Efficient total syntheses and structural verification of both diospongins A and B via a common δ-lactone intermediate

Article abstract of DOI:10.1021/jo061296f

(Chemical Equation Presented) The total syntheses of the two aryl C-glycoside natural products diospongins A and B are described. The key reactions involved stereoselective reductions of the appropriate oxocarbenium cations that were derived from a common

Full text of DOI:10.1021/jo061296f

Efficient Total Syntheses and Structural
Verification of Both Diospongins A and B via a
Common δ-Lactone Intermediate
Kailas B. Sawant and Michael P. Jennings*
Department of Chemistry, 500 Campus DriVe,
The UniVersity of Alabama, Tuscaloosa, Alabama 35487-0336
FIGURE 1. Structures of (-)-diospongins A and B.
jenningm@bama.ua.edu
ether cores with two aromatic side chains. With these three
tunable functional groups via a fairly simple molecular scaffold,
a variety of analogues could be prepared with the expectation
of discovering a novel and more active inhibitor of bone
resorption based on the privileged R-or â-C-glycoside subunit.
However, the true structure of diospongin B (vs that of
diospongin A) is still unresolved.5 Based on the disclosure report
ReceiVed June 22, 2006
1
by Kadota, H NMR data strongly supports that diospongin B
possesses the R-C-glycoside subunit and diospongin A retains
the â-C-glycoside.3 Based on the anti-osteoporotic activity of
1 and uncertain configurations of both 1 and 2, we decided to
undertake the total syntheses of diospongins A and B.3
The total syntheses of the two aryl C-glycoside natural
products diospongins A and B are described. The key
reactions involved stereoselective reductions of the appropri-
ate oxocarbenium cations that were derived from a common
δ-lactone intermediate.
Based on our previous reports of utilizing a δ-lactone as a
precursor to â-C-glycoside subunits of natural products, we
proposed that the key transformations to both targets rest with
stereoselective nucleophilic additions to the appropriate oxo-
carbenium cations.6 Thus, the synthesis of diospongin A can
be envisioned to include a lithium enolate addition (derived from
acetophenone) to the common lactone intermediate (3) to
provide lactol 5 as highlighted in Scheme 1. Subsequent
oxocarbenium formation and stereoselective reduction of the
oxocarbenium intermediate 4 should provide the â-C-glycoside
2. Likewise, a Mukaiyama-type aldol reaction of the TMS enol
ether derived from acetophenone with the hydrogen-substituted
oxocarbenium cation 6 should provide diospongin B (1). Thus,
in turn, the full protected lactol 7 would readily be derived from
the DIBAL reduction of the common lactone intermediate 3.
The first order of business was the completion of the central
intermediate δ-lactone 3 as highlighted in Scheme 2. Thus,
attention was first focused on the introduction of the bromoac-
etate functionality in order to examine the stereoselective
intramolecular Reformatsky lactone formation reaction sequence.
With this in mind, esterification of the free secondary hydroxyl
moiety resident in the known alcohol 87 (derived via a Keck
allylation of benzaldehyde in 92% ee as Mosher esters) with
bromoacetyl bromide and pyridine provided 9 in 73% yield as
shown in Scheme 2. Ensuing oxidative cleavage via the modified
Johnson-Lemieux protocol of the terminal alkene moiety
resident in 9 furnished the extremely labile â-bromo acetyl
Osteoporosis is a skeletal disease in which bone mineral
density (BMD) has been reduced and the bone microarchitecture
disrupted. It is often referred to as a “silent disease” because
bone loss can occur without symptoms. Osteoporosis is a major
public health concern for approximately 45 million Americans,
or 55% of the people 50 years of age and older. In the United
States, roughly10 million individuals are estimated to already
have the disease and almost 34 million more are anticipated to
have low bone mass, placing them at increased risk for
osteoporosis. Of the 10 million Americans estimated to have
osteoporosis, 80% are female. Although more prevalent in
Caucasians, significant risk has been reported in people of all
ethnic backgrounds. While osteoporosis is often thought of as
an elder person’s disease, it can strike at any age.1
While some therapies that block osteoblast-mediated bone-
resorption are available (i.e., Fosamax2 and Actonel3), small
molecule natural products with very high levels of anti-
osteoporotic activity may very well be suited as alternative or
additive therapeutic treatment strategies. One such natural
product that has exerted potent inhibitory activities on bone
resorption induced by parathyroid hormone in a bone organ
culture system is (-)-diospongin B (1). The proposed R-C-
glycoside compound 1 was isolated from the rhizomes of
Dioscorea spongiosa via bioassay-guided fractionation and
exhibited potent inhibitory activities of 45Ca release at 200 µM
(30.5%) and 20 µM (18.2%).4 As shown in Figure 1, the two
diospsongins [A (2) and B] both possess six-membered cyclic
(4) Yin, J.; Kouda, K.; Tezuka, Y.; Le Tran, Q.; Miyahara, T.; Chen,
Y.; Kadota, S. Planta Med. 2004, 70, 54.
