Preparation of Bicyclo[3.2.0]heptane-2-endo,7-endo-diols: 1,3-Diols with a Chiral Rigid Backbone

Article abstract of DOI:10.1021/jo035324v

The easily available bicyclo[3.2.0]hept-3-en-6-ones (1a-f) have been converted into the corresponding bicyclo[3.2.0]heptane-2-endo,7-endo-diols (4a-f) in an efficient and stereoselective fashion. This preparation opens a route to a family of 1,3-diols wit

Full text of DOI:10.1021/jo035324v

SCHEME 1
P r ep a r a tion of
Bicyclo[3.2.0]h ep ta n e-2-en d o,7-en d o-d iols:
1,3-Diols w ith a Ch ir a l Rigid Ba ck bon e†
Francesca Peri, Enrico Binassi, Antonio Manetto,
Emanuela Marotta, Andrea Mazzanti, Paolo Righi,
Noemi Scardovi, and Goffredo Rosini*
Dipartimento di Chimica Organica “A. Mangini”,
Alma Mater Studiorum-Universita` di Bologna Viale del
Risorgimento n.4, I-40136 Bologna, Italy
rosini@ms.fci.unibo.it
“bicyclo[3.2.0]hept-3-en-6-one approach”1b has been ex-
tended to the synthesis of important intermediates for
primary prostaglandins.8 Also, an efficient procedure has
been devised to effect the resolution and the absolute
configuration assignment of the corresponding endo-
alcohols, easily available by a highly stereoselective
reduction.9 Moreover, parallel studies were performed to
successfully achieve the microbial kinetic resolution of
racemic mixtures of the ketones and the alcohols.10
Besides the fast and spectacular progress in the asym-
metric synthesis using organometallic reagents,11 a clear
understanding of the origin of enantioselectivity is still
to be achieved for many asymmetric reactions. There still
is a need for chiral, nonracemic scaffolds suitable for
systematic structural changes to produce the broadest
possible electronic and stereochemical diversity. These
systematic variants would facilitate the analysis of the
ligand-metal-substrate interactions that may be re-
sponsible for enantioselection.
Received September 8, 2003
Abstr a ct: The easily available bicyclo[3.2.0]hept-3-en-6-
ones (1a -f) have been converted into the corresponding
bicyclo[3.2.0]heptane-2-endo,7-endo-diols (4a -f) in an ef-
ficient and stereoselective fashion. This preparation opens
a route to a family of 1,3-diols with a chiral rigid backbone,
potentially suitable as nonracemic precursors for bidentate
ligands in asymmetric synthesis.
Bicyclo[3.2.0]hept-3-en-6-ones (1) are valuable com-
pounds available through practical and efficient proce-
dures on either the laboratory1 or industrial scale.2
Recently, our attention was attracted by the results of
Roberts and co-workers.12 They prepared the enantiopure
1,4-bis-phospinite ligands with a bicyclo[3.2.0]heptane
backbone for rhodium-catalyzed asymmetric hydrogena-
tion of R-acetamidocinnamic acid derivatives affording
enantioenriched (R)-phenylalanines (Scheme 1).
Their peculiar wedge-shaped structure, consisting of
two condensed rings with different sizes and functional
groups, make them useful as versatile intermediates in
organic synthesis by allowing straightforward chemo-
selective, regioselective, and stereoselective manipula-
tions. Grandisol and lineatin,3 filifolone,4 raikovenal,5 and
unsaturated bicyclic lactones4,6,7 have been prepared by
using this family of precursors. More recently, the
(8) Marotta, E.; Righi, P.; Rosini, G. Org. Lett. 2000, 2, 4145.
