Total synthesis of α-deamino-3-(β-D-glucopyranosyloxy)kynurenine

Article abstract of DOI:10.1016/S0040-4020(00)00285-4

α-Deamino-3-β-glucopyranosyloxy)kynurenine, a yellow, fluorescent compound isolated from human lens, was synthesized in 8 steps (10% overall yield) from commercially available 3-methoxy-2-nitrobenzaldehyde. Key events included preparation and glucosylatio

Full text of DOI:10.1016/S0040-4020(00)00285-4

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 3673±3677
Total Synthesis of a-Deamino-3-(b-d-
glucopyranosyloxy)kynurenine
*
H. Keith Chenault, Jie Yang and Douglass F. Taber
Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA
Received 21 December 1999; accepted 30 March 2000
AbstractÐa-Deamino-3-(b-d-glucopyranosyloxy)kynurenine, a yellow, ¯uorescent compound isolated from human lens, was synthesized
in 8 steps (10% overall yield) from commercially available 3-methoxy-2-nitrobenzaldehyde. Key events included preparation and gluco-
sylation of methyl 4-(3-hydroxy-2-nitrophenyl)-4-oxobutanoate followed by reduction of the nitro group and deprotection. q 2000 Elsevier
Science Ltd. All rights reserved.
Introduction
a-Deamino-3-(b-d-glucopyranosyloxy)kynurenine (1) is
the most recently identi®ed member of a series of UV-®lter-
ing agents isolated from the protein-free extract of human
eye lens.1 Other known members of this class of compound
are 3-(b-d-glucopyranosyloxy)-l-kynurenine (2),2,3 kynur-
enine (3),2,3 and 3-hydroxy-l-kynurenine (4).4 A structur-
ally related glucoside, 2-amino-3-(b-d-glucopyrano-
syloxy)acetophenone (5),5 has been isolated from the inso-
luble protein fraction of human lens. The three glucosides
To provide material in a quantity suitable for further study,
are unusual both because glucoside formation in mamma-
we have devised a practical synthesis of 1. During the
course of our work, another synthesis of 1 was also
lian tissue is rare and because these compounds are found in
the lenses of primates but not in the lenses of other animals.2
Although compounds 1±5 may serve as photoprotective
reported.9
®lters,6 they limit the frequency range of visual perception
by primates7 and may contribute to cataract formation
Results and Discussion
through photosensitization of molecular oxygen.2,8 Access
to these compounds in order to study their biological and
photophysical properties is clearly desirable.
We initially investigated ortho-metalation/acylation of a
suitably protected 2-aminophenol, such as 7 (Scheme 1),
as a route to assemble the aglycone portion of 1. Although
the dianion of 7 could be generated (3.0 equiv. of tBuLi in
ether, 278 to 2208C) and successfully formylated or deut-
erated, reactions of the dilithium salt of 7 with active acyl
derivatives (anhydride, acid chloride, and Weinreb amide10)
of succinic acid led only to recovered 7 (Table 1). Appar-
ently, the hard aryl anion prefers to deprotonate the acyl
Keywords: glycosidation; lithiation; natural products; NMR.
* Corresponding author. Current address: Dupont Central Research and
Development, Experimental Station, P.O. Box 80328, Wilmington, DE
19880-0328, USA. Tel.: 11-302-695-7861; fax: 11-302-695-3786;
Scheme 1.
e-mail: h-keith.chenault@usa.dupont.com
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00285-4

3674
H. K. Chenault et al. / Tetrahedron 56 (2000) 3673±3677
Table 1. ortho-Metalation reactions of 7
yield. Apparently, this glycosylation requires the phenoxide
anion as the nucleophile, and silver imidazolate is able to
deprotonate 12 but not 10.
Toward synthesizing the actual aglycone, we set about to
allylate 3-methoxy-2-nitrobenzaldehyde (14). Although
allylmagnesium bromide failed to give the desired product
in reasonable yield, reaction of 14 with allyltrimethylsi-
lane16 in the presence of TiCl4 gave 15 in 90% yield
(Scheme 3). While hydroboration of 15 as the free alcohol17
using BH3´THF or 2 mol equivalents of dicyclohexylborane
generated in situ18 failed to generate 16 satisfactorily,19
exposure of 15 to a slight excess of borane (previously
treated with a substoichiometric amount of cyclohexene)
followed by basic H2O2 produced diol 16 in good yield
and high regioselectivity. Oxidation of 16 with Jones
reagent gave the desired ketoacid in modest yield. Demeth-
ylation of 17 with LiCl in DMF at re¯ux20 followed by
esteri®cation of the reaction residue by BF3´OEt2 in
methanol at re¯ux produced the desired aglycone 18.