(5) Chandrasekhar and co-workers allege to have been the first to
1
synthesize (-)-diospongin B. However, their NMR spectral data (both H
and 13C) do not match either of the proposed (-)-diospongin structures,
thus casting doubt on their claim. For more detailed information see:
Chandrasekhar, S.; Shyamsunder T.; Jaya Prakash, S.; Prabhakar, A.;
Jagadeesh, B. Tetrahedron Lett. 2006, 47, 47.
(1) The facts mentioned in this manuscript were taken from the National
Osteoporosis Foundation’s website at: http://www.nof.org/osteoporosis/
diseasefacts.htm, accessed 6/22/06.
(2) Sebba, A. I.; Bonnick, S. L.; Kagan, R.; Thompson, D. E.; Skalky,
C. S.; Chen, E.; de Papp, A. E. Curr. Med. Res. Opin. 2004, 20, 2031.
(3) Lipton, A. Oncologist 2004, 9, 38.
(6) (a) Jennings, M. P.; Clemens, R. T. Tetrahedron Lett. 2005, 46, 2021.
(b) Ding, F.; Jennings, M. P. Org. Lett. 2005, 7, 2321. (c) Sawant, K. B.;
Ding, F.; Jennings, M. P. Tetrahedron Lett. 2006, 47, 939.
(7) Keck, G. E.; Tarbet, K. H.; Geraci, L. S. J. Am. Chem. Soc. 1993,
115, 8467.
10.1021/jo061296f CCC: $33.50 © 2006 American Chemical Society
Published on Web 08/31/2006
J. Org. Chem. 2006, 71, 7911-7914
7911

SCHEME 1. Retrosynthetic Analyses of (-)-Diospongins A
and B
SCHEME 3. Synthesis of Lactone 3a
a Reagents and conditions: (a) acryloyl chloride (2 equiv), DMAP (0.05
equiv), Et3N (2.2 equiv), CH2Cl2, rt, 2 h, 68%; (b) 13 (0.05 equiv), CH2Cl2,
50 °C, 3 h, 90%; (c) H2O2 (3.5 equiv), NaOH (0.6 equiv), MeOH, 0 °C
then rt, 4 h, then PPTS (0.05 equiv), benzene, 80 °C, 0.5 h, 85%; (d) (PhSe)2
(1.5 equiv), NaBH4 (3 equiv), HOAc (4 equiv), THF/EtOH (1:1), 0 °C, 1.5
h, 81%.
SCHEME 2. Synthesis of Lactone 3 via a Reformatsky
Cyclizationa
SCHEME 4. Synthesis of 1a
a Reagents and conditions: (a) bromoacetyl bromide (2.5 equiv), pyridine
(2 equiv), CH2Cl2, 0 °C to rt, 6 h, 73%; (b) OsO4 (0.02 equiv), NaIO4 (4
equiv), dioxane/H2O (3:1), rt, 5 h, 43%; (c) SmI2 (3 equiv), CH2Cl2, 0 °C,
2 h, 32%.
a Reagents and conditions: (a) Et3N (6 equiv), DMAP (0.09 equiv),
Et3SiCl (3 equiv), THF, rt, 6 h, 89%; (b) DIBAL (1.3 equiv), CH2Cl2, -78
°C, 2.5 h, 99%; (c) Ac2O (1.8 equiv), pyridine (1.5 equiv), DMAP (1 equiv),
CH2Cl2, 0 °C to rt, 5 h, 91%; (d) BF3‚OEt2 (2 equiv), 1-phenyl-1-
trimethylsiloxyethylene (2.5 equiv), CH2Cl2, -78 °C, 2 h, 81%. TESCl )
triethylsilyl chloride; DIBAL ) diisobutylaluminum hydride; Ac ) acetyl.
