6 (s′) J C-F ) 245.6
Hz, 178.0 (s′), 194.6 (s′); exact mass m/z calcd for C33H44FO8-
SSi (M - C4H9) 647.2510, found 647.2522.
(3r,3a â,4r,5r,6a â)- a n d (3r,3a â,4â,5r,6a â)-(()-2,2-Bis-
(1,1-d im et h ylet h yl)h exa h yd r o-5-(m et h oxym et h oxy)-3-
(p h en ylm eth oxy)m eth yl-2H-cyclop en t[d ]-[1,2]oxa silol-4-
ylm eth yl 2,2-Dim eth ylpr opion ate (36). A solution of Bu3SnH
(77.6 µL, 0.29 mmol) and AIBN (11.8 mg, 0.07 mmol) in dry
PhMe (6 mL) was added over 6 h (syringe pump) to a stirred
and heated (100 °C) solution of 35 (127 mg, 0.18 mmol) in dry
PhMe (60 mL). Stirring at 100 °C was continued for 1 h after
the end of the addition, and the mixture was cooled to room
temperature and evaporated. Flash chromatography of the
residue over silica gel (1 × 18 cm), using 1:9 EtOAc-hexane,
gave 36 (76.1 mg, 79%) as an inseparable mixture of diastereo-
isomers. The ratio of the diastereoisomers could not be
(3a r,4r,5â,6a r)-(()-Hexa h yd r o-5-(m eth oxym eth oxy)-2-
oxocyclop en t a [b]fu r a n -4-ylm et h yl 2,2-Dim et h ylp r op i-
on a te (7). KMnO4 (110 mg) and CuSO4‚5H2O (11 mg) were
added consecutively to a stirred solution of 38 (16.7 mg, 0.054
mmol) in CH2Cl2 (4 mL). The heterogeneous mixture was
stirred vigorously for 12 h and then filtered through a pad (2.5
× 1 cm) of Celite, using CH2Cl2. Evaporation of the filtrate
and flash chromatography of the residue over silica gel (1 ×
12 cm), using 1:1 EtOAc-hexane, gave 7 (10.3 mg, 63%) as a
1
calculated from the H NMR spectrum; however, the relative
colorless oil: FTIR (CH2Cl2 cast) 1729, 1776 cm-1 1H NMR
;
intensities of the 13C NMR peaks indicated preferential forma-
tion of one of them. The compounds were used directly in the
next step, but the major isomer was characterized by reductive
removal of the pivaloyl group:
(CD2Cl2, 300 MHz) δ 1.21 (s, 9 H), 2.05-2.20 (m, 1 H), 2.21-
2.42 (m, 2 H), 2.51 (dd, J ) 17.8, 2.4 Hz, 1 H), 2.59-2.71 (m,
1 H), 2.81 (dd, J ) 17.8, 10.2 Hz, 1 H), 3.33 (s, 3 H), 3.93-
4.10 (m, 3 H), 4.59 (q, J ) 6.9 Hz, 2 H), 4.95 (ddd, J ) 6.8, 6.8,
2.4 Hz, 1 H); 13C NMR (CDCl3, 50.3 MHz) δ 27.1 (q′), 35.4 (t′),
37.9 (t′), 38.8 (s′), 39.9 (d′), 51.6 (d′), 55.6 (q′), 63.9 (t′), 78.9
(d′), 83.5 (d′), 95.5 (t′), 176.6 (s′), 178.2 (s′); exact mass m/z
calcd for C15H24NaO6 (M + Na) 323.1471, found 323.1478.
P h en ylm eth yl 2-Deoxy-r/â-D-er yth r o-p en tofu r a n osid e
(39). Concentrated hydrochloric acid (1 drop) was added to a
stirred solution of 2-deoxy-D-ribose (415.0 mg, 3.09 mmol) in
BnOH (7.5 mL). Stirring at room temperature was continued
for 10 min (TLC control, silica, 1:9 MeOH-CH2Cl2), by which
time reaction was over. Anhydrous MgCO3 (415.0 mg) was
added, and the resultant slurry was stirred for 5 min and then
filtered through a sintered disk, the insoluble material being
washed with PhMe. The filtrate was evaporated at room
temperature (water aspirator), and the remaining BnOH was
removed at room temperature under diffusion pump vacuum
(>0.001 mmHg). The residue remaining after 24 h was
dissolved in CH2Cl2 (1 mL) and purified by flash chromatog-
DIBAL-H (1 M in PhMe, 0.342 mL, 0.342 mmol) was added
dropwise to a stirred and cooled (-78 °C) solution of the above
ester (73.1 mg, 0.137 mmol) in CH2Cl2 (8 mL). After 30 min,
MeOH (1 mL), Na2SO4‚10H2O (220 mg), Celite (500 mg), and
water (0.2 mL) were added in that order, and stirring was
continued for 1 h without recharging the cold bath. The
resulting slurry was filtered through a short pad of Celite,
which was washed with EtOAc (20 mL). Evaporation of the
filtrate and flash chromatography of the residue over silica
gel (2 × 18 cm), using 10% to 30% EtOAc-hexane, gave the
major derived alcohol (43.3 mg, 70%) as a colorless oil: 1H
NMR (CD2Cl2, 200 MHz) δ 0.95 (s, 9 H), 1.05 (s, 9 H), 1.68-
1.82 (m, 1 H), 2.12-2.22 (m, 2 H), 2.32-2.55 (m, 2 H), 2.60
(br s, 1 H), 3.35 (s, 3 H), 3.55-3.98 (m, 5 H), 4.31-4.42 (m, 1
H), 4.45-4.52 (m, 2 H), 4.52-4.70 (m, 2 H), 7.25-7.37 (m, 5
H); 13C NMR (CDCl3, 50.3 MHz) δ 20.4 (s′), 21.9 (s′), 27.8 (q′),
28.6 (q′), 29.2 (d′), 40.7 (t′), 43.5 (q′), 47.9 (d′), 55.4 (d′), 63.0

Applications of 5-Endo-trigonal Cyclization
J . Org. Chem., Vol. 64, No. 8, 1999 2785
raphy over silica gel (3 × 22 cm), using first 50:50 EtOAc-
hexane (to remove remaining BnOH), followed by 1:9 MeOH-
CH2Cl2, to give 39 (569.5 mg, 80%) as a colorless oil, which
was a ca. 5:3 inseparable mixture of anomers. A sample, highly
(HR electrospray) m/z calcd for C19H28NaO6 (M + Na) 375.1784,
found 375.1780. The anomeric configuration was assigned on
the basis of a TROESY NMR (600 MHz) experiment.