Entry
Electrophile
DMF
Product
Yield (%)
1
85
2
3
4
D2O
86
78
81
7
7
Coupling of 18 and 9 proceeded ef®ciently in the presence
of silver imidazolate and zinc chloride to afford glucoside
19 as a single diastereomer (Scheme 4). Catalytic reduction
of 19 over Pd-C gave 20, which was deacetylated in metha-
nol that had not been previously dried to give the free acid,
1, directly.
The identity of 1 was established by agreement of its NMR
data with the partial 1H and 13C spectra reported.1 The struc-
5
75
1
ture of 1 was further con®rmed and its H and 13C reso-
then D2O
nances were assigned by NOE difference, COSY, HMQC,
and HMBC experiments.
donor. Treatment of the dilithium salt of 7 with 1 equiv. of
succinyl chloride prevented deuterium incorporation in the
aromatic ring upon subsequent quench and work-up with
D2O (Table 1, entries 2 and 5). This behavior stands in
stark contrast to the usual tendency of organolithium
reagents to add ef®ciently not only to acid chlorides but
also to the ketones thus produced.10±12 Also surprising is
the apparent failure of succinyl chloride to undergo dehy-
drohalogenation and generate a ketene intermediate, which
itself would be a highly reactive acylating agent.13 Although
a softer aryl anion, such as a magnesium, manganese, zinc,
or copper salt, would probably undergo succinylation satis-
factorily,14 we also found that protected aminophenol 10
was not readily glycosylated by tetra-O-acetylglucopyrano-
syl bromide (9) in the presence of silver imidazolate15
(Scheme 2). We therefore turned to an aglycone intermedi-
ate in which a nitro group served as the precursor to the
amino group.
Conclusion
In conclusion, we have developed a practical synthesis of
¯uorescent glucoside 1, con®rmed its structure, and made
1
full assignment of its H and 13C NMR spectra. Further
study is required to determine the role of 1 and related
glucosides as UV ®lters in human lens and as possible
causative agents in the aging of human lens, particularly
in the generation of cataracts.
Experimental
General procedures
Methylene chloride and THF were puri®ed by distillation
under nitrogen from CaH2 or sodium/benzophenone, respec-
tively. All reactions were conducted under nitrogen in ¯ame
or oven-dried glassware with magnetic stirring, unless noted
In a model study, glucosylation of 2-nitrophenol (12)
proceeded smoothly to give aryl glucoside 13 in 76%
Scheme 2.

H. K. Chenault et al. / Tetrahedron 56 (2000) 3673±3677
3675
Scheme 3.
otherwise. TLC was performed on 2.5£10 cm plates coated
with 250 mm-thick silica gel GF. Column chromatography
a 1 M solution in CH2Cl2) over 15 min. After 10 min at rt,
4.8 mL of allyltrimethylsilane (3.45 g, 30 mmol) was added
all at once. After 10 more min, the reaction mixture was
diluted with ether, washed with water and brine, dried
(Na2SO4), and concentrated. Bulb-to-bulb distillation of
the residual brown oil (5 Torr, bath temperatureˆ1608C)
gave 15 as a pale yellow oil (4.10 g, 92%). Rf (1:2
EtOAc±hexanes) 0.65. 1H NMR d 2.19 (d, Jˆ3.2 Hz,
1H), 2.47 (m, 1H), 2.59 (m, 1H), 3.89 (s, 3H), 4.73 (m,
1H), 5.15 (m, 2H), 5.78 (m, 1H), 6.96 (d, Jˆ8.3 Hz, 1H),
7.17 (d, Jˆ7.7 Hz, 1H), 7.44 (dd, Jˆ7.7, 8.3 Hz, 1H). 13C
NMR (even) d 43.3, 115.0, 119.8, 137.2, 150.9; (odd) d
56.9, 69.0, 111.9, 118.9, 131.6, 133.9. IR (neat) 3418,
1852, 1609, 1531, 1438 cm21. HRLSIMS calcd for
C11H14NO4 (M1H1) 224.0923, found 224.0910.
