Stereoselective synthesis of highly substituted tetrahydrofurans

Full text of DOI:10.1021/jo010131y

J . Org. Chem. 2001, 66, 4091-4093
4091
Sch em e 1. Gen er a l Str a tegy F ollow ed for th e
Syn th esis of Su bstitu ted Tetr a h yd r ofu r a n s 5
Ster eoselective Syn th esis of High ly
Su sbstitu ted Tetr a h yd r ofu r a n s
Tushar K. Chakraborty,* Sanjib Das, and
T. Venugopal Raju
Indian Institute of Chemical Technology,
Hyderabad 500 007, India
chakraborty@iict.ap.nic.in
Received February 2, 2001
Saturated oxygen heterocycles, essential structural
components of large number of organic natural products,1
are attracting increased attention as organic chemists
develop new methodologies for their synthesis.2 In this
paper, we describe an efficient strategy for the synthesis
of highly substituted tetrahydofurans3 1-4 following an
acid-catalyzed cycloetherification method. The idea ema-
conditions by a suitably positioned oxygen atom in the
same molecule giving the tetrahydrofuran framework of
5. The acyclic precursor 6 was, in turn, prepared from a
chiral aldehyde 7 using a diastereoselective Grignard
addition reaction. A novel radical-mediated method
developed by us recently6 for the regioselective opening
of trisubstituted 2,3-epoxy alcohols 9 at the more sub-
stituted 2-position using cp2Ti(III)Cl, and cyclohexa-1,4-
diene provided the chiral 1,3-diol 8, the precursor of 7.
The same method has now been extended here for the
first time to open a disubstituted epoxy alcohol also giving
exclusively the 1,3-diol that was used for the synthesis
of 4. Sharpless kinetic resolution7 of the allylic alcohols
10 provided the requisite chiral epoxy alcohols 9. It was
to demonstrate the practical utility of our radical-
mediated epoxide opening methodology that we under-
took the syntheses of these polysubstituted tetrahydro-
furan moieties. The four key reactionssSharpless kinetic
resolution, our radical-mediated regioselective epoxide
ring-opening reaction, a diastereoselective Grignard ad-
dition reaction, and finally, a facile acid-catalyzed cyclo-
etherification stepsoutline the essence of our present
work.
Scheme 2 unfolds the details of the route followed for
the synthesis of 1. The starting 1,3-diol 12 was prepared
from the allylic alcohol 11 in two stepssSharpless
catalytic kinetic resolution using natural diisopropyl (+)-
L-tartrate (85% ee determined by Mosher’s ester method)
followed by treatment of the resulting epoxy alcohol with
cp2TiCl and cyclohexa-1,4-diene according to the reported
procedure.8 Acetonide protection of the diol using cata-
lytic amount of camphorsulfonic acid (CSA) in CH2Cl2 and
2,2-dimethoxypropane and subsequent debenzylation by
hydrogenation furnished the intermediate 13 in 92%
yield. Oxidation of the primary hydroxyl group using
nated from the known4 susceptibility of linear molecules
having SN2 active sites to undergo spontaneous ring
closure, induced by heteroatoms at the γ-position to
produce thermodynamically favorable five-membered
cyclic products, a concept exploited by us recently to
synthesize furanoid sugar amino acids.5 The basic strat-
egy followed in our present work for the synthesis of
substituted tetrahydrofuran 5 is summarized in Scheme
1. A facile leaving group X in the γ-position of the acyclic
precursor 6 is knocked off smoothly under very mild
(1) For recent reviews, see: (a) Alali, F. Q.; Liu, X.-X.; McLaughlin,
J . L. J . Nat. Prod. 1999, 62, 504-540. (b) Norcross, R. D.; Paterson, I.
Chem. Rev. 1995, 95, 2041-2114.
(2) For reviews, see: (a) Elliott, M. C. J . Chem. Soc., Perkin Trans.
1 2000, 1291-1318. (b) Elliott, M. C. J . Chem. Soc., Perkin Trans. 1
1998, 4175-4200. (c) Harmange, J .-C.; Figade`re, B. Tetrahedron:
Asymmetry 1993, 4, 1711-1754. (d) Kotsuki, H. Synlett 1992, 97-106.
(e) Boivin, T. L. B. Tetrahedron 1987, 43, 3309-3362.
