Convergent stereocontrol in Peterson olefinations. Application to the synthesis of (±)-3-hydroxybakuchiol and corylifolin

Article abstract of DOI:10.1021/jo0259459

The iron-catalyzed Kirmse reaction was used to generate neopentyl α-silyl thioethers that were elaborated to meroterpenes using two complementary routes: one route involved a sila-Pummerer rearrangement, and the other route involved a Peterson olefination. While severe eclipsing interactions undermined the efficiency of the stereospecific sila-Pummerer rearrangement, they made it possible to stereoselectively generate E olefins without isolation or separation of syn- and anti-β-silyl alkoxides. Addition of a neopentyl α-silyl alkyllithium intermediate to an aryl aldehyde generated a mixture of syn- and anti-β-silyl alkoxides. The syn-β-silyl alkoxide eliminated stereospecifically at -78°C to give an E olefin, whereas the anti-β-silyl alkoxide was unreactive. The reaction mixture was then acidified and heated to induce stereospecific elimination of the anti isomer to give the same E olefin via a complementary cationic pathway. This route was used to complete the first synthesis of the meroterpene (±)-3-hydroxybakuchiol. In addition, we synthesized another meroterpene corresponding to the natural product corylifolin and offer evidence that the structure of corylifolin was misassigned.

Full text of DOI:10.1021/jo0259459

Con ver gen t Ster eocon tr ol in P eter son Olefin a tion s. Ap p lica tion to
th e Syn th esis of (()-3-Hyd r oxyba k u ch iol a n d Cor ylifolin
J oe B. Perales, Narubumi F. Makino, and David L. Van Vranken*
Department of Chemistry, University of California, Irvine, California 92697-2025
dlvanvra@uci.edu
Received May 17, 2002
The iron-catalyzed Kirmse reaction was used to generate neopentyl R-silyl thioethers that were
elaborated to meroterpenes using two complementary routes: one route involved a sila-Pummerer
rearrangement, and the other route involved a Peterson olefination. While severe eclipsing
interactions undermined the efficiency of the stereospecific sila-Pummerer rearrangement, they
made it possible to stereoselectively generate E olefins without isolation or separation of syn- and
anti-â-silyl alkoxides. Addition of a neopentyl R-silyl alkyllithium intermediate to an aryl aldehyde
generated a mixture of syn- and anti-â-silyl alkoxides. The syn-â-silyl alkoxide eliminated
stereospecifically at -78 °C to give an E olefin, whereas the anti-â-silyl alkoxide was unreactive.
The reaction mixture was then acidified and heated to induce stereospecific elimination of the anti
isomer to give the same E olefin via a complementary cationic pathway. This route was used to
complete the first synthesis of the meroterpene (()-3-hydroxybakuchiol. In addition, we synthesized
another meroterpene corresponding to the natural product corylifolin and offer evidence that the
structure of corylifolin was misassigned.
I. In tr od u ction
glandulosa, Linne´, “J esuit tea”, is even more sensitive
than bakuchiol and has not been previously synthesized.6
Vinyl-substituted quaternary centers are central to
meroterpene structure. If there existed an efficient
method to convert R-silyl thioethers to E-styrenes, the
Kirmse reaction would be ideally suited for the synthesis
of meroterpenes. We hoped to develop a method to
convert R-silyl thioethers to E-styrenes and then use the
method to synthesize 3-hydroxybakuchiol 1 and coryli-
folin 2 (Figure 1).
The precise construction of carbon-carbon bonds is a
central challenge in organic synthesis. Bonds to quater-
nary carbons are among the most difficult to form, yet
the metal-catalyzed Kirmse reaction1 of allyl sulfides
provides a powerful efficient method for the creation of
quaternary centers. When used in conjunction with
trimethylsilyldiazomethane (TMSD), iron catalysts obvi-
ate the need for syringe pump addition.2 Kirmse reactions
with TMSD can be used to generate R-silyl thioethers
attached to vinyl-substituted quaternary centers (Scheme
1). R-Silyl thioethers are versatile handles for further
elaboration.3
Corylifolin, a newly isolated meroterpene, is a weak
inhibitor of DNA polymerase.4 However, more complex
meroterpenes such as bakuchiol have diverse biological
activities, including antitumor, antimutagenic, anti-
inflammatory, insect hormonal, and Staphylococcus au-
reus inhibitory activity.5 Bakuchiol is highly sensitive to
acid and oxygen due to the electron-rich hydroxystyrene
moiety. 3-Hydroxybakuchiol 1 isolated from Psoralea
II. Resu lts a n d Discu ssion
A. Gen er a tion of Hom oa llyl r-silyl Th ioeth er s
Usin g th e Ir on -Ca ta lyzed Kir m se Rea ction . The
R-silyl thioethers 4 were accessed by an iron(II)-catalyzed
Kirmse reaction of allyl thioethers 3 with trimethylsilyl-
diazomethane, TMSD (Scheme 1).7 Reactions were car-
ried out by heating the allylic sulfide 3 with 5 mol %
iron(II) chloride diphenylphospinoethane (dppeFeCl2) in
refluxing 1,2-dichloroethane for 1 h followed by addition
of TMSD to give the R-silyl thioether 4. Preincubation of
* To whom correspondence should be addressed. Fax: 949-824-5871.
(1) Kirmse, W.; Kapps, M. Chem. Ber. 1968, 101, 994-1003.
(2) (a) Aggarwal, V. K.; Ferrara, M.; Hainz, R.; Spey, S. E.
Tetrahedron Lett. 1999, 40, 8923-8927. (b) Carter, D. S.; Van Vranken,
D. L. Org. Lett. 2000, 2, 1303-1305.
(3) (a) Block, E.; Aslam, M. Tetrahedron 1988, 44, 281-324. (b)
Cohen, T.; Sherbine, J . P.; Matz, J . R.; Hutchins, R. R.; McHenry, B.
M.; Willey, P. R. J . Am. Chem. Soc. 1984, 106, 3245-3252. (c) Ager,
D. J . J . Chem. Soc., Perkin Trans. 1 1986, 183-194. (d) Ager, D. J . J .
Chem. Soc., Perkin Trans. 1 1986, 195-204.
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Prod. 1998, 61, 362-366. (b) Backhouse, C. N.; Delporte, C. L.; Negrete,
R. E.; Erazo, S.; Zun˜iga, A.; Pinto, A.; Cassels, B. K. J . Ethnophar-
macology 2001, 78, 27-31.
