Use of Electrochemical Methods as an Alternative to Tin Reagents for the Reduction of Vinyl Halides in Inositol Synthons

Article abstract of DOI:10.1021/jo990382v

Several vinyl halides previously used in inositol syntheses were subjected to electrochemical reduction. The unreactivity of allylic alcohols or allylic ethers at the applied potentials allowed the selective reduction of vinyl halides to olefins. Electrochemical methods provide for selective reduction of vinyl iodides over vinyl bromides, with better yields than analogous tin methodology. Cinnamyl ethers were reductively cleaved at -3.2 V (vs Ag/AgNO₃) in the presence of alkyl allyl ethers to provide selective deprotection. The electrochemical reduction of vinyl halides in the presence of a vinyloxirane or vinylaziridine is accompanied by the solvolysis of the strained rings. Yields and conditions are reported and compared to those from standard tin-induced dehalogenation.

Full text of DOI:10.1021/jo990382v

J . Org. Chem. 1999, 64, 4909-4913
4909
Use of Electr och em ica l Meth od s a s a n Alter n a tive to Tin Rea gen ts
for th e Red u ction of Vin yl Ha lid es in In ositol Syn th on s
Tomas Hudlicky,* Christopher D. Claeboe, Larry E. Brammer, J r., Lukasz Koroniak,†
Gabor Butora, and Ion Ghiviriga‡
Department of Chemistry, University of Florida, Gainesville, Florida 32611-7200
Received March 2, 1999
Several vinyl halides previously used in inositol syntheses were subjected to electrochemical
reduction. The unreactivity of allylic alcohols or allylic ethers at the applied potentials allowed the
selective reduction of vinyl halides to olefins. Electrochemical methods provide for selective reduction
of vinyl iodides over vinyl bromides, with better yields than analogous tin methodology. Cinnamyl
ethers were reductively cleaved at -3.2 V (vs Ag/AgNO3) in the presence of alkyl allyl ethers to
provide selective deprotection. The electrochemical reduction of vinyl halides in the presence of a
vinyloxirane or vinylaziridine is accompanied by the solvolysis of the strained rings. Yields and
conditions are reported and compared to those from standard tin-induced dehalogenation.
In tr od u ction
C5 (mCPBA; H3O+)4 was followed by reduction of the
vinyl halide (nBu3SnH/AIBN) to the protected conduritol
F (4),5 as shown in Scheme 1. This manuscript describes
the electrochemical reduction of vinyl halides in various
inositol synthons as an alternative to the use of tin
reagents.
The synthesis of conduritols, inositols, and condu-
ramines from cyclohexdiene-cis-diols (2), obtained by
enzymatic oxidation of halobenzenes with Escherichia
coli J M109 (pDTG601), has been demonstrated in our
laboratories.1 Of particular importance to the second
generation synthesis of these compounds is its overall
efficiency and the “green” or environmentally benign
nature of the transformations that follow the enzymatic
step.1e
Resu lts a n d Discu ssion
Five inositol intermediates (used in previous studies
and that we require in large quantities for our current
research on inositol oligomers)6 were investigated (Table
1, entries 1-5). For each compound, we compared the
yields from electrochemical reduction (mercury pool
cathode) to those obtained with trialkyltin hydrides.
The starting materials for the halide reductions were
produced by means of synthetic techniques optimized in
our laboratories during previous ventures into inositol
synthesis.7 The anti epoxide 14 and related compounds
Electrochemical methods2 of oxidation and reduction
offer a versatile and nonstoichiometric alternative to
widely used metal-based reagents. In particular, electro-
chemical reduction of aryl and vinyl halides has been
documented in both mechanistic and synthetic studies.3
We have already investigated the electrochemical oxida-
tion of the C4-C5 double bond of 2 as an alternative to
oxidation by mCPBA.4 For example, in an earlier syn-
thesis of conduritol F, oxidative functionalization at C4-
(3) (a) Fry, A.; Mitnick, M. A.; Reed, R. G. J . Org. Chem. 1970, 4,
1232. (b) Bhuvaneswari, N.; Venkatachalam, C. S.; Balasubramanian,
K. K. Tetrahedron Lett. 1992, 33, 1499. (c) Urove, G. A.; Peters, D. G.;
Mubarak, M. S. J . Org. Chem. 1992, 57, 786. (d) Miller, L. L.; Rienkena,
E. J . Org. Chem. 1969, 34, 3359. (e) Fry, A. J .; Mitnick, M. A. J . Am.
Chem. Soc. 1969, 91, 6207.