(3) For some recent reports on the syntheses of substituted tetrahy-
drofurans, see: (a) Ruan, Z.; Dabideen, D.; Blumenstein, M.; Mootoo,
D. R. Tetrahedron 2000, 56, 9203-9211. (b) Vares, L.; Rein, T. Org.
Lett. 2000, 2, 2611-2614. (c) Barrow, R. A.; Moore, R. E.; Li, L.-H.;
Tius, M. A. Tetrahedron 2000, 56, 3339-3351. (d) Micalizio, G. C.;
Roush, W. R. Org. Lett. 2000, 2, 461-464. (e) Pilli, R. A.; Riatto, V. B.;
Vencanto, I. Org. Lett. 2000, 2, 53-56. (f) Morimoto, Y.; Iwai, T.;
Kinoshita, T. J . Am. Chem. Soc. 1999, 121, 6792-6797. (g) Sinha, S.
C.; Keinan, E.; Sinha, S. C. J . Am. Chem. Soc. 1998, 120, 9076-9077.
(h) Ley, S. V.; Brown, D. S.; Clase, J . A.; Fairbanks, A. J .; Lennon, I.
C.; Osborn, H. M. I.; Stokes, E. S. E.; Wadsworth, D. J . J . Chem. Soc.,
Perkin Trans. 1 1998, 2259-2276. (i) Ramirez, M. A.; Padro´n, J . M.;
Palazo´n, J . M.; Martin, V. S. J . Org. Chem. 1997, 62, 4584-4590. (j)
Reggelin, M.; Weinberger, H.; Heinrich, T. Liebigs Ann. 1997, 1881-
1886. (k) Ishihara, J .; Miyakawa, J .; Tsujimoto, T.; Murai, A. Synlett
1997, 1417-1419. (l) Cassidy, J . H.; Marsden, S. P.; Stemp, G. Synlett
1997, 1411-1413. (m) Amano, S.; Fujiwara, K.; Murai, A. Synlett 1997,
1300-1302. (n) Berninger, J .; Koert, U.; Eisenberg-Ho¨hl, C.; Knochel,
P. Chem. Ber. 1995, 128, 1021-1028.
(5) (a) Chakraborty, T. K.; Ghosh, S.; J ayaprakash, S.; Sharma, J .
A. R. P.; Ravikanth, V.; Diwan, P. V.; Nagaraj, R.; Kunwar, A. C. J .
Org. Chem. 2000, 65, 6441-6457. (b) Chakraborty, T. K.; J ayaprakash,
S.; Srinivasu, P.; Chary, M. G.; Diwan, P. V.; Nagaraj, R.; Sankar, A.
R.; Kunwar, A. C. Tetrahedron Lett. 2000, 41, 8167-8171. (c)
Chakraborty, T. K.; J ayaprakash, S.; Diwan, P. V.; Nagaraj, R.;
J ampani, S. R. B.; Kunwar, A. C. J . Am. Chem. Soc. 1998, 120, 12962-
12963.
(6) Chakraborty, T. K.; Dutta, S. J . Chem. Soc., Perkin Trans. 1
1997, 1257-1259.
(7) (a) Katsuki, T.; Martin, V. S. Org. React. 1996, 48, 1-299. (b)
Gao, Y.; Hanson, R. M.; Klunder, J . M.; Ko, S. Y.; Masamune, H.;
Sharpless, K. B. J . Am. Chem. Soc. 1987, 109, 5765-5780.
(8) Chakraborty, T. K.; Das, S. Chem. Lett. 2000, 80-81.
(4) Dehmlow, H.; Mulzer, J .; Seilz, C.; Strecker, A. R.; Kohlmann,
A. Tetrahedron Lett. 1992, 33, 3607-3610.
10.1021/jo010131y CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/03/2001

4092 J . Org. Chem., Vol. 66, No. 11, 2001
Notes
Sch em e 2. Ster eoselective Syn th esis of
Com p ou n d 1
diastereomers from the Grignard reaction step during the
synthesis of 3 were treated separately, after acetonide
deprotection, with catalytic amounts of CSA in CH2Cl2
and 2,2-dimethoxypropane giving mixtures of five- and
six-membered acetonide rings that were separated chro-
matographically after aqueous workup. The 1H NMR
spectrum of the five-membered acetonide from the major
anti isomer showed a coupling constant of 7.3 Hz of the
vicinal protons CH(O)-CH(O) of the 1,3-dioxolane ring.