Ê
was performed on ¯ash-grade silica gel (60 A, 230±
400 mesh).
Unless speci®ed otherwise, 1H NMR and 13C NMR spectra
(400 and 101 MHz, respectively) were recorded using
CDCl3 as the solvent. A JVERT pulse sequence differen-
tiated 13C nuclei bearing an even number of hydrogen atoms
from those bearing an odd number. IR spectra were obtained
of samples as neat oils or KBr pellets. Liquid secondary ion
mass spectra (LSIMS) were obtained using Cs1 (15 eV) as
the ionizing beam and either glycerol or p-nitrobenzyl alco-
hol as the matrix. In some cases, NaI was added to the
matrix to enhance the relative intensity of the quasi-mole-
cular ion. Elemental analysis was performed by Micro-
Analysis, Inc.
1-(3-Methoxy-2-nitrophenyl)-1,4-butanediol (16). Cyclo-
hexene (1.28 g, 16 mmol) and 15 mL of THF were
combined in a 250-mL round-bottomed ¯ask. The ¯ask
was cooled in an ice-water bath and BH3´THF (24 mL of
a 1 M solution in THF) was added. After 10 min, 15 (4.55 g,
1-(3-Methoxy-2-nitrophenyl)-3-buten-1-ol (15). To
a
solution of 3-methoxy-2-nitrobenzaldehyde (3.62 g,
20 mmol) in 20 mL of CH2Cl2 was added TiCl4 (10 mL of
Scheme 4.

3676
H. K. Chenault et al. / Tetrahedron 56 (2000) 3673±3677
20 mmol) in 15 mL of THF was added. The ice bath was
removed and the reaction was stirred for 30 min while
warming to rt. With caution, 10 mL of 3.0 M NaOH
followed by 3.42 mL of 30% aqueous H2O2 were added
over 10 min. The reaction was stirred vigorously for
5 min, diluted with ether, and washed sequentially with
saturated aqueous NH4Cl, water, and brine. The organic
layer was dried (Na2SO4) and concentrated. Chromato-
graphy of the residue gave 16 as a pale yellow solid
(3.69 g, 75%), mp 1038C. Rf (1:3 EtOAc±hexanes) 0.15.
1H NMR d 1.69 (m, 2H), 1.86 (m, 2H), 3.67 (m, 2H),
3.89 (s, 3H), 4.70 (m, 1H), 6.95 (d, Jˆ8.3 Hz, 1H), 7.20
(d, Jˆ7.8 Hz, 1H), 7.43 (dd, Jˆ7.8, 8.3 Hz, 1H). 13C NMR
(even) d 29.5, 36.2, 63.0, 138.2, 140.2, 150.8; (odd) d
56.9, 69.9, 111.7, 118.9, 131.6. IR (KBr) 3320, 1527,
1372, 1280, 1058, 1019 cm21. HRLSIMS calcd for
C11H16NO5 (M1H1) 242.1028, found 242.1027. Anal.
calcd for C11H15NO5: C, 54.77; H, 6.27; N, 5.81. Found:
C, 54.91; H, 6.42; N, 5.80.
followed by 19 as a yellow foam (38 mg, 83% based on
starting material consumed). Rf (1:1 EtOAc±hexanes)
0.28. H NMR d 2.05 (s, 3H), 2.10 (s, 3H), 2.14 (s, 3H),
1
2.17 (s, 3H), 2.67±2.84 (m, 2H), 3.12±3.33 (m, 2H), 3.69 (s,
3H), 3.79±3.94 (m, 1H), 4.24±4.29, (m, 2H), 4.99±5.35 (m,
4H), 7.52±7.58 (m, 2H), 7.62±7.67 (m, 1H) 13C NMR
(even) d 27.7, 34.9, 61.6, 131.3, 140.8, 148.2, 169.2,
169.2, 170.1, 170.4, 172.7, 195.8; (odd) d 20.4, 20.5,
20.7, 21.0, 51.9, 67.9, 70.2, 72.0, 72.3, 100.5, 123.6,
123.8, 131.1 IR (KBr) 1743, 1699 cm21. HRLSIMS calcd
for C25H29NO15Na (M1Na1) 606.1462, found 606.1449.
