Enantioselective construction of cyclic ethers by an aldol-cyclization sequence

Article abstract of DOI:10.1021/jo961904z

We have modified the substrate used in deconjugative aldol-cyclizations by incorporating the Evans chiral auxiliary. The deconjugative aldol step, using boron enolates, gave the expected products with complete syn-aldol stereochemistry. These compounds could then undergo an iodine-mediated cyclization to form optically active products. Oxetanes and fused ring tetrahydrofurans were easily assembled with a variety of substitutiion patterns and with excellent enantiocontrol. The deconjugation of acyclic chiral enimides resulted in the loss of control of olefin geometry. However, these compounds did appear to cyclize with excellent enantiocontrol.

Full text of DOI:10.1021/jo961904z

5048
J . Org. Chem. 1997, 62, 5048-5056
En a n tioselective Con str u ction of Cyclic Eth er s by An
Ald ol-Cycliza tion Sequ en ce
Paul Galatsis,*,1 Scott D. Millan, and George Ferguson
Department of Chemistry and Biochemistry, University of Guelph, Guelph, Ontario N1G 2W1, Canada
Received October 8, 1996X
We have modified the substrate used in deconjugative aldol-cyclizations by incorporating the Evans
chiral auxiliary. The deconjugative aldol step, using boron enolates, gave the expected products
with complete syn-aldol stereochemistry. These compounds could then undergo an iodine-mediated
cyclization to form optically active products. Oxetanes and fused ring tetrahydrofurans were easily
assembled with a variety of substitution patterns and with excellent enantiocontrol. The
deconjugation of acyclic chiral enimides resulted in the loss of control of olefin geometry. However,
these compounds did appear to cyclize with excellent enantiocontrol.
In tr od u ction
of these and other compounds. Consequently, new
methods for the assembly of these fragments in a
stereospecific and ultimately enantiospecific manner is
desirable.
Substituted cyclic ethers, oxetanes and tetrahydro-
furans, in particular, are a common structural subunit
found in a variety of natural products. Oxetanocin2 (1)
and paclitaxel3 (2) incorporate the oxetane ring, while
the more common tetrahydrofuran ring can be found in
such compounds as (-)-nonactic acid4 (3), citreoviral5 (4),
and monensin6 (5). From this small sample, one can see
the varied substitution pattern and stereochemical ar-
rangements that need to be addressed in the synthesis
X Abstract published in Advance ACS Abstracts, J uly 1, 1997.
(1) Address correspondence to this author at Parke-Davis Pharma-
ceutical Research, 2800 Plymouth Rd., Ann Arbor, MI 48105 (e-mail:
galatsp@aa.wl.com).
(2) (a) Nittsuma, S.; Ichikawa, Y.-I.; Kato, K.; Takita, T. Tetrahedron
Lett. 1987, 28, 3967. (b) Norbeck, D. W.; Kramer, J . B. J . Am. Chem.
Soc. 1988, 110, 7213. (c) Hambalek, R.; J ust, G. Tetrahedron Lett. 1990,
31, 5445. (d) Hambalek, R.; J ust, G. Tetrahedron Lett. 1990, 31, 4693.
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Storer, R.; Myers, P. L.; Wallis, C. J . Tetrahedron: Asymmetry 1990,
1, 525. (f) Wang, Y.; Fleet, G. W. J .; Storer, R.; Myers, P. L.; Wallis, C.
J .; Doherty, O.; Watkin, D. J .; Vogt, K.; Witty, D. R.; Wilson, F. X.
Peach, J . M. Tetrahedron: Symmetry 1990, 1, 527. (g) Saksena, A. K.;
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Suzuki, Y.; Tao, C.; Vu, P.; Tang, S.; Zhang, P.; Murthi, K. K.; Gentile,
L. N.; Liu, J . H. J . Am. Chem. Soc. 1994, 116, 1597. (b) Holton, R. A.;
Kim, H.-B.; Somoza, C.; Liang, F.; Biediger, R. J .; Boatman, P. D.;
Shindo, M.; Smith, C. C.; Kim, S.; Nadizadeh, H.; Suzuki, Y.; Tao, C.;
Vu, P.; Tang, S.; Zhang, P.; Murthi, K. K.; Gentile, L. N.; Liu, J . H. J .
Am. Chem. Soc. 1994, 116, 1599. (c) Nicolaou, K. C.; Yang, Z.; Liu, J .
J .; Ueno, H.; Nantermet, P. G.; Guy, R. K.; Claiborne, C. F.; Renaud,
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367, 630. (d) Masters, J . J .; Link, J . T.; Snyder, L. B.; Young, W. B.;
Danishefsky, S. J . Angew. Chem., Int. Ed. Engl. 1995, 34, 1723 and
references therein.
(4) (a) Beck, G.; Henseleit, E. Chem. Ber. 1971, 104, 21. (b) Zak, J .;
Schmidt, U. Angew. Chem., Int. Ed. Engl. 1975, 14, 432. (c) Arco, M.
J .; Trammell, M. H.; White, J . D. J . Org. Chem. 1976, 41, 2075. (d)
Bartlett, P. A.; J ernstedt, K. K. Tetrahedron Lett. 1980, 21, 1607. (e)
Bartlett, P. A.; Meadows, J . D.; Ottow, E. J . Am. Chem. Soc. 1984,
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1985, 26, 231. (b) Williams, D. R.; White, F. H. Tetrahedron Lett. 1985,
26, 2529. (c) Bowden, M. C.; Patel, P.; Pattenden, G. Tetrahedron Lett.
1985, 26, 4793. (d) Hatekeyama, S.; Matsui, Y.; Suzuki, M.; Sakurai,
K.; Takano, S. Tetrahedron Lett. 1985, 26, 6485. (e) Trost, B. M.; Lynch,
J . K.; Angle, S. R. Tetrahedron Lett. 1987, 28, 375. (f) Bowden, M. C.;
Pattenden, G. Tetrahedron Lett. 1988, 29, 711. (g) Suh, H.; Wilcox, C.
S. J . Am. Chem. Soc. 1988, 110, 470.
(6) (a) Schmid, D.; Fukuyama, T.; Akasaka, K.; Kishi, Y. J . Am.
Chem. Soc. 1979, 101, 259. (b) Fukuyama, T.; Wang, C.-L. J .; Kishi,
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Soc. 1979, 101, 262. (d) Collum, D. B.; McDonald, J . H., III; Still, W.
C. J . Am. Chem. Soc. 1980, 102, 2117, 2118, 2120.
The varied substituents, substitution pattern, and
stereochemistry superimposed upon the conformational
mobility of the tetrahydrofuran ring or the strain of the
oxetane ring provides a challenge in synthesis to the
chemist. Solutions to this challenge have resulted in a
variety of ingenious methods for their construction.
These methods7,8 include electrophile-induced (proton,
halogen, metal, and chalogenide) reactions, oxidative
cyclizations, ester enolate Claisen reactions, radical
reactions, epoxide ring opening reactions, Michael addi-
tions, cycloadditions, and the use of carbohydrate precur-
sors. In recent years, a renaissance in the electrophile-
mediated cyclization of unsaturated alcohols has
occurred.9,10 However, this resurgence has focused on the
(7) For excellent reviews see: (a) Semple, J . E.; J oullie, M. M.
Heterocycles 1980, 14, 1825. (b) Bartlett, P. D. Asymmetric Synthesis
1984, 3, 411. (c) Boivin, T. L. B. Tetrahedron 1987, 43, 3309. (d)
Cardillo, G.; Orena, M. Tetrahedron 1990, 46, 3321. (d) Harmange,
L.-C.; Figadere, B. Tetrahedron: Asymmetry 1993, 4, 1711.
(8) For recent examples see: (a) Ronn, M.; Backvall, J .-E.; Ander-
sson, P. G. Tetrahedron Lett. 1995, 36, 7749. (b) Zhang, H.; Mootoo,
D. R. J . Org. Chem. 1995, 60, 8135. (c) Petasis, N. A.; Lu, S.-P. J . Am.
Chem. Soc. 1995, 117, 6394.
S0022-3263(96)01904-4 CCC: $14.00 © 1997 American Chemical Society

Enantioselective Construction of Cyclic Ethers
J . Org. Chem., Vol. 62, No. 15, 1997 5049
Ta ble 1. Resu lts of Sequ en ce on Im id e 7
Sch em e 1
entry
R
8 (% yield)a
% yielda (9/10 ratio)
1
2
3
4
Me (a )
Et (b)
iPr (c)
Ph (d )
90
88
74
76
47 (12:1)
48 (19:1)
40 (24:1)
nab
a
Based on isolated, chromatographically pure material. b Reac-
5-endo-trig mode of ring closure rather than the 5-exo-
trig mode that is predicted by Baldwin’s rules. We and
others9,10 have shown the feasibility of this method for
the assembly of these systems. In synthetic terms, the
endo mode of ring closure provides for increased func-
tionality in the ring, i.e., the iodine, after cyclization,
resides on the ring rather than on some pendent sub-
stituent. This results in an additional functional group
by which the ring may be further elaborated.
tion products decomposed.
tioselectivity of the deconjugative aldol step would have
to address the double bond geometry in the deconjugation
process. Since the cyclization appears to obey the Stork-
Eschenmoser hypothesis, in that net anti addition of the
alcohol and iodine across the alkene is observed, complete
control of olefin geometry is crucial for high enantiocon-
trol in this step. Consequently, it was decided that the
most facile procedure would be to make use of the vast
amount of information associated with the use of chiral
auxiliaries in the aldol reaction.11 While the majority of
this work was on saturated systems, there was one
example of an unsaturated system.12 Therefore, it was
decided to make use of the Evans’ chiral auxiliary, since
they are readily available and have been shown to exhibit
great enantiocontrol.11 We now wish to report our studies
in which the enantiospecific variation of our deconjuga-
tive aldol-cyclization sequence has been accomplished.
We have developed a deconjugative aldol-cyclization
sequence10 (see Scheme 1) for the construction of cyclic
ethers. This involved dienolate formation followed by
kinetic aldolization at the R-position to generate a species
with a homoallylic moiety. This unsaturated alcohol
substructure could undergo an iodine-mediated cycliza-
tion to afford the cyclic ether derivative. This sequence
provided ready access to these compounds in two steps
with excellent relative stereocontrol of the resultant four
stereocenters. Proper choice of aldol diastereomer (syn
or anti) and olefin geometry (E or Z) would allow one to
essentially construct all the possible isomers for any
substitution pattern. A combinatorial library of these
compounds could be used as a repository of building
blocks in the synthesis of various natural products. For
example, in an approach to polyether antibiotics, if R or
R′ (see Scheme 1) was, or could be converted to, a
carbonyl function (aldehyde or ketone), then the product
of the cyclization step could serve as the electrophile in
a subsequent deconjugative aldol step. In such a fashion,
a polyether antibiotic could be assembled by an iterative
manner. A benefit of this approach is that one could
easily assemble analogues for structure-function rela-
tionships.
Resu lt a n d Discu ssion
These investigations began by constructing the chiral
imide of crotonic acid. Following the procedure of
Evans,12 crotonyl chloride was treated with the lithiated
oxazolidinone derived from L-valine to produce imide 7.
This substrate permitted us to examine the two-step
sequence without the further complication of the olefin
geometry. Aldol reactions with a series of aldehydes via
the boron enolate gave the desired syn aldols 8 in good
to excellent yields (see Table 1). The chiral auxiliary
performed its function without perturbing the deconju-
gation chemistry.
In an effort to expand the scope of this method, we
wished to extend the chemistry into the chiral manifold,
i.e., develop a variation of this sequence for the synthesis
of optically active cyclic ethers. In order to exert enan-
tiocontrol over our method, we needed to address the
potential sites of control in both steps. From an exami-
nation of our earlier work, it became obvious that if
control of absolute stereochemistry could be accomplished
in the deconjugative aldol step, then excellent enantio-
control could be obtained in the cyclization step by chiral
induction. The chirality generated in the aldol product
would direct the cyclization by controlling the allowed
conformations that could be adopted in the transition
state of the cyclization reaction. Furthermore, the enan-
With these compounds in hand, we were now able to
study the cyclization step with the chiral auxiliary intact.
Cyclization using the standard conditions, 3 equivalents
each of iodine and sodium bicarbonate in acetonitrile,
afforded oxetanes 9 and 10 (see Table 1). No tetrahy-
drofuran formation was observed. This stands in sharp
contrast to our previous results with the methyl ester,
in which a mixture of oxetane and tetrahydrofuran was
obtained.10a For compounds 9, 10, 13, and 14, the
(9) (a) Evans, R. D.; Magee, J . W.; Schauble, J . H. Synthesis 1988,
862. (b) Kang, S. H.; Hwang, T. S.; Kim, W. J .; Lim, J . K. Tetrahedron
Lett. 1990, 31, 5917. (c) Kang, S. H.; Hwang, T. S.; Kim, W. J .; Lim, J .