The corresponding coupling constant in the five-mem-
bered acetonide from the minor syn isomer was 5.6 Hz.
These values, which are in conformity with previous
literature reports,12 support the assigned stereochemistry
of the products of the Grignard reaction. The two-step
cycloetherification processsmesylation followed by treat-
ment with acidsproceeded nicely to give the final tetra-
hydrofurans 2-4 in 65-80% yields.
The relative stereochemistries of two final products 2
and 3 were further confirmed by 1H NOE difference
spectroscopic studies. While irradiation of the C2-H
signal of compound 2 at δ 4.02 enhanced the peaks of
C3-H and C4-H, that of C5-H peak at 4.56 ppm showed
NOE of C4- and C3-H resonances. Similarly, in compound
3, irradiation of C2-H peak at 4.2 ppm caused 2% and
1% enhancements of C3- and C4-H signals, respectively
and C5-H showed NOE with C3- and C4-H. The stereo-
chemistries of 1 and 4 were similarly assigned.
It was already shown by us that the Ti(III)-induced
ring opening of 2,3-epoxy alcohols can be used to syn-
thesize stereoselectively various diastereomers of the “2-
methyl-1,3-diol” stereotriad.6 Excellent diastereoselec-
tivities were achieved in the nucleophilic addition to the
aldehydes 7. The final cyclization reaction gave single
isomer in each of the four cases studied. A combination
of these reactions has established an efficient protocol
employed here for the stereoselective construction of
highly substituted tetrahydrofuran rings that may find
useful applications in organic synthesis.
SO3-pyridine complex gave an aldehyde, which was
treated with PhMgBr to get selectively the anti product
14 with an approximately 4:1 anti/syn ratio in 75% yield
from 13. The isomers could be easily separated by
standard silica gel column chromatography. The forma-
tion of the anti product as the major diastereomer is
consistent with the nonchelate controlled Felkin-Anh
model.9 The PhCH(OH) chemical shift of 14 in its D2O-
1
exchanged H NMR spectrum appeared as a doublet at
δ 4.51 with a coupling constant of 7 Hz, which is in
agreement with the theoretical coupling constants of
similar products.10,11
Treatment of 14 with methanesulfonyl chloride (MsCl)
and Et3N gave an intermediate mesylate, which was used
directly in the next step after aqueous workup without
purification. Finally, the crucial cycloetherification reac-
tion was carried out smoothly using a catalytic amount
of CSA in CH2Cl2-MeOH (2:1) that deprotected the
acetonide ring with concomitant ring closure giving the
cyclized tetrahydrofuran product 1 in 80% yield from 13.
The other tetrahydrofurans 2-4 were synthesized
following the same method as described above in Scheme
2 for the synthesis of 1. The Sharpless kinetic resolution
of the allylic alcohols 10 with catalytic amounts of
tartrates (L-tartrate for 2 and 4; D-tartrate for 3) gave
the requisite chiral epoxy alcohols 9, with 75% ee for the
trisubstituted epoxy alcohols (for 2 and 3) and 96% ee
for the disubstituted compound (for 4). The Ti(III)-
mediated epoxide ring opening gave exclusively the 1,3-
diols in excellent yields. In substrates with R2 ) Me, the
diastereoselectivity was 5:1 in favor of the expected
isomers, (R)-Me- (for 2) and (S)-Me-diols (for 3). In the
Grignard addition step (7 f 6), the selectivities varied
from 2:1 to 4:1 in favor of the anti products. Higher
selectivities were observed with bulkier Grignard re-
agents and in substrates with R2 * H. The purified
Exp er im en ta l Section
Gen er a l P r oced u r es. All reactions were carried out in oven-
or flame-dried glassware with magnetic stirring under nitrogen
atmosphere using dry, freshly distilled solvents, unless otherwise
noted. Reactions were monitored by thin-layer chromatography
(TLC) carried out on 0.25 mm silica gel plates with UV light, I2,
7% ethanolic phosphomolybdic acid-heat, and 2.5% ethanolic
anisaldehyde (with 1% AcOH and 3.3% concentrated H2SO4)-
heat as developing agents. Silica gel finer than 200 mesh was
used for flash column chromatography. Yields refer to chro-
matographically and spectroscopically homogeneous materials
unless otherwise stated. IR spectra were recorded as neat liquids
or CHCl3 solutions. NMR spectra were recorded on 400 and 500
MHz spectrometers at room temperature of ∼21 °C in CDCl3
using tetramethylsilane as internal standard or the solvent
signal as secondary standard, and the chemical shifts are shown
in δ scales. Multiplicities of NMR signals are designated as s
(singlet), d (doublet), t (triplet), q (quartet), br (broad), m
(multiplet, for unresolved lines), etc. 13C NMR spectra were
recorded with complete proton decoupling. Mass spectra were
obtained under electron impact (EI) and liquid secondary ion
mass spectrometric (LSIMS) techniques.
