Diastereoselective carboxyl migrations of 3-arylbenzofuranones

Article abstract of DOI:10.1021/jo7021444

(Chemical Equation Presented) Mixed benzofuranyl carbonates derived from chiral chloroformates rearranged in the presence of nucleophilic catalysts to give C-carboxylated benzofurans with variable dr. The use of chiral nucleophilic catalysts gave modest i

Full text of DOI:10.1021/jo7021444

SCHEME 1
Diastereoselective Carboxyl Migrations of
3-Arylbenzofuranones
Gorka Peris*,† and Edwin Vedejs
Department of Chemistry, UniVersity of Michigan,
Ann Arbor, Michigan 48109
gorka.peris@yale.edu
ReceiVed October 2, 2007
Mixed benzofuranyl carbonates derived from chiral chloro-
formates rearranged in the presence of nucleophilic catalysts
to give C-carboxylated benzofurans with variable dr. The
use of chiral nucleophilic catalysts gave modest improvement
in dr, but better results were obtained by optimizing auxiliary
and catalyst. Thus, 8k was obtained with 9:1 dr.
As part of our effort to access the original (incorrect) structure
of diazonamide A,1,2 we have investigated the DMAP-induced
Black rearrangement3 of 3-arylbenzofuranone-derived enol
carbonates. Although the Black rearrangement is limited to the
highly stabilized aromatic enolate environment of 3-arylben-
zofuranones, this approach has been pursued independently by
us and other groups in very similar contexts,4 as it is particularly
well suited to the objective of controlling absolute configuration
at the quaternary R carbon adjacent to the benzofuranone
carbonyl.
In a model study starting from 3-phenylbenzofuranone 1,5
we found that a mixed enol carbonate 3a derived from the
Whitesell chiral auxiliary2d rearranged to 5a with good facial
selectivity (8:1 dr, Scheme 1).2a However, introduction of
additional substituents at the R-phenyl group (i.e., 6, Scheme
2) resulted in modest diastereoselectivity in the range of 2-3:
1.2a,6 Furthermore, separation of diastereomers was difficult, and
key intermediates could not be purified without resorting to
preparative HPLC. In an attempt to circumvent these problems,
we investigated related rearrangements catalyzed by chiral
nucleophiles, including TADMAP (A, Figure 1).7 In those
studies, enantioselectivities with catalyst A were modest unless
the Black rearrangement was conducted at -40 °C. This
required 20 mol % catalyst and a time scale of ca. 24 h, even
† Current address: Department of Chemistry, Yale University, P.O. Box
208107, New Haven, CT 06520.
(1) (a) Lindquist, N.; Fenical, W.; Vanduyne, G. D.; Clardy, J. J. Am.
Chem. Soc. 1991, 113, 2303-2304. (b) Li, J.; Jeong, S.; Esser, L.; Harran,
P. G. Angew. Chem., Int. Ed. 2001, 40, 4765-4770. (c) Li, J.; Burgett, A.
W. G.; Esser, L.; Amezcua, C.; Harran, P. G. Angew. Chem., Int. Ed. 2001,
40, 4770-4773.
FIGURE 1. Chiral DMAP derivatives.
(2) (a) Vedejs, E.; Wang, J. B. Org. Lett. 2000, 2, 1031-1032. (b) Vedejs,
E.; Barda, D. A. Org. Lett. 2000, 2, 1033-1035. (c) Vedejs, E.; Zajac, M.
A. Org. Lett. 2001, 3, 2451-2454. (d) Whitesell, J. K. Chem. ReV. 1992,
92, 953-964.
with the least hindered derivatives of 3, and there was reason
to doubt that rates would be sufficient for the intended
application in hindered substrates such as 7 (Scheme 2). A
suitably reactive and enantioselective chiral DMAP catalyst (B,
Figure 1) for the Black rearrangement has been described by
(3) Black, T. H.; Arrivo, S. M.; Schumm, J. S.; Knobeloch, J. M. J.
Org. Chem. 1987, 52, 5425-5430.
(4) Moody, C. J.; Doyle, K. J.; Elliott, M. C.; Mowlem, T. J. J. Chem.
Soc., Perkin Trans. 1 1997, 2413-2419.
(5) Padwa, A.; Dehm, D.; Oine, T.; Lee, G. A. J. Am. Chem. Soc. 1975,
97, 1837-1845.