K. Tetrahedron Lett. 1991, 32, 4015. (d) Lipshutz, B. H.; Barton, J . C.
J . Am. Chem. Soc. 1992, 114, 1084. (e) Bedford, S. B.; Bell, K. E.;
Fenton, G.; Hayes, C. J .; Knight, D. W.; Shaw, D. Tetrahedron Lett.
1992, 33, 6511. (f) Mihelich, E. D.; Hite, G. A. J . Am. Chem. Soc. 1992,
114, 7318. (g) Kang, S. H.; Lee, S. B. Tetrahedron Lett. 1993, 34, 1955.
(h) Barks, J . M.; Knight, D. W.; Weingarten, G. G. J . C. S., Chem.
Commun. 1994, 719. (i) Barks, J . M.; Knight, D. W.; Seaman, C. J .;
Weingarten, G. G. Tetrahedron Lett. 1994, 35, 7259. (j) Lipshutz, B.
H.; Tirado, R. J . Org. Chem. 1994, 59, 8307.
(11) For excellent reviews see: (a) Evans, D. A.; Nelson, J . V.; Taber,
T. R. Top. Stereochem. 1982, 13, 1. (b) Heathcock, C. A. Asymmetric
Synthesis 1984, 3, 111. (c) Franklin, A. S.; Paterson, I. Contemp. Org.
Synth. 1994, 317.
(12) (a) Evans, D. A.; Sjogren, E. B.; Bartoli, J .; Dow, R. L.
Tetrahedron Lett. 1986, 27, 4957. (b) Gage, J . R.; Evans, D. A. Org.
Synth. 1989, 68, 83.
(10) (a) Galatsis, P.; Millan, S. D.; Nechala, P.; Ferguson, G. J . Org.
Chem. 1994, 59, 6643. (b) Galatsis, P.; Parks, D. J . Tetrahedron Lett.
1994, 35, 6611. (c) Galatsis, P.; Manwell, J . J . Tetrahedron Lett. 1995,
36, 8179.

5050 J . Org. Chem., Vol. 62, No. 15, 1997
Galatsis et al.
Ta ble 2. Resu lts of Sequ en ce on Im id e 11
entry
R
12 (% yield)a
% yielda (13/14 ratio)
1
2
3
4
Me (a )
Et (b)
64
70
72
64
70
63 (>98:<2)
84 (82:18)
40 (81:19)
20b
Ph (d )
a
Based on isolated, chromatographically pure material. b Reac-
tion product decomposed but appeared to be a single isomer.
formation of the oxetane is easily discerned via the
primary iodide moiety. The carbon of the primary iodide
is very diagnostic and appears between -24 ppm for
methyl iodide to about +10 ppm for alkyl iodides due to
the heavy atom effect.13 We have observed this same
chemical shift attribute in several of our other com-
pounds.10,14,15 The corresponding tetrahydrofuran would
contain a secondary iodide, which would show a carbon
shift significantly further downfield (ca. 20-40 ppm).
F igu r e 1.
F igu r e 2.
Ta ble 3. Resu lts of Sequ en ce on Im id e 15
entry
R
16 (% yield)a
17 (% yield)a
1
2
3
4
Me (a )
Et (b)
iPr (c)
Ph (d )
87
88
86
84
83
81
61
83
One can also note from Table 1 that excellent facial
selectivity was obtained in the cyclization step. The
relative stereochemistry was determined by NOE mea-
surements, while the absolute stereochemistry is as-
sumed to be that which one would expect to be induced
by the chiral auxiliary (the latter was shown to be true
in an other system by X-ray analysis, vide infra). The
inability to isolate products from the phenyl derivative
in the analogous methyl ester series was also observed
in our earlier work.10 Since phenyl products can be
obtained in other systems (see Table 2 and our previous
work10), this would tend to indicate that the phenyl ring
does not perturb the cyclization chemistry. However, the
phenyl substituent, in this system, may render the
product less stable, thus giving rise to decomposition
products. Figure 1 shows the potential transition struc-
tures for the observed products. The structure leading
to the major product experiences an A1,3 strain between
the vinyl hydrogen and the imide group. This interaction
is absent in the transition structure leading to the minor
product; however, there appears be a 1,3-transannular
interaction between the iodomethyl and R groups in the
developing oxetane ring. This nonbonding interaction
may override the allylic strain, giving rise to the observed
product. This is substantiated by the fact that as the R
group becomes more sterically demanding one observed
a
Based on isolated, chromatographically pure material.
increased selectivity in the cyclization (see Table 1).
These results indicated that the sequence could be carried
out using the chiral auxiliary, so we proceeded to examine
other substrates.
We next constructed 11 by coupling the chiral imide
and 3,3-dimethylacrylic acid. Exposure of 11 to the two-
step sequence gave the oxetanes 13 and 14 by way of
aldol 12. The results for this series are summarized in
Table 2. The aldol reaction gave exclusively the R-alkyl-
ated deconjugated product with excellent enantiocontrol.
The control observed in our earlier work with the methyl
esters eroded in the cyclizations of 12.10b While 12a
cyclized with complete control, and in improved yield, to
the corresponding oxetane, 12b and 12c exhibited aver-
age stereocontrol in the cyclization step. Unexpectedly,
12d proved to be problematic, and the inability to isolate
a stable product was contrary to our previous efforts.10b
In this last case, the poor yield could be partly rational-
ized by the fact this compound tended to undergo a retro-
aldol reaction, as judged by the formation of benzalde-
hyde in the reaction. The relative stereochemistry (see
Figure 2) of the major product could still be rationalized
on steric grounds using a transition state based on
similar arguments as before.
(13) (a) Evans, R. D.; Magee, J . W.; Schauble, J . H. Synthesis 1988,
862. (b) Pretsch, E.; Clerc, K.; Seibl, J .; Simon, W. Spectral Data For
Structure Determination Of Organic Compounds, 2nd ed.; Springer-
Verlag: Berlin, 1989. (c) Silverstein, R. M.; Bassler, G.C.; Morrill, T.
C. Spectrometric Identification Of Organic Compounds, 5th ed.; J ohn
Wiley & Sons, Inc.: New York, 1991.
In a series related to 11, 15 was subjected to the same
sequence of steps to produce 17 by way of 16 (see Table
3). The aldol reaction proceeded in excellent yield with
(14) (a) Galatsis, P.; Millan, S. D. Tetrahedron Lett. 1991, 32, 7493.
(b) Galatsis, P.; Millan, S. D.; Faber, T. J . Org. Chem. 1993, 58, 1215.
(15) In compounds 14a , 13/14c, and 13d , the shift of the primary
iodide carbon comes at about 14 ppm. This downfield shift can easily
be rationalized if one considers the fact that for these compounds this
carbon is also neopentyl. The “â-effect” due to the additional methyl
substituent is sufficient to cause the observed change in chemical shift
(∼6 ppm).13 This value is still far removed from where we have been
observing THF iodide shifts (20-30 ppm).

Enantioselective Construction of Cyclic Ethers
J . Org. Chem., Vol. 62, No. 15, 1997 5051
so, then cyclization of pure 19 should give rise to 20 with
excellent enantiocontrol. The origin of this loss of olefin
geometry is currently under scrutiny, and preliminary
results have been published.16
Con clu sion s
We have demonstrated that the deconjugative aldol-
cyclization sequence can be extended by the use of chiral
auxiliaries for the construction of optically active prod-
ucts. Oxetanes and fused ring tetrahydrofurans can
easily be assembled with a variety of substitution pat-
terns with excellent enantiocontrol. The deconjugation
of chiral pentenimides resulted in the loss of control of
olefin geometry. However, these compounds did appear
to cyclize with excellent enantiocontrol.
Exp er im en ta l Section
F igu r e 3. X-ray structure of 17a .
Gen er a l P r oced u r es a n d Ma ter ia ls. Melting points were
taken on a Fischer-J ohns melting point apparatus and are
uncorrected. 1H and 13C NMR spectra were recorded in CDCl3
at 400 and 100 MHz, respectively, unless specified otherwise.
Combustion analyses were performed by M-H-W Laboratories,
Phoenix, AZ. All solvents used for chromatography were
distilled prior to use. Reactions were monitored by TLC using
E. Merck precoated silica gel 60 F-250 (0.25 mm thickness)
aluminum-backed plates. The plates were visualized by
immersion in p-anisaldehyde solution and warming on a
hotplate. E. Merck silica gel 60 (70-230 mesh) was used for
column chromatography. All solvents were reagent grade, and
anhydrous solvents were dried prior to use as follows: CH2-
Cl2 was distilled from CaH2, while ether and THF were
distilled from benzophenone ketyl. Compounds obtained from
commercial sources were used directly as received.
Gen er a l P r otocol for Asym m etr ic Ald ol Rea ction s. To
a -78 °C solution of the imide in dry dichloromethane (4 mL/
mmol) was added dibutylboryl triflate (1.2 equiv) and stirred
for 5 min. The solution was then treated with dry triethyl-
amine (1.4 equiv). After 1 h at -78 °C and 15 min at 0 °C,
the solution was recooled to -78 °C and treated with the
appropriate aldehyde (1-1.4 equiv). After 1 h at -78 °C and
1 h at 0 °C, the solution was partitioned between 30 mL each
of 1 M sodium bisulfate and ethyl acetate/hexanes (1:1). The
organic layer was washed with brine and concentrated in
vacuo. The resulting oil was redissolved in ether (5 mL), cooled
to 0 °C, and treated with 1 mL each of pH 7 phosphate buffer
and 30% hydrogen peroxide. After being stirred for 1 h at 0
°C, the reaction mixture was poured into water (25 mL) and
ethyl acetate/hexanes (1:1) (25 mL), extracted with ether (3×),
washed once with saturated sodium bicarbonate, dried (an-
hydrous sodium sulfate), filtered, and concentrated in vacuo.
Compounds 7 and 8a -d have been previously prepared,11a
but to our knowledge the optical rotations for 8 have not been
reported. The optical rotations we obtained for these com-
pounds were as follows. (2′S,3′R,4S)-3-(2′-Eth en yl-3′-h y-
d r oxy-1′-oxobu tyl)-4-(m eth yleth yl)-2-oxa zolid in on e (8a ):
[R]D ) -8.9° (c 0.247, CHCl3). (2′S,3′R,4S)-3-(2′-Eth en yl-3′-
h yd r oxy-1′-oxop en t yl)-4-(m et h ylet h yl)-2-oxa zolid in on e
(8b): [R]D ) -13.1° (c 0.420, CHCl3). (2′S,3′R,4S)-3-(2′-
Eth en yl-3′-h ydr oxy-4′-m eth yl-1′-oxobu tyl)-4-(m eth yleth yl)-
2-oxa zolid in on e (8c): [R]D ) -17.3° (c 0.486, CHCl3).
(2′S,3′R,4S)-3-(2′-Eth en yl-3′-h yd r oxy-1′-oxobu tyl-3′-p h en -
yl)-4-(m eth yleth yl)-2-oxa zolid in on e (8d ): [R]D ) -19.6° (c
0.224, CHCl3).
Ta ble 4. Resu lts of Sequ en ce on Im id e 18
entry
R
19 (% yield) (Z:E)a
20 (% yield)a
1
2
3
4
Me (a )
Et (b)
iPr (c)
Ph (d )
98 (70:30)
70 (69:31)
81 (69:31)
84 (69:31)
74
77
81
63
a
Based on isolated, chromatographically pure material.
only one product being detected. Contrary to the situa-
tion with 11, the cyclizations proceeded in excellent yield
and with excellent stereocontrol. However, now the only
product formed was the fused-ring tetrahydrofuran. No
oxetane could be isolated. This structural assignment
constitutes a correction of our initially published work
on the methyl ester derivative.10b A similar occurrence
was experienced by workers in related work.9j The initial
NOE measurements lead us to the conclusion that a
spiro-oxetane system had resulted. Subsequently, we
have been able to obtain crystals of 17a , which unam-
biguously confirm the formation of the fused-ring system
(see Figure 3). This X-ray structure provided confirma-
tion of the absolute stereochemistry in addition to the
stereochemistry generated in the aldol step. The pre-
dicted syn aldol diastereomer would give rise to the
observed tetrahydrofuran stereochemistry.
The final series investigated was (E)-pentenimide 18.
While the aldol reaction proceeded in good to excellent
yield with only one aldol isomer being isolated, loss of
double bond geometry was now witnessed (see Table 4)
with (Z)-19 as the major isomer isolated. In all the other
systems, we always had observed complete inversion of
double bond geometry in these deconjugative aldol reac-
tions, including the methyl ester derivative of 18.10a
Gen er a l P r otocol for Iod oeth er ifica tion of r-Vin yl
â-Hyd r oxy Im id es 8a -d . To a solution containing dry
acetonitrile (5 mL), iodine (3.0 equiv), and sodium bicarbonate
(3.0 equiv) was added R-vinyl â-hydroxy imide 8. The mixture
was stirred for 24 h and then quenched with 0.2 M sodium
thiosulfate and extracted with ether (3×). The ether layer was
Attempts to equilibrate the olefinic mixture all failed.