(9) Marotta, E.; Pagani, I.; Righi, P.; Rosini, G.; Bertolasi, V.; Medici,
A. Tetrahedron: Asymmetry 1995, 6, 2319.
(10) (a) Fantin, G.; Fogagnolo, M.; Medici, A.; Pedrini, P.; Rosini,
G. Tetrahedron: Asymmetry 1994, 5, 1635. (b) Fantin, G.; Fogagnolo,
M.; Medici, A.; Pedrini, P.; Marotta, E.; Monti. M.; Righi, P. Tetrahe-
dron: Asymmetry 1996, 7, 277. (c) Fantin, G.; Fogagnolo, M.; Marotta,
E.; Medici, A.; Pedrini, P.; Righi, P. Chem. Lett. 1996, 7, 511.
(11) For recent monographs and reviews, see, inter alia: (a) Noyori,
R. Asymmetric Catalysis in Organic Synthesis; J ohn Wiley: New York,
1994. (b) Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Verlag: New
York, 1993; Wiley-VCH: New York, 2000. (c) Comprehensive Asym-
metric Catalysis; J acobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer: Heidelberg, 1999. (d) Noyori, R.; Ohkuma, T. Angew. Chem.,
Int. Ed. 2001, 40, 40. (e) Burk, M. J . Acc. Chem. Res. 2000, 33, 363. (f)
Brunner, H. Curr. Org. Chem. 2002, 6, 441. (g) Helmchen, G.; Pfaltz,
A. Acc. Chem. Res. 2000, 33, 336. (h) Seebach, D.; Beck, A. K.; Heckel,
A. Angew. Chem., Int. Ed. 2001, 40, 92. (i) RajanBabu, T. V. Curr.
Org. Chem. 2003, 7, 301. (j) Steinhagen, H.; Helmchen, G. Angew.
Chem., Int. Ed. Engl. 1996, 35, 2337. (k) Shibasaki, M.; Sasai, H.; Arai,
T. Angew. Chem., Int. Ed. Engl. 1997, 36, 1236.
† Dedicated to Prof. Luciano Caglioti.
(1) (a) Rosini, G.; Confalonieri, G.; Marotta, E.; Rama, F.; Righi, P.
Org. Synth. 1997, 74, 158 and literature cited therein. (b) Marotta,
E.; Righi, P.; Rosini, G. Org. Proc. Res. Devel. 1999, 3, 206.
(2) Rosini, G.; Serra, R.; Rama, F.; Confalonieri, G. ENICHEM S.p.
A.-Istituto G. Donegani S.p.A.- Eur. Patent Spec. No. 922001957.5-
Pub. No. 0521 571 B1 (Sep13, 1995); US Patent no. 5,191,125 (Mar 2,
1993).
(3) Confalonieri, G.; Marotta, E.; Rama, F.; Righi, P.; Rosini, G.;
Serra, R.; Venturelli, F. Tetrahedron 1994, 50, 3235.
(4) Marotta, E.; Pagani, I.; Righi, P.; Rosini, G. Tetrahedron 1994,
50, 7645.
(5) Rosini, G.; Laffi, F.; Marotta, E.; Pagani, I.; Righi, P. J . Org.
Chem. 1998, 63, 2389.
(6) Marotta, E.; Piombi, B.; Righi, P.; Rosini, G. J . Org. Chem. 1994,
59, 7526.
(7) These unsaturated bicyclic lactones are key intermediates for
the preparation of linearly condensed triquinane sesquiterpenes ac-
cording to the elegant Curran’s radical cascade methodology: Curran,
D. P.; Rakiewicz, D. M. J . Am. Chem. Soc. 1985, 107, 1448; Tetrahedron
1985, 41, 3943.
(12) (a) Adger, B.; Berens, U.; Griffiths, M. J .; Kelly, M. J .; McCague,
R.; Miller, J . A.; Palmer, C. F.; Roberts, S. M.; Selke, R.; Vitinius, U.;
Ward, G. Chem. Commun. 1997, 1713. (b) Derrien, N.; Dousson, C.
B.; Roberts, S. M.; Berens, U.; Burk, M. J .; Ohff, M. Tetrahedron:
Asymmetry 1999, 10, 3341.