P h en ylm eth yl 2-Deoxy-5-O-(2,2-d im eth ylp r op a n oyl)-
3-O-(m eth oxym eth yl)-r/â-D-er yth r o-p en tofu r a n ose (42).
5% Pd-C (15.0 mg) was added to a solution of 41R (472.0 mg,
1.34 mmol) in EtOH (95%, 15 mL), and the mixture was
shaken in a Parr bottle under H2 (50 psi) until all the starting
material was consumed (ca. 12 h, TLC control, silica gel, 2:3
EtOAc-hexane), the apparatus being opened periodically for
examination by TLC. The mixture was filtered through a pad
of silica gel (4 × 3 cm), using EtOAc (50 mL). Evaporation of
the filtrate and flash chromatography of the residue over silica
gel (3 × 15 cm), using 3:2 EtOAc-hexane, gave 42 (323.2 mg,
92%) as a colorless oil containing both anomers and small
amounts of the open-chain isomer. These compounds were used
directly in the next step.
enriched in one of the anomers: FTIR (CH2Cl2 cast) 3386 cm-1
;
1H NMR (CDCl3, 200 MHz) δ 2.05-2.20 (m, 1 H), 2.29-2.40
(m, 1 H), 2.61 (br s, 2 H), 3.60-3.78 (m, 2 H), 4.05-4.15 (m, 1
H), 4.50-4.60 (m, 2 H), 4.72-4.82 (m, 1 H), 5.34 (dd, J ) 5.6,
2.1 Hz, 1 H), 7.28-7.48 (m, 5 H); 13C NMR (CDCl3, 50.3 MHz)
δ 42.5 (t′), 63.6 (t′), 70.0 (t′), 72.2 (d′), 87.6 (d′), 103.7 (d′), 127.8
(d′), 128.0 (d′), 128.5 (d′), 137.2 (s′); exact mass (HR electro-
spray) m/z calcd for C12H16NaO4 (M + Na) 247.0946, found
247.0947.
P h en ylm eth yl 2-Deoxy-5-O-(2,2-d im eth ylp r op a n oyl)-
r-D-er yth r o-p en tofu r a n osid e (40r) a n d P h en ylm eth yl
2-Deoxy-5-O-(2,2-d im eth ylp r op a n oyl)-â-D-er yth r o-p en to-
fu r a n osid e (40â). A solution of diethyl azodicarboxylate
(248.7 mg, 1.428 mmol) and t-BuCO2H (145.8 mg, 1.4279
mmol) in dry THF (5 mL) was added to a stirred and warmed
(60 °C) solution of alcohols 39 (320.1 mg, 1.428 mmol) and Ph3P
(374.5 mg, 1.428 mmol) in THF (2.5 mL), contained in a flask
fitted with a condenser (Ar atmosphere). Stirring at 60 °C was
continued for 3 h, the mixture was cooled to room temperature,
and the solvent was evaporated. Flash chromatography of the
residue [the material was taken up in CH2Cl2 (0.5 mL), and
the solution was applied to the column] over silica gel (3 × 22
cm), using 1:4 EtOAc-hexane, gave 39 (86.4 mg, 27%), 40R
(94.08 mg, 22%), and 40â (157.53 mg, 36%) (combined yield is
83%, based on conversion) as colorless oils. The stereochemical
assignment was inferred from the assignment made to com-
pound 41R (see below).
(2R,3S)-2-Hyd r oxy-3-(m eth oxym eth oxy)-5-h exen yl 2,2-
Dim eth ylp r op a n oa te (43). n-BuLi (2.5 M in hexane, 2.53
mL, 6.33 mmol) was added dropwise to a stirred suspension
of Ph3PCH3Br (2.223 g, 6.33 mmol) in dry PhMe (25 mL), and
the resulting yellow slurry was stirred at room temperature
for 3 h. A solution of lactols 42 (550.7 mg, 2.11 mmol) in dry
PhMe (7.5 mL) was added dropwise by syringe pump, and the
mixture was then heated at 50 °C for 10 h. The mixture turned
brown, and a white solid formed. The mixture was cooled to
room temperature, diluted with water (30 mL), and extracted
with EtOAc. The combined organic extracts were washed with
water, saturated aqueous NH4Cl (20 mL), and brine and dried
(MgSO4). Evaporation of the solvent and flash chromatography
of the residue over silica gel (3.5 × 22 cm), using 1:4 EtOAc-
Compound 40R: [R]25 ) 104.5° (c 2.58, MeOH); FTIR
hexane, gave 43 (372.2 mg, 72%) as a pale yellow oil: [R]25
)
D
D
(CH2Cl2 cast) 1731, 3508 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ
1.21 (s, 9 H), 2.02 (dd, J ) 13.8, 0.6 Hz, 1 H), 2.20 (ddd, J )
13.8, 6.3, 4.8 Hz, 1 H), 2.74 (d, J ) 10.6 Hz, 1 H), 4.00-4.18
(m, 3 H), 4.23 (dt, J ) 2.0, 4.5 Hz, 1 H), 4.55 (d, J ) 11.8 Hz,
1 H), 4.80 (d, J ) 11.8 Hz, 1 H), 5.27 (dd, J ) 5.5, 1.4 Hz, 1
H), 7.20-7.40 (m, 5 H); 13C NMR (CD2Cl2, 50.3 MHz) δ 27.3
(q′), 39.0 (s′), 41.5 (t′), 64.4 (t′), 69.5 (t′), 73.3 (d′), 85.5 (d′),
104.0 (d′), 128.0 (d′), 128.3 (d′), 128.8 (d′), 138.3 (s′), 178.4 (s′);
exact mass (HR electrospray) m/z calcd for C17H24NaO5 (M +
Na) 331.1521, found 331.1528.