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Soman, R.; Dev, S. Agric. Biol. Chem. 1980, 44, 1483-1487. (c)
Prikhod’ko, V. A.; Bondarenko, A. S.; Mishenkova, E. L. Mikrobiol. Zh.
(Kiev) 1980, 42, 646-650. (d) Smirnov, V. V.; Romanenko, V. M.;
Prikhod’ko, V. A. Mikrobiol. Zh. (Kiev) 1984, 46, 72-74. (e) Wall, M.
E.; Wani, M. C.; Manikumar, G.; Abraham, P.; Taylor, H.; Hughes, T.
J .; Warner, J .; McGivney, R. J . Nat. Prod. 1988, 51, 1084-91. (f) Ryu,
S. Y.; Choi, S. U.; Lee, C. O.; Zee, O. P. Arch. Pharm. Res. 1992, 15,
356-359. (g) Ferrandiz, M. L.; Gil, B.; Sanz, M. J .; Ubeda, A.; Erazo,
S.; Gonzalez, E.; Negrete, R.; Pacheco, S.; Paya, M.; Alcaraz, M. J . J .
Pharm. Pharmacol. 1996, 48, 975-980.
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(7) Warning, diazo compounds are potentially explosive.
10.1021/jo0259459 CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/29/2002
J . Org. Chem. 2002, 67, 6711-6717
6711

Perales et al.
the sila-Pummerer reaction, typical conditions (m-CPBA,
-40 °C) were employed for oxidation of R-silyl thioether
4b to the corresponding sulfoxide.11 Unfortunately, at
-40 °C, where m-CPBA has good solubility, the syn
R-silyl sulfoxide 7 underwent sila-Pummerer rearrange-
ment to generate a thioacetal that competitively con-
sumed the oxidizing agent. Insufficient oxidant left
unreacted R-silyl thioether 4b; however, excess oxidant
would have epoxidized the trisubstituted olefin if the
temperature were raised. Rather than optimize the
oxidant stoichiometry, we switched to dimethyldioxirane
(DMDO),12 which is more soluble than m-CPBA. Sila-
Pummerer rearrangement is much slower than sulfide
oxidation at -78 °C. Thus, 1 equiv of DMDO at -78 °C
cleanly generated the sulfoxide. Since thiacarbenium ions
can participate in thia-Prins cyclizations, a solution of
potassium acetate in acetic acid was added to favor
formation of the desired thioacetal intermediate. The
thioacetal was hydrolyzed to aldehyde 5 using aq potas-
sium hydroxide. The overall yield of aldehyde 5 was 52%
(Scheme 2).
F IGURE 1.
the catalyst with the allylic sulfide is required for
consistent and efficient conversion.8 While the mecha-
nistic details have yet to be determined, it is presumed
that the reaction proceeds through an iron carbene
intermediate that is attacked by the thioether to form a
sulfonium ylide complex.2b,9 The sulfonium ylide could
undergo a [2,3]-sigmatropic rearrangement either with10
or without involvement of the metal.
SCHEME 1. Ir on -Ca ta lyzed Kir m se Rea ction of
Allyl Th ioeth er s
SCHEME 2. Ster eosp ecific Rea ction of r-Silyl
Su lfoxid es
Both alkyl and aryl thioethers give good yields. The
smaller more nucleophilic ethyl thioether 3a gave a
slightly higher level of diastereoselection (3.4:1) than the
phenyl thioether 3b (2:1). In a previous study, the Kirmse
reaction of phenyl methallyl thioether 17 with ferrous
bromide and (R)-2,2′-bis(diphenylphosphino)-1,1′-binaph-
thyl gave a good yield but no enantioselection.2b Conse-
quently, the issue of enantioselection was set aside for
this study. When the catalyst loading was reduced from
5 to 2 mol %, the yield of R-silyl thioether 4b was
diminished (63%). However with 5 mol % catalyst, the
reaction can be scaled up (up to 5 g) without a significant
decrease in yield.
We considered two methods to convert the R-silyl
thioether into an E-styryl moiety: (1) an oxidative
approach involving sulfoxide formation, sila-Pummerer
reaction, and Horner-Wadsworth-Emmons olefination
and (2) a reductive approach involving reductive lithia-
tion followed by Peterson olefination. Peterson olefina-
tions employing R-silyl thioethers generate mixtures of
E and Z isomers with yields between 60 and 70%.
Unfortunately, when the R-silyl thioether is adjacent to
a quaternary center the olefination yields do not exceed
35%.3c While the Peterson olefination is more direct than
the oxidative approach, the discouraging precedents led
us to first explore the longer but more propitious oxida-
tive approach.
The desired aldehyde 5 was accompanied by a desilyl-
ated sulfoxide 6 (40%). Since the sila-Pummerer proceeds
through a syn-elimination, eclipsing interactions are
important in the transition state. Vedejs has shown that
different diastereomers of highly congested R-silyl sul-
foxides undergo Pummerer rearrangements at signifi-
cantly different rates.13 The syn R-silyl sulfoxide 7 readily
eliminates at a temperature less than -40 °C (Scheme
3). In contrast, the anti R-silyl sulfoxide 8 is incapable of
adopting the required syn conformation, even up to a
temperature of 90 °C. Under the saponification condi-
tions, the remaining R-silyl sulfoxide 8 is desilylated to
give sulfoxide 6. Ethyl thioether 4a gave similar results
in the sila-Pummerer reaction.
SCHEME 3. Ster eosp ecific Rea ction of r-Silyl
Su lfoxid es
B. Hom ologa tion of th e Neop en tyl r-silyl Th io-
eth er Usin g a Sila -P u m m er er Rea ction . To induce
(8) Prabharasuth, R.; Van Vranken, D. L. J . Org. Chem. 2001, 66,
5256-5258.
(9) McCrindle, R.; Arsenault, G. J .; Farwaha, R.; McAlees, A. J .;
Sneddon, D. W. J . Chem. Soc., Dalton Trans. 1989, 761-766.
6712 J . Org. Chem., Vol. 67, No. 19, 2002

Convergent Stereocontrol in Peterson Olefinations
Although 40% of the R-silyl thioether did not produce
the desired aldehyde 5, the remaining sulfoxide 6 was
converted to aldehyde 5 by a traditional Pummerer
rearrangement. Addition of a solution of potassium
acetate in trifluoroacetic anhydride to a solution of
sulfoxide 6 produced aldehyde 5 in 60% yield (Scheme
4). Thus, the overall yield of aldehyde 5 from R-silyl
thioether 4b was 76%.