(7) (a) Shaw, S. A.; Aleman, P.; Vedejs, E. J. Am. Chem. Soc. 2003,
125, 13368-13369. (b) Shaw, S. A.; Aleman, P.; Christy, J.; Kampf, J.
W.; Va, P.; Vedejs, E. J. Am. Chem. Soc. 2006, 128, 925-934.
(6) Wang, J. Ph.D. Thesis, University of Wisconsin, Madison, 1997.
10.1021/jo7021444 CCC: $40.75 © 2008 American Chemical Society
Published on Web 01/08/2008
1158
J. Org. Chem. 2008, 73, 1158-1161

TABLE 1. Chiral Auxiliary and Nucleophile Survey in the
Rearrangement of 1 to 5
FIGURE 2. Structure of the major diastereomer of rac-5k.
In principle, greater reactivity allows a broader range of
temperatures for optimization of dr with hindered substrates,
so heteroatom-substituted chloroformates were investigated
based on the premise that electron-withdrawing groups would
enhance reaction rates. Electron demand adjacent to the carbonyl
group in enol carbonate 3 is expected to accelerate nucleophilic
attack. Furthermore, the same electronic effect would increase
the rate for recombination of ion pair 4 by destabilizing the
cationic fragment. In the event, the pantolactone-derived enol
carbonate 3e rearranged to 5e within a minute at 0 °C upon
treatment with 0.2 equiv of DMAP. Although selectivity was
minimal (dr ) 1.4:1.0, Table 1, entry 4) and 5e was contami-
nated with an unknown byproduct, the dramatic increase in
reactivity stimulated the search for chiral auxiliaries containing
electron-withdrawing substituents.
entry
OR*
Nuc (equiv)
solvent
dr (°C)
method
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
b
c
d
e
f
f
f
g
h
i
DMAP (0.2)
DMAP (0.2)
DMAP (3)
DMAP (0.2)
DMAP (0.2)
DMAP (0.6)
Bu3P (5)
DMAP (3)
DMAP (3)
DMAP (3)
DMAP (0.2)
DMAP (3)
DMAP (3)
Bu3P (5)
(R)-A (0.1)
(S)-A (0.1)
(R)-C (0.1)
(S)-C (0.1)
(R)-D (0.1)
(S)-D (0.1)
DCM
DCM
THF
DCM
THF
2.2:1.0 (rt)
1.5:1.0 (rt)
1.6:1.0 (rt)
1.4:1.0 (0)
3.1:1.0 (0)
4.0:1.0 (-40)
5:5:1.0 (0)
1.0:1.0 (0)
2.0:1.0 (0)
1.4:1.0 (0)
2.2:1.0 (0)
1.9:1.0 (rt)
2.8:1.0 (0)
2.3:1.0 (0)
2.1:1.0 (rt)
1.3:1.0 (rt)
1.0:1.6 (rt)
4.0:1.0 (rt)
1.0:1.1 (rt)
1.3:1.0 (rt)
A
A
B
A
A
A
A
B
B
B
A
B
B
A
A
A
A
A
A
A
THF
DCM
DCM
DCM
THF
DCM
DCM
THF
DCM
DCM
DCM
DCM
DCM
DCM
DCM
j
k
k
k
k
k
k
k
k
k
D-Glucose acetonide11 has been used as a chiral auxiliary in
other applications,12 and was easily converted to the chlorofor-
mate 2f. Carboxyl migration to 5f was very fast (<1 min, 0.2
equiv of DMAP, THF, 0 °C) and diastereocontrol was promising
(dr ) 3.1:1.0, Table 1, entry 5). The high reactivity allowed
evaluation of the carboalkoxyl migration at -40 °C using 0.6
equiv of DMAP, resulting in 5f with dr ) 4.0:1.0 (Table 1,
entry 6). Three other carbohydrate derivatives 3g-i were also
evaluated. For convenience, these reactions were conducted
using excess DMAP as the base for conversion to the enol
carbonate as well as to induce the rearrangement. Diastereose-
lectivity was no better than 2:1 dr (Table 1, entries 8-10), and
only one of the product diastereomer pairs (5h) could be
separated.
Fu et al.,8 but the lack of a commercial source, or a short
synthesis for the optimum catalyst, raised concerns. We therefore
initiated a broader survey of the chiral auxiliary approach to
learn whether acceptable diastereoselectivities as well as reaction
rates might be encountered.