(4) In preliminary experiments, syn epoxide ii was made by the
electrochemical generation of bromohydrin i; the procedure for the
electrochemical generation of i was adapted from unpublished results
† Undergraduate research participant. Present address: Adam
Mickiewicz University, Chemistry Department, 60-780 Poznan, Poland.
‡ To whom inquiries regarding 2D-NMR data should be addressed.
(1) For comprehensive reviews of arene cis-diol chemistry see: (a)
Brown, S. M.; Hudlicky, T. In Organic Synthesis: Theory and Applica-
tions; Hudlicky, T., Ed.; J AI Press: Greenwich, CT, 1993; Vol. 2, pp
113-176. (b) Widdowson, D. A.; Ribbons, D. W.; Thomas, S. D. J anssen
Chim. Acta 1990, 8, 3. (c) Carless, H. A. J . Tetrahedron: Asymmetry
1992, 3, 795. (d) Hudlicky, T.; Reed, J . W. In Advances in Asymmetric
Synthesis; Hassner, A., Ed.; J AI Press: Greenwich, CT, 1995; p 271.
(e) Hudlicky, T. In Green Chemistry: Designing Chemistry for the
Environment; Anastas, P. T., Williamson, T., Eds.; ACS Symposium
Series 626, American Chemical Society: Washington, DC., 1996;
Chapter 14. (f) Hudlicky, T.; Thorpe, A. J . J . Chem. Soc., Chem.
Commun. 1996, 1993. (g) Hudlicky, T. Chem. Rev. 1996, 96, 3. (h)
Hudlicky, T.; Entwistle, D. A.; Pitzer, K. K.; Thorpe, A. J . Chem. Rev.
1996, 96, 1195. (i) Grund, A. D. SIM News 1995, 45, 59. (j) Boyd, D.
R. Nat. Prod. Rep. 1998, 309. (j) Hudlicky, T.; Gonzalez, D.; Gibson,
D. T. Aldrichimica Acta 1999, in press.
of G. Butora and L. Koroniak. This procedure provides
a nice
alternative to the synthesis of ii, whose protected version has been
reported: Carless, H. A. J . J . Chem. Soc., Chem. Commun. 1992, 234.
(2) For reviews on electrochemical methods of synthesis, see: (a)
Lund, H.; Baizer, M. M. Organic Electrochemistry: An Introduction
and a Guide; Marcel Dekker: New York, 1991. (b) Volke, J .; Liska, F.
In Electrochemistry in Organic Synthesis; Springer-Verlag: New York,
1994; pp 1-44, 90. (c) Utley, J . J . Chem. Soc. Rev. 1997, 26, 157. (d)
Saiganesh, R.; Balasubramanian, K. K.; Venkatachalam, C. S. J .
Electroanal. Chem. 1989, 262, 221. For recent applications, see: (e)
Rossen, K.; Volante, R. P.; Reider, P. J . Tetrahedron Lett. 1997, 38,
777. (f) Frey, D. A.; Wu, N.; Moeller, K. D. Tetrahedron Lett. 1996, 37,
8317. (g) Moeller, K. D. Topics in Current Chemistry; Springer-
Verlag: Berlin, 1997; Vol. 185, p 50.
(5) Hudlicky, T.; Luna, H.; Olivo, H.; Andersen, C.; Nugent, T.; Price,
J . D. J . Chem. Soc., Perkin Trans. 1 1991, 2907.
(6) Hudlicky, T.; Abboud, K. A.; Entwistle, D. A.; Fan, R.; Maurya,
R.; Thorpe, A. J .; Bolonick, J .; Myers, B. Synthesis 1996, 897.