10.1021/jo035324v CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/15/2004
J . Org. Chem. 2004, 69, 1353-1356
1353

SCHEME 2
SCHEME 3a
TABLE 1. Ster eoselective P r ep a r a tion of Ra cem ic
en d o-Alcoh ols 5 a n d Th eir Con ver sion to th e
Cor r esp on d in g Boc Der iva tives 6
endo-alcohol
Boc,derivative
entry
substrate
(yield, %)
(yield, %)
1
2
3
4
5
6
1a
1b
1c
1d
1e
1f
5a (91)
5b (91)
5c (90)
5d (92)
5e (98a)
5fc (99)
6a (70)
6b (74)
6c (60)
6d (76)
6e (91)b
6fc (70)
a
Key: 1:1 solution of NaHCO3 5%/Na2SO3 20%.
a
endo: 88%; exo: 8%. b Referenced to crude product. c Exo/endo
TABLE 2. Ster eosp ecific Iod oca r bon a ta tion ,
Hyd r olysis, a n d Hyd r ogen olysis of Boc Der iva tives 6a -f
) 3:1.
Boc
iodocarbonate
(yield, %)
iodo diol endo,endo-diol
entry derivative
(yield, %)
(yield, %)
The major limitation of Roberts’ approach is that the
synthetic scheme is “one-target oriented”. The bicyclo-
[3.2.0]hept-2-en-6-one is the only easily available member
of this family of bicycloketones, and thus the efficiency
of the possible ligands may be tuned and optimized by
changing only the aryls of phosphinite groups.
1
2
3
4
5
6
6a
6b
6c
6d
6e
6fb
7a (90)
7ba
8a (60)
8b (66)
8c (67)
8d (70)
8e (88)
8fc (65)
4a (65)
4b (72)
4c (75)
4d (63)
4e (99)
4fc (92)
7ca
7d a
7ea
7fa
a
b
Not isolated. exo/endo ) 3:1.
Therefore, we were attracted by the possibility of using
bicyclo[3.2.0]hept-3-en-6-ones (1) to prepare a set of chiral
bidentate, nonracemic ligands with a diversely substi-
tuted bicyclo[3.2.0]heptane framework (4). These new
ligands will be characterized by an endo,endo-1,3 rela-
tionship of the hydroxyl groups, nested in a four contigu-
ous chirality center cavity (Scheme 2). The aim of the
present study is not only to prepare another asymmetric
catalytic system but also to improve the understanding
of the factors in chiral ligand design concerning the
bicyclo[3.2.0]heptane backbone by exploring a variety of
possible derivatives and chiral ligand modifications.
Herein, we report a successful preparation of signifi-
cant representatives of this class of diols. Our task has
been the search for an efficient and general procedure
for the conversion of bicyclo[3.2.0]hept-3-en-6-ones (1)
into bicyclo[3.2.0]heptane-2-endo,7-endo-diols (4).
We previously observed that the wedge shape of bicylic
compounds 1 allows a highly stereoselective reduction of
the carbonyl group by treatment with lithium aluminum
hydride in tetrahydrofuran (THF) at low temperature.
The desired endo-alcohols 5 were obtained in excellent
yields (Table 1) when the reduction was carefully per-
formed at -60 °C allowing the temperature to rise slowly
to ambient temperature before quenching.
by reaction of the sodium alkoxide with Boc-Im (Table
1). Then, a totally regio- and stereocontrolled iodocar-
bonate cyclization of compound 6a occurred when induced
by iodine monobromide (IBr) in dichloromethane (DCM)
according to the procedure developed by Duan and
Smith.13,14
Though cyclic iodocarbonate 7a could be isolated in
good yield, we observed that these intermediates some-
times undergo occasional decomposition during the pu-
rification. To avoid this risk, crude iodocarbonates 7b-f
were converted in situ into the corresponding iododiols
8b-f by hydrolysis with trifluoroacetic acid (Table 2).
