Camphor-based α-bromo ketones for the asymmetric Darzens reaction

Article abstract of DOI:10.1021/jo001031f

(1R)-2endo-Bromoacetyl-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (endo-2-bromoacetylisoborneol)4 and its trimethylsilyl ether 3 are presented as efficient reagents for the asymmetric Darzens reaction. From the α,β-epoxy ketone adducts the chiral inductor camphor is removed, by treatment with ceric(IV) ammonium nitrate, to yield the corresponding epoxy acids which are isolated as their dicyclohexylammonium salts.

Full text of DOI:10.1021/jo001031f

J . Org. Chem. 2000, 65, 9007-9012
9007
Ca m p h or -Ba sed r-Br om o Keton es for th e Asym m etr ic Da r zen s
Rea ction
Claudio Palomo,*,† Mikel Oiarbide,† Arun K. Sharma,† M. Concepcio´n Gonza´lez-Rego,†
Anthony Linden,‡ J esu´s M. Garc´ıa,§ and Alberto Gonza´lez§
Departamento de Quı´mica Orga´nica, Facultad de Qu´ımica, Universidad del Paı´s Vasco, Apdo 1072,
20080 San Sebastia´n, Spain, Organisch-chemisches Institut der Universita¨t Zu¨rich, Winterthurerstrasse
190, CH-8057 Zu¨rich, Switzerland, and Departamento de Qu´ımica Aplicada, Universidad Pu´blica de
Navarra, 31006-Pamplona, Spain
E-mail: qoppanic@sq.ehu.es
Received J uly 10, 2000
(1R)-2-endo-Bromoacetyl-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (endo-2-bromoacetylisoborneol) 4
and its trimethylsilyl ether 3 are presented as efficient reagents for the asymmetric Darzens
reaction. From the R,â-epoxy ketone adducts the chiral inductor camphor is removed, by treatment
with ceric(IV) ammonium nitrate, to yield the corresponding epoxy acids which are isolated as
their dicyclohexylammonium salts.
The reaction of R-halo esters with aldehydes or ketones
promoted by base often results in the formation of R,â-
epoxy (or glycidic) esters, the classical Darzens reaction,1
or in the formation of halohydrins which then can be
cyclized to the corresponding R,â-epoxy esters. The asym-
metric version of this reaction has been realized by using
chiral R-metalated methyl aryl sulfoxides,2 chiral R-ha-
logenated imide enolates,3 chiral benzaldehyde-chro-
mium complexes,4 and chiral R-halo esters.5 Some ex-
amples on the enantioselective Darzens reaction have
also been documented; however, in all but a few cases,6
the enantioselectivities are still rather poor.7 On the other
hand, competitive reactions8 such as the Favorskii rear-
rangement, the nucleophilic addition at the carbonyl
group, and the nucleophilic substitution of the halide
have prevented R-halo ketones and R-halo aldehydes from
being used in such a reaction.9 Exceptionally, an R-bromo
R′-hydroxy ketone, where no R′-hydrogen atoms are
present, has been used. In this instance, the obtained R′-
hydroxy R,â-epoxy ketone adduct generates, by oxidative
cleavage of the R′-hydroxy ketone moiety, the correspond-
ing R,â-epoxy ester.10 However, to the best of our knowl-
edge, there are no reports concerning the asymmetric
version of the later approach, which would involve the
use of chiral ketone reagents. In connection to this, we
have recently reported on the use of the methyl ketone 2
(Scheme 1) for highly diastereoselective “acetate” aldol
and Mannich reactions.11 We now report on the prepara-
tion of R-halo ketones 3-5 and their use for the asym-
metric Darzens reaction.
The bromo ketones 3 and 4 needed for the study were
prepared according to a standard procedure, via the
corresponding silyl enol ether and using N-bromosuccin-
imide (NBS) as the brominating agent, as shown in
(7) Polymers of r-amino acids as catalysts: (a) J ulia, S.; Guixer, J .;
Masana, J .; Rocas, J .; Colonna, S.; Annunziata, R.; Molinari, H. J .
Chem. Soc., Perkin Trans. 1 1982, 1317. (b) Annunziata, R.; Banfi, S.;
Colonna, S. Tetrahedron Lett. 1985, 26, 2471. (c) Adger, B. M.; Karkley,
J . V.; Bergeron, S.; Cappi, M. W.; Flowerdew, B. E.; J ackson, M. P.,
McCague, R.; Nugent, T. C.; Roberts, S. M. J . Chem. Soc., Perkin Trans.
