Regio- and stereoselective addition of Grignard and organolithium reagents to 4-hydroxy-2-cyclopentenones

Full text of DOI:10.1021/jo0106389

9026
J . Org. Chem. 2001, 66, 9026-9029
Sch em e 1
Regio- a n d Ster eoselective Ad d ition of
Gr ign a r d a n d Or ga n olith iu m Rea gen ts to
4-Hyd r oxy-2-cyclop en ten on es
Aurelio G. Csa´ky¨,* Myriam Mba, and J oaqu´ın Plumet*
Departamento de Quı´mica Orga´nica I, Facultad de
Quı´mica, Universidad Complutense, 28040 Madrid, Spain
csaky@quim.ucm.es
Received J une 22, 2001
4-Hydroxy-2-cyclopentenones and their O-silyl deriva-
tives 1 constitute valuable synthetic intermediates. In
particular, their regio- and stereocontrolled transforma-
tion into the 4,5-disubstituted 3-hydroxycyclopentanones
2 is a cornerstone in the synthetic approach to prostag-
landins and related bioactive compounds.1,2 In this way,
it is well-known that the additions of dialkylcuprates or
Grignard reagents in the presence of copper(I) salts to
compounds 1 proceed in a 1,4-anti fashion with respect
to the bulky O-silyl substituent (Scheme 1).
Electrophilic capture of the intermediate enolates
affords cyclopentanones 2 with a 3,4-anti-4,5-anti ster-
eochemistry in a three-component coupling. Similar
findings have been reported for the reaction of silyl-
protected 2-substituted 4-hydroxy-2-cyclopentenones 3
with organocopper reagents. However, to increase the
synthetic potential of compounds 1 and 3, other stereo-
chemical arrangements in the hydroxycyclopentanones
2 would be desirable. In this way, the concept of ligand-
assisted nucleophilic addition first developed by Liotta
et al.3 in the reaction of quinones with nucleophilic
reagents can be an appealing possibility.
Sch em e 2
On the basis of this idea, in this paper we wish to
account for the regio- and stereocontrolled transformation
of cyclopentenones 3 and 4 into the 2,3-disubstituted 3,5-
syn-dihydroxycyclopentenes 5 and 6 and into the 3,4-syn-
4,5-anti-3-hydroxycyclopentanones 7 using organolithium
or Grignard reagents (Scheme 1).
Ring opening4 of (2-furyl)carbinols 8 followed by O-
silylation of the resulting 4-hydroxy-2-cyclopentenones
4 with TBS-Cl afforded the 2-akyl- and 2-aryl-4-(tbutyl-
silyl)-2-cyclopentenones 3 (Scheme 2). The addition of
either organolithium or Grignard reagents in THF solu-
tion and in the absence of Cu(I) salts or any added
cosolvent to the O-TBS-cyclopentenones 3 afforded the
corresponding 1,2-addition products 5 (3,5-syn) in a
highly regio- and stereoselective fashion.5 No traces of
the diastereomeric 3,5-anti products were observed in the
crude reaction mixture.6 The results are gathered in
Table 1.
However, when the reactions with Grignard reagents
were carried out starting from the O-unprotected cyclo-
pentenones 4 in THF solution, the 1,4-addition products
7 (3,4-syn-4,5-anti) were obtained with high regioselec-
tivity with no need of added Cu(I) salts or cosolvents7
and with 3,4-syn stereochemistry (Scheme 3). This ste-
reoselectivity was found to be opposite8 to that observed
(1) For reviews, see: (a) Noyori, R.; Suzuki, M. Angew. Chem., Int.
Ed. Engl. 1984, 23, 847-876. (b) Perlmutter, P. In Conjugate Addition
in Organic Synthesis; Pergamon: Oxford, 1992. (c) Collins, P. W.;
Djuric, S. W. Chem. Rev. 1993, 93, 1533-1564. (d) Nicolau, K. C.;
Sorensen, E. J . In Classics in Total Synthesis; VCH: Weinheim,
Germany, 1996.
(2) For leading recent references, see: (a) Myers, A. B.; Hammond,
M.; Wu, Y.; Xiang, J .-N.; Harrington, P. M.; Kuo, E. Y. J . Am. Chem.