(7) (a) Hudlicky, T.; Price, J . D.; Olivo, H. F. Synlett 1991, 645. (b)
Hudlicky, T.; Price, J . D.; Fan, R.; Tsunoda, T. J . Am. Chem. Soc. 1990,
112, 9439. (c) Hudlicky, T.; Fan, R.; Tsunoda, T.; Luna, H.; Andersen,
C.; Price, J . D. Isr. J . Chem. 1991, 31, 229. (d) Desjardins, M.;
Brammer, L. E., J r.; Hudlicky, T. Carbohydr. Res. 1997, 304, 39. (e)
Brammer, L. E., J r.; Hudlicky, T. Tetrahedron: Asymmetry 1998, 9,
2011.
10.1021/jo990382v CCC: $18.00 © 1999 American Chemical Society
Published on Web 05/29/1999

4910 J . Org. Chem., Vol. 64, No. 13, 1999
Hudlicky et al.
Sch em e 1
compared to a 67% tin reduction. There was no reaction
of chloro derivative 5b under the conditions; however,
its reduction by nBu3SnH-AIBN afforded 6 in 36%
yield.7c
After the completion of our preliminary results (Table
1, entries 1-5), we wished to determine whether the
electrochemical method is comparable in efficiency to the
larger-scale nBu3SnH experiments we have previously
used.5,7e A larger electrochemical cell was constructed to
accommodate a scale of 1-5 g of starting material.
Compound 7a was chosen for scale-up because of its ease
of preparation and its general relationship to the other
conduritol precursors. Unfortunately, the scale-up pro-
cess did not result in an appreciable increase in the
overall yield of the reduced product 8 over that from
reduction with nBu3SnH. Perhaps the most problematic
step in the process was the separation of the product from
the supporting electrolyte. Although the greatest yield
(59%) was obtained with nBu4NBF4 as the charge carrier,
it was the most difficult to separate from the product.
On the other hand, the easiest charge carrier to remove
from the reaction mixture (Et4N+pTsO-, by recrystalli-
zation from ethyl acetate) gave the poorest yield (6%).
Selectivity Stu d ies. Iodobromodiol 9 (prepared by
fermentation of iodobromobenzene with Pseudomonas
putida)1j was examined in an effort to effect a selective
electrochemical reduction of the vinyl iodide over the
vinyl bromide. Constant potential electrolysis of 9 at -2.3
V resulted in the desired cis-bromodienediol 10 in 73%
yield, a yield superior to that from the reduction with
n-Bu3SnH. The electrolyses were completed in less than
15 min at this potential.
were produced by means of m-CPBA in dichloromethane
at 0 °C (Scheme 1, iii). Compound 14 was subjected to
treatment with KOH in DME-H2O to afford protected
tetrol 3, whose absolute stereochemistry corresponds to
that of conduritol F. The conduritol C precursors (5a and
5b) were generated by treating cyclohexadiene-cis-diol
2, protected as the acetonide, with 1,3-dibromo-5,5-
dimethylhydantoin (DBH) to produce a bromohydrin,
whose closure (10% NaOH, DME) afforded the syn
epoxide.4 The epoxide was opened with KOH in DME-
H2O, as previously reported.7d,e Osmylation of protected
cis-diols 2 (OsO4, NMO, 3:1 acetone-H2O) afforded
conduritol E precursors 7a and 7b. The reduction of these
compounds (Table 1, entries 1-5) forms the basis of our
study.
Cyclic a n d Lin ea r Sw eep Volta m m etr y. Cyclic and
linear sweep measurements were performed with a gold
working electrode and a platinum auxiliary electrode,
with a Ag/Ag+ reference electrode (0.5785 V vs normal
hydrogen electrode) consisting of a silver wire immersed
in a 0.1 M solution of silver nitrate in acetonitrile. The
voltammetry of all compounds was hampered by adsorp-
tion of material on the working electrode. In general for
these compounds, the reduction waves were broad (with
Ep - Ep/2 > 100 mV) and exhibited a cathodic shift with
increasing sweep rate. Reproducible voltammograms
were obtained by polishing the electrode surface between
successive sweeps, and by continuous stirring and de-
gassing of the solution. (Specific voltammetric data is
provided in the Supporting Information.)