3-(4-Methoxy-4-oxobutanoyl)-2-aminophenyl tetra-O-
acetyl-b-d-glucopyranoside (20). A solution of 6 (32 mg,
0.055 mmol) in 5 mL of methanol was stirred with 8 mg of
5% Pd-C under an atmosphere of H2 at rt for 3 h. The reac-
tion mixture was ®ltered and concentrated. Chromatography
of the residue (1:3 EtOAc±hexane with 1% Et3N) afforded 7
(26 mg, 86%) as a pale yellow foam. Rf (1:1 EtOAc±
1
hexanes) 0.48. H NMR d 2.04 (s, 3H), 2.05 (s, 3H), 2.08
4-(3-Methoxy-2-nitrophenyl)-4-oxobutanoic acid (17). A
solution of 0.10 g of CrO3 in 2 mL of 80% aqueous H2SO4
was added dropwise over 5 min to a solution of 16 (360 mg,
1.49 mmol) in 15 mL of acetone. After 30 min, 5 g of silica
gel was added, and the mixture was evaporated to dryness.
The residue was placed on a column of silica gel and eluted
to give 17 (208 mg, 55%) as pale brown needles, mp 1398C.
(s, 3H), 2.20 (s, 3H), 2.71 (m, 2H), 3.30 (t, Jˆ6.6 Hz, 2H),
3.71 (s, 3H), 3.86 (ddd, Jˆ2.4, 5.1, 9.9 Hz, 1H), 4.18 (dd,
Jˆ2.4, 12.3 Hz, 1H), 4.31 (dd, Jˆ5.1, 12.3 Hz, 1H), 4.96
(m, 1H), 5.16 (m, 1H), 5.29±5.34 (m, 2H), 6.51 (br s, 2H),
6.55 (dd, Jˆ7.8, 8.2 Hz, 1H), 7.04 (dd, Jˆ1.0, 7.8 Hz, 1H),
7.53 (dd, Jˆ1.0, 8.2 Hz, 1H). 13C NMR (even) d 28.8, 34.1,
61.8, 117.8, 142.2, 144.6, 169.4, 169.9, 170.1, 170.5, 173.6,
199.7; (odd) d 20.5, 20.6, 20.7, 20.8, 51.8, 68.2, 71.1, 72.1,
72.2, 100.3, 113.9, 118.9, 125.5. IR (KBr) 1748, 1689,
1640 cm21 HRLSIMS calcd for C25H31NO13Na (M1Na1)
576.1693, found 576.1711.
1
Rf (1:9 acetone/CH2Cl2) 0.30. H NMR (250 MHz) d 2.80
(t, Jˆ6.5 Hz, 2H), 3.23 (t, Jˆ6.5 Hz, 2H), 3.93 (s, 3H), 7.25
(d, Jˆ8.2 Hz, 1H), 7.42 (d, Jˆ7.9 Hz, 1H), 7.55 (dd, Jˆ7.9,
8.2 Hz, 1H). 13C NMR (DMSO-d6) (even) d 28.4, 40.0,
131.8, 140.2, 152.4, 174.0, 197.9; (odd) d 57.8, 118.8,
122.2, 132.8. IR (KBr) 1698, 1695, 750, 668 cm21
.
a-Deamino-3-(b-d-glucopyranosyloxy)kynurenine (1).
To a solution of 7 (26 mg, 0.047 mmol) in 5 mL of methanol
was added 0.20 mL of 0.025 M NaOMe in methanol. After
14 h at rt, the reaction mixture was concentrated. The resi-
due was chromatographed on reverse-phase silica gel
(Analtech, C18-bonded) with water to give 8 (14 mg, 80%
yield) as a yellow crystalline solid. Rf (1:5:94 AcOH-EtOH-
EtOAc) 0.22. 1H NMR (D2O) d 2.49 (t, Jˆ6.8 Hz, 2H, Ha),
3.23 (t, Jˆ6.8 Hz, 2H, Hb), 3.48 (m, 1H, H40), 3.55 (m, 1H,
H50), 3.58 (m, 1H, H30), 3.60 (m, 1H, H20), 3.74 (dd, Jˆ5.5,
12.5 Hz, 1H, H60a), 3.89 (dd, Jˆ2.0, 12.5 Hz, 1H, H60b),
4.99 (d, Jˆ7.1 Hz, 1H, H10), 6.75 (dd, Jˆ7.9, 8.3 Hz, 1H,
H5), 7.28 (dd, Jˆ1.1, 7.9 Hz, 1H, H4), 7.67 (dd, Jˆ1.1,
8.3 Hz, 1H, H6). 13C NMR (D2O) d 32.2 (Ca), 36.2 (Cb),
60.8 (C60), 69.7 (C40), 73.2 (C30), 75.8 (C20), 76.5 (C50),
101.9 (C10), 116.2 (C5), 119.6 (C1), 120.7 (C4), 126.4 (C6),
141.4 (C2), 145.2 (C3), 182.3 (CO2H), 204.7 (CvO).