1 1997, 3501. For recent reviews on this subject, see: (d) Ebrahim, S.;
Wills, M. Tetrahedron Asymmetry 1997, 8, 3163. (e) Pu, L. Tetrahe-
dron: Asymmetry 1998, 9, 1457. Chiral crown catalysts: (f) Bako´, P.;
Szo¨llo˜sy, A.; Bombicz, P.; To˜ke, L. Synlett 1997, 291. Chiral lithium
amides: (g) Takahasi, T.; Muraoka, M.; Capo, M.; Koga, K. Chem.
Pharm. Bull. 1995, 43, 1821. Phase-transfer catalyzed conditions: (h)
Arai, S.; Shioiri, T. Tetrahedron Lett. 1998, 39, 2145. (i) Arai, S.; Shirai,
Y.; Ishida, T.; Shioiri, T. Tetrahedron 1999, 55, 6375.
(8) For more detailed information on this subject, see: (a) Shibata,
I.; Yamasaki, H.; Baba, A.; Matsuda, H. J . Org. Chem. 1992, 57, 6909.
(b) Wedler, C.; Kunath, A.; Schinck, H. Angew. Chem., Int. Ed. Engl.
1995, 34, 2028.
(9) For Darzens reaction with r-haloketones, see: (a) Enders, D.;
Hett, R. Synlett 1998, 961. (b) Barluenga, J .; Baragan˜a, B.; Concello´n,
J . M.; Pin˜era-Nicola´s, A.; D´ıaz, M. R.; Garc´ıa-Granda, S. J . Org. Chem.
1999, 64, 5048. For the chemistry of R-haloketones, see: (c) De Kimpe,
N.; Verhe´, R. The Chemistry of Haloketones, R-Haloaldehydes and
R-Haloimines, Patai, S.; Rappoport, Z., Eds; J ohn Wiley: New York,
1988.
† Universidad del Pa´ıs Vasco.
‡ Organisch-chemisches Institut der Universita¨t Zu¨rich.
§ Universidad Pu´blica de Navarra.
(1) For reviews, see: (a) Newman, M. S.; Magerlein, B. J . Org. React.
1949, 5, 413. (b) Ballester, M. Chem. Rev. 1955, 55, 283. (c) Rosen, T.
In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Heathcock, C. H., Eds.; Pergamon: Oxford, 1991; Vol. 2, p 409.
(2) (a) Durst, T.; Viau, R.; Van Den Elzen, R.; Nguyen, C. H. J .
Chem. Soc. Chem. Commun. 1971, 1334. (b) Solladie, G.; Matloubi,
M. F.; Luttmann, C.; Mioskowski, C. Helv. Chim. Acta 1982, 65, 1602.
(3) (a) Abbdel-Magid, A.; Pridgen, L. N.; Eggleston, D. S.; Lantos, I.
J . Am. Chem. Soc. 1986, 108, 4595. (b) Pridgen, L. N.; Abbdel-Magid,
A. F.; Lantos, I.; Shilcrat, S.; Eggleston, D. S. J . Org. Chem. 1993, 58,
5107. (c) Commerc¸on, A.; Bezard, D.; Bernard, F.; Bourzat, J . D.
Tetrahedron Lett. 1992, 33, 5185. (d) Wang, Y.-C.; Su, D.-W.; Lin, C.-
M.; Tseng, H.-L.; Li, C.-L.; Yan, T. H. Tetrahedron Lett. 1999, 40, 3577.
(e) Wang, Y.-C.; Li, C.-L.; Tseng, H.-L.; Chuang, S.-C.; Yan, T.-H.
Tetrahedron: Asymmetry 1999, 10, 3249.
(4) Baldoli, C.; Del Buttero, P.; Maiorana, S. Tetrahedron 1990, 46,
7823 and references therein.
(5) (a) Sisido, K.; Nakanishi, O.; Nozaki, H. J . Org. Chem. 1961,
26, 4878. (b) Schwartz, A.; Madan, P. B.; Mohacsi, E.; O’Brien, J . P.;
Todaro, L. J .; Coffen, D. L. J . Org. Chem. 1992, 57, 851. (c) Ohkata,
K.; Kimura, J .; Shinohara, Y.; Takagai, R.; Hiraga, Y. J . Chem. Soc.