Cohen has reported that when 1-(dimethylamino)-
naphthalene (DMAN) is reduced with lithium wire at
-70 °C in THF, lithium 1-(dimethylamino)naphthalene
(LDMAN) is formed in 60-70% yield after 8 h.15 Consis-
tent with this report, when LDMAN was formed at -45
°C in THF from lithium wire (scrubbed free of the
passivation layer), residual lithium wire remained after
3.5 h. Since the presence of the unreacted lithium was
obscured by the dark opaque solution, the LDMAN
solution was separated from the residual lithium using
a cannula chilled with dry ice.
SCHEME 4. P u m m er er Oxid a tion of Su lfoxid e 6
When thioether was reductively lithiated with LDMAN
at -78 °C over 30 min and then quenched with CD3OD,
the desulfurated product 12 was isolated in 94% yield
as a 76:24 mixture of deuterated and protonated products
(Scheme 6). Thus, within less than 30 min at -78 °C,
about one-fourth of the R-silyl alkyllithium 11 was
protonated by a species in the reaction mixture.
Stereoselective olefination of aldehyde 5 was accom-
plished with a Horner-Wadsworth-Emmons reaction.
Deprotonation of phosphonate 9 with potassium tert-
butoxide followed by addition of aldehyde 5 provided
olefin 10 with greater than 100:1 E/Z selectivity as
determined by GC (Scheme 5).
SCHEME 6. Com p etitive P r oton a tion of
r-Silyllith iu m 11
SCHEME 5. Ster eoselective
Hor n er -Wa d sw or th -Em m on s Olefin a tion
When the R-silyl alkyllithium 11 was quenched im-
mediately with CD3OD at -78 °C, the ratio of deuterated
product to protonated product 12 was increased to 90:
10. Thus, the available neopentyllithium intermediate 11
was generated from the thioether 4b in about 85% yield
but had to be used immediately.
Thus the desired styrene 10 was obtained in 60%
overall yield with high E selectivity from the R-silyl
thioether 4b. Unfortunately, failure of the anti R-silyl
sulfoxide 8 to undergo the sila-Pummerer rearrangement
had forced us to salvage unreacted sulfoxide in a second
step prior to olefination. Given the lengthiness of this
reaction sequence, we turned our attention to the more
direct reductive approach for conversion of the R-silyl
thioether 4b to a styryl moiety.
C. Hom ologa tion of th e Neop en tyl r-silyl Th io-
eth er Usin g a P eter son Olefin a tion . Hindered R-silyl
thioethers are poor substrates for the reductive lithiation/
Peterson olefination sequence when lithium naphthalen-
ide is used for the reductive lithiation step.3c However,
improvements have been reported for each step of this
sequence. First, lithium 1-(dimethylamino) naphthalen-
ide (LDMAN) offers the promise of a higher reduction
potential and easier removal of byproducts. Second,
potassium salts facilitate formation of the four-membered-
ring siliconate intermediate in the Peterson olefination
step.14
When 3,4-dibenzyloxybenzaldehyde 13 was added to
R-silyl alkyllithium 11 at -78 °C and allowed to warm
to rt over 8 h, the olefination products were formed as a
disappointing 1.7:1 ratio of Z and E isomers, respectively.
Under basic conditions, the Peterson olefination proceeds
through a stereospecific syn elimination. Thus, the
formation of E and Z isomers can be attributed to
uncontrolled formation of syn- and anti-â-silyl alkoxides
in the addition step. With no way to control addition to
the aldehyde, the prospects for stereoselective olefination
seemed bleak. According to a comprehensive 1990 re-
view16 of the Peterson olefination, “To be a useful reaction
for the stereoselective synthesis of alkenes, the Peterson
reaction requires the stereospecific preparation of â-hy-
droxysilanes.” This fatalistic view of the Peterson olefi-
nation has not changed in the past 10 years.
To our delight, when the Peterson olefination was
quenched at -78 °C, only the E isomer was obtained.
Presumably, at low temperature, elimination of the syn-
â-silyl alkoxide 15 was facile whereas elimination of the
anti-â-silyl alkoxide 14 was prevented by severe eclipsing
interactions (Scheme 7). However, there are two comple-
(10) Wu, Y. D.; Houk, K. N.; Marshall, J . A. J . Org. Chem. 1990,
55, 1421142-3.
(11) (a) Kocienski, P. J . J . Chem. Soc., Chem. Commun. 1980, 1096-
1097. (b) Kocienski, P. J . Tetrahedron Lett. 1980, 21, 1559-1562.
(12) (a) Adam, W.; Chan, Y. Y.; Cremer, D.; Gauss, J .; Scheutzow,
D.; Schindler, M. J . Org. Chem. 1987, 52, 2800-2803. (b) Adam, W.;
Bialas, J .; Hadjiarapoglou, L. Chem. Ber. 1991, 124, 2377.
(13) (a) Vedejs, E.; Mullins, M. Tetrahedron Lett. 1975, 24, 2017-
2020. (b) Carey, F. A.; Dailey, J . D. J .; Hernandez, O.; Tucker, J . R. J .
Org. Chem. 1976, 41, 3975-3978.
(14) (a) Cohen, T.; Bhupathy, M. Acc. Chem. Res. 1989, 22, 152-
161. (b) Cohen, T.; J ung, S. H.; Romberger, M. L.; McCullough, D. W.
Tetrahedron Lett. 1988, 29, 25-26.
(15) Cohen, T.; Kreethadumrongdat, T.; Liu, X.; Kulkarni V. J . Am.
Chem. Soc. 2001, 123, 3478-3483.
(16) Ager, D. J . Org. React. 1990, 38, 1-223.
J . Org. Chem, Vol. 67, No. 19, 2002 6713

Perales et al.
mentary ways to generate E-alkenes form â-hydroxy-
silanes. Under basic conditions, syn-â-hydroxysilanes
generate E-alkenes via syn-siloxide eliminations.17 Under
acidic conditions, anti-â-hydroxysilanes generate E-alk-
enes via â-silylcarbocations. Thus, the severe eclipsing
interactions that debilitated the sila-Pummerer approach
could provide a unique advantage in the Peterson olefi-
nation.
out using the Akiyama protocol (AlCl3/dimethylaniline)
to afford (()-3-hydroxybakuchiol in 75% yield (Scheme
9).19 Neither the optical rotation or the absolute stereo-
chemistry of 3-hydroxybakuchiol have been reported.