Finally, these latter compounds gave the 2-endo,7-
endo-diols 4a -f by palladium-catalyzed hydrogenolysis
in the presence of sodium hydrogen carbonate. The yields
reported in Tables 1 and 2 are referenced to products
isolated and purified by flash chromatography.
The relative configurations of the intermediates as well
as of the final products were determined spectroscopically
(see the Supporting Information). Moreover, the X-ray
crystal structural analyses of compound 8c clearly indi-
cate the endo,endo relationship of the hydroxyl groups,
both opposite to the exo-iodine on C3 (Figure 1).15
We then faced the preparation of an enantiopure
representative of bicyclo[3.2.0]heptane-2-endo-7-endo-
diols. In doing so, we tried to improve the procedure to
have a faster, more compact synthetic scheme. The
Bicyclic endo-alcohols 5 became the key precursors for
the regio- and stereospecific functionalization of the
carbon,carbon double bond of the five-membered ring. In
fact, we considered that the C6 endo hydroxy group could
play a pivotal role in the hydroxylation of the double bond
through an intramolecular reaction. Scheme 3 depicts the
synthetic scheme of the general procedure applied to
bicyclic ketone 1a .
(13) Duan, J . J .-W.; Smith, A. B., III. J . Org. Chem. 1993, 58, 3703.
(14) The carbonate moiety acts as a temporary tether. The reaction
generates two new stereo centres in one step, through an intra-
molecular process.
(15) Crystallographic data have been deposited with the Cambridge
Crystallographic Data Centre, CCDC number 227177.
endo-Alcohols 5a -f were converted into the corre-
sponding tert-butyl carbonates 6a -f in fair to good yields
1354 J . Org. Chem., Vol. 69, No. 4, 2004

removal of the solvent, 6 mL of anhydrous THF was added and
the mixture was cooled to -10 °C. Keeping the temperature
under -5 °C, a solution of the alcohol (2 mmol dissolved in 6
mL of THF) was slowly dropped into the suspension. After 30
min (when the development of gases was ceased), a solution of
BOC-imidazole (0.530 g, 1.05 equiv, dissolved in 4 mL of THF)
was dropped into the reaction mixture, without exceeding 0 °C.
The reaction was monitored by TLC and stopped after the
disappearance of the starting material. The reaction mixture was
diluted with pentane, and the solid imidazole precipitated during
the reaction was filtered on a Celite pad, washing the solid
residue twice with pentane. The organic solution obtained was
washed with water (2 × 5 mL) and brine (1 × 5 mL) and dried
over MgSO4. After evaporation of the solvent, a crude oil was
obtained. Pentane was added (6 mL), and a solid precipitate of
imidazole was formed. The mixture was filtered, and after
evaporation of the solvent the procedure was repeated until no
more solid was formed after the addition of pentane. The crude
BOC derivatives were obtained in quantitative yields; all the
crude products contained small traces of BOC-imidazole (max
2-3%) and were used as such for the following reactions.
Analytical samples were obtained by flash chromatography. For
spectroscopic and analytical data of compounds 6a -f, see the
Supporting Information.
F IGURE 1. X-ray structure of compound 8c.
SCHEME 4a
P r oced u r e for th e Syn th esis of Iod o Diols 8. A solution
of the BOC-derivative (1 mmol in 11 mL of DCM) was cooled,
under N2 atmosphere, to -78 °C. A solution of IBr (1.8 mmol in
5 mL DCM) was slowly dropped into the reaction mixture,
keeping the temperature around -70 °C. The reaction was kept
in the dark until the disappearance of the starting material as
monitored by TLC. The mixture was then diluted with Et2O,
and 6 mL of a 1:1 solution of NaHCO3 5%/Na2SO3 20% was
added. The mixture was warmed to 0 °C and stirred at this
temperature for 15-20 min until the organic phase turned
colorless or pale yellow. The organic solution obtained was
washed with brine (1 × 5 mL) and dried over MgSO4. After
evaporation of the solvent, the crude iodocarbonate derivatives
were obtained in quantitative yields and were used as such for
the following reactions. For 7a , an analytically pure sample was
obtained as reported below. The crude oil obtained was dissolved
in 1.2 mL of THF, and 1.2 mL of H2O was added. The mixture
was cooled to 0 °C, and 0.23 mL of CF3COOH was added. The
reaction was then warmed to room temperature and monitored
by TLC (DCM/Et2O 5:1) until disappearance of the starting
material. The reaction mixture was diluted with DCM and
neutralized, adding a NaHCO3 satd solution until effervescence
ceased. The organic solution obtained was washed with brine
(1 × 5 mL) and dried over MgSO4. After evaporation of the
solvent, the crude iodo diol derivatives were obtained in the
yields reported for each product. For spectroscopic and analytical
data of compounds 8a -f, see the Supporting Information.