Since this mixture could not be separated by chromatog-
raphy, it was subjected to the conditions for cyclization.
This resulted in the formation of 20 as a mixture of
diastereomers, the ratio of which matched the starting
olefinic ratio. Presumably, these two diastereomers were
formed from the two olefinic geometries in 19. If this is
(16) Galatsis, P.; Manwell, J . J .; Millan, S. D. Tetrahedron Lett.
1996, 37, 5261.

5052 J . Org. Chem., Vol. 62, No. 15, 1997
Galatsis et al.
washed once with brine, dried (anhydrous sodium sulfate),
filtered and concentrated in vacuo.
afforded 9c (113 mg, 38%) and 10c (6 mg, 2%). (2S,3S,4R)-
2-(Iod om eth yl)-4-(m eth yleth yl)-3-[[(4S)-4-(m eth yleth yl)-
2-oxa zolid in -3-yl]ca r bon yl]oxeta n e (9c): IR (CCl4) 2962,
2 934, 2879, 1785, 1713, 1470, 1426, 1392, 1354, 1313, 1287,
1253, 1212, 1172, 1122, 1067, 1044, 1024, 994, 966, 911, 865
Cycliza tion of 8a . The general procedure was followed
using iodine (3.93 mmol, 997 mg), sodium bicarbonate (3.93
mmol, 330 mg) and 8a (1.31 mmol, 300 mg). Chromatography
(20% ethyl acetate/80% hexanes) on 25 g of silica gel afforded
9a (202 mg, 43%) and 10a (18.5 mg, 4%, mp 131-132 °C).
(2S,3S,4R)-2-(Iod om et h yl)-4-m et h yl-3-[[(4S)-4-(m et h yl-
eth yl)-2-oxa zolid in -3-yl]ca r bon yl]oxeta n e (9a ): IR (CCl4)-
2968, 2931, 2901, 2876, 1791, 1759, 1710, 1484, 1470, 1420,
1386, 1354, 1339, 1310, 1252, 1215, 1177, 1134, 1067, 1038,
cm-1 1H NMR δ 4.57 (ddd, 1H, J ) 10.0, 5.6, 1.2 Hz), 4.23
;
(AB portion of an ABX, 2H, J ab ) 9.2 Hz, J ax ) 7.2 Hz, J bx
)
3.6 Hz, ∆νab ) 41.4 Hz), 4.03 (ddd, 1H, J ) 6.8, 4.8, 3.2 Hz),
3.80 (d, 1H, J ) 9.6 Hz), 3.23 (brs, 1H), 3.18 (dd, 1H, J ) 10.4,
5.6 Hz), 2.97 (dd, 1H, J ) 10.0, 10.0 Hz), 2.27 (m, 1H), 2.07
(m, 1H), 1.10 (d, 3H, J ) 6.8 Hz), 0.95 (d, 3H, J ) 6.4 Hz),
0.94 (d, 3H, J ) 6.4Hz), 0.93 (d, 3H, J ) 6.4 Hz); 13C NMR δ
166.8, 119.6, 82.5, 72.2, 69.5, 58.9, 44.7, 30.1, 29.3, 19.7, 18.6,
18.3, 16.9, 3.8; HRMS exact mass for C14H22INO4 (M - I) calcd
268.1549, found 268.1538; [R]D ) +23.5° (c 0.340, CHCl3).
(2R,3S,4R)-2-(Iod om eth yl)-4-(m eth yleth yl)-3-[[(4S)-4-(m e-
th yleth yl)-2-oxa zolid in -3-yl]ca r bon yl] oxeta n e (10c): IR
(CCl4) 2964, 2930, 2877, 1785, 1742, 1695, 1487, 1470, 1389,
1368, 1339, 1302, 1281, 1232, 1203, 1125, 1099, 1070, 1047,
1
1021, 954, 911, 868 cm-1; H NMR δ 4.65 (ddd, 1H, J ) 8.8,
6.0, 1.6 Hz). 4.51 (q, 1H, J ) 6.4 Hz), 4.25 (AB portion of an
ABX, 2H, J ab ) 9.2 Hz, J ax ) 7.2 Hz, J bx ) 3.2 Hz, ∆νab ) 44.2
Hz), 4.05 (ddd, 1H, J ) 7.2, 5.2, 3.6 Hz), 3.19 (dd, 1H, J )
10.4, 6.0 Hz), 3.02 (dd, 1H, J ) 10.4, 8.8 Hz), 2.96 (m, 1H),
2.26 (m, 1H), 1.49 (d, 3H, J ) 6.8 Hz), 0.96 (d, 3H, J ) 6.0
Hz), 0.94 (d, 3H, J ) 6.0 Hz); 13C NMR δ 165.8, 120.0, 72.9,
71.6, 69.5, 58.7, 47.8, 30.1, 18.5, 17.1, 16.9, 3.6; HRMS exact
mass for C12H18IN04 (M - I) calcd 240.1236, found 240.1245;
[R]D ) +24.1° (c 0.216, CHCl3). (2R,3S,4R)-2-(Iod om eth yl)-
4-m et h yl-3-[[(4S)-4-(m et h ylet h yl)-2-oxa zolid in -3-yl]ca r -
bon yl]oxeta n e (10a ): IR (film) 2957, 2936, 2921, 2872, 1765,
1695, 1493, 1463, 1418, 1401, 1367, 1342, 1297, 1242, 1221,
1203, 1180, 1166, 1141, 1121, 1101, 1066, 1050, 1032, 988, 968,
870, 858, 809, 765, 728 cm-1; 1H NMR δ 4.92 (dt, 1H, J ) 8.0,
6.8 Hz), 4.77 (dq, 1H, J ) 6.8, 6.8 Hz), 4.48 (dt, 1H, J ) 8.0,
3.6 Hz), 4.28 (dd, 1H, J ) 6.8, 6.0 Hz), 4.26 (AB portion of an
ABX, 2H, J ab ) 8.8 Hz, J ax ) 8.8 Hz, J bx ) 3.6 Hz, ∆νab ) 28.0
Hz), 3.44 (AB portion of an ABX, 2H, J ab ) 9.6 Hz, J ax ) 6.0
Hz, J bx ) 8.0 Hz, ∆νab ) 31.4 Hz), 2.42 (m, 1H), 1.53 (d, 3H, J
) 6.4 Hz), 0.93 (d, 3H, J ) 6.8 Hz), 0.89 (d, 3H, J ) 6.8 Hz);
13C NMR δ 169.7, 153.8, 77.5, 75.5, 63.5, 58.4, 51.3, 28.2, 23.6,
17.9, 14.8, 10.1; HRMS exact mass for C12H18INO4 (M - I)
calcd 240.1236, found 240.1234; [R]D ) +24.1° (c 0.384, CHCl3).
Cycliza tion of 8b. The general procedure was followed
using iodine (2.59 mmol, 656 mg), sodium bicarbonate (2.59
mmol, 217 mg), and 8b (0.862 mmol, 220 mg). Chromatog-
raphy (20% ethyl acetate/80% hexanes) on 25 g of silica gel
afforded 9b (108 mg, 33%, mp 106-107 °C) and 10b (50 mg,
15%, mp 92-93 °C). Both compounds were recrystallized from
hexanes-ethyl acetate (2:1). (2S,3S,4R)-4-E t h yl-2-(iod o-
m eth yl)-3-[[(4S)-4-(m eth yleth yl)-2-oxa zolid in -3-yl]ca r bo-
n yl]oxeta n e (9b): IR (film) 2969, 2938, 2896, 2875, 1707,
1487, 1448, 1420, 1392, 1362, 1353, 1328, 1316, 1283, 1239,
1214, 1190, 1177, 1119, 1084, 1056, 1047, 1019, 994, 971, 957,
910, 897, 887, 859, 797, 781, 753, 707, 665, 646, 623 cm-1; 1H
NMR δ 4.59 (ddd, 1H, J ) 8.8, 5.6, 1.2 Hz), 4.23 (AB portion
of an ABX, 2H, J ab ) 9.2 Hz, J ax ) 7.2 Hz, J bx ) 3.6 Hz, ∆νab
) 10.4 Hz), 4.21 (t, 1H, J ) 7.2 Hz), 4.03 (ddd, 1H, J ) 7.6,
5.6, 3.6 Hz), 3.18 (dd, 1H, J ) 10.0, 5.6 Hz), 3.06 (brs, 1H),
2.99 (dd, 1H, J ) 10.0, 8.8 Hz), 2.26 (m, 1H), 1.96 (m, 1H),
1.69 (m, 1H), 1.01 (t, 3H, J ) 7.6 Hz), 0.95 (d, 3H, J ) 6.4
Hz), 0.93 (d, 3H, J ) 7.6 Hz); 13C NMR δ 165.7, 119.6, 78.2,
72.0, 69.5, 58.8, 45.9, 30.1, 24.3, 18.5, 16.9, 9.8, 3.7; HRMS
exact mass for C13H20INO4 (M - 1) calcd 254.1397, found
254.1400; [R]D ) +29.4° (c 0.384, CHCl3). (2R,3S,4R)-4-Eth yl-
2-(iodom eth yl)-3-[[(4S)-4-(m eth yleth yl)-2-oxazolidin -3-yl]-
ca r bon yl]oxeta n e (10b): IR (film) 2958, 2941, 2885, 1769,
1695, 1494, 1473, 1451, 1423, 1402, 1378, 1337, 1310, 1293,
1231, 1201, 1166, 1141, 1057, 1038, 968, 938, 894, 867, 818,
1
983, 917, 868, 720 cm-1; H NMR δ 4.78 (dt, 1H, J ) 7.6, 6.8
Hz), 4.50 (m, 2H), 4.43 (t, 1H, J ) 7.6 Hz), 4.26 (AB portion of
an ABX, 2H, J ab ) 9.2 Hz, J ax ) 9.2 Hz, J bx ) 3.6 Hz, ∆νab
)
24.0 Hz), 3.43 (AB portion of an ABX, 2H, J ab ) 10.0 Hz, J ax
) 6.4 Hz, J bx ) 7.6 Hz, ∆νab ) 14.6 Hz), 2.42 (m, 1H), 1.94 (m,
1H), 0.96 (d, 3H, J ) 6.8 Hz), 0.94 (d, 3H, J ) 6.8 Hz), 0.90 (d,
3H, J ) 6.8 Hz), 0.84 (d, 3H, J ) 6.8 Hz); 13C NMR δ 170.3,
153.7, 83.1, 78.4, 63.4, 58.6, 47.2, 33.8, 28.3, 18.0, 16.7, 16.1,
14.9, 9.6; HRMS exact mass for C14H22INO4 (M - I) calcd
268.1549, found 268.1540; [R]D ) +64.8° (c 0.650, CHCl3).
(4S)-3-(3′-Meth yl-1′-oxo-2′-bu ten yl)-4-(1-m eth yleth yl)-
2-oxa zolid in on e (11). To a solution containing dry tetrahy-
drofuran (50 mL) and the oxazolidinone at -78 °C was added
n-butyllithium (12.2 mmol, 4.9 mL, 2.5 M in hexanes) dropwise
via syringe. After being stirred for 1 h, freshly distilled 3,3-
dimethylacryloyl chloride (12.2 mmol, 1.45 g) was added via
syringe. The yellow solution was stirred at -78 °C for 45 min
and then warmed to room temperature and quenched with
saturated ammonium chloride solution. The bulk of the
tetrahydrofuran was stripped off under vacuum and the
resulting solution poured into water and extracted with ether
(3×). The combined organic layers were washed once with 15%
sodium hydroxide, once with brine, dried (anhydrous sodium
sulfate), filtered, and concentrated in vacuo. Chromatography
(20% ethyl acetate/80% hexanes) on 45 g of silica gel afforded
a white solid. Recrystallization from hexanes afforded 11 (1.90
g, 88%, mp 38-39 °C): IR (film) 3098, 2966, 2932, 2882, 1775,
1682, 1632, 1489, 1391, 1365, 1302, 1255, 1211, 1185, 1144,
1123, 1102, 1084, 1055, 1027, 1006, 980, 928, 858, 777, 756,
720 cm-1
;
1H NMR δ 6.94 (s,1H), 4.47 (dt, 1H, J ) 8.8, 3.6
Hz), 4.20 (AB portion of an ABX, 2H, J ab ) 8.4 Hz, J ax ) 8.4
Hz, J bx ) 3.2 Hz, ∆νab ) 27.4 Hz), 2.38 (m, 1H), 2.16 (d, 3H, J
) 1.2 Hz), 1.97 (d, 3H, J ) 1.2 Hz), 0.91 (d, 3H, J ) 6.8 Hz),
0.87 (d, 3H, J ) 6.8 Hz); 13C NMR δ 165.0, 159.0, 154.0, 115.8,
63.1, 58.3, 28.5, 28.0, 21.3, 18.0, 14.7; [R]D ) +91.7° (c 0.504,
CHCl3). Anal. Calcd for C11H17NO3: C, 62.54; H, 8.07.