HRLSIMS (M1Na1) calcd for C16H21NO9Na 394.1114,
found 394.1118.
HRLSIMS calcd for C11H12NO6 (M1H1) 254.0664, found
254.0653. Anal. calcd for C11H11NO6: C, 52.18; H, 4.38; N,
5.53. Found: C, 52.51; H, 4.41; N 5.59.
Methyl
4-(3-hydroxy-2-nitrophenyl)-4-oxobutanoate
(18). A solution of LiCl (80 mg, 1.89 mmol) and 17
(130 mg, 0.51 mmol) in 10 mL of 95% aqueous DMF was
heated at re¯ux for 4 h. The reaction mixture was diluted
with ethyl acetate, washed sequentially with 5% aqueous
HCl, water, and brine, dried (Na2SO4), and concentrated.
The residue was dissolved in 20 mL of dry methanol and
0.5 mL of BF3´OEt2 was added. The reaction was heated at
re¯ux for 1 h, and then concentrated. The residue was chro-
matographed to give 18 (59 mg, 45%) as a yellow oil. Rf
1
(1:3 EtOAc±hexanes) 0.32. H NMR d 2.83 (t, Jˆ6.6 Hz,
2H), 3.09 (t, Jˆ6.6 Hz, 2H), 3.73 (s, 3H), 6.94 (dd, Jˆ1.1,
7.3 Hz, 1H), 7.23 (dd, Jˆ1.1, 8.5 Hz, 1H), 7.61 (dd, Jˆ7.3,
8.5 Hz, 1H), 10.51 (br s, 1H) 13C NMR (even) d 28.4, 38.1,
115.0, 140.3, 155.6, 173.4, 200.7; (odd) d 52.4, 119.0,
121.6, 137.4. IR (KBr) 1734, 1699 cm21. HRMS (EI)
calcd for C11H11NO6 253.0586, found 253.0577.
Acknowledgements
3-(4-Methoxy-4-oxobutanoyl)-2-nitrophenyl
acetyl-b-d-glucopyranoside (19). To a mixture of 18
(32 mg, 0.126 mmol) and (156 mg, 0.380 mmol)
tetra-O-
We are grateful to Dr Steve Bai for his advice and help with
the NMR experiments. We also thank Dr Alfredo Castro for
his pioneering work on this project.
9
dissolved in 6 mL of CH2Cl2 was added silver imidazolate
(66 mg, 0.377 mmol) followed by 0.38 mL of 1.0 M ZnCl2
in ether. After stirring 16 h at rt in the dark, the reaction
mixture was ®ltered, and the ®ltrate was concentrated. Chro-
matography of the residue gave recovered 18 (12 mg)
References
1. (a) Truscott, R. J. W.; Wood, A. M.; Carver, J. A.; Sheil, M. M.;

H. K. Chenault et al. / Tetrahedron 56 (2000) 3673±3677
3677
Stutchbury, G. M.; Zhu, J.; Kilby, G. W. FEBS Lett. 1994, 348,
173±176. (b) Inoue, A.; Satoh, K. Bioorg. Med. Chem. Lett. 1994,
4, 2303±2306.
13. Baigrie, L. M.; Seiklay, H. R.; Tidwell, T. T. J. Am. Chem.
Soc. 1985, 107, 5391±5396.
14. (a) Jabri, N.; Alexakis, A.; Normant, J. F. Tetrahedron Lett.
1983, 24, 5081±5084. (b) Jabri, N.; Alexakis, A.; Normant, J. F.
Tetrahedron 1986, 42, 1369±1380. (c) Cahiez, G.; Laboue, B.