3-Hydroxybakuchiol decomposes in the presence of oxy-
gen; a H NMR sample stored in DMSO-d6 at rt under-
went nearly complete decomposition over 12 h. However,
samples frozen in DMSO are stable.
1
We hypothesized that we could use acid to induce
elimination of the unreacted anti-â-hydroxysilane 14 via
a cationic pathway (Scheme 7). If successful, this would
allow us to execute a stereoselective Peterson olefination
from a mixture of syn- and anti-â-hydroxysilanes.
SCHEME 9. Syn th esis of (()-3-Hyd r oxyba k u ch iol
SCHEME 7. Ster eocon ver gen t P eter son
Olefin a tion fr om a Mixtu r e of Dia ster eom er ic
â-Silyl Alk oxid es
D. Syn th esis of “Cor ylifolin ”. To test the generality
of our synthetic route to the meroterpenes, we used the
reductive/Peterson olefination strategy for the synthesis
of corylifolin, a meroterpene recently isolated from Pso-
ralea corylifolia.4a The iron-catalyzed Kirmse reaction of
methallyl phenylthioether 172b proceeded in 89% yield
using 5 mol % dppeFeCl2 (Scheme 10). The R-silyl
thioether 182b was reductively lithiated using LDMAN
and then subjected to the convergent sequence of stereo-
specific eliminations previously described to produce
E-styrene 19 in 68% yield as the desired E isomer (>50:1
diastereoselection). Deprotection of the phenol generated
E-styrene 2 in 90% yield.
SCHEME 10. Syn th esis of Cor ylifolin
To implement this convergent strategy, aldehyde 13
was added to R-silyl alkyllithium 11 at -78 °C, followed
by anhydrous potassium acetate. After 3 h at -78 °C,
acetic acid was added and the reaction was warmed to
rt over 5 min. The acid-catalyzed elimination was slow
even at rt, so the reaction was heated at 60 °C for 8 h.
This sequence of basic and acidic Peterson olefination
conditions (Scheme 8) afforded the E olefin 16 in 68%
yield with exceptional selectivity (77:1 E/Z by GCMS).
1
The structure of 2 was confirmed using H NMR, 13C
NMR, IR, and low- and high-resolution mass spectrom-
etry. Unfortunately, while the spectroscopic data for
compound 2 and corylifolin were similar, they clearly did
not match. In the spectra of synthetic compound 2, the
methyl groups are magnetically equivalent, consistent
SCHEME 8. Ster eoselective Syn th esis of
E-Alk en es by a P eter son Olefin a tion
1
with an achiral structure. In contrast, in the H NMR
and 13C NMR data reported for corylifolin the two methyl
groups were magnetically inequivalent, suggesting a
diastereotopic relationship.
At the present time, it is not possible to assign a
structure for corylifolin based on the published data.
However, it seems clear that corylifolin does not have the
structure originally reported.
The p-hydroxystyrene moiety of bakuchiol makes it
unstable to both oxygen6 and acid,18 so it is not surprising
that 3-hydroxybakuchiol 1 was converted to the diacetate
prior to full characterization. To accommodate the sensi-
tive catechol moiety, the deprotection of 16 was carried
III. Con clu sion
In conclusion, we have used the iron-catalyzed Kirmse
reaction to generate neopentyl R-silyl thioethers that
(17) Hudrlik, P. F.; Peterson, D. J . Am. Chem. Soc. 1975, 97, 1464-
1468.
(18) Prakasa Rao, A. S. C.; Nayak, U. R.; Dev, S. Tetrahedron 1974,
30, 1107-1114.
(19) Akiyama, T.; Hirofuji, H.; Ozaki, S. Tetrahedron Lett. 1991, 32,
1321-1324.
6714 J . Org. Chem., Vol. 67, No. 19, 2002

Convergent Stereocontrol in Peterson Olefinations
r-Silyl Th ioeth er 4b. A solution of allyl sulfide 3b (5.00
g, 20.3 mmol) and [1,2-bis(diphenylphosphino)ethane]dichloro-
iron(II) (533 mg, 1.02 mmol) in 1,2-dichloroethane was refluxed
for 1 h. A solution of trimethylsilyldiazomethane (2.0 M in
hexanes, 15.2 mL, 31 mmol) was added. The reaction mixture
was refluxed for 1 h, filtered through a plug of silica gel (1:9
EtOAc/hexanes) to remove iron salts, and concentrated in
vacuo to give a pale yellow oil. The oil was chromatographed
on silica gel (hexanes) to give R-silyl thioether 4b a colorless
oil (6.00 g, 89%): Rf ) 0.29 (hexanes); 1H NMR (500 MHz,
CDCl3) δ 7.39 (m, 2H), 7.26 (m, 2H), 7.15 (m, 1H), 5.87 (dd, J
) 17.5, 10.8 Hz, 0.33H), 5.82 (dd, J ) 17.5, 10.8 Hz, 0.67H),
5.00 (m, 3H), 2.53 (s, 0.33H), 2.51 (s, 0.67H), 1.82 (m, 2H),
1.67 (s, 2H), 1.65 (s, 1H), 1.60 (m, 1H), 1.55 (s, 2H), 1.53 (s,
1H), 1.48 (m, 1H), 1.16 (s, 1H), 1.15 (s, 2H), 0.24 (s, 6H), 0.20
(s, 3H); 13C NMR (125 MHz, CDCl3) δ 146.2, 146.1, 131.1,
131.0, 129.2, 128.7, 128.6, 125.5, 125.4, 124.8, 124.7, 112.7,
112.5, 47.7, 47.2, 45.6, 45.1, 25.6, 23.4, 23.0, 22.3, 21.4, 17.5,
1.0, 0.9; IR (thin film) 3069, 2963, 1637, 1482, 1408, 1024, 914,
837, 735 cm-1; MS (EI) 332, 255, 195; HRMS (EI) m/z calcd
were elaborated to meroterpenes using two complemen-
tary routes: the first route involved a sila-Pummerer
rearrangement and the second route involved a Peterson
olefination. Severe eclipsing interactions undermined the
efficiency of the sila-Pummerer rearrangement. Steric
effects limited the yield of the sila-Pummerer rearrange-
ment to about 50%. The syn-R-silyl sulfoxide 7 underwent
facile sila-Pummerer rearrangement at - 40 °C, whereas
the anti-R-silyl sulfoxide 8 failed to undergo the sila-
Pummerer reaction up to 90 °C. Fortunately, the type of
eclipsing interactions that thwarted the sila-Pummerer
route proved to be indispensable in the Peterson olefi-
nation route. Even though addition of the neopentyl
R-silyllithium 11 to aldehyde 13 generated an inseparable
mixture of syn- and anti-â-silyl alkoxides, we were able
to convergently transform them into E styrenes with high
stereoselectivity. The syn-â-silyl alkoxide eliminated
stereospecifically at -78 °C to give the E olefin 16,
whereas the anti â-silyl alkoxide was unreactive. The
reaction mixture was then acidified and heated to induce
stereospecific elimination of the anti isomer to give the
same E olefin 16 via the complementary cationic path-
way. This route was used to complete the first synthesis
of the meroterpene (()-3-hydroxybakuchiol 1. In addition,
we synthesized meroterpene 2 corresponding to the
natural product corylifolin. The spectroscopic data re-
ported for corylifolin do not match the data we obtained
for meroterpene 2 and were not consistent with the
proposed achiral structure.