Syn th esis of 13. To a solution of 128 (700 mg, 3.13 mmol) in
dry CH2Cl2 (9 mL), 2,2-dimethoxypropane (0.77 mL, 6.26 mmol),
and CSA (7 mg, 0.031 mmol) were added sequentially at 0 °C.
After being stirred for 1 h at the same temperature, the reaction
(9) Anh, N. T.; Eisenstein, O. Nouv. J . Chim. 1977, 1, 61-70.
(10) Chakraborty, T. K.; Das, S. J . Ind. Chem. Soc. 1999, 76, 611-
616.
(11) Smith, A. B., III; Wood, J . L.; Wong, W.; Gould, A. E.; Rizzo, C.
J .; Barbosa, J .; Komiyama, K.; Omura, S. J . Am. Chem. Soc. 1996,
118, 8308-8315.
(12) (a) Lorenz, K.; Lichtenthaler, F. W. Tetrahedron Lett. 1987, 28,
6437-6440. (b) Roush, W. R.; Brown, R. J .; DiMare, M. J . Org. Chem.
1983, 48, 5083-5093.

Notes
J . Org. Chem., Vol. 66, No. 11, 2001 4093
mixture was quenched with saturated NaHCO3 solution, ex-
tracted with EtOAc, washed with brine, dried (Na2SO4), and
concentrated in vacuo. Purification by column chromatography
(SiO2, 4-10% EtOAc in petroleum ether eluant) afforded the
acetonide-protected benzyl ether (785 mg, 95%) as a syrupy
liquid. It was dissolved in EtOAc (8 mL), Pd on charcoal (10%,
150 mg) was added and subjected to hydrogenation under
atmospheric pressure using a H2-balloon. After 2 h, the reaction
mixture was filtered through a short pad of Celite, and the filter
cake was washed with EtOAc. The filtrate and the washings
were combined and concentrated in vacuo. Purification by
column chromatography (SiO2, 25-30% EtOAc in petroleum
ether eluant) afforded 13 (500 mg, 97%) as a syrupy liquid:
Rf ) 0.3 (silica gel, 25% EtOAc in petroleum ether); [R]22D -14.2
(c 1.6, CHCl3); IR (neat) νmax 3488, 2992, 2940, 1456, 1376, 1224
temperature slowly and stirred for 2 h. It was then diluted with
ether, washed with saturated aqueous NaHCO3 solution and
brine, dried (Na2SO4), and concentrated in vacuo. Purification
by column chromatography (SiO2, 10-20% EtOAc in petroleum
ether eluant) afforded the tetrahydrofuran 1 (184 mg, 80%) as
a syrupy liquid: Rf ) 0.5 (silica gel, 25% EtOAc in petroleum
ether); [R]22D -38.8 (c 2, CHCl3); IR (neat) νmax 3425, 3000, 2950,
1500, 1050 cm-1 1H NMR (CDCl3, 400 MHz) δ 7.4-7.2 (m, 5
;
H), 4.86 (d, J ) 5.2 Hz, 1 H), 4.48 (dq, J ) 7.1, 6.3 Hz, 1 H),
4.21 (q, J ) 5.2 Hz, 1 H), 2.33 (ddq, J ) 7.3, 7.1, 5.2 Hz, 1 H),
1.76 (d, J ) 5.2 Hz, 1 H), 1.29 (d, J ) 6.3 Hz, 3 H), 1.05 (d, J )
7.3 Hz, 3 H); 13C NMR (CDCl3, 125 MHz) δ 142.01, 128.35,
127.28, 125.37, 84.68, 81.38, 77.50, 40.12, 17.30, 7.62; MS (EI)
m/z 192 (2) [M+]; HRMS (EI) calcd for C12H16O2 [M+] 192.1150,
found 192.1155.