Soc. 1996, 118, 10006-10007. (b) Kawata, S.; Yoshimura, F.; Irie, J .;
Ehara, H.; Hirama, M. Synlett 1997, 250-252. (c) Rodr´ıguez, A.;
Nomen, M.; Spur, B. W.; Godfroid, J .-J . Eur. J . Org. Chem. 1999,
2655-2662 and references cited therein.
(3) Salomon, M.; J amison, M. L.; McCormick, M.; Liotta, D.; Cherry,
D. A.; Mills, J . E.; Shah, R. D.; Rodgers, J . D.; Maryanoff, C. A. J . Am.
Chem. Soc. 1988, 110, 3702-3704. See also: Beak, P.; Meyers, A. I.
Acc. Chem. Res. 1986, 19, 356.
(5) The 3,5-syn stereochemistry of compounds 5 has been assigned
by NOE measurements. Thus, an increase of the H-5 signal (δ 4.64-
4.56, m) of 7a (R1 ) Ph, R2 ) Me) was observed upon irradiation of
the CH3 (δ 1.31, s).
(6) Determined on the 1H NMR spectra (CDCl3, 300 MHz) of the
crude reaction mixtures.
(7) Compare with the procedure described in ref 3.
(8) 3,4-Syn addition has been recently reported for the reaction of
trialkylaluminum reagents to cyclopentenones 6 (R1 ) SO2Ph or CO2-
Me). See: (a) Yakura, T.; Tanaka, K.; Iwamoto, M.; Nameki, M.; Ikeda,
M. Synlett 1999, 1313-1315. (b) Yakura, T.; Tanaka, K.; Kitano, T.;
Uenishi, J .; Ikeda, M. Tetrahedron 2000, 56, 7715-7721.
(4) Piancatelli, G.; D’Auria, M.; D’Onofrio, F. Synthesis 1994, 867-
889 and references cited therein. See also: D’Auria, M. Heterocycles
2000, 52, 185-194.
10.1021/jo0106389 CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/20/2001

Notes
J . Org. Chem., Vol. 66, No. 26, 2001 9027
Sch em e 3
Ta ble 1. Rea ction of Cyclop en ten on es 3 w ith
Or ga n olith iu m or Gr ign a r d Rea gen ts
Sch em e 4
no.
3
R1
R2Ma
5 (%)b
1
2
3
4
5
3a
3a
3a
3b
3b
Ph
Ph
Ph
Me
Me
MeLi
MeMgI
PhLi
PhLi
PhMgBr
5a (70)
5a (90)
5b (90)
5c (50)
5c (75)
a
THF was used as a solvent. Reactions with R2Li (1.1 equiv)
were carried out from -78 °C to room temperature, and reactions
with R2MgX (1.1 equiv) were carried out at reflux temperature.
b
Isolated yields after silica gel chromatography (2:1 Hx-EtOAc).
Ta ble 2. Rea ction of Cyclop en ten on es 4 w ith
Or ga n olith iu m or Gr ign a r d Rea gen ts
no.
4
R1
R2Ma
7:6b (%)c
1
2
3
4
5
6
7
4a
4a
4a
4a
4b
4a
4b
Ph
Ph
Ph
Ph
Me
Ph
Me
MeMgI
7a :6a ) 90:10 (7a , 60)
7b:6b ) 95:05 (7b, 65)
7c:6c ) 95:05 (7c, 70)
7d :6d ) 95:05 (7d , 65)
7e:6e ) 90:10 (7e, 65)
7a :6a ) 0:100 (6a , 65)
7e:6e ) 0:100 (6b, 70)
of the Grignard species to the â-vinyl carbon of the
starting 4-hydroxycyclopentenones 4 (Scheme 4), which
should take place in a syn fashion.3,9 Conversely, coor-
dination of the organomagnesium species to the oxygen
at carbon C-4 would not be possible in the presence of
the bulky TBS group in compounds 3, and thus inter-
molecular addition would take place in a 1,2-fashion from
the less encumbered diastereotopic face of the carbonyl
group, with anti diastereoselectivity. On the other hand,
organolithiums, which are harder nucleophiles than
organomagnesium reagents, would always give 1,2-
addition irrespective of the substitution at C-4 of the
starting cyclopentenone. This addition takes place op-
posite to the bulky substituent at C-4 (TBSO or RLi-O
complex), affording cyclopentenones 5 or 6 (3,5-syn).