for C20H32SSi 332.1994, found 332.1985. Anal. Calcd for C20H32
SSi: C, 72.22; H, 9.70. Found: C, 72.14; H, 9.79.
-
Ald eh yd e 5 a n d Su lfoxid e 6. To a cooled (-78 °C) solution
of thioether 4b (1.50 g, 4.52 mmol) in CH2Cl2 (29 mL) was
added dimethyldioxirane (0.074 M in acetone, 61.0 mL, 4.5
mmol). A solution of potassium acetate in acetic acid (5% v/v,
70 mL) was added after 30 min, and the reaction mixture was
allowed to warm to rt. After 6 h at rt, the reaction mixture
was poured into H2O and extracted with CH2Cl2. The organic
layer was washed with saturated aq NaHCO3, dried over
MgSO4, and concentrated in vacuo to give a yellow oil (1.60
g).
The mixture of thioacetal and un-rearranged R-silyl sulfox-
ide was dissolved in ethanol (41 mL), and aq KOH (1.0 M, 13.6
mL, 13.6 mmol) was added. After being stirred for 1 h, the
reaction mixture was diluted with saturated aq NaCl, ex-
tracted with EtOAc, dried over MgSO4, and concentrated in
vacuo to give a yellow oil. The oil was chromatographed over
silica gel (2% EtOAc in hexanes and 10% EtOAc in hexanes)
to give aldehyde 5 as a colorless oil (0.39 g, 52%). Spectroscopic
data for aldehyde 5 matched the literature values.22 Sulfoxide
6 was also obtained as a colorless oil in 95% purity as
determined by 1H NMR (0.50 g, 40%): Rf ) 0.24 (10:90 EtOAc/
Exp er im en ta l Section
Gen er a l Exp er im en ta l P r oced u r es. Reactions, analysis,
purification, identity, and purity were performed or deter-
mined as previously described.20 Additionally, dimethyldioxi-
rane (DMDO) was prepared and titrated immediately before
use.12 Potassium tert-butoxide and aluminum trichloride were
purified by sublimation, trifluoroacetic anhydride was distilled
from P2O5 and lithium wire was washed with hexane and
scraped free of oxides under an argon atmosphere prior to use.
All Peterson olefination reactions were run with an oven dried
glass encased magnetic stir bar under an argon atmosphere.
The transfer of LDMAN solutions employed a cannula that
was chilled with an aluminum foil cover that contained dry
ice.
1
hexanes); H NMR (500 MHz, CDCl3) δ 7.90 (d, J ) 7.4 Hz,
2H), 7.63 (m, 1H), 7.54 (m, 2H), 5.79 (dd, J ) 17.4, 10.8 Hz,
1H), 5.05 (t, J ) 7.0 Hz, 1H), 5.03 (d, J ) 10.8 Hz, 1H), 4.97
(d, J ) 17.4 Hz, 1H), 3.15 (s, 2H), 1.89 (m, 2H), 1.66 (s, 3H),
1.59 (m, 2H), 1.57 (s, 3H) 1.31 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 143.7, 141.8, 133.4, 131.8, 129.1, 127.8, 123.9, 113.2,
65.4, 40.6, 40.5, 25.6, 22.8, 22.7, 17.6; IR (thin film) 2967, 2919,
1633, 1576, 1371, 1148, 1086, 1023, 914, 690 cm-1; MS (EI)
276, 258, 177, 149, 135; HRMS (EI) m/z calcd for C17H24OS
276.1548, found 276.1547.
r-Silyl Th ioeth er 4a . A solution of allyl sulfide 3a 21 (0.14
g, 0.71 mmol) and [1,2-bis(diphenylphosphino)ethane]dichloro-
iron(II) (21 mg, 4.0 × 10-5 mol) in 1,2-dichloroethane was
refluxed for 1 h. A solution of trimethylsilyldiazomethane (2.0
M in hexanes, 0.59 mL, 1.2 mmol) was added. The reaction
mixture was refluxed for 1 h, filtered through a plug of silica
gel (1:9 EtOAc/hexanes) to remove iron salts, and concentrated
in vacuo to give a pale yellow oil. The oil was chromatographed
on silica gel (hexanes) to give R-silyl thioether 4a as a colorless
oil (0.19 g, 89%): Rf ) 0.34 (hexanes); 1H NMR (500 MHz,
CDCl3) δ 5.84 (dd, J ) 17.5, 10.8 Hz, 1H), 5.07 (t, J ) 7.1 Hz,
1H), 5.03 (dd, J ) 10.8, 1.4 Hz, 1H), 4.95 (dd, J ) 17.5, 1.4
Hz, 1H), 2.62 (dq, J ) 11.8, 7.5 Hz, 1H), 2.49 (dq, J ) 11.8,
7.4 Hz, 1H), 1.85 (m, 2H), 1.68 (m, 4H), 1.58 (s, 3H), 1.51 (m,
2H), 1.19 (m, 3H), 1.11 (s, 2.3H), 1.08 (s, 0.7H), 0.14 (s, 7.4H),
0.12 (s, 1.6H); 13C NMR (125 MHz, CDCl3) δ 146.3, 131.1,
124.9, 112.2, 45.6, 45.2, 40.1, 31.5, 25.7, 23.4, 21.9, 17.7, 14.6,
Ald eh yd e 5, by P u m m er er Oxid a tion . To a solution of
sulfoxide 6 (49 mg, 0.17 mmol) in benzene (1.0 mL) was added
trifluoroacetic anhydride (0.13 mL, 0.89 mmol). The solution
was poured into saturated aq NaHCO3 and extracted with
EtOAc. The organic layer was washed with saturated aq NaCl,
dried over MgSO4, and concentrated in vacuo to give a yellow
oil. The oil was chromatographed over silica gel (3% EtOAc in
hexanes) to give aldehyde 5 as a colorless oil (18 mg, 60%).