P r oced u r e for th e P r ep a r a tion of Ra cem ic Diols 4. A
solution of the starting iodo diol (1 mmol) in methanol (10 mL)
in a steel autoclave was flushed with argon. To this solution were
then added 10% Pd/C (37 mg) and solid K2CO3 (140 mg). The
mixture was then stirred under 5 atm of hydrogen for 48 h. After
this time, TLC analysis showed a complete reaction. The mixture
was filtered on a Celite pad and washed with methanol. After
the solvent was evaporated under moderate vacuum, the residue
was partitioned between methylene chloride and water. The
aqueous layer was back-extracted with more methylene chloride.
The organic phases were combined, dried over MgSO4, filtered,
and concentrated under moderate vacuum. Most of the crude
materials were found to be pure enough by NMR analysis. When
needed they can be purified by chromatography over a short pad
of silica gel.
a
Key: 1:1 solution of NaHCO3 5%/Na2SO3 20%.
bicyclic endo-alcohol 5c played as benchmark. It was
resolved by using (-)-camphanic acid chloride as the
resolving agent.
Then, compound (-)-(1R,5S,6S)-5c9 was converted into
the corresponding tert-butyl carbonate (+)-6c ([R]D +126.9,
c 1.61, CHCl3) that gave the iodocarbonate (-)-7c ([R]D
-33.7, c 1.22, CHCl3) by reaction with IBr. Treatment
with LiAlH4 in THF at -70 °C gave rise to a fast
carbonate reduction to give the intermediate iododiol 8c
that could be isolated and purified. However, if the
reaction was protracted for several hours at room tem-
perature or at 50 °C, a slow hydrodeiodination occurred
affording the desired endo,endo-diol (-)-(1S,2R,5R,7S)-
4c ([R]D -33.8, c 1.09, CHCl3) in a 35% overall yield from
the endo-alcohol 5c (Scheme 4).
In conclusion, we have developed a simple and efficient
methodology for the preparation of a variety of bicyclo-
[3.2.0]heptane-2-endo,7-endo-diols with high regio- and
stereoselectivity. This route will be extended to the
preparation of enantiomerically pure representatives of
a new and large family of bidentate ligands having the
bicyclo[3.2.0]heptane as common backbone. Our goal is
to try these new compounds in a wide variety of enan-
tioselective reactions and to start studies on the structure-
efficiency relationship by exploiting the many points of
diversity that this bicyclo[3.2.0]heptane framework offers.
4,4-Dim eth ylbicyclo[3.2.0]h ep ta n e-2,7-d iol (4a ). Colorless
1
oil. TLC (Et2O): Rf 0.52 UV-vis and Ce(IV). H NMR δ (ppm):
4.80-4.65 (bs, 2H); 4.55 (m, 1H); 4.35 (m, 1H); 2.88 (m, 1H);
2.55 (m, 1H); 1.90-1.60 (m, 4H); 0.80 (s, 3H); 0.70 (s, 3H). 13C
NMR δ (ppm): 77.0; 65.6; 47.4; 44.1; 41.5; 40.0; 33.7; 28.3; 22.9.