In conclusion, a highly regio- and stereoselective
method for the 1,2- or 1,4-addition reactions to 4-hydroxy-
2-cyclopentenones has been devised, which makes use of
readily available organolithium and Grignard reagents.
This procedure allows for stereochemistry complemen-
tary to that observed in the 1,4-addition of organocu-
prates and makes possible the attachment of aromatic
groups to carbons C-2 and C-3 of cyclopentenones 5 or 6
EtMgBr
PhMgBr
p-F-C6H5-MgBr
MeMgI
MeLi
MeLi
a
THF was used as a solvent. Reactions with R2Li (2.2 equiv)
were carried out from -78 °C to room temperature, and reactions
with R2MgX (2.2 equiv) were carried out at reflux temperature.
Determined by integration of the 1H NMR spectra (CDCl3, 300
b
MHz) of the crude reaction mixtures. c Isolated yields after silica
gel chromatography (2:1 Hx-EtOAc).
in the addition of cuprate reagents to cyclopentenones
3, as evidenced by the comparison of the spectroscopic
data of compounds 9a and 10a (R1 ) Ph, R2 ) Me).
On the other hand, the reaction of organolithium
reagents with cyclopentenones 4 took place in a 1,2-
fashion to afford compounds 6 (3,5-syn), with the same
stereoselectivity previously observed for the addition of
organolithium and organomagnesium reagents to the
TBS derivatives 3, as produced by the conversion of
compounds 6 into the related O-TBS derivatives 5
(Scheme 3). The results are given in Table 2.
The stereochemical outcome of the addition reactions
with organomagnesium reagents may be understood on
the basis of an intramolecular chelation-directed delivery
(9) For related models, see: Felkin, H.; Swierczewski, G.; Tambute´,
A. Tetrahedron Lett. 1969, 9, 707-710.

9028 J . Org. Chem., Vol. 66, No. 26, 2001
Notes
(1H, B part of ABX system, 3J ) 6.3 Hz, 3J ) 13.5 Hz), 2.12
(1H, A part of ABX system, 3J ) 3.7 Hz, 3J ) 13.5 Hz), 0.80
(9H, s), 0.01 (6H, s); 13C NMR (50.5 MHz, CDCl3) δ 149.3, 145.3,
133.9, 132.9, 128.5, 128.3, 127.9, 127.7, 126.8, 125.0, 86.2, 73.6,
56.1, 26.1, 18.4 Anal. Calcd for C23H30O2Si: C, 75.36; H, 8.25.
Found: C, 75.48; H, 8.44.
and carbons C-4 and C-5 of cyclopentanones 7, which are
of interest for further elaboration into biologically active
targets.10
Exp er im en ta l Section
(1S*,4R*)-4-(tBu tyld im eth ylsilyloxy)-2-m eth yl-1-p h en yl-
Silica gel 60 F254 was used for TLC, and the spots were
detected with UV and vainilline solution. Flash column chro-
matography was carried out on silica gel 60. IR spectra have
been recorded as CHCl3 solutions. 1H and 13C NMR spectra were
recorded at 200 or 300 MHz and 50.5 or 75.5 MHz, respectively.
MS was carried out at 70 eV. The 4-hydroxy-2-cyclopentenones
4 were prepared from furans 8 as previously reported.3
Syn th esis of Cyclop en ten on es 3: Gen er a l P r oced u r e.
To a solution of 4 (2.48 mmol) in pyridine (12.4 mL) were added
TBS-Cl (748 mg, 4.96 mmol) and DMAP (60 mg, 0.49 mmol).