P r ep a r a tive Electr och em istr y. We envisioned elec-
trochemical reduction (controlled potential) as a competi-
tive alternative to more typical methods of halide reduc-
tion (e.g., nBu3SnH, LiAlH4, silanes, or Al-amalgam) in
these and related systems. Our goal was to optimize the
yield of the reduction while keeping the complexity of the
electrochemical apparatus to a minimum. (See the Ex-
perimental Section for details.) Our investigation began
with the protected conduritol precursors in their halo-
genated form (Table 1, entries 1-5). Optimized electrore-
duction of the brominated conduritol F precursor (3a ) at
-3.2 V resulted in a 62% yield of the protected product
4. The yield obtained from nBu3SnH-AIBN for the same
precursor was 80%. Similar results were obtained for the
other conduritol precursors (entries 2-5): 59% yield with
electrochemical reduction of 5a at -3.0 V compared to
78% reduction with n-Bu3SnH, 57% electroreduction of
7a at -3.0 V vs 85% tin reduction, and 50% electrore-
duction of the iodo conduritol precursor 7b at -3.0 V
A compound that could, at least theoretically, undergo
a radical cyclization in tandem with the halide reduction
was cinnamyl ether 11, Scheme 2. The cinnamoyl pro-
tected diol 11 was subjected to conditions of tin-mediated
radical cyclization in order to produce a standard against
which the results of electrochemical reduction could be
measured. As expected, Bu3SnH treatment provided the
cyclized material as a 4:1 mixture of diastereomers. (The
structure assignment can be found in the Supporting
Information.) The linear sweep voltammogram of 11
showed a broad reduction peak at -3.2 V.
Preliminary bulk electrolyses were conducted at a
constant -2.4 V on a gold foil rather than a mercury pool.
Electrolysis resulted in the cleavage of the cinnamyl
groups to afford an allylic alcohol and the acetonide-
protected diol 12. It was necessary to revert to the
mercury pool working electrode because an extensive
amount of adsorption was observed as the amount of
starting material for successive electrolyses was in-
creased. Other experiments using the Hg-pool cathode
led to the same product (12). Although no radical cycliza-
tion was observed (in agreement with the studies of Fry,3e
who has shown the initially formed radical undergoes
rapid reduction to an anion), the result is interesting
because of its potential as a method for mild deprotection
of alcohols or diols.
Str u ctu r a l An a lysis. Detailed information about the
structures of compounds 11, 13a , and 13b was obtained
by NMR analysis (TOCSY, HSQC, and NOE); it is
included in the Supporting Information.
Red u ction of Br om ovin yl Oxir a n es, a n d Azir i-
d in es. Epoxide 14 and aziridine 17 (Table 1, entries 8
and 9) were also investigated. The nBu3SnH reduction
of these materials resulted in dehalogenation products,

Electrochemical Reduction of Vinyl Halides
J . Org. Chem., Vol. 64, No. 13, 1999 4911
Ta ble 1. Red u ction of Vin yl Ha lid es
a
b
Reference 5. Nguyen, B. V.; York, C.; Hudlicky, T. Tetrahedron Lett. 1997, 53, 8807. c Nugent, T.; Hudlicky, T. J . Org. Chem. 1998,
63, 510. Reference 7c. e Reference 7. f Akgu¨n, H.; Gonzales, D.; Martinot, T.; Hudlicky, T. Unpublished results. g Charge carrier: nBu4NOH.
Reference 7b. Tian, X.; Maurya, R.; Ko¨nigsberger, K.; Hudlicky, T. Synlett 1995, 1125.
d
h
i

4912 J . Org. Chem., Vol. 64, No. 13, 1999
Hudlicky et al.