IR (neat): 3318; 2954; 1465, 1127, 1115, 1068. m/z: 138 (10);
123 (14); 95 (97); 73 (48); 69 (45); 41 (100). Anal. Calcd for
C9H16O2: C, 69.19; H, 10.32. Found: C, 68.81; H, 10.22.
Exp er im en ta l Section
P r oced u r e for th e Syn th esis of BOC Der iva tives 6. NaH
(50% w/w; 0.288 g; 3 equiv) was washed, under nitrogen
atmosphere, with anhydrous petroleum ether (2 × 5 mL). After
J . Org. Chem, Vol. 69, No. 4, 2004 1355

2-Meth ylbicyclo[3.2.0]h ep ta n e-2,7-d iol (4b). Colorless oil.
TLC (DCM/Et2O 5:1) Rf 0.2, Ce(IV). H NMR δ (ppm): 4.80 (bs,
described.9 It was then quantitatively converted to the corre-
1
sponding BOC derivative (+)-(1R,5S,6S)-6c, [R]21 +126.9 (c
D
2H); 4.35 (m, 1H); 2.50 (m, 1H); 2.38 (m, 1H); 2.20 (m, 2H); 1.7-
1.4 (m, 4H); 1.10 (s, 3H). 13C NMR δ (ppm): 83.0; 65.6; 50.2;
40.1; 36.8; 31.4; 30.4; 29.1. IR (neat): 3314; 2947; 1179, 1115,
1094. m/z: 124 (15); 109 (28); 87 (56); 81 (100); 67 (21); 53 (21).
Anal. Calcd for C8H14O2: C, 67.57; H, 9.92. Found: C, 67.48; H,
9.93.
2,5-Dim eth ylbicyclo[3.2.0]h ep ta n e-2,7-d iol (4c). White
solid. Mp: 52-53 °C. TLC (DCM/Et2O 5:1) Rf 0.19 Ce(IV). 1H
NMR δ (ppm): 4.54 (bs, 2H), 4.46 (q with further fine couplings,
1H, J ) 6.9 Hz), 2.31-2.10 (m, 2H), 2.01 (d with further fine
couplings, 1H, J ) 8.2 Hz,), 1.91-1.81 (dd, 1H, J ) 12.9, 6.6
Hz), 1.79-1.69 (dd, 1H, J ) 12.4, 6.6 Hz), 1.57-1.46 (dd, 1H, J
) 12.6, 6.9 Hz), 1.42-1.28 (m, 1H), 1.15 (s, 3H), 1.05 (s, 3H).
13C NMR δ (ppm): 82.9, 63.9, 55.2, 42.5, 41.2, 39.1, 38.3, 29.4,
26.8. I. R. (KBr): 3221, 2921, 1446, 1368, 1284, 1166, 1062, 1035,
968. m/z:138 (7), 123 (9), 97 (69), 95 (78), 87 (41), 67 (27), 55
(29), 43 (100), 41 (58). Anal. Calcd for C9H16O2: C, 69.19; H,
10.32. Found: C, 69.25; H, 10.42.
Bicyclo[3.2.0]h ep ta n e-2,7-d iol (4d ). Pale yellow oil. TLC
(DCM/Et2O 5:1) Rf 0.20 Ce(IV). 1H NMR δ (ppm): 4.52 (bs
shifting, 2H), 4.40 (q, 1H, J ) 7.8 Hz), 4.32 (q, 1H, J ) 8.1 Hz),
2.83-2.72 (m, 1H), 2.52 (dtd, 1H, J ) 12.8, 8.8, 2.5 Hz), 2.22
(quin, 1H, J ) 6.9 Hz), 2.13-1.92 (m, 2H), 1.72-1.42 (m, 3H).
13C NMR δ (ppm): 78.2, 66.1, 44.1, 37.2, 34.1, 30.4, 30.3. Anal.
Calcd for C7H12O2: C, 65.60; H, 9.44. Found: C, 65.49; H, 9.48.
Anal. Calcd for C8H14O2: C, 67.57; H, 9.92. Found: C, 67.80; H,
10.02.