The mixture was stirred for 24 h at room temperature. Filtration
of the reaction mixture, rinsing with CH2Cl2 (2 × 5 mL), and
evaporation of the solvent afforded an oil that was purified by
chromatography (2:1 hexane-ethyl acetate).
cyclop en t-2-en ol (5c): colorless oil; IR (CHCl3) ν 3425 cm-1
;
1H NMR (200 MHz, CDCl3) δ 7.29-7.15 (5H, m), 5.59 (1H, m),
4.69 (1H, m), 2.59 (1H, B part of ABX system, 3J ) 6.6 Hz, 3J )
13.9 Hz), 1.99 (1H, A part of ABX system, 3J ) 3.6 Hz, 3J )
13.9 Hz), 1.47 (3H, s), 0.83 (9H, s), 0.00 (6H, s); 13C NMR (50.5
MHz, CDCl3) δ 147.8, 144.6, 131.2, 128.2, 126.6, 127.8, 85.8, 74.0,
54.1, 25.9, 18.1, 11.9. Anal. Calcd for C18H28O2Si: C, 71.00; H,
9.27. Found: C, 71.25; H, 9.51.
(1S*,3R*)-1-Me t h yl-5-p h e n yl-cyclop e n t -4-e n e -1,3-d iol
(6a ): colorless oil; IR (CHCl3) ν 3280 cm-1; 1H NMR (200 MHz,
3
CDCl3) δ 7.56-7.49 (2H, m), 7.27-7.19 (3H, m), 5.94 (1H, d, J
) 2.3 Hz), 4.61 (1H, m), 2.44 (1H, B part of ABX system, 3J )
3
3
6.9 Hz, J ) 14.2 Hz), 1.94 (1H, A part of ABX system, J ) 2.9
Hz, 3J ) 14.2 Hz), 1.32 (3H, s); 13C NMR (50.5 MHz, CDCl3) δ
151.2, 134.4, 130.5, 128.2, 127.8, 127.5, 82.1, 72.7, 52.0, 26.5.
Anal. Calcd for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.92;
H, 7.61.
4-(tBu t yld im et h ylsilyloxy)-2-p h en ylcyclop en t -2-en on e
(3a ): 90%, white solid, mp 58-59 °C (MeOH); IR (CHCl3) ν 1700
cm-1; 1H NMR (300 MHz, CDCl3) δ 7.68-7.65 (2H, m), 7.51 (1H,
d, 3J ) 2.3 Hz), 7.38-7.33 (3H, m), 4.98 (1H, m), 2.91 (1H, B
part of ABX system, 3J ) 5.7 Hz, 3J ) 18.0 Hz), 2.47 (1H, A
part of ABX system, 3J ) 2.4 Hz, 3J ) 18.0 Hz), 0.91 (9H, s),
0.15 (3H, s), 0.13 (3H, s); 13C NMR (75.5 MHz, CDCl3) δ 204.0,
157.3, 143.5, 130.6, 128.9, 128.4, 127.5, 68.3, 46.6, 25.7, 18.1.
Anal. Calcd for C17H24O2Si: C, 70.78; H, 8.39. Found: C, 70.99;
H, 8.42.
(1S*,3R*)-1,5-Dim eth ylcyclop en t-4-en e-1,3-d iol (6b): col-
1
orless oil; IR (CHCl3) ν 3390 cm-1; H NMR (200 MHz, CDCl3)
δ 5.44 (1H, m), 4.48 (1H, m), 2.34 (1H, B part of ABX system, 3J
3
3
) 6.9 Hz, J ) 14.3 Hz), 1.78 (1H, A part of ABX system, J )
3.0 Hz, J ) 14.3 Hz), 1.69 (3H, s), 1.21 (3H, s); 13C NMR (50.5
3
MHz, CDCl3) δ 149.1, 128.9, 81.4, 73.0, 50.7, 25.6, 11.3. Anal.
Calcd for C7H12O2: C, 65.60; H, 9.44. Found: C, 65.75; H, 9.61.