Sch em e 2
age. A 0.1 M solution of the charge carrier (Et4NBr or
nBu4NBF4) in acetonitrile was added to the cell (50 mL per
100 mg starting material) and allowed to equilibrate with the
divided cell (a fritted chamber). Excess oxygen was expelled
from the electrochemical cell by passing an argon stream
through the reaction mixture for 10-20 min. The starting
material was dissolved in acetonitrile and added to the main
compartment. The reduction was performed at a constant
potential (see Table 1) until TLC analysis indicated disap-
pearance of the starting material.
Sch em e 3
After the reaction was complete, the reaction mixture was
decanted from the Hg pool and the solvent evaporated to yield
a solid constisting of the product and the charge carrier. The
product was extracted with warm EtOAc (when was used) or
with water (for nBu4NBF4) The fractions in the former case
were dried over MgSO4 and filtered through Celite. Solvent
(ethyl acetate or water) was then evaporated at reduced
pressure to afford a product that typically required purification
by column chromatography (10% H2O deactivated flash silica
gel) followed by recrystallization.
Electr och em ica l Red u ction of 14 a n d 17. To 100 mL of
1 M Bu4NOH in methanol in an electrolysis cell was added
250 mg of either 14 or 17. The mixture was electrolyzed for 1
h at -2.4 V. Upon completion of the reaction, the solvent was
evaporated, and the resulting solid was extracted with ethyl
acetate (3 × 100 mL). The extract was concentrated in vacuo
to yield crude product 15 or 18. The product was purified by
column chromatography (1:1 EtOAc-hexane).
16 in 50% yield and 19 in 83% yield, respectively. As one
goal of our research is the development of a cost-effective
tandem enzymatic-electrochemical synthesis of inositols,
a major step toward that end would be debromination of
the bromo epoxides and aziridines accompanied by ring-
opening by nucleophiles. With that in mind, we subjected
14 and 17 to electrolysis in the presence of nBu4NOH in
methanol, anticipating that the electrolyte would serve
as a source of hydroxide.
The constant potential electrolysis of 14 resulted in a
50% yield of 15, the methylated derivative of protected
conduritol F, and also a precursor to (-)-pinitol7b (Scheme
3). We concluded that the methoxide ion was opened of
the epoxide (23) whereas the electrolysis effected the
debromination in an overall CE-type process. The elec-
trochemical reduction of the aziridine 17 under the same
conditions produced methoxy-substituted dehalogenated
tosylamide 18 (potential amino inositol synthon)8 in 98%
yield.
[3a S-(3a R,4R,5â,7a R)]-4-[(p-Tolu en esu lfon yl)a m in o]-5-
m eth oxy-3a,4,5,7a-tetr ah ydr o-2,2-dim eth yl-1,3-ben zodiox-
ole (20): Rf ) 0.45 (1:1 EtOAc-hexane); [R]23.5 ) 6.5° (c )
D
0.11, CHCl3); mp ) 113-114 °C; IR (KBr, 3%) 3201, 1317,
1
1100, 1065 cm-1; H NMR (300 MHz, CDCl3) δ 7.82 (d, J )