Tetr a h yd r ofu r a n 2: Rf ) 0.55 (silica gel, 20% EtOAc in
petroleum ether); [R]22D -2.1 (c 0.47, CHCl3); IR (neat) νmax 3425,
2950, 2925, 2850, 1100, 1075 cm-1; 1H NMR (CDCl3, 500 MHz)
δ 7.7-7.2 (m, 15 H), 4.56 (d, J ) 7.3 Hz, 1 H), 4.02 (dt, J ) 8.8,
3 Hz, 1 H), 3.94-3.83 (m, 2 H), 3.65 (ddd, J ) 9.4, 7.3, 4.8 Hz,
1 H), 2.03-1.78 (m, 3 H), 1.68 (d, J ) 4.8 Hz, 1 H), 1.10 (d, J )
6.7 Hz, 3 H), 1.07 (s, 9 H); 13C NMR (CDCl3, 125 MHz) δ 141.40,
135.59, 134.00, 133.91, 129.57, 129.53, 128.47, 127.63, 127.61,
125.82, 85.43, 84.43, 80.76, 60.65, 47.24, 37.77, 26.88, 19.22,
14.38; MS (LSIMS) m/z 460 (8) [M+ ].
1
cm-1; H NMR (CDCl3, 200 MHz) δ 4.03 (dq, J ) 6.8, 5.4 Hz, 1
H), 3.74-3.50 (m, 2 H), 3.42 (dt, J ) 7.4, 2.8 Hz, 1 H), 2.03 (dd,
J ) 7.6, 5.2 Hz, 1 H), 1.68 (m, 1 H), 1.37 (s, 6 H), 1.10 (d, J )
6.8 Hz, 3 H), 0.86 (d, J ) 7.0 Hz, 3 H); 13C NMR (CDCl3, 125
MHz) δ 100.47, 75.60, 64.96, 64.18, 35.71, 25.01, 24.02, 16.33,
11.55; MS (EI) m/z 159 (10) [M+ - CH3]; HRMS (EI) calcd for
C8H15O3 [M+ - CH3] 159.1021, found 159.1018.
Syn th esis of 14. To an ice-cooled solution of 13 (450 mg, 2.6
mmol) in CH2Cl2 (4 mL) and DMSO (5.2 mL) were sequentially
added Et3N (1.8 mL, 13 mmol) and SO3-py (2.07 gm, 13 mmol).
The reaction mixture was stirred at 0 °C for 1 h, quenched with
saturated aqueous NH4Cl solution, extracted with ether, washed
with brine, dried (Na2SO4), and concentrated in vacuo. The
residue was used directly in the next step without further
purification. The crude aldehyde was dissolved in dry ether (10
mL) and cooled to 0 °C, and PhMgBr (0.5 M in ether, 10 mL)
was added to it. After being stirred for 1 h at the same
temperature, the reaction mixture was quenched with saturated
aqueous NH4Cl solution, extracted with EtOAc, washed with
brine, dried (Na2SO4), and concentrated in vacuo. Purification
by column chromatography (SiO2, 7-12% EtOAc in petroleum
ether eluant) afforded the anti compound 14 (485 mg, 75%) as
the major diastereomer: Rf ) 0.65 (silica gel, 25% EtOAc in
Tetr a h yd r ofu r a n 3: Rf ) 0.45 (silica gel, 25% EtOAc in
petroleum ether); [R]22D 11.5 (c 2.7, CHCl3); IR (neat) νmax 3450,
2975, 2950, 1100 cm-1 1H NMR (CDCl3, 500 MHz) δ 7.7-7.3
;
(m, 10 H), 4.21 (ddd, J ) 9.2, 5.7, 4.7 Hz, 1 H), 3.91 (dd, J ) 6.1,
4.7 Hz, 1 H), 3.84 (dq, J ) 6.4, 4.7 Hz, 1 H), 3.78 (dd, J ) 7.4,
5.7 Hz, 2 H), 2.29 (ddq, J ) 7.4, 6.1, 4.7 Hz, 1 H), 1.82-1.65
(two m, 2 H), 1.56 (br s, 1 H), 1.23 (d, J ) 6.4 Hz, 3 H), 1.04 (s,
9 H), 0.95 (d, J ) 7.4 Hz, 3 H); 13C NMR (CDCl3, 125 MHz) δ
135.57, 135.55, 134.00, 133.91, 129.50, 129.49, 127.57, 127.55,
80.09, 78.72, 76.80, 61.30, 40.05, 34.14, 26.86, 19.63, 19.18, 7.67;
MS (LSIMS) m/z 399 (40) [M+ + H], 421 (20) [M+ + Na]; HRMS
(LSIMS) calcd for C24H35O3Si [M+ + H] 399.2355, found 399.2348.