P h osp h on a te 9. To 3,4-dimethoxybenzyl alcohol (4.3 mL,
30 mmol) was added a solution of phosphorus tribromide (1.0
M, 59 mL, 60 mmol). After 7 h, the reaction mixture was
poured into a cold (0 °C) solution of H2O and NaHCO3 (15 g,
180 mmol). The mixture was extracted with CH2Cl2, dried over
MgSO4, filtered, and concentrated in vacuo to give a yellow
oil (6.4 g). The oil was dissolved in o-xylene (100 mL), and
0.9; IR (thin film) 3078, 2963, 1633, 1449, 1004, 861, 833 cm-1
;
MS (EI) 284, 255, 147; HRMS (EI) m/z calcd for C20H32SSi
284.1994, found 284.1985. Anal. Calcd for C16H32SSi: C, 67.53;
H, 11.33. Found: C, 67.63; H, 11.45.
(21) Torii, S.; Uneyama, K.; Ishihara, M.; Ito, K. J P Patent 51 133
252, 1976.
(20) Perales, J . B.; Van Vranken, D. L. J . Org. Chem. 2001, 66,
7270-7274.
(22) Michelot, D.; Lorne, R.; Huynh, C.; J ulia, S. Bull. Soc. Chim.
Fr. 1976, 1482-1488.
J . Org. Chem, Vol. 67, No. 19, 2002 6715

Perales et al.
triisopropyl phosphite (7.5 mL, 30 mmol) was added. The
solution was heated at reflux for 79 h. The solution was cooled
to 25 °C, washed with H2O, dried over MgSO4, and concen-
trated in vacuo. The resulting oil was chromatographed over
silica gel (EtOAc) to give a pale yellow oil that was further
purified by Kugelrohr distilation (0.1 mmHg, 165 °C) to yield
phosphonate 9 as a colorless oil (5.89 g, 63%): Rf ) 0.28
in THF (4.0 mL). Potassium acetate (0.50 g, 5.1 mmol) was
added along with potassium hydride (0.30 mL, 30 wt %
dispersion in mineral oil, approximately 2.2 mmol). The
solution was maintained at -78 °C for 3 h.
Acetic acid (15 mL) was added, and the frozen mixture was
then warmed to 60 °C to induce anti elimination of the
remaining â-silyl alcohol. The solution was maintained at 60
°C for 8 h and then cooled to 25 °C. The solution was diluted
with H2O, and excess acetic acid was neutralized with NaH-
CO3. The aqueous solution was extracted with ether, and the
ether layer was then washed with 1.0 M aq KOH, 1.0 M aq
HCl, saturated aq NaHCO3, and saturated aq NaCl and dried
over MgSO4. The mixture was then filtered and concentrated
in vacuo to give a yellow oil. The oil was chromatograhped
with silica gel (3% EtOAc in hexanes) to give trans-styrene
16 as a colorless oil (186 mg, 68%): Rf ) 0.35 (10:90 EtOAc/
1
(EtOAc); H NMR (500 MHz, CDCl3) δ 6.95 (m, 1H), 6.89 (m,
2H), 4.66 (d,sept J ) 6.2, 1.5 Hz, 2H), 3.93 (s, 3H), 3.92 (s,
3H), 3.11 (d, J ) 21.2 Hz, 2H), 1.34 (d, J ) 6.2 Hz, 6H), 1.24
(d, J ) 6.2 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ 148.7, 147.9,
124.3 (d, 9.0 Hz), 122.0 (d, 7.8 Hz), 113.1 (5.8 Hz), 111.1, 70.4
(d, 6.9 Hz), 55.9, 55.8, 34.2 (d, 139.8 Hz), 24.1 (d, 3.5 Hz), 23.9
(d, 5.0 Hz); IR (thin film) 1595, 1514, 1243, 1105, 995, cm-1
;
MS (FAB) 317, 289, 233, 154; HRMS (FAB) m/z calcd for
C
C
15H25O5P 316.1440, found 316.1430. Anal. Calcd for
15H25O5P: C, 56.95; H, 7.97. Found: C, 56.84; H, 8.17.
1
hexanes); H NMR (500 MHz, CDCl3) δ 7.46 (d, J ) 7.4 Hz,
2H), 7.43 (d, J ) 7.3 Hz, 2H), 7.32 (m, 6H), 7.00 (s, 1H), 6.87
(s, 2H), 6.20 (d, J ) 16.2 Hz, 1H), 6.01 (d, J ) 16.2 Hz, 1H),
5.86 (dd, J ) 17.5, 10.7 Hz, 1H), 5.16 (s, 2H), 5.14 (s, 2H),
5.10 (t, J ) 7.1 Hz, 1H), 5.03 (dd, J ) 10.7, 1.3 Hz, 1H), 5.00
(dd, J ) 17.5, 1.3 Hz, 1H), 1.94 (m, 2H), 1.67 (s, 3H), 1.58 (s,
3H), 1.48 (m, 2H), 1.18 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
149.2, 148.3, 145.9, 137.4, 137.4, 136.4, 131.9, 131.3, 128.5,
128.4, 127.8, 127.7, 127.4, 127.3, 126.7, 124.8, 119.7, 115.3,
112.9, 111.9, 71.5, 71.5, 42.5, 41.3, 25.7, 23.4, 23.2, 17.6; IR
(thin film) 3024, 2967, 2909, 2861, 1600, 1576, 1505, 1452,
1424, 1129, 1014, 967, 905, 795, 729 cm-1; MS (EI) 452, 361,
281, 207, 177, 91; HRMS (EI) m/z calcd for C32H36O2 452.2715,
found 452.2718.
tr a n s-Styr en e 10. To a cooled (0 °C) solution of phospho-
nate 9 (1.57 g, 4.96 mmol) in THF (16.5 mL) was added
potassium tert-butoxide (557 mg, 4.96 mmol). After 1 h at 0
°C, the solution of phosphonate anion was cooled to -78 °C,
and a solution of aldehyde 5 (235 mg, 1.41 mmol) in THF (6.0
mL) was added. After 1 h at -78 °C, the reaction mixture was
warmed to rt, stirred for 2 h, and quenched with aq NH4Cl.