Found: C, 62.66; H, 8.11.
(2′S,3′R,4S)-3-(3′-H yd r oxy-2′-(1-m et h ylet h en yl)-1′-ox-
obu tyl)-4-(m eth yleth yl)-2-oxa zolid in on e (12a ). The gen-
eral protocol for the asymmetric aldol reaction was followed
using imide 11 (1.42 mmol, 300 mg), dibutylboryl triflate (1.70
mmol, 0.47 mL), triethylamine (1.99 mmol, 0.28 mL), and
acetaldehyde (1.99 mmol, 0.16 mL). Chromatography (25%
ethyl acetate/75% hexanes) on 25 g of silica gel afforded 12a
(254 mg, 70%): IR (film) 3518, 3092, 2971, 2933, 2879, 1780,
1691, 1642, 1492, 1457, 1370, 1303, 1209, 1109, 1063, 1026,
1
772, 721, 693 cm-1; H NMR δ 4.89 (dt, 1H, J ) 8.0, 6.0 Hz),
4.62 (q, 1H, J ) 6.0 Hz), 4.48 (dt, 1H, J ) 8.0, 3.6 Hz), 4.38 (t,
1H, J ) 6.0 Hz), 4.26 (AB portion of an ABX, 2H, J ab ) 9.2
Hz, J ax ) 9.2 Hz, J bx ) 4.0 Hz, ∆νab ) 25.6 Hz), 3.43 (AB
portion of an ABX, 2H, J ab ) 10.0 Hz, J ax ) 6.0 Hz, J bx ) 7.6
Hz, ∆νab ) 24.8 Hz), 2.43 (m, 1H), 1.88-1.74 (m, 2H), 0.93 (d,
3H, J ) 7.2 Hz), 0.92 (t, 3H, J ) 7.2 Hz), 0.89 (d, 3H, J ) 6.4
Hz); 13C NMR δ 170.0, 153.8, 79.8, 78.1, 63.5, 58.5, 49.0, 29.9,
28.2, 17.9, 14.8, 9.8, 8.1; HRMS exact mass for C13H20INO4
(M - I) calcd 254.1392, found 254.1397; [R]D ) +67.5° (c 0.114,
CHCl3).
1
977, 937, 902, 859, 786, 757, 727 cm-1; H NMR δ 5.12 (brs,
1H), 5.04 (s, 1H), 4.48 (dt, 1H, J ) 8.4, 3.2 Hz), 4.45 (d, 1H, J
) 6.4 Hz), 4.26 (m, 2H), 4.20 (dd, 1H, J ) 9.2, 3.6 Hz), 2.63
(brs, 1H), 2.30 (m, 1H), 1.90 (s, 3H), 1.22 (d, 3H, J ) 6.4 Hz),
0.90 (d, 3H, J ) 7.6 Hz), 0.81 (d, 3H, J ) 6.8 Hz); 13C NMR δ
173.9, 153.3, 139.6, 117.4, 67.0, 62.9, 58.0, 56.5, 28.1, 22.3, 20.7,
17.9, 14.3; HRMS exact mass for C13H21NO4 (M - MeCHO)
calcd 211.1208, found 211.1154; [R]D ) -30.8° (c 0.312, CHCl3).
(2′S,3R,4S)-3-(3′-Hyd r oxy-2′-(1-m eth yleth en yl)-1′-oxo-
p en tyl)-4-(m eth yleth yl)-2-oxa zolid in on e (12b). The gen-
eral protocol for the asymmetric aldol reaction was followed
Cycliza t ion of 8c. The general procedure was followed
using iodine (2.23 mmol, 565 mg), sodium bicarbonate (2.23
mmol, 187 mg), and 8c (0.743 mmol, 200 mg). Chromatogra-
phy (20% ethyl acetate/80% hexanes) on 25 g of silica gel

Enantioselective Construction of Cyclic Ethers
J . Org. Chem., Vol. 62, No. 15, 1997 5053
using imide 11 (1.42 mmol, 300 mg), dibutylboryl triflate (1.70
mmol, 0.47 mL), triethylamine (1.99 mmol, 0.28 mL), and
propanal (1.99 mmol, 0.20 mL). Chromatography (20% ethyl
acetate/80% hexanes) on 25 g of silica gel afforded 12b (201
mg, 72%): IR (film) 3521, 3088, 2967, 2936, 2882, 1783, 1695,
1643, 1487, 1466, 1389, 1370, 1302, 1204, 1149, 1124, 1062,
3.2 Hz, ∆νab ) 22.2 Hz), 4.22 (d, 1H, J ) 6.8 Hz), 3.75 (ABq,
2H, J ab ) 10.4 Hz, ∆νab ) 7.5 Hz), 2.40 (m, 1H), 1.45 (s, 3H),
1.44 (d, 3H, J ) 6.0 Hz), 0.94 (d, 3H, J ) 6.8 Hz), 0.88 (d, 3H,
J ) 6.8 Hz); 13C NMR δ 168.5, 154.0, 80.0, 70.6, 63.8, 58.7,
52.3, 28.4, 22.8, 22.4, 20.6, 18.0, 14.7; HRMS exact mass for
C13H20INO4 (M - I) calcd 254.1392, found 254.1394; [R]D
)
1026, 982, 906, 859, 775, 753, 726 cm-1 1H NMR δ 5.12 (t,
;
+53.2° (c 0.438, CHCl3).
1H, J ) 1.2 Hz), 5.04 (s, 1H), 4.54 (d, 1H, J ) 6.4 Hz), 4.49
(dt, 1H, J ) 8.8, 3.2 Hz), 4.24 (AB portion of an ABX, 2H, J ab
) 8.8 Hz, J ax ) 8.8 Hz, J bx ) 3.2 Hz, ∆νab ) 29.8 Hz), 4.00 (m,
1H), 2.68 (m, 1H), 2.31 (dsept, 1H, J ) 7.2, 4.0 Hz), 1.90 (brs,
3H), 1.52 (m, 2H), 1.00 (t, 3H, J ) 7.4 Hz), 0.91 (d, 3H, J )
7.2 Hz), 0.82 (d, 3H, J ) 7.2 Hz); 13C NMR δ 173.2, 153.3,
139.6, 117.2, 72.2, 62.8, 58.0, 54.7, 28.0, 27.7, 22.4, 17.9, 14.3,
10.3; HRMS exact mass for C14H23NO4 (M - H2O) calcd
251.1521, found 251.1518; [R]D ) -34.2° (c 0.424, CHCl3).
(2′S,3′R,4S)-3-(3′-Hydr oxy-2′-(1-m eth yleth en yl)-4′-m eth -
yl-1′-oxop en t yl)-4-(m et h ylet h yl)-2-oxa zolid in on e (12c).
The general protocol for the asymmetric aldol reaction was
followed using imide 11 (0.946 mmol, 200 mg), dibutylboryl
triflate (1.14 mmol, 0.29 mL), triethylamine (1.33 mmol, 0.19
mL), and isobutyraldehyde (1.33 mmol, 0.12 mL). Chroma-
tography (20% ethyl acetate/80% hexanes) on 25 g of silica gel
afforded 12c (172 mg, 64%): IR (film) 3537, 3090, 2975, 2934,
2877, 1781, 1693, 1639, 1495, 1470, 1374, 1199, 1108, 1007,
Cycliza tion of 12b. The general protocol was followed
using iodine (1.67 mmol, 424 mg), sodium bicarbonate (1.67
mmol, 140 mg), and 12b (0.557 mmol, 150 mg) for 13 h.
Chromatography (25% ethyl acetate/75% hexanes) on 25 g of
silica gel afforded two inseparable isomers 13b and 14b (4.6:
1) (184 mg, 84%). (3S,4R)-4-Eth yl-2-(iod om eth yl)-2-m eth -
yl-3-[[(4S)-4-(m et h ylet h yl)-2-oxa zolid in -3-yl]ca r b on yl]-
oxeta n e (13b, 14b): IR (film) 2973, 2932, 2881, 1787, 1738,
1695, 1490, 1467, 1389, 1366, 1306, 1214, 1121, 1061, 1041,
983, 946, 871, 781, 756, 721 cm-1; 1H NMR δ 4.94 (dt, 1H, J )
7.2, 7.2 Hz), 4.88 (dt, 1H, J ) 6.8, 6.8 Hz), 4.45 (dt, 1H, J )
8.4, 3.2 Hz), 4.41 (dt, 1H, J ) 8.0, 3.2 Hz), 4.28 (AB portion of
an ABX, 2H, J ab ) 9.2 Hz, J ax ) 9.2 Hz, J bx ) 2.8 Hz, ∆νab
)
25.0 Hz), 4.32-4.24 (m, 3H), 4.21 (d, 1H, J ) 6.8 Hz), 3.74
(ABq, 2H, J ab ) 10.8 Hz, ∆νab ) 16.2 Hz), 3.47 (ABq, 2H, J ab
) 9.6 Hz, ∆νab ) 38.7 Hz), 2.52-2.36 (m, 2H), 1.92-1.76 (m,
2H), 1.77 (s, 3H), 1.76-1.62 (m, 2H), 1.47 (s, 3H), 0.95 (d, 3H,
J ) 7.2 Hz), 0.94 (d, 3H, J ) 6.8 Hz), 0.92-0.85 (m, 12H); 13
C
978, 908, 860, 789, 753, 721, 648 cm-1
;
1H NMR δ 5.10 (m,
NMR δ 169.1, 168.6, 154.0, 153.9, 80.7, 80.2, 76.2, 75.2, 63.8,
63.6, 59.1, 58.7, 50.5, 50.0, 29.6, 29.6, 29.3, 28.4, 28.2, 22.9,
20.4, 18.2, 18.0, 15.0, 14.7, 12.7, 8.3, 8.2; HRMS exact mass
for C14H22INO4 (M - I) calcd 268.1549, found 268.1546.
Cycliza tion of 12c. The general protocol was followed
using iodine (1.16 mmol, 298 mg), sodium bicarbonate (1.16
mmol, 98 mg), and 12c (0.388 mmol, 110 mg) for 14 h.
Chromatography (25% ethyl acetate/75% hexanes) on 25 g of
silica gel afforded a mixture of two inseparable isomers 13c
and 14c (5.2:1) (119 mg, 75%). (3S,4R)-2-(Iod om eth yl)-2-
m eth yl-4-(m eth yleth yl)-3-[[(4S)-4-(m eth yleth yl)-2-oxa zo-
lid in -3-yl]ca r bon yl]oxeta n e (13c, 14c): IR (film) 2965,
2930, 2873, 1782, 1735, 1691, 1491, 1467, 1392, 1367, 1300,
1H), 5.09 (brs, 1H), 4.76 (d, 1H, J ) 7.2 Hz), 4.47 (dt, 1H, J )
8.8, 3.2 Hz), 4.24 (AB portion of an ABX, 2H, J ab ) 9.2 Hz, J ax
) 9.2 Hz, J bx ) 2.8 Hz, ∆νab ) 31.6 Hz), 3.86 (m, 1H), 2.35 (d,
1H, J ) 3.6 Hz), 2.29 (dsept, 1H, J ) 7.2, 4.0 Hz), 1.87 (brs,
3H), 1.70 (m, 1H), 0.97 (d, 3H, J ) 7.2 Hz), 0.93 (d, 3H, J )
6.4 Hz), 0.88 (d, 3H, J ) 6.8 Hz), 0.80 (d, 3H, J ) 7.2 Hz); 13
C
NMR δ 172.8, 153.3, 140.1, 117.6, 75.2, 62.8, 58.0, 52.6, 30.9,
28.0, 21.8, 19.9, 17.8, 16.7, 14.3; HRMS exact mass for C15H25
-
NO4 (M - iPrCHO) calcd 211.1208, found 211.1171; [R]D
-28.3° (c 0.805, CHCl3).