Chiral chloroformates and the related cyanoformates have
been used to carboxylate enolates with mixed success.9 The best
results (9-13:1 dr) were obtained by Braun and co-workers
using (+)-menthyl chloroformate for the carboxylation of
branched derivatives of phenylacetate enolates or dianions. Of
course, these intermolecular carboxylations are mechanistically
distinct compared to the Black reaction proceeding via ion pair
4 (Scheme 1) with recombination of enolate and N-carboxy-
lpyridinium subunits, but the presence of a conjugated aryl
π-system in the substrate enolates of Braun provided an
encouraging analogy. Accordingly, the enol menthyl carbonate
3b was prepared using the commercially available 2b/Et3N, and
was treated with 20 mol % DMAP at rt. This gave the expected
C-carboxylated product 5b as inseparable diastereomers with
marginal dr ) 2.2:1.0 over 20 min at rt (Table 1, entry 1).
The chloroformate 2c was examined next because the parent
alcohol10 embodied the framework of the Whitesell alcohol
precursor of 2a and 3a, but with an enlarged π surface and a
relatively polar sulfonyl group that might help organize the
transition state. After uneventful conversion to the enol carbon-
ate 3c, treatment with DMAP afforded 5c with low dr ) 1.5:
1.0 (Table 1, entry 2). The even more extensive π surface of
BINOL derivative 3d was also ineffective (1.6:1.0 dr for 5d,
Table 1, entry 3).
Finally, two mandelate-derived auxiliaries13 were tested under
similar conditions. The resulting enol carbonates 3j and 3k
rearranged effortlessly to 5j (dr ) 2.2:1.0, Table 1, entry 11)
and 5k (dr ) 2.8:1.0, Table 1, entry 13), respectively. Although
the diastereomers were not separable by chromatography, the
major diastereomer of rac-5k formed from rac-3k + DMAP
was isolated with dr ) 24:1 by trituration with ether (49% yield).
Relative stereochemistry for the major diastereomer purified by
recrystallization was established by X-ray crystallography
(Figure 2).
Improved dr in some of the enol carbonate rearrangements
was observed using nucleophilic phosphine catalysts. Thus, 3f
(glucose acetonide series) was treated with 0.6 equiv of Bu3P
(THF, 12 h, 0 °C) to give the rearranged product 5f with dr )
4.9:1.0. However, the parent benzofuranone 1 was also formed,
and was already present in the reaction mixture prior to aqueous
workup. This side reaction was initially attributed to ion pair
enolate protonation in 4f by adventitious water, but extensive
measures to ensure anhydrous conditions did not completely
(11) Schmidt, O. T. Methods Carbohydr. Chem. 1963, 2, 318-325.
(12) (a) Bird, C. W.; Lewis, A. Tetrahedron Lett. 1989, 30, 6227-6228.
(b) Riediker, M.; Duthaler, R. O. Angew. Chem., Int. Ed. Engl. 1989, 28,
494-495. (c) Duthaler, R. O.; Herold, P.; Lottenbach, W.; Oertle, K.;
Riediker, M. Angew. Chem., Int. Ed. Engl. 1989, 28, 495-497.
(13) (a) Methyl, mandelate: Crosignani, S.; White, P. D.; Linclau, B. J.
Org. Chem. 2004, 69, 5897-5905. (b) Benzyl mandelate: Khumtaveeporn,
K.; Ullmann, A.; Matsumoto, K.; Davis, B. G.; Jones, J. B. Tetrahedron:
Asymmetry 2001, 12, 249-261.
(8) Hills, I. D.; Fu, G. C. Angew. Chem., Int. Ed. 2003, 42, 3921-3924.
(9) (a) Kunisch, F.; Hobert, K.; Welzel, P. Tetrahedron Lett. 1985, 26,
5433-5436. (b) Trypke, W.; Steigel, A.; Braun, M. Synlett 1992, 827-
829.
(10) Sarakinos, G.; Corey, E. J. Org. Lett. 1999, 1, 1741-1744.
J. Org. Chem, Vol. 73, No. 3, 2008 1159

SCHEME 2
suppress the formation of 1. The best ratio of 5f:1 ) 9:1 was
obtained in scrupulously dried dichloromethane, and a small
improvement in dr (5.5:1.0, Table 1, entry 7) was also observed.