Tetr a h yd r ofu r a n 4: Rf ) 0.5 (silica gel, 25% EtOAc in
petroleum ether); [R]22D 30.4 (c 1, CHCl3); IR (CHCl3) νmax 3418,
2924, 1453, 1025 cm-1; 1H NMR (CDCl3, 400 MHz) δ 7.47-7.24
(m, 10 H), 5.36 (dd, J ) 7.6, 7.2 Hz, 1 H), 5.03 (d, J ) 5.1 Hz, 1
H), 4.41 (ddt, J ) 6.6, 5.7, 5.1 Hz, 1 H), 2.73 (ddd, J ) 12.9, 7.2,
6.6 Hz, 1 H), 2.14 (ddd, J ) 12.9, 7.6, 6.6 Hz, 1 H), 1.81 (d, J )
5.7 Hz, 1 H); 13C NMR (CDCl3, 125 MHz) δ 143.17, 140.69,
128.53, 127.70, 127.45, 125.59, 125.53, 86.94, 79.37, 79.30, 42.75;
MS (LSIMS) m/z 239 (12) [M+ - H]; HRMS (LSIMS) calcd for
petroleum ether); [R]22 9.8 (c 1, CHCl3); IR (neat) νmax 3536,
D
3440, 2976, 2928, 2888, 1440, 1376, 1224, 1184 cm-1; H NMR
1
(CDCl3, 200 MHz) δ 7.38-7.30 (m, 5 H), 4.54 (dd, J ) 6.6, 3.4
Hz, 1 H), 4.09 (dq, J ) 6.6, 4.8 Hz, 1 H), 3.41 (dd, J ) 7.4, 6.6
Hz, 1 H), 3.07 (d, J ) 3.4 Hz, 1 H), 1.77 (m, 1 H), 1.39 and 1.35
(two s, 6 H), 1.05 (d, J ) 6.6 Hz, 3 H), 0.41 (d, J ) 6.8 Hz, 3 H);
13C NMR (CDCl3, 125 MHz) δ 140.04, 128.19, 127.91, 127.23,
100.71, 79.17, 76.34, 65.0, 36.37, 25.31, 23.96, 16.43, 11.40; MS
(EI) m/z 235 (4) [M+ - CH3]; HRMS (EI) calcd for C14H19O3
[M+ - CH3] 235.1334, found 235.1329.
Tetr a h yd r ofu r a n 1. To a solution of 14 (300 mg, 1.2 mmol)
in CH2Cl2 (5 mL) were sequentially added Et3N (0.33 mL, 2.4
mmol) and MsCl (0.14 mL, 1.8 mmol) at 0 °C. After being stirred
for 0.5 h at the same temperature, the reaction mixture was
quenched with saturated aqueous NH4Cl solution, extracted with
ether, washed with brine, dried (Na2SO4), and concentrated in
vacuo. The residue was used directly in the next step without
further purification.
C
16H16O2 [M+] 240.1150, found 240.1151.
Ack n ow led gm en t. We thank Drs. A. C. Kunwar
and M. Vairamani for NMR and mass spectroscopic
assistance, respectively, UGC, New Delhi, for research
fellowship (to S.D.) and CSIR, New Delhi, for Young
Scientist Award Research Grant (to T.K.C.).
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of 1-4. This material is available via the Internet at
http://pubs.acs.org.
To a solution of the crude mesylate in CH2Cl2/MeOH (2:1, 6
mL) was added CSA (28 mg, 0.12 mmol) at 0 °C under nitrogen
atmosphere. The reaction mixture was allowed to come to room
J O010131Y