)
(2′S,3′S,4S)-3-[3′-Hyd r oxy-1′-oxo-(3′-m eth ylbu ten yl)-3′-
p h en yl]-4-(m eth yleth yl)-2-oxa zolid in on e (12d ). The gen-
eral protocol for the asymmetric aldol reaction was followed
using imide 11 (1.42 mmol, 300 mg), dibutylboryl triflate (1.70
mmol, 0.47 mL), triethylamine (1.99 mmol, 0.28 mL), and
benzaldehyde (1.43 mmol, 0.15 mL). Chromatography (25%
ethyl acetate/75% hexanes) on 25 g of silica gel afforded a white
solid that was recrystallized from hexanes to give 12d (315
mg, 70%, mp 95-96 °C): IR (film) 3507, 3088, 3063, 3034,
2970, 2927, 2880, 1783, 1697, 1643, 1488, 1457, 1391, 1374,
1305, 1205, 1145, 1105, 1068, 1028, 979, 910, 862, 787, 764,
1276, 1212, 1223, 1093, 1054, 990, 874, 783, 752, 719 cm-1
;
1H NMR δ 4.63 (dd, 1H, J ) 8.8, 7.2 Hz), 4.60 (dd, 1H, J )
8.4, 7.6 Hz), 4.46 (dt, 1H, J ) 8.4, 3.2 Hz), 4.43 (dt, 1H, J )
7.6, 3.6 Hz), 4.39 (d, 1H, J ) 7.2 Hz), 4.35-4.24 (m, 2H), 4.29
(AB portion of an ABX, 2H, J ab ) 9.2 Hz, J ax ) 9.2 Hz, J bx
)
3.2 Hz, ∆νab ) 26.6 Hz), 4.24 (d, 1H, J ) 6.8 Hz), 3.73 (ABq,
2H, J ab ) 10.4 Hz, ∆νab ) 18.1 Hz), 3.49 (ABq, 2H, J ab ) 9.6
Hz, ∆νab ) 15.3 Hz), 2.50 (m, 1H), 2.41 (m, 1H), 2.00 (m, 1H),
1.89 (m, 1H), 1.76 (s, 3H), 1.47 (s, 3H), 0.96 (d, 3H, J ) 6.4
Hz), 0.95 (d, 3H, J ) 7.2 Hz), 0.95-0.93 (m, 9H), 0.89 (d, 3H,
J ) 7.2 Hz), 0.79 (d, 3H, J ) 6.4 Hz), 0.77 (d, 3H, J ) 6.8 Hz);
13C NMR δ 169.2, 168.7, 154.0, 153.8, 80.3, 80.1, 79.7, 78.9,
63.7, 63.6, 59.2, 58.8, 49.3, 48.6, 34.0, 33.8, 29.3, 28.4, 28.1,
22.9, 20.1, 18.3, 18.1, 17.4, 17.3, 16.2, 16.1, 15.0, 14.7, 12.4;
HRMS exact mass for C15H24INO4 (M - I) calcd 282.1705,
found 282.1692.
Cycliza tion of 12d . The general protocol was followed
using iodine (1.89 mmol, 480 mg), sodium bicarbonate (1.89
mmol, 159 mg), and 12d (0.630 mmol, 200 mg) for 48 h.
Chromatography (25% ethyl acetate/75% hexanes) on 25 g of
silica gel afforded 13d (56 mg, 20%). (3S,4S)-2-(Iod om eth yl)-
2-m eth yl-4-p h en yl-3-[[(4S)-4-(m eth yleth yl)-2-oxa zolid in -
3-yl]ca r b on yl]oxet a n e (13d ): IR (film) 3086, 3065, 3032,
2968, 2928, 2876, 1780, 1696, 1486, 1451, 1388, 1351, 1304,
1272, 1209, 1181, 1144, 1123, 1102, 1039, 995, 913, 874, 815,
757, 736, 701 cm-1; 1H NMR δ 7.42-7.28 (m, 5H), 6.10 (d, 1H,
J ) 7.2 Hz), 4.48 (dt, 1H, J ) 8.0, 3.2 Hz), 4.37 (d, 1H, J ) 7.6
Hz), 4.28 (AB portion of an ABX, 2H, J ab ) 9.2 Hz, J ax ) 9.2
Hz, J bx ) 3.2 Hz, ∆νab ) 18.0 Hz), 3.84 (ABq, 2H, J ab ) 10.8
Hz, ∆νab ) 31.0 Hz), 2.46 (m, 1H), 1.58 (s, 3H), 0.97 (d, 3H, J
) 6.8 Hz), 0.92 (d, 3H, J ) 6.8 Hz); 13C NMR δ 168.1, 153.9,
141.3, 128.6, 128.0, 125.0, 80.7, 74.2, 63.9, 58.9, 53.9, 28.5, 23.0,
19.6, 18.1, 14.7; HRMS exact mass for C17H22INO4 (M - I)
calcd 316.1549, found 316.1538.
1
704, 627 cm-1; H NMR δ 7.43-7.38 (m, 2H), 7.35-7.24 (m,
3H), 5.16 (m, 2H), 5.14 (d, 1H, J ) 2.4 Hz), 4.96 (d, 1H, J )
8.0 Hz), 4.21 (dt, 1H, J ) 8.8, 3.2 Hz), 4.02 (AB portion of an
ABX, 2H, J ab ) 9.2 Hz, J ax ) 2.8 Hz, J bx ) 8.8 Hz, ∆νab ) 40.6
Hz), 2.76 (d, 1H, J ) 2.4 Hz), 2.25 (dsept, 1H, J ) 6.8, 3.6
Hz), 1.80 (s, 3H), 0.85 (d, 3H, J ) 6.8 Hz), 0.78 (d, 3H, J )
7.2); 13C NMR δ 171.8, 153.2, 141.3, 139.8, 128.3, 127.9, 126.8,
117.3, 73.2, 62.9, 58.1, 57.2, 28.2, 21.8, 17.9, 14.5. Anal. Calcd
for C18H23NO4: C, 68.12; H, 7.30. Found C, 68.20; H, 7.13;
[R]D ) -48.3° (c 0.352, CHCl3).
Gen er a l P r otocol for Iod oeth er ifica tion of r-P r op en yl
â-Hyd r oxy Im id es 12a -d . To a solution containing dry
acetonitrile (5 mL), iodine (3.0 equiv), and sodium bicarbonate
(3.0 equiv) was added R-propenyl â-hydroxy imide 12. The
mixture was stirred for 12-48 h and then quenched with 0.2
M sodium thiosulfate solution and extracted with ether (3×).
The ether layer was washed once with brine, dried (anhydrous
sodium sulfate), filtered, and concentrated in vacuo.
Cycliza tion of 12a . The general protocol was followed
using iodine (2.07 mmol, 525 mg), sodium bicarbonate (2.07
mmol, 174 mg), and 12a (0.689 mmol, 176 mg) for 12 h.
Chromatography (25% ethyl acetate/75% hexanes) on 25 g of
silica gel afforded 14a (166 mg, 63%). (2R,3S,4R)-2,4-Di-
m eth yl-2-(iod om eth yl)-3-[[(4S)-4-(m eth yleth yl)-2-oxa zo-
lid in -3-yl]ca r bon yl]oxeta n e (14a ): IR (film) 2972, 2929,
2874, 1785, 1739, 1692, 1490, 1542, 1392, 1340, 1206, 1122,
(4S)-3-(1′-Oxo-2′-cyclopen ten yleth yl)-4-(1-m eth yleth yl)-
2-oxa zolid in on e (15). To a solution containing dry tetrahy-
drofuran (40 mL) and the oxazolidinone at -78 °C was added
n-butyllithium (6.92 mmol, 2.7 mL, 2.5 M in hexanes) dropwise
1
1048, 982, 947, 920, 876, 786, 753, 720 cm-1; H NMR δ 5.17
(dq, 1H, J ) 6.0, 6.0 Hz), 4.44 (dt, 1H, J ) 8.0, 3.2 Hz), 4.27
(AB portion of an ABX, 2H, J ab ) 9.2 Hz, J ax ) 9.2 Hz, J bx
)

5054 J . Org. Chem., Vol. 62, No. 15, 1997
Galatsis et al.
via syringe. After 30 min of stirring, freshly distilled acid
chloride (6.92 mmol, 1.00 g) was added via syringe. The
solution was stirred at -78 °C for 30 min and then warmed
to room temperature and quenched with saturated ammonium
chloride solution. The bulk of the tetrahydrofuran was
stripped off under vacuum and the resulting solution poured
into water and extracted with ether (3×). The combined
organic layers were washed once with 15% sodium hydroxide
and brine, dried (anhydrous sodium sulfate), filtered, and
concentrated in vacuo. Chromatography (20% ethyl acetate/
80% hexanes) on 30 g of silica gel afforded a solid. Recrys-
tallization from hexanes afforded 15 (1.16 g, 85%, mp 54-55
°C): IR (film) 2966, 2876, 1781, 1678, 1634, 1490, 1453, 1380,
1306, 1249, 1202, 1065, 1041, 1005, 981, 951, 871, 760, 710
cm-1; 1H NMR δ 7.21 (brs, 1H), 4.48 (dt, 1H, J ) 8.8, 3.6 Hz),
4.21 (AB portion of an ABX, 2H, J ab ) 9.2 Hz, J ax ) 9.2 Hz,
J bx ) 3.6 Hz, ∆νab ) 25.0 Hz), 2.79 (m, 2H), 2.53 (brt, 2H, J )
7.6 Hz), 2.39 (m, 1H), 1.76 (m, 2H), 1.67 (m, 2H), 0.91 (d, 3H,
J ) 6.8 Hz), 0.87 (d, 3H, J ) 6.8 Hz); 13C NMR δ173.2, 164.8,
154.1, 110.8, 63.0, 58.3, 36.8, 33.9, 28.5, 26.4, 25.4, 18.0, 14.6;
[R]D ) +89.6° (c 1.29, CHCl3). Anal. Calcd for C13H19N03: C,
65.80; H, 8.07. Found: C, 65.61; H, 8.06.
(2′S,3′R,4S)-3-[2′-(1-Cyclop en t en yl)-3′-h yd r oxy-1′-ox-
obu tyl]-4-(m eth yleth yl)-2-oxa zolid in on e (16a ). The gen-
eral protocol for the asymmetric aldol reaction was followed
using imide 15 (1.26 mmol, 300 mg), dibutylboryl triflate (1.52
mmol, 0.38 mL), triethylamine (1.77 mmol, 0.25 mL), and
acetaldehyde (2.48 mmol, 0.14 mL). Chromatography (30%
ethyl acetate/70% hexanes) on 25 g of silica gel afforded 16a
(307 mg, 87%):. IR (film) 3516, 2972, 2927, 2876, 2848, 1782,
1694, 1495, 1466, 1370, 1304, 1200, 1145, 1100, 1062, 1020,
980, 951, 858, 797, 776. 715 cm-1; 1H NMR δ 5.75 (t, 1H, J )
1.6 Hz), 4.62 (d, 1H, J ) 5.2 Hz), 4.47 (dt, 1H, J ) 8.4, 3.2
Hz), 4.25-4.20 (m, 1H), 4.21 (AB portion of an ABX, 2H, J ab
) 9.2 Hz, J ax ) 9.2 Hz, J bx ) 3.2 Hz, ∆νab ) 32.0 Hz), 2.97 (s,
1H), 2.54 (m, 1H), 2.38-2.20 (m, 4H), 1.86 (m,2H), 1.17 (d,
3H, J ) 6.8 Hz), 0.88 (d, 3H, J ) 7.2 Hz), 0.78 (d, 3H, J ) 6.4
Hz); 13C NMR δ 173.7, 153.2, 137.4, 131.9, 67.0, 62.8, 57.9,
51.4, 34.9, 32.4, 27.9, 23.3, 20.5, 17.8, 14.2; HRMS exact mass
for C15H23NO4 (M - H2O) calcd 263.1521, found 263.1523; [R]D
) -30.3° (c 0.984, CHCl3).
(2′S,3′R,4S)-3-[2′-(1-Cyclop en ten yl)-3′-h yd r oxy-1′-oxo-
p en tyl]-4-(m eth yleth yl)-2-oxa zolid in on e (16b). The gen-
eral protocol for the asymmetric aldol reaction was followed
using imide 15 (1.26 mmol, 300 mg), dibutylboryl triflate (1.52
mmol, 0.38 mL), triethylamine (1.77 mmol, 0.25 mL), and
propanal (1.77 mmol, 0.13 mL). Chromatography (25% ethyl
acetate/75% hexanes) on 25 g of silica gel afforded 16b (328
mg, 88%): IR (film) 3528, 3055, 2966, 2934, 2878, 2848, 1786,
1695, 1489, 1467, 1374, 1305, 1201, 1104, 1060, 1030, 978, 780,
714 cm-1; 1H NMR δ 5.75 (t, 1H, J ) 2.0 Hz), 4.72 (d, 1H, J )
4.4 Hz), 4.49 (dt, 1H, J ) 8.4, 3.2 Hz), 4.23 (AB portion of an
ABX, 2H, J ab ) 9.2 Hz, J ax ) 9.2 Hz, J bx ) 3.6 Hz, ∆νab ) 31.2
Hz), 3.97 (m, 1H), 3.03 (d, 1H, J ) 2.0 Hz), 2.57 (m, 1H), 2.38-
2.22 (m, 4H), 1.95-1.75 (m, 2H), 1.49 (m, 2H), 0.98 (t, 3H, J
) 7.2 Hz), 0.90 (d, 3H, J ) 6.8 Hz), 0.79 (d, 3H, J ) 7.2 Hz);
13C NMR δ 174.0, 153.2, 137.5, 131.9, 72.4, 62.8, 58.0, 49.6,
34.9, 32.4, 28.0, 27.5, 23.4, 17.9, 14.2, 10.3; HRMS exact mass
for C16H25NO4 (M - H2O) calcd 277.1678, found 277.1669; [R]D
) -22.4° (c 0.348, CHCl3).