Attempts to further improve diastereoselectivity at lower tem-
perature were frustrated by increased formation of 1 (exclusive
product at -40 °C). Qualitatively similar results were found in
the mandelate series. Thus, when Bu3P was used to induce the
rearrangement of enol carbonate 3k, conversion to 5k (dr )
2.3:1.0, Table 1, entry 14) took place (10 min, 0 °C), but
formation of 1 could not be avoided (4:1 5k:1). The same
problem was encountered if Bu3P was replaced by PhMe2P as
the catalyst. The empirical correlation between enolate proto-
nation and the presence of potentially acidic C-H bonds next
to positive phosphorus in the intermediate ion pair 4k (Nu )
Bu3P, PhMe2P) suggests the possibility of internal proton-
transfer pathways, but convincing evidence for this conjecture
was not obtained. In any event, the Bu3P-induced rearrangement
of 3k formed the same major diastereomer of 5k (Figure 2) as
in the reaction catalyzed by DMAP.
diastereomers of 8f (dr ) 2.9:1.0). It was necessary to conduct
this experiment in the presence of an added equivalent of
chloroformate 2f to prevent the formation of considerable
amounts of the starting benzofuranone 6. Diastereoselectivity
did not improve at -20 °C, and the absolute stereochemistry
of the products was not assigned.
Similarly, 6 was treated with the chloroformate 2k and Et3N
followed by rearrangement of 7k using excess DMAP in the
presence of added 2k to afford 8k with dr ) 1.8:1.0 as
inseparable diastereomers. On the other hand, 8k was isolated
with a much improved dr ) 9:1 (44% yield) using Bu3P as the
catalyst in a similar experiment. The parent benzofuranone 6
was also recovered (3:1 8k:6), as in the other phosphine-
catalyzed rearrangements, despite extreme measures taken to
maintain anhydrous conditions (glove box conditions; freshly
distilled reagents); unfortunately, even after an extensive survey
of conditions, diastereomers could not be separated by chro-
matography at this stage. Nevertheless, the high dr obtained
with the Bu3P/substrate 7/chloroformate 2k combination was
acceptable from the standpoint of solving the problem of
asymmetric diazonamide A quaternary carbon synthesis.
We have shown elsewhere2a that the absolute sense of
stereoinduction in the rearrangement of 3a is not affected by
the presence of o-alkoxy and m-Br substituents in the 3-phenyl
group of the benzofuranone substrate. On the basis of this
analogy and the known sense of stereoinduction of the benzyl
mandelate auxiliary (Figure 2), the major diastereomer of 8k
can be tentatively assigned as shown in Figure 3.
Next, we evaluated the available chiral DMAP derivatives
of Figure 1 as catalysts for the rearrangement of the enantio-
merically pure mandelate substrate 3k. Our intent was to amplify
the native diasteresoselectivity of the DMAP rearrangement of
3k to 5k (DCM, rt, dr ) 1.9:1.0, Table 1, entry 12), given that
eventual diastereomer separation in related systems would afford
enantiomerically pure products. Catalyst (R)-A proved to be the
matched enantiomer for carbonate 3k. However, the rearrange-
ment produced 5k with nearly the same dr (2.1:1.0, Table 1,
entry 15) as with DMAP, while the mismatched enantiomer
(S)-A afforded 5k with decreased dr (1.3:1.0, Table 1, entry
16). The major diastereomer of 5k was the same with (R)-A,
(S)-A, and DMAP (see Figure 2). These sobering diastereose-
lectivities reflect the presence of an O-carboxyl substituent that
is not optimal for TADMAP (A) regardless of catalyst config-
uration.7
The commercially available DMAP derivatives C and D were
tested next as surrogates for the highly selective catalyst B (vide
supra).8 The (S) enantiomer of C matched the diastereofacial
preference of the mandelate auxiliary, and favored the diaste-
reomer of 5k shown in Figure 2 with somewhat higher dr )
4.0:1.0 (Table 1, entry 18). On the other hand, (R)-C reversed
selectivity with dr ) 1.0:1.6 (Table 1, entry 17; under these
conditions the minor diastereomer of 5k is as drawn in Figure
2). A similar experiment was performed with catalyst D.