Chem. Commun. 1996, 2411. (d) Tokagi, R.; Kimura, J .; Shinohara,
Y.; Ohba, Y.; Takezono, K.; Hiraga, Y.; Kojima, S.; Ohkata, K. J . Chem.
Soc., Perkin Trans. 1 1998, 689.
(6) (a) Corey, E. J .; Choi, S. Tetrahedron Lett. 1991, 32, 2857. (b)
Corey, E. J .; Lee, D.-H.; Choi, S. Tetrahedron Lett. 1992, 33, 6735. (c)
S.-i. Kiyooka, K. A. Shahid Tetrahedron Asymmetry 2000, 11, 1537.
(10) Mukaiyama, T.; Yura, T.; Iwasawa, N. Chem. Lett. 1985, 809.
(11) (a) Palomo, C.; Oiarbide, M.; Aizpurua, J . M.; Gonza´lez, A.;
Garc´ıa, J . M.; Landa, C.; Odriozola, I.; Linden, A. J . Org. Chem. 1999,
64, 8193. (b) Palomo, C.; Oiarbide, M.; Gonza´lez-Rego, C.; Sharma, A.
K.; Garc´ıa, J . M.; Gonza´lez, A.; Landa, C.; Linden, A. Angew. Chem.,
Int. Ed. 2000, 39, 1063. See also: (c) Palomo, C.; Gonza´lez, A.; Garc´ıa,
J . M.; Landa, C.; Oiarbide, M.; Rodr´ıguez, S.; Linden, A. Angew. Chem.,
Int. Ed. Engl. 1998, 37, 180.
10.1021/jo001031f CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/02/2000

9008 J . Org. Chem., Vol. 65, No. 26, 2000
Palomo et al.
Ta ble 1. Da r zen s Con d en sa tion of th e Lith iu m En ola te
of 4 w ith Rep r esen ta tive Ald eh yd esa
Sch em e 1
aldehyde 6
a , PhCHO
b, 4-MeOC6H4CHO
c, 4-ClC6H4CHO
d , CH3CHO
e, CH3CH2CHO
f, CH3(CH2)2CHO
g, CH3(CH2)3CHO
selectivity ratio 9:10b
yield, %c
g97:3
g97:3
g97:3
5:95
20:80
37:63
35:65
91d
e
93d
93
86
86
96
a
Reactions carried out on a 1 mmol scale; ketone:aldehyde 1:1.5.
For entries a-c only one isomer was detected by 13C NMR; for
b
other entries, the diastereomeric ratio was determined by inte-
grating the easily distinguisable doublets corresponding to the R-H
to the carbonyl group in the 1H NMR spectra. Typical coupling
constants for both isomers: J cis ) 2 Hz, J trans ) 5 Hz. c Yield of
the mixture of diastereomers after purification by column chro-
d
matography unless otherwise stated. Isolated yields of pure
compound 9. e Unstable adduct. Extensive decomposition was
observed within a few hours.
Sch em e 2
drins 7 (anti) and 8 (syn), respectively, no traces of either
7 or 8 was detected in the crude reaction products.
On the other hand, previous studies have established
that the size of the R-OR group is one of the main
stereochemical control elements in lithium-mediated
ketone aldol reactions.15 In particular, it has been found
that aldol reactions involving the metal enolates of
R-hydroxy ethyl ketones provide substantially lower
levels of diastereoselectivity than those involving the
more sterically demanding R-trimethylsilyloxy deriva-
tives.16 On the basis of this evidence, we next examined
the Darzens reaction of the silylated bromo ketone 3. In
this case, the reaction of the lithium enolate of ketone 3,
generated by treatment of 3 with 1 equiv of LDA, with
benzaldehyde (Scheme 3) led to an almost equimolar
mixture of epoxides 11 and 12. The reaction conversion
at -78 °C was uncomplete and warming to ambient
temperature was necessary for complete disappearance
of starting 3. Compounds 11 and 12 were separated by
HPLC and each isomer was submitted to a single-crystal
X-ray structure analysis. On the other hand, desilylation
of 11 provided in 90% yield a product which was identical
to that directly obtained from Darzens condensation
between the dianion of 4 and benzaldehyde. Therefore
compounds 11 and 9a are correlated and the configura-
tion for the remaining compounds 9b,c was established
by analogy. When the reaction of the lithium enolate of
3 with aliphatic aldehydes was evaluated (Scheme 3), no
epoxide formation took place at all. In these cases, the
corresponding intermediate halohydrins 13 and 15 were
produced instead,17 in good yields and very high diaste-
reoselectivity, as shown in Table 2. The reaction failed