(2′S,3′R,4S)-3-[2′-(1-Cyclop en ten yl)-3′-h yd r oxy-4′-m eth -
yl-1′-oxop en t yl]-4-(m et h ylet h yl)-2-oxa zolid in on e (16c).
The general protocol for the asymmetric aldol reaction was
followed using imide 15 (1.26 mmol, 300 mg), dibutylboryl
triflate (1.52 mmol, 0.38 mL), triethylamine (1.77 mmol, 0.25
mL), and isobutyraldehyde (1.77 mmol, 0.16 mL). Chroma-
tography (25% ethyl acetate/75% hexanes) on 25 g of silica gel
afforded 16c (335 mg, 86%): IR (film) 3530, 3056, 2965, 2874,
2850, 1785, 1696, 1494, 1467, 1387, 1303, 1201, 1147, 1120,
1098, 1063, 1026, 1007, 975, 856, 829, 775, 716, 700 cm-1; 1H
NMR δ 5.80 (t, 1H, J ) 2.0 Hz), 4.96 (1H, J ) 5.2 Hz), 4.48
(dt, 1H, J ) 8.4, 3.6 Hz), 4.24 (AB portion of an ABX, 2H, J ab
) 9.2 Hz, J ax ) 9.2 Hz, J bx ) 2.8 Hz, ∆νab ) 32.4 Hz), 3.76
(ddd, 1H, J ) 6.8, 5.2, 2.4 Hz), 2.91 (d, 1H, J ) 2.8 Hz), 2.58
(m, 1H), 2.38-2.22 (m, 4H), 1.85 (m, 2H), 1.68 (m, 1H), 0.97
(d, 3H, J ) 6.4 Hz), 0.96 (d, 3H, J ) 6.8 Hz), 0.90 (d, 3H, J )
7.2 Hz), 0.79 (d, 3H, J ) 6.8 Hz); 13C NMR δ 173.9, 153.2,
137.8, 132.2, 75.7, 62.8, 58.0, 47.5, 34.5, 32.3, 31.1, 28.0, 23.4,
19.6, 17.9, 17.7, 14.2; HRMS exact mass for C17H25NO4 (M -
H2O) calcd 291.1834, found 291.1837; [R]D ) -23.6° (c 0.488,
CHCl3).
(2′S,3′S,4S)-3-[2′-(1-Cyclop en t en yl)-3′-h yd r oxy-1′-ox-
obu tyl-3′-p h en yl]-4-(m eth yleth yl)-2-oxa zolid in on e (16d ).
The general protocol for the asymmetric aldol reaction was
followed using imide 15 (1.26 mmol, 300 mg), dibutylboryl
triflate (1.52 mmol, 0.38 mL), triethylamine (1.77 mmol, 0.25
mL), and benzaldehyde (1.27 mmol, 0.13 mL). Chromatogra-
phy (30% ethyl acetate/70% hexanes) on 25 g of silica gel
afforded 16d (366 mg, 84%, mp 90-91 °C). IR (film) 3503,
3062, 3037, 2965, 2932, 2853, 1781, 1697, 1492, 1456, 1391,
1372, 1301, 1206, 1102, 1063, 1027, 976, 777, 757, 704 cm-1
;
1H NMR δ 7.41-7.22 (m, 5H), 5.84 (brs, 1H), 5.13 (m, 2H),
4.25 (dt, 1H, J ) 8.4, 3.2 Hz), 4.04 (AB portion of an ABX, 2H,
J ab ) 8.8 Hz, J ax ) 2.8 Hz, J bx ) 8.48 Hz, ∆νab ) 33.0 Hz),
2.94 (d, 1H, J ) 1.2 Hz), 2.47 (m, 1H), 2.35 (m, 2H), 2.26 (m,
1H), 2.04 (m, 1H), 1.83 (m, 2H), 0.86 (d, 3H, J ) 6.8 Hz), 0.77
(d, 3H, J ) 7.2 Hz); 13C NMR δ 172.4, 153.2, 141.3, 137.8,
132.2, 128.2, 127.8, 126.7, 73.1, 62.9, 58.1, 52.6, 34.0, 32.5, 28.1,
23.3, 17.9, 14.4; [R]D ) -21.3° (c 0.785, CHCl3). Anal. Calcd
for C20H25NO4: C, 69.95; H, 7.34. Found: C, 70.04; H, 7.27.
Gen er a l P r otocol for Iod oeth er ifica tion r-Cyclop en -
ten yl â-Hyd r oxy Im id es 16a -d . To a solution containing
dry acetonitrile (5 mL), iodine (3.0 equiv), and sodium bicar-
bonate (3.0 equiv) was added R-propenyl â-hydroxy imide 16.
The mixture was stirred for 12-22 h and then quenched with
0.2 M sodium thiosulfate solution and extracted with ether
(3×). The ether layer was washed once with brine, dried
(anhydrous sodium sulfate), filtered, and concentrated in
vacuo.
Cycliza tion of 16a . The general protocol was followed
using iodine (1.98 mmol, 503 mg), sodium bicarbonate (1.98
mmol, 167 mg), and 16a (0.661 mmol, 186 mg) for 12 h.
Chromatography (30% ethyl acetate/70% hexanes) on 25 g of
silica gel afforded 17a (223 mg, 83%, mp 100-101 °C) as a
solid, which was recrystallized from hexanes. (1R,3R,4S,5S)-
5-Iod o-3-m eth yl-4-[[(4S)-4-(m eth yleth yl)-2-oxa zolid in -3-
yl]ca r bon yl]-2-oxa sp ir o[3.4]octa n e (17a ): IR (film) 2967,
2934, 2875, 1780, 1697, 1488, 1468, 1388, 1302, 1236. 1205,
1111, 1062, 1022, 1005, 976, 939, 887, 859, 827, 804, 762, 716
1
cm-1; H NMR δ 5.10 (d, 1H, J ) 9.2 Hz), 4.91 (dd, 1H, J )
6.0 3.2 Hz), 4.57 (dt, 1H, J ) 8.4, 3.6 Hz), 4.32 (dq, 1H, J )
9.2, 6.0 Hz), 4.26 (AB portion of an ABX, 2H, J ab ) 9.2 Hz, J ax
) 9.2 Hz, J bx ) 3.6 Hz, ∆νab ) 28.8 Hz), 2.53 (m, 1H), 2.34 (m,
1H), 2.20 (m, 1H), 1.94 (m, 3H), 1.69 (m, 1H), 1.27 (d, 3H, J )
6.0 Hz), 1.02 (d, 3H, J ) 7.2 Hz), 0.95 (d, 3H, J ) 6.8 Hz); 13
C
NMR δ 170.3, 153.4, 95.6, 76.5, 62.8, 60.9, 58.4, 48.9, 41.1,
31.3, 28.3, 25.2, 19.5, 18.0, 14.9; [R]D ) +34.1° (c 0.824, CHCl3).
Anal. Calcd for C15H22INO4: C, 44.24; H, 5.44. Found: C,
44.44; H, 5.59. Crystals of 17a , suitable for single-crystal
X-ray analysis, were obtained by recrystallization from hex-
anes. Details of the crystal structure analysis (cell data, data
collection, processing and refinement) are concisely sum-
marized in Table 1 (Supporting Information). Full details are
available from the authors or from the Cambridge Crystal-
lographic Data Centre.17
Cycliza tion of 16b. The general protocol was followed
using iodine (2.69 mmol, 683 mg), sodium bicarbonate (2.69
mmol, 226 mg), and 16b (0.897 mmol, 265 mg) for 13 h.
Chromatography (25% ethyl acetate/75% hexanes) on 25 g of
silica gel afforded 17b (305 mg, 81%). (1R,3R,4S,5S)-3-Eth yl-
5-iodo-4-[[(4S)-4-(m eth yleth yl)-2-oxazolidin -3-yl]car bon yl]-
2-oxa sp ir o[3.4]octa n e (17b): IR (film) 2966, 2939, 2879,
1785, 1738, 1694, 1490, 1467, 1385, 1300, 1207, 1105, 1058,
1
1020, 1002, 953, 909, 845, 757, 714 cm-1; H NMR δ 5.15 (d,
1H, J ) 9.2 Hz), 4.83 (dd, 1H, J ) 5.2, 1.6 Hz), 4.57 (dt, 1H,
J ) 8.4, 4.0 Hz), 4.26 (AB portion of an ABX, 2H, J ab ) 8.8
Hz, J ax ) 8.8 Hz, J bx ) 4.0, ∆νab ) 26.4 Hz), 4.29-4.18 (m,
(17) The author has deposited atomic coordinates for 17a with the
Cambridge Crystallographic Data Centre. The coordinates can be
obtained, on request, from the Director, Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.

Enantioselective Construction of Cyclic Ethers
J . Org. Chem., Vol. 62, No. 15, 1997 5055
1H), 2.55 (ddd, 1H, J ) 14.4, 10.0, 8.0 Hz), 2.34 (m, 1H), 2.19
(m, 1H), 1.92 (m, 3H), 1.75 (dtd, 1H, J ) 15.6, 7.6, 2.0 Hz),
1.59 (m, 2H), 1.03 (d, 3H, J ) 6.4 Hz), 0.95 (d, 3H, J ) 7.2
Hz), 0.88 (t, 3H, J ) 7.6 Hz); 13C NMR δ 170.5, 153.4, 95.5,
82.0, 62.8, 58.7, 58.5, 49.4, 40.7, 30.6, 28.3, 27.5, 24.9, 18.0,
14.9, 9.7; HRMS exact mass for C16H24INO4 (M - I) calcd
294.1705, Found 294.1673; [R]D ) +34.9° (c 1.23 CHCl3).
Cycliza tion of 16c. The general protocol was followed
using iodine (2.06 mmol, 522 mg), sodium bicarbonate (2.06
mmol, 173 mg), and 16e (0.685 mmol, 212 mg) for 13 h.
Chromatography (25% ethyl acetate/75% hexanes) on 25 g of
silica gel afforded 17c (182 mg, 61%). (1R,3R,4S,5S)-5-Iod o-
3-(m eth yleth yl)-4-[[(4S)-4-(m eth yleth yl)-2-oxa zolid in -3-
yl]ca r bon yl]-2-oxa sp ir o[3.4]octa n e (17c): IR (film) 2969,
2939, 2875, 1783, 1742, 1696, 1490, 1468, 1441, 1387, 1303,
1273, 1205, 1102, 1053, 1021, 977, 847, 760, 711 cm-1; 1H NMR
δ 5.20 (d, 1H, J ) 8.8 Hz), 4.75 (d, 1H, J ) 5.2 Hz), 4.56 (dt,
hyde (2.27 mmol, 0.13 mL). Chromatography (30% ethyl
acetate/70% hexanes) on 20 g silica gel afforded 19a (277 mg,
81%) as an inseparable mixture of two isomers (cis/trans )
2.3:1): IR (film) 3540, 2972, 2927, 2877, 1780, 1696, 1493,
1454, 1381, 1319, 1206, 1105, 1065, 1021, 981, 931, 869, 762,
717 cm-1; 1H NMR δ 5.89 (dq, 1H, J ) 10.8, 6.8 Hz), 5.86 (m,
1H), 5.57 (ddq, 1H, J ) 15.2, 9.2, 1.6 Hz), 5.49 (ddq, 1H, 10.8,
9.6, 1.6 Hz), 4.92 (dd, 1H, J ) 9.6, 3.6 Hz), 4.48 (m, 4H), 4.25
(AB portion of an ABX, 2H, J ab ) 8.8 Hz, J ax ) 9.2 Hz, J bx
)
2.8 Hz, ∆νab ) 35.6 Hz), 4.22 (m, 1H), 4.14 (m, 2H), 2.83 (brs,
2H), 2.33 (m, 2H), 1.75 (ddd, 6H, J ) 13.6, 7.2, 2.0 Hz), 1.19
(d, 3H, J ) 6.8 Hz), 1.17 (d, 3H, J ) 6.0 Hz), 0.90 (d, 6H, J )
7.6 Hz), 0.84 (d, 3H, J ) 6.8 Hz), 0.83 (d, 3H, J ) 7.2 Hz); 13
C
NMR δ 175.0, 174.8, 153.6, 153.5, 133.0, 131.5, 123.6. 123.2,
68.5, 67.7, 63.1, 63.0, 58.2, 58.1, 52.1, 47.7, 28.2, 28.0, 19.8,
19.7, 18.2, 17.8, 14.5, 14.4, 13.9; HRMS exact mass for C13H21
-
NO4 (M - H2O) calcd 237.1365, found 237.1353.