The biphasic mixture was extracted with ether, washed with
saturated aq NaCl, dried over MgSO4, and concentrated in
vacuo to give a yellow oil which was chromatographed over
silica gel (4% EtOAc in hexanes) to give trans-styrene 10 as a
colorless oil (336 mg, 79%): Rf ) 0.19 (10% EtOAc in hexanes);
1H NMR (500 MHz, D3CN) δ 7.00 (d, J ) 1.9 Hz, 1H), 6.90
(dd, J ) 8.2, 1.9 Hz, 1H), 6.85 (d, J ) 8.2 Hz, 1H), 6.28 (d, J
) 16.3 Hz, 1H), 6.17 (d, J ) 16.3 Hz, 1H), 5.94 (dd, J ) 17.1,
11.1 Hz, 1H), 5.13 (m, 1H), 5.03 (m, 2H), 3.80 (s, 3H), 3.78 (s,
3H), 1.97 (m, 2H), 1.66 (s, 3H), 1.58 (s, 3H), 1.50 (m, 2H), 1.20
(s, 3H); 13C NMR (125 MHz, D3CN) δ 150.3, 149.7, 147.2, 136.8,
132.1, 132.0, 127.8, 125.8, 120.0, 112.8, 112.3, 110.1, 56.4, 56.3,
43.4, 42.1, 25.8, 24.1, 23.6, 17.7; IR (thin film) 2967, 1600, 1510,
1029, 910, 795 cm-1; MS (EI) 300, 285, 257, 217; HRMS (EI)
m/z calcd for C20H28O2 300.2089, found 300.2091. Anal. Calcd
for C20H28O2: C, 79.96; H, 9.39. Found: C, 80.05; H, 9.56.
3-Hyd r oxyba k u ch iol 1. To a solution of bis-benzyl ether
16 (53 mg, 0.12 mmol) and dimethylaniline (0.10 mL, 0.78
mmol) in CH2Cl2 (0.6 mL) was added AlCl3 (89 mg, 0.67 mmol).
An exothermic reaction ensued, and the reaction mixture
turned dark red. After 30 min, the reaction mixture was
poured into aq HCl (1.0 M) and saturated with sodium
potassium tartrate. The mixture was extracted with EtOAc,
washed with saturated aq NaHCO3 and saturated aq NaCl,
dried over MgSO4, and concentrated in vacuo to give a pale
yellow oil. The oil was chromatographed with silica gel (40%
ether in pentane) to give 3-hydroxybakuchiol 1 as a colorless
oil (27 mg, 75%). As previously described,6 pure 3-hydroxy-
bakuchiol was unstable, either neat or as a solution in CDCl3
or DMSO, with complete decompositon occurring within 24 h.
3-Hydroxybakuchiol was stable when frozen in DMSO: Rf )
Alk ylsila n e 12. To a cooled (-45 °C) mixture of lithium
(13 mg, 1.9 mmol) in THF (4.4 mL) was added 1-(dimethyl-
amino)naphthalene (0.28 mL, 1.7 mmol). The reaction mixture
was maintained at -45 °C for 3.5 h and then cooled to -78
°C. A solution of R-silyl thioether 4b (0.23 g, 0.68 mmol) in
THF (4.4 mL) was then added. After 5 min at -78 °C, the
solution of alkyllithium was quenched with saturated aq NH4-
Cl and warmed to 25 °C. The reaction mixture was poured
into ether and washed with aq KOH (1.0 M), aq HCl (1.0 M),
aq saturtaed NaHCO3, and aq saturated NaCl. The solution
was dried over MgSO4, filtered, and concentrated in vacuo to
give a pale yellow oil. The oil was chromatographed over silica
gel (hexanes) to give alkylsilane 12 (0.14 g, 92%). When the
alkyllithium was quenched with CD3OD, after 25 min, the
reduced product 12 was isolated in 94% yield as a 76:24
mixture of deuterated and protonated product: Rf ) 0.55
1
0.22 (40:60 ether/pentane); H NMR (500 MHz, DMSO-d6) δ
8.85 (s, 2H), 6.79 (s, 1H), 6.65 (m, 2H), 6.11 (d, J ) 16.3 Hz,
1H), 5.95 (d, J ) 16.3 Hz, 1H), 5.88 (dd, J ) 17.5, 10.7 Hz,
1H), 5.10 (t, J ) 7.1 Hz, 1H), 5.01 (d, J ) 10.7 Hz, 1H), 4.98
(d, J ) 17.5 Hz, 1H), 1.89 (m, 2H), 1.63 (s, 3H), 1.53 (s, 3H),
1.43 (m, 2H), 1.13 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ
145.9, 145.3, 144.8, 133.9, 130.5, 128.9, 126.8, 124.7, 117.7,
115.6, 112.8, 111.8, 42.0, 30.4, 25.5, 23.0, 22.8, 17.5; IR (thin
film) 3273, 2967, 2919, 1600, 1514, 1024, 995, 971, 900, 819,
800 cm-1; MS (EI) 272, 257, 189; HRMS (EI) m/z calcd for
C
18H24O2 272.1776, found 272.1778.
1
(hexanes); H NMR (500 MHz, CDCl3) δ 5.76 (dd, J ) 17.5,
tr a n s-Styr en e 19. To a cooled (-45 °C) mixture of lithium
10.8 Hz, 1H), 5.07 (m, 1H), 4.91 (dd, J ) 10.8, 1.5 Hz, 1H),
4.88 (dd, J ) 17.5, 1.5 Hz, 1H), 1.86 (m, 2H), 1.67 (s, 3H), 1.58
(s, 3H), 1.32 (m, 2H), 1.04 (s, 3H), 0.75 (s, 2H), 0.02 (s, 9H);
13C NMR (125 MHz, CDCl3) δ 149.0, 130.9, 125.0, 110.2, 44.4,
39.4, 30.7, 25.7, 25.4, 23.3, 17.6, 0.9; IR (thin film) 3072, 2957,
1633, 1410, 1252, 1000, 838 cm-1; MS (EI) 224, 209; HRMS
(EI) m/z calcd for C14H28Si 224.1960, found 224.1963.