29.4° (c 1.24, MeOH); FTIR (CH2Cl2 cast) 1730, 3486 cm-1; 1H
NMR (CD2Cl2, 200 MHz) δ 1.21 (s, 9 H), 2.40-2.50 (m, 2 H),
2.75 (d, J ) 6.4 Hz, 1 H), 3.40 (s, 3 H), 3.60-3.70 (m, 1 H),
3.75-3.90 (m, 1 H), 4.10 (dd, J ) 11.6, 6.8 Hz, 1 H), 4.20 (dd,
J ) 11.6, 3.6 Hz, 1 H), 4.64 (AB q, ∆νAB ) 8.2 Hz, J ) 6.8 Hz,
2 H), 5.00-5.20 (m, 2 H), 5.75-6.00 (m, 1 H); 13C NMR
(CD2Cl2, 75.5 MHz) δ 27.4 (q′), 35.7 (t′), 39.1 (s′), 56.1 (q′), 65.7
(t′), 71.5 (d′), 80.1 (d′), 97.3 (t′), 117.6 (t′), 134.9 (d′), 179.0 (s′);
exact mass (HR electrospray) m/z calcd for C13H24NaO5 (M +
Na) 283.1521, found 283.1526.
Compound 40â: [R]25 ) -48.9° (c 1.68, MeOH); FTIR
(2R,3S)-2-[[(1,1-Dim et h ylet h yl)d im et h ylsilyl]oxy]-3-
(m et h oxym et h oxy)-5-h exen yl 2,2-Dim et h ylp r op a n oa t e
(44). Imidazole (196.7 mg, 2.89 mmol) and t-BuMe2SiCl (379.8
mg, 2.52 mmol) were added consecutively to a stirred solution
of 43 (355.0 mg, 1.364 mmol) in dry CH2Cl2 (10 mL). Stirring
was continued at room temperature for 10 h, at which point
all the starting material had been consumed. The mixture was
diluted with water (10 mL) and extracted with EtOAc. The
combined organic extracts were washed with water (10 mL)
and brine, dried (MgSO4), and evaporated. Flash chromatog-
raphy of the residue over silica gel (2.5 × 22 cm), using 1:4
EtOAc-hexane, gave 44 (453.0 mg, 89%) as a colorless oil:
D
(CH2Cl2 cast) 1730, 3453 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ
1.21 (s, 9 H), 2.13 (dt, J ) 13.5, 5.7 Hz, 1 H), 2.29 (ddd, J )
13.5, 6.8, 2.0 Hz, 1 H), 2.38 (br s, 1 H), 4.00-4.10 (m, 1 H),
4.17 (d, J ) 5.8 Hz, 2 H), 4.40 (br s, 1 H), 4.42 (d, J ) 11.7 Hz,
1 H), 4.74 (d, J ) 5.4, 2.0 Hz, 1 H), 5.27 (dd, J ) 5.4, 2.0 Hz,
1 H), 7.20-7.40 (m, 5 H); 13C NMR (CD2Cl2, 50.3 MHz) δ 27.3
(q′), 39.0 (s′), 42.0 (t′), 65.5 (t′), 69.7 (t′), 72.9 (d′), 84.3 (d′),
103.8 (d′), 127.9 (d′), 128.3 (d′), 128.7 (d′), 138.4 (s′), 178.7 (s′);
exact mass (HR electrospray) m/z calcd for C17H24NaO5 (M +
Na) 331.1521, found 331.1520.
P h en ylm eth yl 2-Deoxy-5-O-(2,2-d im eth ylp r op a n oyl)-
3-O-(m eth oxym eth yl)-r-D-er yth r o-p en tofu r a n osid e (41r).
i-Pr2NEt (0.18 mL, 134.0 mg, 1.037 mmol) was added dropwise
to a stirred and cooled (0 °C) solution of alcohol 40R (106.5
mg, 0.3458 mmol) in CH2Cl2 (6 mL). After 15 min, CH3OCH2-
Cl (0.08 mL, 1.037 mmol) was added dropwise over 5 min, and
stirring was continued for 1 h. The cold bath was removed,
stirring was continued for 12 h, and the mixture was diluted
with water (10 mL) and extracted with CH2Cl2. The combined
organic extracts were washed with brine, dried (Na2SO4), and
evaporated. Flash chromatography of the residue over silica
gel (2 × 15 cm), using 1:4 EtOAc-hexane, gave 41R (112.2
[R]25D ) -1.72° (c 0.94, MeOH); FTIR (CH2Cl2 cast) 1730 cm-1
;
1H NMR (CD2Cl2, 400 MHz) δ 0.10 (s, 6 H), 0.90 (s, 9 H), 1.21
(s, 9 H), 2.30-2.40 (m, 2 H), 3.35 (s, 3 H), 3.65 (dt, J ) 4.0, 6.0
Hz, 1 H), 3.82-3.85 (m, 1 H), 4.02 (dd, J ) 11.4, 4.9 Hz, 1 H),
4.17 (dd, J ) 11.4, 4.3 Hz, 1 H), 4.65 (AB q, ∆νAB ) 12.5 Hz,
J ) 6.7 Hz, 2 H), 5.00-5.20 (m, 2 H), 5.75-6.00 (m, 1 H); 13
C
NMR (CD2Cl2, 50.3 MHz) δ -4.51 (q′, two coincident peaks),
18.3 (s′), 26.0 (q′), 27.4 (q′), 35.5 (t′), 39.0 (s′), 56.0 (q′), 65.8
(t′), 72.6 (d′), 78.3 (d′), 96.5 (t′), 117.2 (t′), 135.6 (d′), 178.5 (s′);
exact mass (HR electrospray) m/z calcd for C19H38NaO5Si (M
+ Na) 397.2386, found 397.2396.