1H, J ) 8.8, 3.6 Hz), 4.25 (AB portion of an ABX, 2H, J ab
)
(2′S,3′R,4S)-3-[(3′-Hyd r oxy-1′-oxo-2′-(l-m eth yleth en yl)-
p en tyl]-4-(m eth yleth yl)-2-oxa zolid in on e (19b). The gen-
eral procedure for the asymmetric aldol reaction was followed
using imide 18 (1.42 mmol, 300 mg), dibutylboryl triflate (1.70
mmol, 0.43 mL), triethylamine (1.99 mmol, 0.28 mL), and
propanal (1.70 mmol, 0.12 mL). Chromatography (25% ethyl
acetate/65% hexanes) on 25 g of silica gel afforded 19b (268
mg, 70%) as an inseparable mixture of two isomers (cis/trans
) 2.2:1): IR (film) 3526, 2966, 2939, 2878, 1781, 1696, 1488,
1466, 1388, 1374, 1301, 1204, 1143, 1124, 1100, 1058, 1024,
9.2 Hz, J ax ) 9.2 Hz, J bx ) 4.4 Hz, ∆νab ) 26.0 Hz), 4.10 (m,
1H), 2.54 (ddd, 1H, J ) 14.4, 9.6, 8.4 Hz), 2.33 (m, 1H), 2.19
(m, 1H), 1.96 (m, 2H), 1.78 (m, 3H), 1.03 (d, 3H, J ) 6.8 Hz),
0.93 (d, 3H, J ) 7.2 Hz), 0.88 (d, 3H, J ) 6.4 Hz), 0.82 (d, 3H,
J ) 7.2 Hz); 13C NMR δ 170.7, 153.4, 95.5, 86.0, 62.7, 58.5,
56.3, 50.1, 40.4, 32.5, 29.9, 28.2, 24.5, 18.3, 18.0, 17.9, 14.9;
HRMS exact mass for C17H26INO4 (M - I) calcd 308.1862,
found 308.1846; [R]D ) +35.0° (c 2.67, CHCl3).
Cycliza tion of 16d . The general protocol was followed
using iodine (2.38 mmol, 603 mg), sodium bicarbonate (2.38
mmol, 200 mg), and 16d (0.792 mmol, 272 mg) for 22 h.
Chromatography (20% ethyl acetate/80% hexanes) on 25 g of
silica gel afforded 17d (308 mg, 83%). (1R,3S,4S,5S)-5-Iod o-
3-p h en yl-4-[[(4S)-4-(m et h ylet h yl)-2-oxa zolid in -3-yl]ca r -
bon yl]-2-oxa sp ir o[3.4]octa n e (17d ): IR (film) 3090, 3066,
3036, 2965, 2934, 2877, 1786, 1737, 1695, 1496, 1459, 1388,
1302, 1206, 1109, 1026, 981, 935, 845, 756, 702, 646 cm-1; 1H
NMR δ 7.30 (m, 5H), 5.48 (d, 1H, J ) 9.2 Hz), 5.19 (d, 1H, J
) 9.6 Hz), 5.14 (dd, 1H, J ) 6.4, 2.8 Hz), 4.48 (ddd, 1H, J )
8.0, 4.0, 4.0 Hz), 4.12 (AB portion of an ABX, 2H, J ab ) 9.2
Hz, J ax ) 4.0 Hz, J bx ) 9.2 Hz, ∆νab ) 13.0 Hz), 2.70 (m, 1H),
2.31 (m, 2H), 2.03 (m, 3H), 1.84 (m, 1H), 1.01 (d, 3H, J ) 6.8
Hz), 0.93 (d, 3H, J ) 7.2 Hz); 13C NMR δ 169.6, 152.9, 138.5,
128.6, 128.5, 126.4, 96.6, 81.8, 62.7, 61.1, 58.4, 47.8, 41.1, 31.7,
28.3, 25.2, 18.0, 14.9; HRMS exact mass for C20H24INO4 (M -
I) calcd 342.1705, found 342.1703; [R]D ) +70.7° (c 0.95,
CHCl3).
981, 862, 794, 777, 757, 719, 646 cm-1
;
1H NMR δ 5.85 (m,
2H), 5.57 (ddq, 1H, J ) 15.2, 9.2, 1.2 Hz), 5.51 (ddq, 1H, J )
11.2, 9.6, 1.6 Hz), 5.00 (dd, 1H, J ) 9.6, 3.6 Hz), 4.54 (dd, 1H,
J ) 9.2, 3.2 Hz), 4.48 (m, 2H), 4.30-4.18 (m, 2H), 4.24 (AB
portion of an ABX, 2H, J ab ) 9.2 Hz, J ax ) 9.2 Hz, J bx ) 3.2
Hz, ∆νab ) 35.2 Hz), 3.86 (m, 2H), 3.13 (d, 1H, J ) 2.0 Hz),
2.88 (d, 1H, J ) 2.4 Hz), 2.33 (m, 2H), 1.76 (dd, 3H, J ) 6.8,
1.2 Hz), 1.72 (dd, 3H, J ) 6.8, 1.2 Hz), 1.49 (m, 4H), 0.98 (t,
3H, J ) 7.2 Hz), 0.95 (t, 3H, J ) 7.2 Hz), 0.89 (d, 6H, J ) 7.2
Hz), 0.83 (d, 6H, J ) 6.8 Hz); 13C NMR δ 175.3, 175.0, 153.6,
153.4, 132.7, 131.3, 123.6, 123.3, 73.7, 72.9, 63.1, 63.0, 58.2,
58.1, 50.4, 46.3, 28.2, 28.1, 27.0, 26.9, 18.2, 17.8, 14.5, 14.4,
14.0, 10.2, 10.1; HRMS exact mass for C14H23NO4 (M + 1) calcd
270.1705, found 270.1695.
(2′S,3′R,4S)-3-[(3′-Hyd r oxy-4′-m eth yl-1′-oxo-2′-(1-m eth -
yleth en yl)p en tyl]-4-(m eth yleth yl)-2-oxa zolid in on e (19c).
The general procedure for the asymmetric aldol reaction was
followed using imide 18 (1.42 mmol, 300 mg), dibutylboryl
triflate (1.70 mmol, 0.43 mL), triethylamine (1.99 mmol, 0.28
mL), and isobutyraldehyde (1.70 mmol, 0.16 mL). Chroma-
tography (15% ethyl acetate/85% hexanes) on 25 g of silica gel
afforded 19c (327 mg, 81%) as a mixture of isomers (cis/trans
) 2.2:1) of which the cis isomer could be separated. Isom er ic
m ixtu r e: IR (film) 3524, 2966, 2927, 2877, 1788, 1700, 1478,
(4S)-3-[1-Oxo-2′-(E)-p en t en yl)-4-(1-m et h ylet h yl)-2-ox-
a zolid in on e (18). Into a dry 100 mL flask containing
oxazolidinone (8.4 mmol, 988 mg) and dry tetrahydrofuran (35
mL) at -78 °C was added n-butyllithium (10 mmol, 4.0 mL,
2.5 M in hexanes) dropwise via syringe. After the mixture
was stirred for 30 min, freshly distilled (E)-2-pentenoyl
chloride (10 mmol, 1.2 g) was added via syringe. The solution
was stirred for 30 min at -78 °C and then warmed to room
temperature. The majority of the solvent was stripped off, the
remaining solution was diluted with ether, and saturated
ammonium chloride was added. The mixture was extracted
with ether (3×), washed once with 15% sodium hydroxide, once
with brine, dried (anhydrous sodium sulfate), filtered, and
concentrated in vacuo. Chromatography (15% ethyl acetate/
85% hexanes) on 45 g of silica gel afforded 1.31 g (74%) of a
pale yellow oil: IR (film) 3901, 2965, 2936, 2874, 1782, 1684,
1637, 1491, 1464, 1391, 1364, 1303, 1261, 1205, 1151, 1122,
1102, 1061, 1049, 1022, 978, 917, 863, 778, 758, 739, 714, 646
1384, 1301, 1207, 1157, 1124, 1091, 975, 870, 781, 726 cm-1
;
1H NMR δ 5.90-5.79 (m, 2H), 5.61-5.50 (m, 2H), 5.19 (dd,
1H, J ) 10.0, 4.0 Hz), 4.74 (dd, 1H, J ) 9.2, 3.2 Hz), 4.47 (m,
2H), 4.24 (AB portion of an ABX, 2H, J ab ) 8.8 Hz, J ax ) 8.8
Hz, J bx ) 3.6, ∆νab ) 35.8 Hz), 4.23 (AB portion of an ABX,
2H, J ab ) 8.8 Hz, J ax ) 8.8 Hz, J bx ) 3.6 Hz, ∆νab ) 30.6 Hz),
3.61 (m, 1H), 3.55 (m, 1H), 3.20 (d, 1H, J ) 2.0 Hz), 2.79 (d,
1H, J ) 2.0 Hz), 2.31 (m, 2H), 1.76 (dd, 3H, J ) 6.8, 1.6 Hz),
1.70 (dd, 3H, J ) 6.4, 1.2 Hz), 1.71-1.62 (m, 2H), 0.98 (d, 6H,
J ) 6.8 Hz), 0.93 (d, 3H, J ) 6.8 Hz), 0.89 (d, 3H, J ) 6.8 Hz),
0.88 (d, 3H, J ) 6.8 Hz), 0.87 (d, 3H, J ) 6.8 Hz), 0.81 (d, 6H,
J ) 7.2 Hz); 13C NMR δ 175.4, 175.1, 153.5, 153.3, 132.4, 131.0,
123.7, 76.8, 76.4, 63.0, 62.9, 58.2, 58.1, 48.2, 44.3, 31.1, 30.8,
28.1, 28.0, 19.4, 19.0, 18.4, 18.2, 18.0, 17.8, 14.6, 14.4, 14.1;
HRMS exact mass for C15H25NO4 (M - H2O) calcd 265.1678,
found 265.1677. Cis isom er : (2′S,3′R,4S)-3-[3′-Hyd r oxy-
4′-m eth yl-1′-oxo-2′-((Z)-1-m eth yleth en yl)p en tyl]-4-(m eth -
yleth yl)-2-oxa zolid in on e: IR (film) 3530, 3023, 2967, 2937,
2878, 1781, 1695, 1488, 1469, 1449, 1387, 1373, 1341, 1305,
1204, 1149, 1125, 1099, 1062, 1029, 1005, 976, 928, 877, 861,
793, 776, 721 cm-1; 1H NMR δ 5.81 (dq, 1H, J ) 10.8, 6.8 Hz),
5.51 (tq, 1H, J ) 10.8, 1.6 Hz), 5.16 (dd, 1H, J ) 10.0, 3.6 Hz),
4.45 (dt, 1H, J ) 8.8, 3.6 Hz), 4.22 (AB portion of an ABX, 2H,
J ab ) 9.2 Hz, J ax ) 9.2 Hz, J bx ) 3.2 Hz, ∆νab ) 36.0 Hz), 3.61-
3.58 (m, 1H), 2.77 (d, 1H, J ) 1.6 Hz), 2.30 (m, 1H), 1.74 (dd,
1
cm-l; H NMR δ 7.27 (dt, 1H, J ) 15.6, 1.2 Hz), 7.19 (dt, 1H,
J ) 15.6, 5.6 Hz), 4.50 (dt, 1H, J ) 8.4, 2.8 Hz), 4.25 (AB
portion of an ABX, 2H, J ab ) 9.2 Hz, J ax ) 8.4 Hz, J bx ) 2.8
Hz, ∆νab ) 26.6 Hz), 2.42 (m, 1H), 2.31 (m, 2H), 1.11 (t, 3H, J
) 7.6 Hz), 0.93 (d, 3H, J ) 7.2 Hz), 0.89 (d, 3H, J ) 6.8 Hz);
13C NMR δ 165.2, 154.0, 152.8, 119.5, 63.3, 58.5, 28.4, 25.8,
18.0, 14.6, 12.2; HRMS exact mass for C11H17NO3 calcd
211.1208, found 211.1197; [R]D ) +96.1° (c 1.42, CHCl3).
(2′S,3′R,4S)-3-[3′-Hyd r oxy-1′-oxo-2′-(1-m eth yleth en yl)-
bu tyl]-4-(m eth yleth yl)-2-oxa zolid in on e (19a ). The general
procedure for the asymmetric aldol reaction was followed using
imide 18 (1.35 mmol, 286 mg), dibutylboryl triflate (1.62 mmol,
0.41 mL), triethylamine (2.27 mmol, 0.32 mL), and acetalde-

5056 J . Org. Chem., Vol. 62, No. 15, 1997
Galatsis et al.