(2R*,3S*,4R*)-4-H yd r oxy-3-m et h yl-2-p h en ylcyclop en -
4-(tBu t yld im et h ylsilyloxy)-2-m et h ylcyclop en t -2-en on e
1
(3b): 90%, colorless oil; IR (CHCl3) ν 1715 cm-1; H NMR (200
ta n on e (7a ): colorless oil; IR (CHCl3) ν 3450, 1740 cm-1 1H
;
MHz, CDCl3) δ 6.98-6.94 (1H, m), 4.78-4.72 (1H, m), 2.59 (1H,
NMR (200 MHz, CDCl3) δ 7.30-7.13 (3H, m), 7.02-6.98 (2H,
m), 4.33 (1H, m), 3.20 (1H, d, 3J ) 12.6 Hz), 2.48-2.46 (2H, m),
2.37-2.13 (1H, m), 1.04 (3H, d, 3J ) 6.7 Hz); 13C NMR (50.5
MHz, CDCl3) δ 216.7, 137.2, 128.5, 126.9, 70.0, 58.4, 48.3, 42.6,
12.9. Anal. Calcd for C12H14O2: C, 75.76; H, 7.42. Found: C,
75.91; H, 7.66.
B part of ABX system, 3J ) 5.9 Hz, 3J ) 18.3 Hz), 2.13 (1H, A
3
3
4
part of ABX system, J ) 2.1 Hz, J ) 18.3 Hz), 1.16 (3H, d, J
) 2.9 Hz), 0.78 (9H, s), 0.01 (3H, s), 0.00 (3H, s); 13C NMR (50.5
MHz, CDCl3) δ 206.3, 157.4, 142.7, 68.8, 45.0, 25.6, 18.0, 9.7.
Anal. Calcd for C12H22O2Si: C, 63.67; H, 9.80. Found: C, 63.77;
H, 9.70.
(2R *,3S *,4R *)-4-H yd r oxy-3-e t h yl-2-p h e n ylcyclop e n -
ta n on e (7b): colorless oil; IR (CHCl3) ν 3450, 1730 cm-1 1H
;
Rea ction of Cyclop en ten on es 3 a n d 4 w ith Gr ign a r d
Rea gen ts: Gen er a l P r oced u r e. To a solution of 3 or 4 (2.56
mmol) in THF (3.0 mL) at 0 °C was added dropwise a 1 M
solution of R2MgX in THF (3.0 mL for compounds 3, 6.0 mL for
compounds 4). The mixture was stirred at reflux temperature
for 2 h, cooled to room temperature, and hydrolyzed with
saturated NH4Cl solution (3.0 mL). The organic layer was
decanted and the aqueous layer extracted with Et2O (3 × 10
mL). The combined organic layers were dried on MgSO4.
Filtration and elimination of the solvent under reduced pressure
afforded an oil that was purified by chromatography (10:1
hexane-Et2O).
NMR (200 MHz, CDCl3) δ 7.31-7.14 (3H, m), 7.03-6.97 (2H,
m), 4.53 (1H, m), 3.26 (1H, d, 3J ) 12.5 Hz), 2.49-2.47 (2H, m),
2.18-2.02 (1H, m), 1.69-1.39 (2H, m), 0.86 (3H, t, 3J ) 7.4 Hz);
13C NMR (50.5 MHz, CDCl3) δ 216.9, 138.0, 128.9, 128.8, 127.2,
67.8, 58.1, 51.8, 48.6, 21.0, 11.8. Anal. Calcd for C13H16O2: C,
76.44; H, 7.90. Found: C, 76.61; H, 8.03.
(2R*,3R*,4R*)-4-H yd r oxy-2,3-d ip h en ylcyclop en t a n on e
(7c): white solid, mp 102-103 °C (hexanes-ethyl acetate); IR
(CHCl3) ν 3460, 1740 cm-1; 1H NMR (200 MHz, CDCl3) δ 7.31-
7.04 (10H, m), 4.50 (1H, m), 4.02 (1H, d, 3J ) 13.1 Hz), 3.68
(1H, dd, 3J ) 3.5 Hz, 3J ) 13.1 Hz), 2.61 (2H, m); 13C NMR (50.5
MHz, CDCl3) δ 214.5, 136.6, 136.2, 128.9, 128.5, 128.4, 128.3,
127.5, 127.0, 70.5, 54.6, 54.3, 46.9. Anal. Calcd for C17H16O2: C,
80.93; H, 6.39. Found: C, 81.11; H, 6.50.