(2R,3S)-2-[[(1,1-Dim et h ylet h yl)d im et h ylsilyl]oxy]-3-
(m eth oxym eth oxy)-5-oxop en tyl 2,2-Dim eth ylp r op a n oa te
(45). Ozonized oxygen was bubbled through a stirred and
cooled (-78 °C) solution of 44 (537.7 mg, 1.4367 mmol) and
Sudan II red (1 mg) in dry CH2Cl2 (10 mL) (protection from
moisture by Drierite tube). When all of the starting material
was consumed (ca. 10 min; discharge of the red color; TLC
control, silica gel, 2:3 EtOAc-hexane), the solution was purged
with oxygen for 10 min. Ph3P (753.7 mg, 2.873 mmol) was
added, the cooling bath was removed, and stirring was
mg, 92%) as a colorless oil: [R]25 ) 106.6° (c 1.06, MeOH);
D
FTIR (CH2Cl2 cast) 1728, 3435 cm-1
;
1H NMR (CD2Cl2, 400
MHz) δ 1.21 (s, 9 H), 2.05 (ddd, J ) 14.1, 2.9, 1.4 Hz, 1 H),
2.27 (ddd, J ) 14.1, 8.3, 5.5 Hz, 1 H), 3.30 (s, 3 H), 4.10-4.18
(m, 2 H), 4.20-4.30 (m, 2 H), 4.46 (d, J ) 12 Hz, 1 H), 4.64
(AB q, ∆νAB ) 8.7 Hz, J ) 6.9 Hz, 2 H), 4.77 (d, J ) 12 Hz, 1
H), 5.27 (dd, J ) 5.5, 1.4 Hz, 1 H), 7.20-7.40 (m, 5 H); 13C
NMR (CD2Cl2, 50.3 MHz) δ 27.3 (q′), 39.0 (s′), 39.8 (t′), 55.7
(q′), 64.1 (t′), 69.5 (t′), 77.7 (d′), 81.6 (d′), 96.6 (t′), 103.6 (d′),
127.9 (d′), 128.2 (d′), 128.6 (d′), 138.8 (s′), 178.4 (s′); exact mass

2786 J . Org. Chem., Vol. 64, No. 8, 1999
Sannigrahi et al.
continued for 2 h, by which time the mixture had attained
room temperature. Evaporation of the solvent and flash
chromatography of the residue over silica gel (2.0 × 18 cm),
using 1:4 EtOAc-hexane, gave 45 (420.9 mg, 83%) as a
tyn yl 2,2-Dim eth ylp r op a n oa te [(+)-32]. Imidazole (7.85 mg,
0.1154 mmol) and t-BuMe2SiCl (34.78 mg, 0.2308 mmol) were
added consecutively to a stirred solution of diol 47a (23.5 mg,
0.0577 mmol) in dry CH2Cl2 (3 mL). Stirring was continued
at room temperature for 1 h, at which point all the starting
material had been consumed and the bis-silylated product
began to form. The mixture was diluted with water (2.5 mL)
and extracted with EtOAc. The combined organic extracts were
washed with water (2.5 mL) and brine, dried (MgSO4), and
evaporated. Flash chromatography of the residue over silica
gel (1 × 10.0 cm), using 1:4 EtOAc-hexane, gave (+)-32 (28.3
mg, 94%) as a colorless oil: [R]25D ) 7.81 (c 1.42, MeOH); FTIR
(CH2Cl2 cast) 1730, 3442 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ
0.14 (s, 3 H), 0.18 (s, 3 H), 0.90 (s, 9 H), 1.20 (s, 9 H), 1.91
(ddd, J ) 14.1, 7.3, 4.2 Hz, 1 H), 2.09 (ddd, J ) 14.0, 7.9, 5.9
Hz, 1 H), 3.15 (d, J ) 6.4 Hz, 1 H), 3.39 (s, 3 H) 3.76-3.91 (m,
2 H), 4.09-4.23 (m, 4 H), 4.58 (s, 2 H), 4.60-4.72 (m, 3 H),
7.24-7.37 (m, 5 H); 13C NMR (CD2Cl2, 50.3 MHz) δ -5.0 (q′),
-4.4 (q′), 18.4 (s′), 25.9 (q′), 27.3 (q′), 39.0 (s′), 40.5 (t′), 56.2
(q′), 57.8 (t′), 60.9 (d′), 65.4 (t′), 71.8 (d′), 71.8 (t′), 78.9 (d′),
81.7 (s′), 87.5 (s′), 97.8 (t′), 128.1 (d′), 128.3 (d′), 128.7 (d′), 138.1
(s′), 178.7 (s′); exact mass (HR electrospray) m/z calcd for
colorless oil: [R]25 ) -16.9° (c 1.28, MeOH); FTIR (CH2Cl2
D
1
cast) 1732 cm-1; H NMR (CD2Cl2, 400 MHz) δ 0.10 (s, 6 H),
0.90 (s, 9 H), 1.21 (s, 9 H), 2.60-2.66 (m, 2 H), 3.35 (s, 3 H),
3.90-4.18 (m, 4 H), 4.65 (AB q, ∆νAB ) 23.0 Hz, J ) 6.8 Hz, 2
H), 9.81 (t, J ) 2.1 Hz, 1 H); 13C NMR (CD2Cl2, 50.3 MHz) δ
-4.61 (q′, two coincident peaks), 18.3 (s′), 25.9 (q′), 27.4 (q′),
39.0 (s′), 45.2 (t′), 56.0 (q′), 65.1 (t′), 72.6 (d′), 74.2 (d′), 96.7
(t′), 178.5 (s′), 201.2 (d′); a satisfactory mass spectrum could
not be obtained.
(2R,3S,5R)- a n d (2R,3S,5S)-2-[[(1,1-Dim eth yleth yl)d i-
m eth ylsilyl]oxy]-5-h ydr oxy-3-(m eth oxym eth oxy)-8-(ph en -
ylm eth oxy)-6-octyn yl 2,2-Dim eth ylp r op a n oa te (46). n-
BuLi (2.5 M in hexane, 1.073 mL, 2.685 mmol) was added
dropwise to a stirred and cooled (-78 °C) solution of benzyl
propargyl ether (1337) (391.9 mg, 2.685 mmol) in THF (10 mL).