8.1 Hz, 2H), 7.25 (d, J ) 8.1 Hz, 2H), 5.87 (dd, J ) 7.5, 10.5
Hz, 2H), 5.72 (d, J ) 7.5 Hz), 4.59 (bs), 4.10 (dd, J ) 3.3, 6.0
Hz, 1H), 3.62 (d, J ) 9.0 Hz, 1H), 3.47 (q, J ) 7.8 Hz, 1H),
3.04 (s, 3H), 2.4 (s, 3H), 1.40 (s, 3H), 1.31 (s, 3H); 13C NMR
(125 MHz, CDCl3) δ 142.4, 139.0, 131.7, 128.9, 127.2, 123.9,
110.4, 77.9, 76.0, 72.0, 56.8, 56.0, 27.7, 25.9, 21.3; HRMS FAB+
(M + H) exact mass calculated for C17H24NO5S 354.1375, found
354.1349. Anal. Calcd for C17H24NO5S: C, 57.77; H, 6.56; N,
3.96. Found C, 57.63; H, 6.46; N, 3.87.
Exp er im en ta l Section
Ha lid e Red u ction s w ith n Bu 3Sn H. To a mixture of
substrate in dry THF was added 1.5 equiv of nBu3SnH (97%),
followed by a catalytic amount of AIBN. The reaction mixture
was heated at reflux until TLC analysis showed the disap-
pearance of starting material, after which time the solvent was
removed under reduced pressure. The crude product was
suspended in hexane and extracted with H2O (3a , 5a , 7a , and
7b) or acetonitrile (11, 14, and 17). For compounds 3a , 5a ,
7a , and 7b, the water was evaporated under reduced pressure;
the product was dissolved in ethyl acetate and then dried over
MgSO4 and filtered through Celite. The solvent was evaporated
and the product recrystallized from ethyl acetate and hexane.
All reactions in nonaqueous media were performed in flame-
dried glassware under argon.
Gen er a l Electr och em ica l Red u ction . The electrolysis
cell consisted of a 200-mL beaker containing a 0.5 cm layer of
Hg as the working electrode, a simple Ag/Ag+ reference
electrode, and a platinum foil in a divided cell as the auxiliary
electrode. An EG & G Princeton Applied Research Poten-
tiostat-Galvanostat Model 263A maintained the desired volt-
(8) (a) Desjardins, M.; Lallemand, M.-C.; Freeman, S.; Hudlicky, T.
J . Chem. Soc., Perkin Trans. 1 1999, 621. (b) Hudlicky, T.; Oppong,
K. A.; Yan, F.; Nguyen, B. V.; York, C. Tetrahedron 1999, in press.

Electrochemical Reduction of Vinyl Halides
J . Org. Chem., Vol. 64, No. 13, 1999 4913
Compounds 11, 14, and 17 required evaporation of the
acetonitrile and subsequent column chromatography (flash
silica gel).
techniques for the dehalogenation of vinyl halides. Elec-
trochemical methods minimize the use of toxic reagents
and solvents, and they reduce or even eliminate the
amount of toxic byproducts produced in traditional
chemical methodology based on tin reagents. The yields
obtained from electrolytic techniques are comparable to
those obtained with tin reagents. We have also shown
that electrochemical techniques are much better than tin
reagents for selective dehalogenation of the dihaloge-
nated cyclohexadiene diols 4. Moreover, we have dem-
onstrated the utility of the cinnamyl group as a potential
protecting group for cyclohexadiene diols, as this func-
tionality is easily removed selectively by means of po-
tentiostatic techniques.
We have also demonstrated the potential for the
incorporation of electrochemical techniques into the
synthesis of conduritols and conduramines. This is of
enormous value to our ongoing research into the develop-
ment of tandem enzymatic-electrochemical syntheses of
inositols, conduritols, conduramines, and amino inositols,
the results of which will be reported in due course. Future
research in this area will focus on replacing mercury in
the electrochemical reactions with materials such as
vitreous carbon in conjunction with current reversal
techniques to reduce adsorbance on the electrode. Our
ultimate goal is to develop “green” syntheses of inositols
and amino inositols employing only electrochemical and
enzymatic procedures in order to reduce the amount of
byproducts and increase the effective mass yield of the
target compounds.9
[3a R-(3a R,4R,5R,7a R)]-6-Br om o-2,2-d im eth yl-4,5-bis(3-
p h en yl-(E)-2-p r op en yloxy)-3a ,4,5,7a -tetr a h yd r o-2,2-d im -
eth yl-1,3-ben zod ioxole (11). To a suspension of sodium
hydride (720 mg, 30 mmol) in 10 mL of dry THF at 0 °C was
added compound 22 (6.52 g, 24.6 mmol), and the resulting
mixture was stirred for 30 min and then warmed to room
temperature. Cinnamyl bromide (13.1 g, 66.5 mmol) dissolved
in 20 mL of dry THF was added. After 24 h, the reaction was
quenched with water. The organic components were extracted
with Et2O (3 × 100 mL). The combined organic layers were
dried over MgSO4 and filtered over Celite, and the ether was
then removed under reduced pressure. Purification of product
was achieved on flash silica gel with a 1:9 ethyl acetate:hexane
as an eluent to yield 4.98 g of the dicinnamyl product as a
yellow solid (40.6%). HPLC of the product displayed a single
peak eluting at 11.3 min in a 80:20 MeCN: H2O (5 mmol Et3N/
AcOH buffer system). Rf ) 0.24 (EtOAC-hexane, 1:9); [R]23.5
D
) -105.5° (c ) 0.11, CHCl3); mp ) 66-69 °C; IR (KBr): 3462,
2983, 1636, 1449, 1369, 1226, 1118, 1050, 964, 856, 691 cm-1
;
HRMS FAB+ (M + H) exact mass calculated for C27H30BrO4
498.1986, found 497.1328. Anal. Calcd for C27H29BrO4: C,
65.19; H, 5.88. Found C, 65.20; H, 5.91. (See Supporting
Information for NMR data.)