aldehyde (10) (readily underwent â-elimination to provide
cinnamaldehyde upon attempted purification) and set the stage
for the intramolecular SmI2-mediated Reformatsky sequence.8
Molander reported that the treatment of a bromoacetyl moiety
with SmI2 readily allowed for the synthesis of a Sm(III) enolate,
which subsequently underwent an intramolecular aldol reaction
with a pendent aldehyde via a double six-membered transition
state to furnish selectively a â-hydroxy lactone with exceptional
diastereoselectivity.9 On the basis of our previous successful
utilization of this chemistry, it was anticipated that treatment
of 10 with SmI2 will provide the initial Sm(III) enolate
intermediate (11) which quickly should undergo cyclization to
provide lactone 3 as a single diastereomer via the proposed
transition state as shown in Scheme 2. As expected, treatment
of 11 with SmI2 quickly underwent cyclization to provide
afforded the dienic ester 12. Treatment of the acrylate ester 12
with Grubbs’ carbene catalyst 13 readily allowed for the
formation of lactenone 14 via a ring-closing olefin metathesis
with a combined yield of 61% over two steps from 8.10,11 An
ensuing stereoselective epoxidation of the corresponding lacten-
one intermediate 14 with basic hydroperoxide provided the
epoxy-lactone 15 in 85% yield. A subsequent regioselective
reduction of the oxirane resident in 15 by means of the in situ
generated PhSeH afforded intermediate 3 and provided gram
quantities of the coveted â-hydroxy lactone,12 which served as
the divergent point for both natural products.
With the lactone 3 readily in hand the final drive to both
diospongins A and B commenced with the designed oxocarbe-
nium chemistry via the common â-hydroxy lactone intermediate
taking center stage. With this in mind, we chose to initially
investigate the synthesis of the R-C-glycoside resident in the
proposed structure of 1. As delineated in Scheme 4, initial
protection of the free hydroxyl moiety of 3 was accomplished
1
lactone 3 as a single diastereomer as observed by H NMR in
a low 32% yield. Although the synthetic sequence delineated
in Scheme 2 provided lactone 3, we were dissatisfied with the
∼15% yield over the two final synthetic operations.
Since gram quantities of 3 were required for the completion
of both 1 and 2, we decided to investigate an alternative strategy
for the synthesis of the desired â-hydroxy lactone based on our
previous approach to (-)-dactylolide as described in Scheme
3.6b Thus, alcohol 8 was subjected to acrylate ester formation
under the standard protocol (acryloyl chloride, Et3N, DMAP)
(10) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett.
1999, 1, 953.
(11) (a) Ghosh, A. K.; Cappiello, J.; Shin, D. Tetrahedron Lett. 1998,
39, 4651. (b) Ramachandran, P. V.; Reddy, M. V. R.; Brown, H. C.
Tetrahedron Lett. 2000, 41, 583.
(12) Miyashita, M.; Suzuki, T.; Hoshino, M.; Yoshikoshi, A. Tetrahedron
1997, 53, 12469.
(8) Yu, W.; Mei, Y.; Kang, Y.; Hua, Z.; Jin, Z. Org. Lett. 2004, 6, 3217.
(9) Molander, G. A.; Etter, J. B.; Harring, L. S.; Thorel, P. J. J. Am.
Chem. Soc. 1991, 113, 8036.
7912 J. Org. Chem., Vol. 71, No. 20, 2006

SCHEME 5. Proposed Synthesis of (-)-Diospongin Aa
SCHEME 6. Synthesis of 2a
a Reagents and conditions: (a) LiHMDS (3.1 equiv), acetophenone (3
equiv), THF, -78 °C, 2 h.
as a TES ether under standard conditions (TESCl, Et3N, DMAP)
in 89% yield to provide 16. Careful reduction of lactone 16
with 1.3 equiv of DIBAL readily allowed for the formation of
the lactol and subsequent acetylation with Ac2O and pyridine
afforded 7.13 Treatment of intermediate 7 with BF3‚OEt2
presumably afforded the oxocarbenium cation. Similar to that
of Woerpel’s reports and our previous observations, it was
predicted that the reactive conformer placed the phenyl ring at
C5 in the pseudoequatorial position with the C3 hydroxyl moiety
in the axial position.6,14 This reactive conformer allowed for
the stereoselective axial approach of the nucleophilic TMS enol
ether (derived from acetophenone) via a chairlike transition state.