Stirring at -78 °C was continued for 1 h, and then aldehyde
45 (378.0 mg, 1.073 mmol) in THF (3.0 plus 2.0 mL as a rinse)
was added dropwise. Stirring was continued for 2 h (TLC
control, silica gel, 2:3 EtOAc-hexane), at which point no
starting material remained. The cold bath was removed and,
after 5 min, water (10 mL) was added. The mixture was
extracted with EtOAc, and the combined organic extracts were
washed with brine and dried (MgSO4). Evaporation of the
solvent and flash chromatography of the residue over silica
gel (3.0 × 22.0 cm), using 1:4 EtOAc-hexane, gave 45 (40 mg,
11%) and 46 (398.2 mg, 71%, or 80% based on conversion),
each as a colorless oil. Compound 46 was isolated as a 1:1.4
mixture (1H NMR, 400 MHz) of diastereoisomers: 1H NMR
(CD2Cl2, 400 MHz) δ 0.10 and 0.11 (two s, 6 H in all), 0.90 (s,
9 H), 1.20 (s, 9 H), 1.80-2.20 (m, 2 H), 2.80 (d, J ) 4.8 Hz)
and 3.05 (d, J ) 6.0 Hz) (the signals at 2.80 and 3.05
correspond to 1 H in all), 3.42 and 3.44 (two s, 3 H in all),
3.80-4.20 (m, 4 H), 4.25 and 4.26 (two s, 2 H in all), 4.52 (s,
2 H), 4.60-4.72 (m, 2 H), 4.72-4.80 (m, 1 H), 7.28-7.40 (m, 5
H).
C
28H46NaO7Si (M + Na) 575.2911, found 575.2901.
(1r,2â,3â)-(()-[(1,1-Dim eth yleth yl)diph en yl[[2-[(2-ph en -
ylm et h oxy)et h yl]-3-[(2-m et h oxyet h oxy)m et h oxy]cyclo-
p en tyl]m eth yl]oxy]sila n e (49). i-Pr2NEt (1.37 mL, 7.91
mmol) was added dropwise to a stirred and cooled (0 °C)
solution of 19 (1.28 g, 2.63 mmol) in CH2Cl2 (10 mL). After 15
min, MEMCl (0.90 mL, 7.91 mmol) was added dropwise over
5 min, and stirring was continued for 1 h. The cold bath was
removed, stirring was continued for 12 h, and the mixture was
diluted with water (100 mL) and extracted with CH2Cl2. The
combined organic extracts were washed with brine, dried
(Na2SO4), and evaporated. Flash chromatography of the
residue over silica gel (3 × 20 cm), using 1:4 EtOAc-hexane,
gave 49 (1.51 g, 100%) as a colorless oil: FTIR (CH2Cl2 cast)
1
1199, 3070 cm-1; H NMR (CD2Cl2, 200 MHz) δ 1.05 (s, 9 H).
1.50-2.10 (m, 8 H), 3.35 (s, 3 H), 3.40-3.70 (m, 8 H), 4.10-
4.20 (m, 1 H), 4.47 (s, 2 H), 4.64 (AB q, ∆νAB ) 18.2 Hz, J )
6.8 Hz, 2 H), 7.20-7.45 (m, 10 H), 7.60-7.70 (m, 5 H); 13C
NMR (CD2Cl2, 50.3 MHz) δ 19.5 (t′), 26.1 (t′), 27.0 (q′), 28.7
(t′), 31.0 (t′), 43.4 (d′), 45.3 (d′), 59.0 (q′), 67.0 (t′), 67.4 (t′),
69.8 (t′), 72.2 (t′), 73.0 (t′), 80.5 (d′), 94.6 (t′), 127.7 (d′), 127.9
(d′), 128.0 (d′), 128.6 (d′), 129.9 (d′), 134.4 (s′), 136.0 (d′), 139.5
(s′); exact mass (HR electrospray) m/z calcd for C35H48NaO5Si
(M + Na) 599.3169, found 599.3171.
(2R,3S,5R)- a n d (2R,3S,5S)-2,5-Dih yd r oxy-3-(m eth oxy-
m et h oxy)-8-(p h en ylm et h oxy)-6-oct yn yl 2,2-Dim et h yl-
p r op a n oa te (47a , 47b). HF (48% in water, 0.4 mL, 11.2
mmol) was added to a stirred solution of 46 (251.2 mg, 0.4812
mmol) in bench MeCN (5 mL). After 30 min, saturated aqueous
NaHCO3 (10 mL) was added dropwise, and the aqueous layer
was extracted with EtOAc. The combined organic extracts were
washed with brine, dried (MgSO4), and evaporated. Flash
chromatography of the residue over silica gel (2 × 40 cm), using
1:4 EtOAc-hexane, gave 47b (69.8 mg, 35.5%) and 47a (98.1
mg, 50%) as a separable mixture (1:1.4) of diastereoisomers.
(1r,2â,3â)-(()-3-[(2-Meth oxyeth oxy)m eth oxy]-2-[2-(ph en -
ylm eth oxy)eth yl]cyclop en ta n em eth a n ol (50). TBAF (1 M
in THF, 4.62 mL, 4.62 mmol) was added dropwise to a stirred
solution of 49 (1.33 g, 2.30 mmol) in dry THF (40 mL). Stirring
was continued for 20 h, by which time reaction was complete
(TLC control, silica gel, 3:4 EtOAc-hexane). The mixture was
diluted with water (100 mL) and extracted with EtOAc. The
combined organic extracts were washed with brine, dried
(Na2SO4), and evaporated. Flash chromatography of the
residue over silica gel (3 × 20 cm), using 3:4 EtOAc-hexane,
gave 50 (758 mg, 96%) as a colorless oil: FTIR (CH2Cl2 cast)
3445 cm-1; 1H NMR (CD2Cl2, 200 MHz) δ 1.20-2.10 (m, 9 H),
3.30 (s, 3 H), 3.40-3.70 (m, 8 H), 4.00-4.10 (m, 1 H), 4.50 (s,
2 H), 4.66 (AB q, ∆νAB ) 18.2 Hz, J ) 6.8 Hz, 2 H), 7.20-7.40
(m, 5 H); 13C NMR (CD2Cl2, 50.3 MHz) δ 26.2 (t′), 28.8 (t′),
30.8 (t′), 43.7 (d′), 45.4 (d′), 59.0 (q′), 66.4 (t′), 67.4 (t′), 69.8
(t′), 72.2 (t′), 73.2 (t′), 80.6 (d′), 94.6 (t′), 127.9 (d′), 128.1 (d′),
128.7 (d′), 139.1 (s′); exact mass (HR electrospray) m/z calcd
for C19H30NaO5 (M + Na) 361.1991, found 361.1989.