2,2-Dim et h yl-7-(p h en ylm et h yl)-(3a R,4R,4a R,
8a R)-
4H,6H,7H-fu r o[2′,3′:4,5]ben zo[d ][1,3]d ioxol-4-yl-3-p h en yl-
(E)-2-p r op en yl Eth er (13). A two-necked flask with con-
denser and three-way stopcock was charged with the starting
material (11; 425 mg, 0.85 mmol) dissolved in 15 mL of dry
THF, and the reaction mixture was brought to reflux, where-
upon 1.5 equiv of nBu3SnH (128 mg) and AIBN (cat.) were
added. Following heating at reflux overnight, completion of
the reaction was verified by TLC, and the reaction mixture
was concentrated under reduced pressure. Flash chromatog-
raphy (1:9 EtOAc-hexane) yielded a colorless oil (216 mg,
66.1%). HPLC analysis (80:20 acetonitrile-water, 5 mmol
AcOH-Et3N buffer) system revealed a pair of diastereomers
in a 4:1 ratio.
Ack n ow led gm en t. The authors thank TDC Re-
search Foundation (fellowships to C.D.C. and L.K.), the
National Science Foundation (CHE-9615112), the En-
vironmental Protection Agency (R826113), and TDC
Research, Inc., for financial support throughout the
course of this study. Special thanks are extended to Prof.
J ames Tanko (Virginia Tech) for his invaluable sugges-
tions.
13a : Rf ) 0.22 (EtOAc-hexane, 1:9); [R]25 ) -38.8 ° (c )
D
0.27, CHCl3); IR (NaCl): 3007, 2933, 1718, 1601, 1495, 1453,
1361, 1236, 1114, 1056, 968, 885 cm-1; HRMS CI; exact mass
calculated for C27H30O4: 418.5328, found 418.2144. Anal. Calcd
for C27H30O4: C, 77.48; H, 7.22. Found: C, 76.53; H, 7.30. (See
Supporting Information for NMR data.)
Su p p or tin g In for m a tion Ava ila ble: Supporting Infor-
mation includes linear sweep voltammetric analyses (com-
pounds 3a , 5a , 5b, 7a , 7b, 9, 11, 14, and 17) and NMR data
for structure and stereochemical proof of compounds 13a and
13b. This material is available free of charge via the Internet
at http://pubs.acs.org.
13b: Rf ) 0.22 (EtOAc-hexane, 1:9); IR (NaCl): 3008, 2934,
1719, 1602, 1496, 1454, 1382, 1326, 1162, 1115, 1058, 969, 886
cm-1. Anal. Calcd for C27H30O4: C, 77.48; H, 7.22. Found C,
77.14; H, 7.70. (See Supporting Information for NMR data.)
Con clu sion s
J O990382V
We have demonstrated that electrochemical techniques
are reasonable alternatives to more traditonal chemical
(9) Hudlicky, T.; Frey, D. A.; Koroniak, L.; Claeboe, C. D. Green
Chem. 1999, 1, 57.