Much to our delight, concomitant removal of the TES group
under the reaction conditions readily proceeded to provide the
coveted (-)-diospongin B (1) in 81% yield. The spectral data
(1H NMR, 500 MHz; 13C NMR, 125 MHz), optical rotation
([R]rtD -22.6, c 0.0114, CHCl3), and HRMS data of the synthetic
(-)-diospongin B were in agreement with the natural sample.
With diospongin B in hand, the final focus shifted to the
completion of diospongin A via a proposed addition of the
lithium enolate derived from acetophenone to lactone 3. With
this in mind and delineated in Scheme 5, treatment of lactone
3 with 1.2 equiv of the enolate anion derived from acetophenone
and LiHMDS surprisingly did not provide the lactol compound
5 as a mixture of two inconsequential diastereomers. Based on
this result, we decided to investigate an alternative strategy (still
utilizing the oxocarbenium cation) in which the nucleophilic
addition of an allyl moiety (via the Grignard reagent) to lactone
3 followed oxidative cleavage of the olefin moiety would
provide a synthetic blueprint to diospongin A.
With this in mind, our attention was focused on the allyl â-C-
glycoside formation followed by final elaboration of the terminal
alkene functional group into the final targeted structure 2. Thus,
treatment of lactone 3 with excess allylmagnesium bromide
readily afforded the lactol intermediate 17 as a mixture of two
diastereomers. Immediate addition of TFA to lactol 17 seem-
ingly provided the oxocarbenium intermediates which were
subsequently reduced with Et3SiH. Similar to that of the
synthesis of diospongin B in Scheme 4 and based on the
observed product, it was assumed that the more reactive
conformer placed the phenyl ring at C5 in the pseudoequatorial
position with the C3 hydroxyl moiety in the axial position. This
reactive conformer allowed for the stereoselective axial approach
of the nucleophilic hydride via a chairlike transition state. As
observed in our previous synthesis of (-)-dactylolide,6b the free
a Reagents and conditions: (a) allylMgBr (3.1 equiv), Et2O/THF (2:1),
-78 °C, 2 h, then Et3SiH (10 equiv), TFA (5 equiv), CH2Cl2, -40 °C,
CH2Cl2, 5 h, 66%; (b) O3, Sudan III indicator, -78 °C, CH2Cl2, 15 min,
95%; (c) PhMgBr (2.75 equiv), Et2O, -78 °C to rt, 5 h, 95%; (d) Dess-
Martin reagent (1.5 equiv), CH2Cl2, 0 °C then rt, 3 h, 96%; (e) 1% HCl,
EtOH, rt, 6 h, 85%. Dess-Martin periodinane ) 1,1,1-tris(acetyloxy)-1,1-
dihydro-1,2-benziodoxo-3-(1H)-one.
secondary hydroxyl group was concomitantly protected as a TES
ether under the reductive conditions for the transformation of
17 to 18.
The overall yield of the five transformations from 3 (nucleo-
philic addition, oxocarbenium formation, Et3SiH reduction of
the oxocarbenium cation, active silylating reagent formation,
and silylation of the free hydroxyl moiety) was a very respect-
able 66%. With the desired â-C-glycoside subunit 18 in hand,
focus was placed on the oxidative cleavage of the terminal
alkene and final addition of the phenyl substituent en route to
2. Hence, ozonolysis of the alkene moiety in 18 was readily
accomplished to provide aldehyde 19 in 95% yield. Ensuing
addition of the final aromatic segment via the Grignard reagent
afforded the corresponding secondary alcohol as a mixture of
diastereomers, which was subsequently oxidized to the ketone
intermediate 20 by means of the Dess-Martin periodinane
reagent in a combined yield of 91% over the two steps from
18.15 Final deprotection of the TES ether with HCl in EtOH
furnished diospongin A (2) in 85% yield. The spectral data (1H
NMR, 360 MHz; 13C NMR, 90 MHz), optical rotation ([R]rt
D
-19.6, c 0.0084, CHCl3), and HRMS data of the synthetic (-)-
diospongin A were in accord with the natural sample. The
geometries of the R-and â-C-glycoside moieties were deduced
and provided further proof of the purported structures of both
1 and 2 via the NOE enhancements as shown in Figure 2.4
In conclusion, we have provided the total syntheses of both
(-)-diospongins A and B, which unequivocally have validated
the structures as proposed by Kadota.4 Based on their spectral
data and in unison with ours, (-)-diospongin B possesses the
R-C-glycoside subunit whereas (-)-diospongin A maintains the
â-C-glycoside moiety. On the basis of the intriguing biological
profile of 1 coupled with the late-stage convergence via the R-C-
glycoside formation sequence, the synthesis of a variety of
(13) Kopecky, D. J.; Rychnovsky, S. D. J. Org. Chem. 2000, 65, 191.