(2r,3r)-(()-1-[(2-Meth oxyeth oxy)m eth oxy]-3-m eth ylen e-
2-[2-(p h en ylm eth oxy)eth yl]cyclop en ta n e (51). Bu3P (0.11
mL, 0.45 mmol) was added dropwise over 5 min to a stirred
solution of 50 (76.4 mg, 0.22 mmol) and 2-nitrophenyl seleno-
cyanate (102.5 mg, 0.45 mmol) in dry THF (2 mL). The
resulting red solution was stirred for 3 h, at which stage no
starting material remained (TLC control, silica gel, 1:5 EtOAc-
hexane). The solvent was evaporated, and the crude selenide
was used directly in the next step.
Compound 47a : [R]25 ) -15.36° (c 0.97, MeOH); FTIR
D
(CH2Cl2 cast) 1728, 3436 cm-1; 1H NMR (CD2Cl2, 200 MHz) δ
1.21 (s, 9 H), 1.80-2.20 (m, 2 H), 2.60 (d, J ) 5.0 Hz, 1 H),
3.10 (d, J ) 5.0, 1 H), 3.35 (s, 3 H), 3.85-3.92 (m, 2 H), 4.00-
4.25 (m, 4 H), 4.55 (s, 2 H), 4.60-4.68 (m, 3 H), 7.30-7.40 (m,
5 H); 13C NMR (CD2Cl2, 50.3 MHz) δ 27.3 (q′), 39.0 (s′), 39.4
(t′), 56.3 (q′), 57.8 (t′), 60.2 (d′), 65.5 (t′), 71.8 (d′), 72.0 (t′),
78.4 (d′), 81.5 (s′), 87.3 (s′), 97.5 (t′), 128.1 (d′), 128.3 (d′), 128.7
(d′), 138.1 (s′) 178.9 (s′); exact mass (HR electrospray) m/z calcd
for C22H32NaO7 (M + Na) 431.2046, found 431.2055.
Compound 47b: [R]25 ) -10.0° (c 1.35, MeOH); FTIR
D
(CH2Cl2 cast) 1728, 3439 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ
1.21 (s, 9 H), 1.90 (ddd, J ) 14.6, 9.0, 3.3 Hz, 1 H), 2.05 (ddd,
J ) 14.6, 3.3 Hz, 1 H), 2.80 (d, J ) 6.0 Hz, 1 H), 2.90 (d, J )
6.0 Hz, 1 H), 3.40 (s, 3 H), 3.80-3.84 (m, 1 H), 3.90-3.96 (m,
1 H), 4.16 (dd, J ) 11.6, 6.7 Hz, 1 H), 4.18-4.21 (m, 3 H), 4.59
(s, 2 H), 4.60-4.68 (m, 1 H), 4.71 (AB q, ∆νAB ) 12.0 Hz, J )
6.7 Hz, 2 H), 7.30-7.40 (m, 5 H); 13C NMR (CD2Cl2, 50.3 MHz)
δ 27.3 (q′), 39.0 (s′), 39.1 (t′), 56.4 (q′), 57.8 (t′), 59.5 (d′), 65.4
(t′), 72.0 (d′), 72.0 (t′), 78.6 (d′), 81.0 (s′), 87.6 (s′), 98.1 (t′),
128.1 (d′), 128.3 (d′), 128.7 (d′), 138.1 (s′) 178.9 (s′); exact mass
(HR electrospray) m/z calcd for C22H32NaO7 (M + Na) 431.2046,
found 431.2057.
(2R,3S,5R)-5-[[(1,1-Dim eth yleth yl)d im eth ylsilyl]oxy]-
2-h yd r oxy-3-(m eth oxym eth oxy)-8-(p h en ylm eth oxy)-6-oc-

Applications of 5-Endo-trigonal Cyclization
J . Org. Chem., Vol. 64, No. 8, 1999 2787
A stirred solution of the crude selenide in dry CH2Cl2 (5 mL)
was cooled to -10 °C, and m-CPBA (78.0 mg, 0.45 mmol) was
added in one portion. Stirring was continued for 1 h, i-Pr2NH
(0.063 mL, 0.45 mmol) was added, and the mixture was
refluxed for 1 h. Evaporation of the solvent and flash chro-
matography of the residue over silica gel (1 × 18 cm), using
1:5 EtOAc-hexane, gave 51 (57.8 mg, 80%) as a yellow oil:
using 1:3 EtOAc-hexane, gave 54 (115.4 mg, 87%) as a pale
1
yellow oil: FTIR (CH2Cl2 cast) 2244 cm-1; H NMR (CD2Cl2,
300 MHz) δ 1.60-2.10 (m, 7 H), 2.30-2.50 (m, 3 H), 3.35 (s, 3
H), 3.40-3.70 (m, 6 H), 4.00-4.10 (m, 1 H), 4.40 (s, 2 H), 4.62
(AB q, ∆νAB ) 25.7 Hz, J ) 6.9 Hz, 2 H), 7.20-7.50 (m, 5 H);
13C NMR (CD2Cl2, 75.4 MHz) δ 20.4 (t′), 25.8 (t′), 29.6 (t′), 30.7
(t′), 38.0 (d′), 44.8 (d′), 59.1 (q′), 67.6 (t′), 69.6 (t′), 72.2 (t′),
73.4 (t′), 80.1 (d′), 94.7 (t′), 120.9 (s′), 127.99 (d′), 128.02 (d′),
128.7 (d′), 139.2 (s′); exact mass (HR electrospray) m/z calcd
for C20H29NNaO4 (M + Na) 370.1994, found 370.2003.