Tetrahedron Lett. 1992, 33, 4439±4442. (d) Cahiez, G.; Chavant,
P. Y.; Metais, E. Tetrahedron Lett. 1992, 33, 5245±5248. (e) Kie¯,
C.; Mannschreck, A. Synthesis 1995, 1033±1037. (f) Evans, P. A.;
Nelson, J. D.; Stanley, A. L. J. Org. Chem. 1995, 60, 2298±2301.
(g) Malanga, C.; Aronica, L. A.; Lardicci, L. Tetrahedron Lett.
1995, 36, 9185±9188. (h) Martin, R.; Romea, P.; Tey, C.; Urpi,
F.; Vilarrasa, J. Synlett 1997, 1414±1416.
2. van Heyningen, R. Nature 1971, 230, 393±394.
3. van Heyningen, R. Exp. Eye Res. 1973, 15, 121±126.
4. Wood, A. M.; Truscott, R. J. W. Exp. Eye Res. 1993, 56, 317±
325.
5. (a) Inoue, A.; Satoh, K. Bioorg. Med. Chem. Lett. 1993, 3, 345±
346. (b) Das, S. K.; Saha, U. K. Bioorg. Med. Chem. Lett. 1994, 4,
1219±1220.
6. (a) Dillon, J.; Atherton, S. J. Photochem. Photobiol. 1990, 51,
465±468. (b) Dillon, J.; Wang, R. H.; Atherton, S. J. Photochem.
Photobiol. 1990, 52, 849±854.
15. Garegg, P. J.; Hultberg, H.; Ortega, C.; Samuelsson, B. Acta
Chem. Scand. B 1982, 36, 513±514.
7. Wald, G. J. Opt. Soc. Am. 1952, 42, 171±177.
8. (a) Zigler Jr., J. S.; Goosey, J. D. Photochem. Photobiol. 1981,
33, 869±874. (b) Stutchbury, G. M.; Truscott, R. J. W. Exp. Eye
Res. 1993, 57, 149±155.
16. (a) Ordoukhanian, P.; Taylor, J.-S. J. Am. Chem. Soc. 1995,
117, 9570±9571. (b) Hosomi, A.; Sakurai, H. Tetrahedron Lett.
1976, 1295±1298.
9. Manthey, M. K.; Jamie, J. F.; Truscott, R. J. W. J. Org. Chem.
1999, 64, 3930±3933.
17. Hydroboration of homoallylic alcohols: (a) Heathcock, C. H.;
Jarvi, E. T.; Rosen, T. Tetrahedron Lett. 1984, 25, 243±246. (b)
Hanson, J. R.; Liman, M. D.; Nagaratnam, S., J. Chem. Res. (S)
10. Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815±
3818.
11. (a) Cunico, R. F.; Clayton, F. J. J. Org. Chem. 1976, 41, 1480±
Â
1997, 282±283. (c) Pegorier, L.; Larcheveque, M. Tetrahedron
Ã
Lett. 1995, 36, 2753±2756.
Ã
1482. (b) Gillet, J. P.; Sauvetre, R.; Normant, J. F. Synthesis 1986,
18. (a) Brown, H. C.; Mandal, A. K.; Kulkarni, S.U. J. Org. Chem.
1977, 42, 1392±1398. (b) Kabalka, G. W.; Yu, S.; Li, N.-S. Tetra-
hedron Lett. 1997, 38, 7681±7682.
355±360. (c) Takahashi, M.; Hatano, K.; Kimura, M.; Watanabe,
T.; Oriyama, T.; Koga, G. Tetrahedron Lett. 1994, 35, 579±582.
12. (a) Posner, G. H.; Whitten, C. E.; McFarland, P. J. Amer.
Chem. Soc. 1972, 94, 5106±5108. (b) Pittman Jr., C. U.; Hanes,
R. M. J. Org. Chem. 1977, 42, 1194±1197. (c) Milstein, D.; Stille,
J. K. J. Am. Chem. Soc. 1978, 100, 3636±3638. (d) Sato, T.;
Naruse, K.; Enokiya, M.; Fujisawa, T. Chem. Lett. 1981, 1135±
1138.
19. Reaction of 15 with BH3´THF followed by basic oxidation
gave 16 in only 20% yield. Similar treatment of 15 using 2 mol
equiv. of dicyclohexylborane gave only recovered starting mater-
ial.
20. Bernard, A. M.; Ghiani, M. R.; Piras, P. P.; Rivoldini, A.
Synthesis 1989, 287±289.