Ironically, both enantiomers of this catalyst gave lower dr
compared to achiral DMAP (Table 1, entries 19 and 20). Thus,
5k was obtained with dr ) 1.3:1.0 (major diastereromer as in
Figure 2) using the “matched” catalyst (S)-D, while the
corresponding reaction using (R)-D was nonselective (dr ) 1.0:
1.1; minor diastereomer as in Figure 2). Thus, only catalyst (S)-C
gave any significant amplification of dr in the above experi-
ments, and the effect was small compared to the enantiofacial
preference reported for the optimal catalyst B combined with
the optimal achiral trichloro-tert-butoxycarbonyl migrating
group.8 In view of these findings, no further experiments were
carried out with the chiral catalysts.
FIGURE 3. Tentative structure of the major diastereomer 8k.
From the results presented above, we conclude that no one
auxiliary or catalyst combination affords consistently high dr
in both benzofuranone series (1 and 6). Fortunately, moderate
to good dr is possible by adjusting the combination of auxiliary
and nucleophilic catalyst to match the specific substrate.
Experimental Section
Isolation of rac-5k (Major Diastereomer) for X-ray Structure
Determination. 3-Phenylbenzofuranone 15 (210 mg, 1.0 mmol, 1.0
equiv) was dissolved in DCM (10 mL, 0.1 M) in a flame-dried
round-bottomed flask; chloroformate 2k (74%/wt, prepared as
before,2a and used as a solid after evaporation of volatiles under
nitrogen stream; 597 mg, 1.5 mmol, 1.5 equiv) was quickly weighed
out and added to this solution, which was then cooled to 0 °C. To
initiate the carboxylation and rearrangement, solid DMAP (Aldrich,
440 mg, 3.6 mmol, 3.6 equiv) was added to the reaction solution.
As DMAP dissolved, blue streaks briefly formed and disappeared
in the reaction mixture. After DMAP dissolved, the reaction solution
The best chiral auxiliaries from the experiments of Table 1
were then tested for carboxyl migration in the more hindered
substrate 7 (Scheme 2). As expected, the reaction was much
slower. Thus, glucose-derived enol carbonate 7f was prepared
from 6 and 2f as usual. Treatment with 2.5 equiv of DMAP
induced rearrangement over 19 h at 0 °C to afford separable
1160 J. Org. Chem., Vol. 73, No. 3, 2008

was placed in the refrigerator at 0 °C. After 18 h, the reaction was
diluted with 100 mL of Et2O and sequentially washed with 100
mL of 10% aq KHSO4 and satd aq NaHCO3. The organic phase
was dried over MgSO4, filtered, and concentrated under reduced
pressure to yield a yellow oil. This was shown to be a 1.9:1.0
mixture of diastereomers by comparing the relative ratios of the
R-carbonyl-proton signals at δ (400 MHz) 6.03 (major dr, 1.9H)
and 6.01 ppm (minor dr, 1.0 H). The two diastereomers coelute in
several chromatography solvents, and they are somewhat sensitive
to silica as determined by the formation of baseline material in
2-D TLC (8:2 hexanes:Et2O). The major diastereomer was isolated
by triturating the crude oil with ∼20 mL of Et2O and allowing the
resulting mixture to stand in the freezer (-23 °C) for 2 days. At
this time the precipitate was isolated by pipetting off the supernatant
and washing the precipitate with minimal Et2O, and drying the
resulting solid under reduced pressure. This yielded 234 mg (49%)
of a white powder highly enriched in the major diastereomer (24:1
dr); the supernatant produced 319 mg of a clear oil enriched in the
minor diastereomer (1:1.3 dr), and contaminated with minor
impurities. X-ray quality crystals of the major diastereomer were
obtained by slowly evaporating a dilute Et2O solution over several
days (∼100 mg in ∼4 mL of Et2O in a capped vial); this process
yielded long needles of pure rac-5k (major diastereomer): analytical
TLC, 8:2 hexanes:EtOAc, Rf 0.35. Mp range 65-68 °C. ES
molecular ion calculated for C30H22O6Na+ 501.1314, found m/z
501.1323, error 2 ppm. IR (neat, cm-1) 3029, 1812, 1743. 1H NMR
(400 MHz, CDCl3) δ 7.60 (1H, d, J ) 7.3 Hz), 7.45-7.17 (18H,
m), 6.03 (1H, s), 5.14 (2H, s). 13C NMR (126 MHz, CDCl3, ppm)
δ 170.8, 167.4, 166.8, 153.6, 134.8, 134.3, 132.6, 130.7, 129.3,
128.8, 128.7, 128.5, 128.3, 127.8, 127.6, 127.2, 126.7, 124.72,
124.66, 111.2, 76.0, 67.4, 62.2.