FTIR (CH2Cl2 cast) 1652, 3070 cm-1 1H NMR (CD2Cl2, 400
;
MHz) δ 1.60-2.00 (m, 4 H), 2.35-2.60 (m, 3 H), 3.30 (s, 3 H),
3.40-3.60 (m, 6 H), 4.07-4.09 (m, 1 H), 4.43 (AB q, ∆νAB
)
11.5 Hz, J ) 11.9 Hz, 2 H), 4.64 (AB q, ∆νAB ) 38.3 Hz, J )
6.9 Hz, 2 H), 4.80 (d, J ) 2.1 Hz, 1 H), 4.86 (d, J ) 2.1 Hz, 1
H), 7.20-7.45 (m, 5 H); 13C NMR (CD2Cl2, 100.6 MHz) δ 27.3
(t′), 29.5 (t′), 29.6 (t′), 46.0 (d′), 58.9 (q′), 67.5 (t′), 69.2 (t′), 72.1
(t′), 73.1 (t′), 79.3 (d′), 94.5 (t′), 105.2 (t′), 127.7 (d′), 127.9 (d′),
128.6 (d′), 139.4 (s′), 154.1 (s′); exact mass (HR electro-
spray) m/z calcd for C19H28NaO4 (M + Na) 343.1885, found
343.1889.
(1r,2r,3r)-(()-2-(2-Hydr oxyeth yl)-3-[(2-m eth oxyeth oxy)-
m eth oxy]cyclop en ta n ea ceton itr ile (55). Pd-C (5%) (9 mg)
was added to a stirred solution of 54 (55.0 mg, 0.163 mmol) in
MeOH (2 mL). The reaction flask was flushed with H2, and
stirring was continued under hydrogen (balloon) until all the
starting material was consumed (ca 30 min, TLC control, silica
gel, 3:2 EtOAc-hexane). The mixture was filtered through a
pad of silica gel (1 × 2 cm), using EtOAc (50 mL). Evaporation
of the filtrate and flash chromatography of the residue over
silica gel (1 × 10 cm), using 3:2 EtOAc-hexane, gave 55 (38.5
mg, 92%) as a colorless oil: FTIR (CH2Cl2 cast) 3442 cm-1; 1H
NMR (CD2Cl2, 200 MHz) δ 1.50-2.15 (m, 8 H), 2.30-2.50 (m,
3 H), 3.35 (s, 3 H), 3.45-3.75 (m, 6 H), 4.05-4.15 (m, 1 H),
4.62 (AB q, ∆νAB ) 14.7 Hz, J ) 6.7 Hz, 2 H); 13C NMR (CD2Cl2,
50.3 MHz) δ 20.4 (t′), 28.5 (t′), 29.3 (t′), 30.8 (t′), 38.1 (d′), 44.6
(d′), 59.0 (q′), 62.0 (t′), 67.7 (t′), 72.2 (t′), 80.3 (d′), 94.8 (t′),
120.8 (s′); exact mass (HR electrospray) m/z calcd for C13H23O4-
NNa (M + Na) 280.1525, found 280.1524.
(1r,2r,3r)-(()-3-[(2-Meth oxyeth oxy)m eth oxy]-2-(2-oxo-
eth yl)cyclop en ta n ea ceton itr ile (56). A mixture of PCC
(56.8 mg, 0.26 mmol) and powdered 4 Å molecular sieves (20
mg) was added to a stirred solution of 55 (52.2 mg, 0.20 mmol)
in dry CH2Cl2 (2 mL). Stirring was continued for 1 h, by which
time oxidation was complete (TLC control, silica gel, 2:3
EtOAc-hexane), and the mixture was applied directly to a
column (1 × 15 cm) of flash chromatography silica gel. The
column was developed using 2:3 EtOAc-hexane, to give 56
(41 mg, 78%) as a colorless oil: FTIR (CH2Cl2 cast) 1722, 2245
cm-1; 1H NMR (CD2Cl2, 400 MHz) δ 1.60-1.75 (m, 1 H), 1.80-
2.05 (m, 3 H), 2.30-2.60 (m, 5 H), 2.65-2.80 (m, 1 H), 3.35 (s,
3 H), 3.42-3.62 (m, 4 H), 4.10-4.20 (m, 1 H), 4.58 (AB q, ∆νAB
) 30.5 Hz, J ) 6.8 Hz, 2 H), 9.80 (t, J ) 1.07 Hz, 1 H); 13C
NMR (CD2Cl2, 50.3 MHz) δ 20.3 (t′), 29.2 (t′), 30.3 (t′), 37.3
(d′), 39.9 (t′), 41.0 (d′), 59.0 (q′), 67.6 (t′), 72.1 (t′), 79.7 (d′),
94.7 (t′), 120.1 (s′), 201.4 (d′); exact mass (HR electro-
spray) m/z calcd for C13H21NNaO4 (M + Na) 278.1373, found
278.1368.
(1r,2r,3r)-(()-3-[(2-Meth oxyeth oxy)m eth oxy]-2-[2-(ph en -
ylm eth oxy)eth yl]cyclop en ta n em eth a n ol (52). BH3‚SMe2
(10.0 M in THF, 0.210 mL, 2.10 mmol) was added dropwise to
a stirred and cooled (-20 °C) solution of 51 (337.3 mg, 1.05
mmol) in dry THF (5 mL). After 30 min, the solution was
warmed to 0 °C (by replacing the acetone-dry ice bath with
an ice bath). Stirring was continued for 1.0 h, the ice bath was
removed, and stirring was continued for 30 min. The mixture
was cooled to 0 °C, and NaOH (3 N, 0.7027 mL) was added
dropwise, followed by 30% aqueous H2O2 (0.24 mL), and
stirring was continued for 30 min. The mixture was diluted
with Et2O (10 mL), washed with water (2 × 10 mL) and brine,
dried (Na2SO4), and evaporated. Flash chromatography of the
residue over silica gel (1.5 × 20 cm), using 15:85 EtOAc-
hexane, gave 52 (303.0 mg, 85%) as a colorless oil: FTIR
(CH2Cl2 cast) 3453 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ 1.60-
1.90 (m, 6 H), 2.05-2.20 (m, 1 H), 2.20-2.30 (m, 1 H), 2.85
(dd, J ) 7.8, 3.0 Hz, 1 H), 3.30 (s, 3 H), 3.40-3.70 (m, 8 H),
4.00-4.10 (m, 1 H), 4.41 (s, 2 H), 4.67 (AB q, ∆νAB ) 30.3 Hz,
J ) 6.9 Hz, 2 H), 7.20-7.45 (m, 5 H); 13C NMR (CD2Cl2, 50.3
MHz) δ 25.2 (t′), 25.6 (t′), 30.9 (t′), 42.0 (d′), 43.6 (d′) 59.0 (q′),
62.8 (t′), 67.7 (t′), 70.0 (t′), 72.1 (t′), 73.3 (t′), 80.1 (d′), 94.3 (t′),
127.8 (d′), 128.0 (d′), 128.7 (d′), 139.2 (s′); exact mass (HR
electrospray) m/z calcd for C19H30NaO5 (M + Na) 361.1991,
found 361.1989.