tr a n s-styr en e 16. To a cooled (-45 °C) mixture of lithium
wire (71 mg, 10 mmol, about 1 cm) in THF (6.0 mL) was added
1-(dimethylamino)naphthalene (0.40 mL, 2.4 mmol). The reac-
tion mixture was maintained at -45 °C for 3.5 h and then
transferred to a cooled (-78 °C) flask under argon using a
chilled cannula. A solution of R-silyl thioether 4b (210 mg, 0.62
mmol) in THF (4.0 mL) was then added followed immediately
by a solution of 3,4-dibenzyloxybenzaldehyde (0.40 g, 1.3 mmol)
(38 mg, 5.4 mmol) in THF (4.5 mL) was added 1-(dimethyl-
amino)naphthalene (0.30 mL, 1.8 mmol). The reaction mixture
was maintained at -45 °C for 3.5 h and then transferred to a
cooled (-78 °C) flask under argon with a chilled cannula. A
solution of R-silyl thioether 18 (160 mg, 0.60 mmol) in THF
(2.0 mL) was added followed immediately by a solution of
4-benzyloxybenzaldehyde (260 mg, 1.2 mmol) in THF (2.0 mL).
Potassium acetate (0.50 g, 5.1 mmol) was added along with
potassium hydride (0.30 mL, 30 wt % dispersion in mineral
oil, approximately 2.2 mmol). The reaction mixture was
maintained at -78 °C for 3 h.
Acetic acid (20 mL) was added, and the frozen mixture was
warmed to 60 °C to induce anti elimination of the remaining
â-silyl alcohol. The reaction mixture was maintained at 60 °C
for 10 h and then cooled to 25 °C. The reaction mixture was
6716 J . Org. Chem., Vol. 67, No. 19, 2002

Convergent Stereocontrol in Peterson Olefinations
diluted with H2O, and excess acetic acid was neutralized with
NaHCO3. The aqueous solution was extracted with ether, and
the ether layer was then washed with 1.0 M aq KOH, 1.0 M
aq HCl, saturated aq NaHCO3, and saturated aq NaCl. The
organic layer was dried over MgSO4 and concentrated in vacuo
to give a yellow solid. The solid was chromatographed on silica
gel (2% ether in pentane) to give trans-styrene 19 as a white
solid (114 mg, 68%): mp 58-60 °C (CH2Cl2); Rf ) 0.31 (2:98
ether/pentane); 1H NMR (500 MHz, CDCl3) δ 7.42 (d, J ) 7.4
Hz, 2H), 7.37 (dd, J ) 7.4, 7.2 Hz, 2H), 7.32 (d, J ) 7.2 Hz,
1H), 7.29 (d, J ) 8.7 Hz, 2H), 6.91 (d, J ) 8.7 Hz, 2H), 6.26 (d,
J ) 16.2 Hz, 1H), 6.07 (d, J ) 16.2 Hz, 1H), 5.89 (dd, J )
17.4, 10.6 Hz, 1H), 5.06 (s, 2H), 5.01 (dd, J ) 17.4, 1.2 Hz,
1H), 4.97 (dd, J ) 10.6, 1.2 Hz, 1H), 1.20 (s, 6H); 13C NMR
(125 MHz, CDCl3) δ 158.0, 147.1, 137.1, 137.0, 130.9, 128.6,
127.9, 127.4, 127.2, 125.6, 114.9, 110.8, 70.1, 39.3, 27.1; IR
(KBr) 2957, 1600, 1510, 1171, 1010, 967, 905, 824, 805; MS
(EI) 278, 263, 187; HRMS (EI) m/z calcd for C20H22O 278.1671,
found 278.1672. Anal. Calcd for C20H22O: C, 86.29; H, 7.97.
Found: C, 86.22; H, 8.21.
“Cor ylifolin ” 2. To a solution of benzyl ether 19 (46 mg,
0.17 mmol) and dimethylaniline (0.090 mL, 0.71 mmol) in CH2-
Cl2 was added AlCl3 (71 mg, 0.53 mmol). An exothermic
reaction ensued, and the reaction mixture turned dark red.
After 1 h, the solution was poured into an aqueous solution of
HCl (1.0 M) and saturated with sodium potassium tartrate.
The mixture was extracted with EtOAc, washed with saturated
aq NaHCO3 and saturated aq NaCl, dried over MgSO4, and
concentrated in vacuo to give a pale yellow oil. The oil was
chromatographed on silica gel (15% EtOAc in hexane) to give
trans-styrene 2 as a white solid (28 mg, 90%): mp 68-74 °C
(CH2Cl2); Rf ) 0.22 (15:85 EtOAc/hexanes); 1H NMR (500 MHz,
acetone-d6) δ 8.27 (s, 1H), 7.25 (d, J ) 8.5 Hz, 2H), 6.78 (d, J
) 8.5 Hz, 2H), 6.28 (d, J ) 16.5 Hz, 1H), 6.09 (d, J ) 16.5 Hz,
1H), 5.92 (dd, J ) 17.5, 10.5 Hz, 1H), 5.01 (d, J ) 17.5 Hz,
1H), 4.95 (d, J ) 10.5 Hz, 1H), 1.19 (s, 6H); 13C NMR (125
MHz, acetone-d6) δ 159.6, 148.1, 136.4, 130.3, 128.1, 126.9,
116.2, 110.0, 39.9, 27.4; IR (KBr) 2947, 1605, 1590, 1095, 995,
971, 805, 676 cm-1; MS (CI, NH4+) 206, 189, 173; HRMS (EI)
m/z calcd for C13H16O 188.1201, found 188.1202. Anal. Calcd
for C13H16O: C, 82.94; H, 8.57. Found: C, 82.91; H, 8.84.
Ack n ow led gm en t. This research was generously
supported by the National Science Foundation CHE-
9623903. D.L.V.V. is a Research Fellow of the Alfred P.
Sloan Foundation. J .B.P. is a recipient of a 2001 Glaxo-
Wellcome Graduate Fellowship in Synthetic Organic
Chemistry. N.F.M. was supported by an Allergan Sum-
mer Research Fellowship.
Su p p or tin g In for m a tion Ava ila ble: NMR spectra 1H
and 13C for compounds 1, 2, 6, 12, 16, and 19 are included.
This information is available free of charge via the Internet
at http://pubs.acs.org.
J O0259459
J . Org. Chem, Vol. 67, No. 19, 2002 6717