(14) (a) Romero, J. A. C.; Tabacco, S. A.; Woerpel, K. A. J. Am. Chem.
Soc. 2000, 122, 168. (b) Ayala, L.; Lucero, C. G.; Romero, J. A. C.;
Tabacco, S. A.; Woerpel, K. A. J. Am. Chem. Soc. 2003, 125, 15521.
(15) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
J. Org. Chem, Vol. 71, No. 20, 2006 7913

Et3SiH (1.81 mL, 11.225 mmol, 10 equiv) and TFA (0.42 mL, 5.613
mmol, 5 equiv) in one portion at -78 °C. The temperature was
allowed to warm to -40 °C, and the reaction was stirred for 0.5 h.
The reaction was quenched with 10 mL of NaHCO3 and extracted
(20 mL × 3) with CH2Cl2. The organic extracts were dried with
anhydrous NaSO4 and concentrated under vacuum. The residue was
purified by flash column chromatography on silica gel (20% EtOAc/
hexanes) to give (2-allyl-6-phenyltetrahydropyran-4-yloxy)trieth-
ylsilane (18) in 66% yield: 1H NMR (360 MHz, CDCl3) δ 7.34
(m, 5H), 5.93 (m, J ) 17.3, 1H), 5.1 (dd, J ) 17.3, 2.3, 2H), 4.9
(dd, J ) 11.6, 2.3, 1H), 4.29 (t, J ) 2.7, 1H), 4.08 (dd, J ) 11.4,
2.3, 1H), 2.33 (m, 2H), 1.82 (m, 1H), 1.7 (m, 2H), 1.52(m, 1H),
1.01 (t, J ) 8.2, 9H), 0.66 (q, J ) 8.0, 6H); 13C NMR (125 MHz,
CDCl3) δ 143.5, 135.1, 128.2, 127.0, 125.8, 116.5, 73.5, 71.6, 65.1,
41.5, 40.7, 38.6, 6.9, 4.9. IR (neat): 2955, 2876, 2253, 1060, 9081,
735, 651 cm-1; [R]25D -44.52 (c 0.0584, CHCl3); Rf at 20% EtOAc/
hexanes 0.17; HRMS (EI) calcd for C20H32O2Si (M+) 332.2172,
found 332.2161.
FIGURE 2. Key NOE enhancements resident in (-)-diospongins A
and B.
analogues to examine the anti-osteoporotic activity of structur-
ally diverse “diospongin B-like” compounds are currently
underway and will be reported in due course.