Rea ction of Cyclop en ten on es 3 a n d 4 w ith Or ga n o-
lith iu m Rea gen ts: Gen er a l P r oced u r e. To a solution of 3
(2.56 mmol) in THF (3.0 mL) at 0 °C was added dropwise a 1 M
solution of MeLi in Et2O (3.0 mL for compounds 3, 6.0 mL for
compounds 4) or a 1.8 M solution of PhLi in cyclohexanes-Et2O
(1.67 mL for compounds 3, 3.34 mL for compounds 4). After the
mixture was stirred for 2 h at room temperature, all operations
were followed as above.
(2R*,3R*,4R*)-3-(4-F lu or op h en yl)-4-h yd r oxy-2-p h en yl-
cyclop en ta n on e (7d ): white solid, mp 106-107 °C (hexane-
ethyl acetate); IR (CHCl3) ν 3460, 1740 cm-1; 1H NMR (200 MHz,
CDCl3) δ 7.35-7.21 (5H, m), 7.18-7.01 (4H, m), 4.54 (1H, m),
3
3
3
3.98 (1H, d, J ) 13.2 Hz), 3.67 (1H, dd, J ) 3.4 Hz, J ) 13.1
(1S*,4R*)-4-(tBu tyld im eth ylsilyloxy)-1-m eth yl-2-p h en yl-
cyclop en t-2-en ol (5a ): white solid, mp 55-56 °C (hexane -
Hz), 2.65 (2H, m); 13C NMR (50.5 MHz, CDCl3) δ 214.2, 162.1
1
4
3
(d, J CF ) 245 Hz), 138.0, 132.4 (d, J CF ) 3 Hz), 129.9 (d, J CF
ethyl acetate); IR (CHCl3) ν 3400 cm-1
;
1H NMR (200 MHz,
2
) 3 Hz), 128.6, 128.4, 127.1, 115.9 (d, J CF ) 21 Hz), 70.5, 54.7,
3
CDCl3) δ 7.55-7.49 (2H, m), 7.27-7.13 (3H, m), 5.87 (1H, d, J
53.9, 46.9. Anal. Calcd for C17H15FO2: C, 75.54; H, 5.59. Found:
C, 75.70; H, 5.71.
) 2.3 Hz), 4.60 (1H, m), 2.33 (1H, B part of ABX system, 3J )
3
3
6.3 Hz, J ) 13.5 Hz), 1.89 (1H, A part of ABX system, J ) 3.2
Hz, 3J ) 13.5 Hz), 1.31 (3H, s), 0.79 (9H, s), 0.01 (3H, s), 0.00
(3H, s); 13C NMR (50.5 MHz, CDCl3) δ 150.6, 134.8, 131.2, 128.2,
127.7, 127.5, 82.1, 73.1, 52.8, 25.9, 25.7, 18.1. Anal. Calcd for
(2S*,3S*,4R*)-4-H yd r oxy-2,3-d im et h ylcyclop en t a n on e
1
(7e): colorless oil; IR (CHCl3) ν 3450, 1735 cm-1; H NMR (200
MHz, CDCl3) δ 4.30 (1H, m), 2.34 (1H, m), 211-1.95 (1H, m),
3
3
1.79-1.61 (1H, m), 1.13 (3H, d, J ) 7.5 Hz), 1.00 (3H, d, J )
7.0 Hz); 13C NMR (50.5 MHz, CDCl3) δ 219.9, 70.6, 47.6, 46.5,
44.6, 13.2, 12.4. Anal. Calcd for C7H12O2: C, 65.60; H, 9.44.
Found: C, 65.73; H, 9.61.
C
18H28O2Si: C, 71.00; H, 9.27. Found: C, 71.16; H, 9.32.