(1r,2r,3r)-(()-[3-[(2-Methoxyethoxy)methoxy]-2-[2-(phen-
ylm et h oxy)et h yl]cyclop en t yl]m et h yl 4-Met h ylp h en yl-
su lfon a te (53). p-TsCl (304.4 mg, 1.596 mmol) was added in
one portion to a stirred solution of 52 (180.0 mg, 0.5322 mmol)
in CH2Cl2 (5 mL) containing dry pyridine (0.5 mL). A catalytic
amount of DMAP was tipped into the solution, and the mixture
was stirred overnight, by which time reaction was complete
(TLC control, silica gel, 1:4 EtOAc-hexane). The mixture was
diluted with water (10 mL) and extracted with CH2Cl2. The
combined organic extracts were washed with brine, dried
(Na2SO4), and evaporated. Flash chromatography of the
residue over silica gel (1.5 × 18 cm), using 1:4 EtOAc-hexane,
gave 53 (254 mg, 97%) as a colorless oil: FTIR (CH2Cl2 cast)
1188 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ 1.50-1.90 (m, 6 H),
1.95-2.10 (m, 1 H), 2.25-2.40 (m, 1 H), 2.45 (s, 3 H), 3.25 (s,
3 H), 3.40-3.60 (m, 6 H), 3.90-4.00 (m, 2 H), 4.10 (dd, J )
9.4, 5.5 Hz, 1 H), 4.42 (s, 2 H), 4.57 (AB q, ∆νAB ) 33.5 Hz, J
) 6.9 Hz, 2 H), 7.20-7.40 (m, 7 H), 7.70-7.80 (m, 2 H); 13C
NMR (CD2Cl2, 50.3 MHz) δ 21.5 (q′), 25.3 (t′), 26.7 (t′), 30.3
(t′), 39.5 (d′), 43.7 (d′) 58.8 (q′), 67.2 (t′), 69.4 (t′), 72.0 (t′), 73.0
(t′), 73.4 (t′), 79.6 (d′), 94.3 (t′), 127.6 (d′), 127.8 (d′), 128.0 (d′),
128.5 (d′), 123.0 (d′), 133.5 (s′), 139.0 (s′), 145.0 (s′); exact mass
[1r,2r(Z),3r]-(()-3-[(2-Meth oxyeth oxy)m eth oxy]-2-(2-
p en ten yl)cyclop en ta n ea ceton itr ile (8). (Me3Si)2NK (0.5 M
in PhMe, 0.49 mL, 0.25 mmol) was added to a slurry of
triphenyl(propyl)phosphonium bromide (100.2 mg, 0.26 mmol)
in dry PhMe (1 mL). The mixture was stirred for 1 h, and the
resultant bright red solution was then left undisturbed for 1
h. The supernatant liquid was drawn up into a syringe, and
an aliquot (ca 1.0 mL, 0.17 mmol) was added dropwise over 5
min to a stirred and cooled (-78 °C) solution of 56 (15.8 mg,
0.06 mmol) in dry PhMe (1 mL). The temperature was
maintained at -78 °C for 1 h, and then the cold bath was
removed. Stirring was continued overnight, leading to a
colorless solution and the formation of Ph3PO. The solvent was
evaporated, and the crude residue was dissolved in CH2Cl2 (0.5
mL). The solution was applied directly to a column of flash
chromatography silica gel (1.0 × 10 cm), and the column was
developed using 1:4 EtOAc-hexane, to give 89 (14.0 mg, 80%)
(HR electrospray) m/z calcd for
515.2080, found 515.2083.
C26H36NaO7S (M + Na)
as a colorless oil: FTIR (CH2Cl2 cast) 2245 cm-1 1H NMR
;
(CDCl3, 300 MHz) δ 0.96 (t, J ) 7.5 Hz, 3 H), 1.60-2.30 (m, 9
H), 2.30-2.50 (m, 3 H), 3.37 (s, 3 H), 3.50-3.70 (m, 4 H), 4.00-
4.10 (m, 1 H), 4.64 (AB q, ∆νAB ) 35.0 Hz, J ) 6.9 Hz, 2 H),
5.25-5.5 (m, 2 H); 13C NMR (CD2Cl2, 100.6 MHz) δ 14.3 (q′),
20.2 (t′), 21.0 (t′), 23.1 (t′), 29.5 (t′), 30.8 (t′), 37.6 (d′), 48.1 (d′),
59.0 (q′), 67.4 (t′), 72.1 (t′), 80.2 (d′), 94.9 (t′), 120.8 (s′), 127.5
(d′), 133.0 (d′); exact mass (HR electrospray) m/z calcd for
(1r,2r,3r)-(()-3-[(2-Meth oxyeth oxy)m eth oxy]-2-[2-(ph en -
ylm eth oxy)eth yl]cyclop en ta n ea ceton itr ile (54). A solu-
tion of 53 (195.5 mg, 0.39 mmol) and NaCN (136.5 mg, 2.8
mmol) in dry DMSO (2.5 mL) was heated at 100 °C for 1 h,
allowed to cool to room temperature, diluted with water (15
mL), and extracted with Et2O. The combined organic extracts
were washed with brine, dried (Na2SO4), and evaporated. Flash
chromatography of the residue over silica gel (1.5 × 20 cm),
C
16H27NNaO3 (M + Na) 304.1889, found 304.1887.

2788 J . Org. Chem., Vol. 64, No. 8, 1999
Sannigrahi et al.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for C, D, 41â, 42, and the epimer of (+)-32, and copies
of NMR spectra for compounds not analyzed. This material is
available free of charge via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. We thank the Natural Sciences
and Engineering Research Council of Canada, and the
Merck Frosst Therapeutic Research Centre, for financial
support. D.L.M. held a Province of Alberta Graduate
Fellowship.
J O982225M