Experimental Section
Diospongin B (1). Acetic acid 6-phenyl-4-triethylsilanyloxytet-
rahydropyran-2-yl ester 7 (23.7 mg, 0.71 mmol) and trimethyl(1-
phenylvinyloxy)silane (37 µL, 0.1775 mmol, 2.5 equiv) were
dissolved in CH2Cl2 (0.5 mL). Upon cooling to -78 °C, BF3‚OEt2
(18 µL, 0.142, 2 equiv) was added dropwise via syringe. On
completion of the reaction as monitored by TLC, the light yellow
solution was quenched with saturated solution of NaHCO3 at -78
°C and reaction allowed to warm to room temperature. The mixture
was extracted (30 mL × 3) with CH2Cl2, and the combined organic
extracts were washed with brine. After drying with anhydrous
sodium sulfate and evaporation of the solvent, the residue was
purified by flash column chromatography on silica gel (20% EtOAc/
hexanes) to give 2-(4-hydroxy-6-phenyltetrahydropyran-2-yl)-1-
phenylethanone (1) in 81% yield: 1H NMR (500 MHz, CDCl3) δ
7.97 (d, J ) 8.4, 2H), 7.58 (t, J ) 7.6, 1H), 7.47 (t, J ) 7.9, 2H),
7.34 (m, 5H), 5.2 (t, J ) 4.4, 1H), 4.23 (m, 1H), 4.03 (m, 1H),
3.45 (dd, J ) 15.8, 6.9, 1H), 3.18 (dd, J ) 15.8, 6.0, 1H), 2.52
(dd, J ) 13.2, 1.6, 1H), 2.07 (dd, J ) 12.6, 1.9, 1H), 1.92 (dd, J
) 15.1, 5.4, 1H), 1.62 (d, J ) 4.3, 1H), 1.5 (dd, J ) 9.5, 3.2, 1H);
13C NMR (125 MHz, CDCl3) δ 198.3, 140.3, 137.3, 133.2, 128.6,
128.5, 128.3, 126.4, 127.1, 72.3, 66.9, 64.3, 44.6, 40.2, 36.8; IR
Diospongin A (2). To solution of 1-phenyl-2-(6-phenyl-4-
triethylsilanyloxytetrahydropyran-2-yl)ethanone (20) (20 mg, 0.05
mmol) in EtOH (1 mL) was added a solution of 1% HCl in EtOH
(1.25 mL). Upon completion, as determined by TLC, the reaction
was quenched with NaHCO3 and the aqueous residue extracted (20
mL × 3) with CH2Cl2. The organic residue was dried with
anhydrous MgSO4 and concentrated under vacuum. The crude was
purified by flash column chromatography on silica gel (40% EtOAc/
hexanes) to furnish desired product in 85% yield: 1H NMR (360
MHz, CDCl3) δ 7.98 (dd, J ) 8.6, 1.4, 2H), 7.56 (dd, J ) 7.5, 2.0,
1H), 7.46 (dd, J ) 8.0, 7.3, 2H), 7.31 (m, 5H), 4.93 (dd, J ) 11.8,
2.0, 1H), 4.65 (m, 1H), 4.37 (m, 1H), 3.42 (dd, J ) 15.9, 5.9 1H),
3.07 (dd, J ) 15.9, 6.8 1H), 1.95 (m, 2H), 1.87 (s, 1H), 1.74 (m,
1H), 1.68 (m, 1H), 1.7 (m, 1H); 13C NMR (90 MHz, CDCl3) δ
198.3, 142.7, 137.3, 133.1, 128.5, 128.3, 128.2, 127.2, 125.8, 73.8,
69.0, 64.7, 45.1, 40.0, 38.5; IR (CDCl3) 3464, 1683, 1596, 1446,
1210, 911; [R]25 -19.6 (c 0.0084, CHCl3); Rf at 40% EtOAc/
D
hexanes 0.21; HRMS (EI) calcd for C19H20O3 (M+) 296.1412, found
296.1425.
(CHCl3) 3464, 1682, 1596, 1452, 1365, 1048 cm-1; [R]25 -22.6
D
Acknowledgment. Support was provided by the University
of Alabama and the NSF (CHE-0115760) for the departmental
NMR facility. We also thank Ms. Ashley Weems for preparing
compound 8.
(c 0.0114, CHCl3); Rf at 20% EtOAc/hexane 0.16; HRMS (EI) calcd
for C19H20O3 (M+) 296.1412, found 296.1416.
(2-Allyl-6-phenyltetrahydropyran-4-yloxy)triethylsilane (18).
To a solution of lactone 3 (203 mg, 1.059 mmol) in 2:1 of Et2O
(10.6 mL) and THF (5.3 mL) was added allylmagnesium bromide
(3.27 mL, 3.265 mmol, 3.083 equiv) at -78 °C. The reaction was
stirred until the starting material was consumed. The mixture was
quenched with water and extracted (30 mL × 3) with CH2Cl2. The
organic extracts were dried with anhydrous NaSO4 and concentrated
under vacuum. The resultant hemiketal (263 mg, 1.1225 mmol)
was dissolved in CH2Cl2 (11.2 mL). To the solution were added
Supporting Information Available: Experimental procedures
and full characterization data for all new compounds. In addition,
1H NMR spectral data for the previously reported compounds are
also accessible. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO061296F
7914 J. Org. Chem., Vol. 71, No. 20, 2006