(1S*,4R*)-4-(tBu tyld im eth ylsilyloxy)-1,2-d ip h en ylcyclo-
p en t-2-en ol (5b): white solid, mp 76-78 °C (hexane-ethyl
acetate); IR (CHCl3) ν 3415 cm-1; 1H NMR (200 MHz, CDCl3) δ
7.31-7.02 (10H, m), 6.26 (1H, d, 3J ) 2.3 Hz), 4.77 (1H, m), 2.53
Syn t h esis of (2R*,3S*,4R*)-4-(tBu t yld im et h ylsilyloxy)-
3-m eth yl-2-p h en yl-cyclop en ta n on e (9a ). To a solution of 7a
(471 mg, 2.48 mmol) in pyridine (12.4 mL) were added TBS-Cl
(748 mg, 4.96 mmol) and DMAP (60 mg, 0.49 mmol). The
mixture was stirred for 24 h at room temperature. Filtration of
(10) For example benzoprostacyclins, see: Larock, R. C.; Lee, N. H.
J . Org. Chem. 1991, 56, 6253-6254 and references cited therein.

Notes
J . Org. Chem., Vol. 66, No. 26, 2001 9029
the reaction mixture, rinsing with CH2Cl2 (2 × 5 mL), and
evaporation of the solvent afforded an oil that was purified by
chromatography (2:1 hexane-ethyl acetate): 90%, white solid,
colorless oil; IR (CHCl3) ν 1745 cm-1; 1H NMR (200 MHz, CDCl3)
δ 7.29-7.12 (3H, m), 7.09-6.99 (2H, m), 3.97-3.85 (1H, m), 2.81
3
3
(1H, d, J ) 12.7 Hz), 2.69 (1H, B part of ABX system, J ) 7.2
Hz, 3J ) 18.5 Hz), 2.26 (1H, A part of ABX system, 3J ) 9.0 Hz,
3J ) 18.5 Hz), 2.30-2.10 (1H, m), 1.04 (3H, d, 3J ) 6.4 Hz), 0.80
(3H, s), 0.02 (3H, s), 0.01 (3H, s); 13C NMR (50.5 MHz, CDCl3)
δ 213.1, 136.5, 128.6, 128.5, 127.0, 62.9, 47.8, 47.5, 25.6, 17.9,
15.9. Anal. Calcd for C18H28O2Si: C, 71.00; H, 9.27. Found: C,
71.21; H, 9.50.
mp 56-57 °C (hexane-ethyl acetate); IR (CHCl3) ν 1745 cm-1
;
1H NMR (200 MHz, CDCl3) δ 7.27-7.10 (3H, m), 7.01-6.96 (2H,
m), 4.31 (1H, m), 3.13 (1H, d, 3J ) 12.5 Hz), 2.42-2.39 (2H, m),
3
2.30-2.17 (1H, m), 0.98 (3H, d, J ) 6.7 Hz), 0.80 (3H, s), 0.02
(3H, s), 0.01 (3H, s), 18.0, 13.5. Anal. Calcd for C18H28O2Si: C,
71.00; H, 9.27. Found: C, 71.25; H, 9.39.
Syn th esis of (2R*,3S*,4S*)-4-(tBu tyld im eth ylsilyloxy)-3-
m eth yl-2-p h en yl-cyclop en ta n on e (10a ). To a solution of CuI
(145 mg, 0.76 mmol) in Et2O (5.0 mL) at 0 °C was added
dropwise a 1.6 M solution of MeLi in Et2O (0.95 mL, 1.52 mmol).
After the mixture was stirred for 10 min, a solution of 3a (199
mg, 0.69 mmol) in Et2O (5 mL) was added. The mixture was
stirred at 0 °C for 2 h and hydrolyzed with saturated NH4Cl
solution (3.0 mL). The organic layer was decanted and the
aqueous layer extracted with Et2O (3 × 10 mL). The combined
organic layers were dried on MgSO4. Filtration and elimination
of the solvent under reduced pressure afforded a pale yellow oil
that was purified by chromatography (10:1 hexane-Et2O): 85%,
Ack n ow led gm en t. This work is dedicated to the
late Prof. Angel Alberola. Ministerio de Ciencia y
Tecnolog´ıa (Project BQU2000-0653) and REPSOL-YPF
are gratefully thanked for financial support.
Su p p or tin g In for m a tion Ava ila ble: 1H and 13C NMR of
compounds 3, 5-7, 9, and 10. This material is available free
of charge via the Internet at http://pubs.acs.org.
J O0106389