5-Meth ylbicyclo[3.2.0]h ep ta n e-2,7-d iol (4e). Pale yellow
oil. TLC (DCM/Et2O 5:1) Rf 0.19 Ce(IV). 1H NMR δ (ppm): 4.47
(q, 1H, J ) 8.0 Hz), 4.41-4.23 (q superimposed with a shifting
bs, 3H, J ) 8.2 Hz), 2.36 (td, 1H, J ) 8.0, 2.4 Hz), 2.22-2.00
(m, 3H), 1.90-1.80 (dd, 1H, J ) 12.6, 6.9 Hz), 1.56-1.47 (dt,
1H, J ) 12.5, 3.9 Hz), 1.38-1.21 (m 1H), 1.06 (s, 3H). 13C NMR
δ (ppm): 78.0, 64.4, 48.7, 42.9, 38.2, 38.1, 35.3, 26.2. IR (neat):
3331, 2947, 1450, 1118, 1074, 1048. m/z: 124, 109, 83, 81, 55,
41. Anal. Calcd for C8H14O2: C, 67.57; H, 9.92. Found: C, 67.51;
H, 9.99.
1.61, CHCl3), according to the method described above. Carbon-
ate (+)-6c (3.56 g; 14.94 mmol) was then subjected to the
iodocarbonatation as described above, and the crude iodocar-
bonate (-)-7c, [R]20 -33.7 (c 1.22, CHCl3), was immediately
D
taken to the following reduction. A solution of the crude
iodocarbonate (-)-7c (1.29 g, 4.19 mmol) in THF (5 mL) was
cooled to -78 °C. LiAlH4 (1 M in THF, 10.5 mL, 10.5 mmol) was
then added dropwise. After the addition was complete, the
cooling bath was removed and the mixture allowed to warm to
room temperature and left stirring overnight. The reaction was
quenched by the careful addition of sat. NH4Cl and the mixture
extracted with 3 × 20 mL of Et2O. The combined organic extracts
were dried over MgSO4 and evaporated to dryness. The crude
material was purified by flash chromatography (DCM/Et2O 5:1)
to afford 0.818 mg (35% yield from 5c) of a white solid. Mp: 56-
1
58 °C. [R]20D: -33.8 (c 1.09, CHCl3). H NMR δ (ppm): 1.07 (s,
3H); 1.14 (s, 3H); 1.33-1.39 (m, 1H); 1.48-1.55 (dd, 1H, J )
6.6, 12.9 Hz); 1.71-1.77 (dd, 1H, J ) 6.6, 12.4 Hz); 1.82-1.89
(dd, 1H, J ) 6.9, 13.5 Hz); 2.02 (bd, 1H); 2.11-2.29 (m, 2H);
4.46 (q, with further fine couplings, 1H, J ) 8.5 Hz); 4.96 (bs,
1H). 13C NMR δ (ppm): 26.6; 29.2; 38.1; 38.9; 41.0; 42.3; 55.0;
63.7; 82.7. IR (KBr): 3239, 2937, 1458, 1377, 1291, 1166, 1084,
1046, 968. m/z (ES+): 179, 157; (ES-): 156, 155. Anal. Calcd
for C9H16O2: C, 69.19; H, 10.32. Found: C, 69.18; H, 10.30.
Ack n ow led gm en t. This work was supported by the
Ministero dell’Universita` e della Ricerca Scientifica e
Tecnologica (MURST), Italy, and by Alma Mater Stu-
diorum-Universita` di Bologna (Italy), Progetto Nazio-
nale “Stereoselezione in sintesi organica”.
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectra of
compounds 4a -f, 6a -f, 7a , and 8a -f; X-ray crystal data of
compound 8c. This material is available free of charge via the
Internet at http://pubs.acs.org.
P r ep a r a tion of th e En a n tiom er ica lly P u r e Liga n d (-)-
4c. Alcohol 5c was resolved according to a method we already
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1356 J . Org. Chem., Vol. 69, No. 4, 2004