tography (8:2 hexanes:Et2O) to yield 170 mg (100%) of the enol
carbonate 7k as a white foam. A portion of this material (80 mg,
0.115 mmol, 1.0 equiv) was exposed to high vacuum for 12 h before
the reaction flask was transferred to the glovebox. The enol
carbonate was dissolved in DCM (freshly distilled from P2O5, 1.2
mL, 0.1 M) and Bu3P (distilled from LAH, 0.14 mL, 0.576 mmol,
5.0 equiv) was slowly syringed in. After 1 h the solution was
removed from the glovebox, diluted with 4 mL of DCM, and
quenched with 0.8 mL of CH3I. The reaction was concentrated
under reduced pressure and the resulting clear oil purified by flash
column chromatography (85:15 Hex:Et2O) to yield 36 mg of 8k
(44%) as an inseparable 9:1 mixture of diastereomers: analytical
TLC, 8:2 hexanes:EtOAc, Rf 0.22. ES molecular ion calculated for
C38H29O8BrNa+ 715.0943, found m/z 715.0950, error 1 ppm. IR
(neat, cm-1) 1814, 1743, 1514, 1214. 1H NMR (500 MHz, CDCl3,
ppm) δ 7.61 (0.1H, dd, J ) 7.8, 1.9 Hz), 7.55 (0.9H, dd, J ) 7.8,
1.5 Hz), 7.45 (2H, d, J ) 8.8 Hz), 7.42-7.35 (2H, m), 7.31-7.23
(5H, m), 7.18-7.08 (6.6H, m), 7.05-7.02 (0.3H, m), 6.94 (0.1H,
t, J ) 7.8 Hz), 6.88-6.82 (3.9H, m), 6.68 (0.1H, d, J ) 8.8 Hz),
5.66 (0.9H, s), 5.64 (0.1H, s), 5.25 (1H, d, J ) 9.8 Hz), 5.11 (1H,
d, J ) 9.8 Hz), 5.03 (1.8H, ABq, J ) 12.2 Hz, ∆V ) 24 Hz), 5.03
(assume 0.1H, d, J ) 12.2 Hz), 4.96 (0.1H, d, J ) 10.7 Hz), 4.84
(0.1H, d, J ) 12.2 Hz), 3.79 (2.7H, s), 3.76 (0.3H, s). 13C NMR
(only major diastereomer signals are reported, 126 MHz, CDCl3,
ppm) δ 170.7, 167.9, 165.8, 159.5, 154.3, 153.7, 135.1, 132.9,
131.7, 130.7, 130.4, 129.3, 129.0, 128.7, 128.5, 128.4, 128.2, 128.1,
127.8, 127.7, 126.9, 126.6, 125.0, 124.9, 117.9, 113.5, 111.0, 75.7,
75.3, 67.0, 61.2, 55.2.
Acknowledgment. This work was supported by the National
Institutes of Health (CA17918). The authors thank Prof. Scott
J. Miller for allowing completion of several key experiments
in his laboratory, and Dr. C. Incarvito for the X-ray structure
of rac-5k.
3-[3-Bromo-2-(4-methoxybenzyloxy)phenyl]-2-oxo-2,3-dihy-
drobenzofuran-3-carboxylic Acid Benzyloxycarbonylphenyl-
methyl Ester (8k). Benzofuranone 62c (104 mg, 0.245 mmol, 1.0
equiv) was placed in an oven-dried flask, dissolved in THF (1.2
mL), and cooled to 0 °C. Then, the chloroformate 2k (1.35 mL of
a 0.2 M solution in THF, 0.270 mmol, 1.1 equiv) and Et3N (38
µL, 0.270 mmol, 1.1 equiv) were sequentially syringed in. After
10 min at 0 °C, volatiles were removed under reduced pressure
and the resulting crude oil was purified by flash column chroma-
Supporting Information Available: Complete experimental
details, characterization data, and X-ray data tables for rac-5k. This
materialisavailablefreeofchargeviatheInternetathttp://pubs.acs.org.
JO7021444
J. Org. Chem, Vol. 73, No. 3, 2008 1161