3H, J ) 6.8, 1.6 Hz), 1.65 (m, 1H), 0.96 (d, 3H, J ) 6.8 Hz),
0.91 (d, 3H, J ) 6.8 Hz), 0.86 (d, 3H, J ) 7.2 Hz), 0.80 (d, 3H,
J ) 6.8 Hz); 13C NMR δ 175.1, 153.5, 131.0, 123.6, 76.8, 63.0,
58.2, 44.3, 31.1, 28.1, 19.4, 18.0, 17.8, 14.5, 14.1; HRMS exact
mass for C15H25NO4 (M - H2O) calcd 265.1678, found 265.1677;
[R]D ) -29.0° (c 1.20, CHCl3).
5.6 Hz), 4.49 (dt, 1H, J ) 8.4, 4.0 Hz), 4.45 (dt, 1H, J ) 8.0,
3.6 Hz), 4.27 (t, 1H, J ) 9.2 Hz), 4.23 (m, 4H), 4.05 (m,1H),
3.98 (m, 2H), 3.62 (dq, 1H, J ) 6.0, 6.0 Hz), 2.40 (m, 2H), 1.85-
1.59 (m, 4H), 1.36 (d, 3H, J ) 6.4 Hz), 1.35 (d, 3H, J ) 6.4
Hz), 0.97-0.92 (m, 18H); 13C NMR δ 172.6, 171.8, 153.5, 153.4,
84.2, 77.1, 63.1, 58.9, 57.5, 32.7, 28.3, 28.2, 28.1, 27.9, 23.6,
(2′S,3′S,4S)-3-[3′-Hyd r oxy-1′-oxo-3′-p h en yl-2′-(1-m et h -
yleth en yl)p r op yl]-4-(m eth yleth yl)-2-oxa zolid in on e (19d ).
The general procedure for the asymmetric aldol reaction was
followed using imide 18 (0.50 mmol, 106 mg), dibutylboryl
triflate (0.61 mmol, 0.16 mL), triethylamine (0.74 mmol, 0.10
mL), and benzaldehyde (0.50 mmol, 0.05 mL). Chromatogra-
phy (30% ethyl acetate/70% hexanes) on 20 g of silica gel
afforded 19d (150 mg, 94%) as an inseparable mixture of two
isomers (cis/trans ) 2.3:1): IR (film) 3507, 3093, 3065, 3034,
2968, 2920, 2877, 1781, 1698, 1490, 1386, 1457, 1304, 1201,
1147, 1121, 1098, 1058, 973, 914, 879, 860, 797, 776, 755, 736,
705 cm-1; 1H NMR δ 7.41-7.20 (m, 10H), 5.87-5.75 (m, 1H),
5.85 (dq, 1H, J ) 10.8, 6.8 Hz), 5.68-5.57 (m, 1H), 5.60 (tq,
1H, J ) 10.0, 2.0 Hz), 5.28 (dd, 2H, J ) 9.6, 6.0 Hz), 4.91 (m,
2H), 4.18 (m, 2H), 4.05 (dd, 2H, J ) 9.2, 2.8 Hz), 3.88 (m, 2H),
2.83 (brs, 2H), 2.26 (m, 2H), 1.72 (dd, 3H, J ) 6.8, 1.3 Hz),
1.54 (dd, 3H, J ) 6.8, 1.6 Hz), 0.85 (d, 6H, J ) 6.8 Hz), 0.79
(d, 6H, J ) 6.8 Hz); 13C NMR δ 173.6, 173.4, 153.3, 153.2,
140.7, 140.6, 133.1, 132.3, 128.1, 127.8, 126.8, 126.7, 124.6,
123.5, 75.3, 74.5, 63.2, 63.1, 58.5, 58.4, 54.0, 49.5, 28.6, 28.4,
18.19, 17.9, 13.5; HRMS exact mass for C18H23NO4 (M -
PhCHO) calcd 211.1208, found 211.1164.
18.0, 17.0, 14.8, 14.7, 10.3, 9.9; HRMS exact mass for C14H22-
INO4 (M - I) calcd 268.1549, found 268.1535.
Cycliza tion of 19c. The general protocol was followed
using iodine (2.35 mmol, 595 mg), sodium bicarbonate (2.35
mmol, 197 mg), and 19c (0.783 mmol, 222 mg) for 13 h.
Chromatography (15% ethyl acetate/85% hexanes) on 25 g of
silica gel afforded two inseparable isomers (69:31) of 20c (259
mg, 81%). (2S,3R,4S)-4-Iod o-5-m eth yl-2-(m eth yleth yl)-3-
[[(4S)-4-(m eth yleth yl)-2-oxazolidin -3-yl]car bon yl]tetr ah y-
d r ofu r a n (20c): IR (film) 2968, 2937, 2875, 1787, 1700, 1491,
1468, 1386, 1301, 1278, 1231, 1200, 1142, 1097, 1061, 1019,
1
974, 911, 868, 849, 773, 757, 712 cm-1; H NMR δ 4.96 (dd,
1H, J ) 10.4, 8.0 Hz), 4.89 (dd, 1H, J ) 7.2, 6.0 Hz), 4.47 (m,
4H), 4.30-4.20 (m, 4H), 3.91 (m, 2H), 3.66 (m, 2H), 2.40 (m,
2H), 1.87 (m, 2H), 1.36 (d, 3H, J ) 6.0 Hz), 1.33 (d, 3H, J )
6.0 Hz), 0.99 (d, 3H, J ) 6.8 Hz), 0.96 (d, 3H, J ) 7.6 Hz),
0.95 (d, 3H, J ) 6.8 Hz), 0.94 (d, 3H, J ) 6.8 Hz), 0.93 (d, 3H,
J ) 7.6 Hz), 0.92 (d, 3H, J ) 6.8 Hz), 0.88 (d, 3H, J ) 6.8 Hz),
0.87 (d, 3H, J ) 6.8 Hz); 13C NMR δ 172.9, 172.3, 153.4, 88.1,
87.9, 83.2, 76.9, 63.1, 63.0, 58.9, 58.8, 54.5, 54.4, 32.8, 32.6,
32.0, 29.4, 28.2, 23.4, 18.8, 18.4, 18.1, 18.0, 17.8, 17.2, 14.9,
14.8; HRMS exact mass for C15H24INO4 (M - I) calcd 282.1705,
found 282.1690.
Gen er a l P r otocol for Iod oeth er ifica tion of r-P r op en yl
â-Hyd r oxy Im id es 19a -d . To a solution containing dry
acetonitrile (5 mL), iodine (3.0 equiv), and sodium bicarbonate
(3.0 equiv) was added R-vinyl â-hydroxy imide 19. The
mixture was stirred for 13-38 h, quenched with 0.2 M sodium
thiosulfate solution, and extracted with ether (3×). The ether
layer was washed once with brine, dried (anhydrous sodium
sulfate), filtered, and concentrated in vacuo.
Cycliza tion of 19d . The general protocol was followed
using iodine (1.89 mmol, 480 mg), sodium bicarbonate (1.89
mmol, 159 mg), and 19d (0.63 mmol, 200 mg) for 38 h.
Chromatography (15% ethyl acetate/85% hexanes) on 25 g of
silica gel afforded a mixture of inseparable isomers (69:31) of
20d (175 mg, 63%, mp 113-115 °C). (2R,3R,4S)-4-Iod o-5-
m eth yl-2-p h en yl-3-[[(4S)-4-(m eth yleth yl)-2-oxa zolid in -3-
yl]ca r bon yl]tetr a h yd r ofu r a n (20d ): IR (CCl4) 3096, 3070,
3033, 3009, 2969, 2931, 2882, 1794, 1695, 1487, 1458, 1380,
1306, 1276, 1241, 1224, 1197, 1142, 1099, 1064, 1024, 995, 969,
Cycliza tion of 19a . The general protocol was followed
using iodine (3.26 mmol, 826 mg), sodium bicarbonate (3.26
mmol, 273 mg), and 19a (1.08 mmol, 277 mg) for 15 h.
Chromatography (25% ethyl acetate/75% hexanes) on 25 g of
silica gel yielded a solid that upon recrystallization from
hexanes afforded two inseparable isomers (70:30) of 20a (305
mg, 74%, mp 40-41 °C). (3S,4R,5S)-2,5-Dim eth yl-3-iod o-
4-[[(4S)-4-(m eth yleth yl)-2-oxa zolid in -3-yl]ca r bon yl] tet-
r a h yd r ofu r a n (20a ): IR (film) 2971, 2930, 2877, 1782, 1693,
1486, 1451, 1390, 1338, 1301, 1282, 1242, 1207, 1144, 1101,
1064, 1022, 996, 975, 949, 878, 853, 834, 789, 775, 735, 714
1
908, 873, 859, 717, 700 cm-1; H NMR δ 7.30 (m, 10H), 5.27
(dd, 1H, J ) 8.8, 2.0 Hz), 5.13 (t, 1H, J ) 8.0 Hz), 5.09 (d, 1H,
J ) 8.8 Hz), 5.00 (d, 1H, J ) 6.2 Hz), 4.72 (dd, 1H, J ) 7.2,
6.4 Hz), 4.54 (dq, 1H, J ) 9.2, 6.0 Hz), 4.42 (m, 2H), 4.20 (dd,
1H, J ) 10.4, 9.6 Hz), 4.13 (m, 4H), 3.98 (dq, 1H, J ) 6.4, 6.4
Hz), 2.40 (m, 2H), 1.53 (d, 3H, J ) 7.2 Hz), 1.47 (d, 3H, J )
7.2 Hz), 0.95 (d, 3H, J ) 7.2 Hz), 0.94 (d, 3H, J ) 6.8 Hz),
0.93 (d, 3H, J ) 7.6 Hz), 0.92 (d, 3H, J ) 6.8 Hz); 13C NMR δ
171.3, 170.7, 152.8, 152.8, 139.1, 138.2, 128.6, 128.5, 126.6,
126.1, 84.7, 84.3, 84.2, 77.4, 63.1, 59.0, 58.9, 30.5, 28.5, 28.4,
27.2, 24.1, 18.0, 17.6, 14.9. Anal. Calcd for C18H22INO4: C,
48.77; H, 5.00. Found: C, 48.52; H, 5.24.
1
cm-1; H NMR δ 4.80 (m, 2H), 4.63 (t, 1H, J ) 5.2 Hz), 4.51
(dt, 1H, J ) 8.4, 3.6 Hz), 4.46 (dt, 1H, J ) 8.4, 3.6 Hz), 4.26
(m, 5H), 4.12 (m, 2H), 3.59 (m, 2H), 2.40 (m, 2H), 1.46 (d, 6H,
J ) 6.0 Hz), 1.37 (d, 3H, J ) 6.4 Hz), 1.36 (d, 3H, J ) 6.4 Hz),
0.97 (d, 3H, J ) 7.2 Hz), 0.96 (d, 3H, J ) 6.8 Hz), 0.95 (d, 3H,
J ) 7.2 Hz), 0.94 (d, 3H, J ) 6.8 Hz); 13C NMR δ 172.3, 171.4,
153.5, 153.4, 82.4, 79.0, 77.3, 63.2, 63.1, 59.6, 59.5, 58.9, 58.8,
32.8, 28.2, 28.1, 27.5, 23.7, 21.1, 20.6, 18.0, 17.9, 17.1, 14.7,
14.1; HRMS exact mass for C13H20INO4 (M - I) calcd 254.1392,
found 254.1395.
Ack n ow led gm en t. This research was supported by
the Natural Sciences and Engineering Research Council
(NSERC) Canada to which we express our sincere
gratitude.
Cycliza tion of 19b. The general protocol was followed
using iodine (2.23 mmol, 565 mg), sodium bicarbonate (2.23
mmol, 187 mg), and 19b (0.743 mmol, 200 mg) for 13 h.
Chromatography (15% ethyl acetate/85% hexanes) on 25 g of
silica gel afforded two inseparable isomers (69:31) of 20b (225
mg, 77%). (2S,3R,4S)-2-Eth yl-4-iod o-5-m eth yl-3-[[(4S)-4-
(m eth yleth yl)-2-oxa zolid in -3-yl]ca r bon yl] tetr a h yd r ofu -
r a n (20b): IR (film) 2965, 2934, 2878, 1784, 1694, 1488, 1464,
1385, 1305, 1263, 1231, 1202, 1144, 1104, 1059, 1019, 974, 908,
Su p p or tin g In for m a tion Ava ila ble: Table 1 (Summary
of Data Collection, Structure Solution and Refinement Details)
and 1H NMR spectra for compounds 9a -c, 10a -c, 12a -c,
13b-d , 14a -c, 16a -c, 17b-d , 18, 19a -d , and 20a -c (29
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
866, 847, 779, 760, 718 cm-1
;
1H NMR δ 4.85 (dd, 1H, J )
10.0, 8.0 Hz), 4.83 (dd, 1H, J ) 7.2, 5.2 Hz), 4.56 (t, 1H, J )
J O961904Z