to go to completion in some cases, but after workup, the
remaining unreacted R-bromo ketone could be easily
separated from the mixture of aldols by column chroma-
tography and reused. In general, syn-aldols 13 were
formed as the major products, typically in a diastereo-
meric ratio of 95:5, over the minor anti-aldols 15. The
Scheme 1. Preparation of the chloro derivative 5, how-
ever, was better accomplished by using a combination of
TMS-Cl and mCPBA as the chlorination agent instead
of NCS.12 Darzens reactions of bromo ketone 4 with
aldehydes (Scheme 2) were carried out by treatment of
4 with 2.5 equiv of LDA, in the presence of LiCl,13 and
subsequent addition of the aldehyde 6. Other bases
examined for that purpose, such as potassium bis-
(trimethylsilyl)amide and sodium bis(trimethylsilyl)-
amide, were less efficient in terms of both chemical yield
and diastereoselectivity. From the results in Table 1, it
is clear that the reaction of the dianion of 4 with aromatic
aldehydes 6a -c proceeded extremelly well to give the
epoxide 9 essentially as the sole diastereomer (for
configurational assignment of 9a -c; see below). The
reaction with aliphatic aldehydes 6d -g gave rise to a
mixture of both 9 and 10 in variable composition, with
10 as the major stereoisomer.14 It appears that aliphatic
aldehydes with large R groups (6f,g) lead to lower
selectivities than the aldehydes with small R groups (6d )
do. Although formation of epoxy ketones 9 and 10 should
take place through cyclization of intermediate bromohy-
(15) For pertinent information on this aspect, see ref 11b and
references therein.
(12) For a review on trimethylsilyl halides-oxidants combinations,
see: Vankar, P. S.; Reddy, M. V. R.; Vankar, Y. D. Org. Prep. Proc.
Int. 1998, 30, 373.
(13) For the influence of LiCl on the stereoselectivity of the aldol
reactions of Li enolates, see ref 11a and references therein.
(14) Relative configurations for compounds 9c-g (trans) and for
10c-g (cis) were established by the value of the vicinal coupling
constants measured for the trans-epoxides 9 (typically 2.5 Hz) and the
cis-epoxides 10 (typically 5.0 Hz), respectively.
(16) Heathcock, C. H.; Buse, C. T.; Kleschick, W. A.; Pirrung, M.
C.; Sohn, J . E.; Lampe, J . J . Org. Chem. 1980, 45, 1066.
(17) The different reactivity observed for benzaldehyde (epoxides 11
and 12 are directly obtained) as compared with aliphatic aldehydes
(halohydrins are isolated instead) can be rooted in the different reaction
temperature employed. In fact, the “aliphatic” halohydrins 13 and 14
cyclized to the epoxides 10 when treated with a weak base at room
temperature.

Camphor-Based R-Bromo Ketones
J . Org. Chem., Vol. 65, No. 26, 2000 9009
Sch em e 3
Ta ble 2. Ald ol Rea ction s of th e Lith iu m En ola te of 3
a n d 5 w ith Alip h a tic Ald eh yd es
entry
R
X
syn:antia
yield, %b
1
2
3
4
5
6
7
8
CH3CH2
Br
Cl
Br
Cl
Br
Br
Cl
Br
92:8
72
89:11
92:8c
89:11
95:5c
94:6c
90:10
94:6c
65d
89
CH3(CH2)2
68d
68
81
CH3(CH2)3
(CH3)2CHCH2
75
PhCH2CH2
53e
a
Diastereomeric ratio determined by 1H NMR, through inte-
grating the signals corresponding to the proton COCHX in both
b
stereoisomers. Yield of pure isomer 13 or 14 after purification
by flash column chromatography. c Corroborated by HPLC ((1%).
d
Unreacted 5 was recovered in 10% yield. e Unreacted 3 was
recovered in 15% yield.
R-chloro ketone 5 led to similar results, although slighly
lower diastereoselectivities were attained (entries 2, 4,
and 7). The configurational assignment for adducts 13
and 14 was primarily made by conversion of compounds
13 and 14 into 10 and definitively by a single-crystal
X-ray analysis of the aldol 13 (R ) nPr).18 Assignment of
the configuration for the minor isomers 15 and 16 was
done by assuming a uniform reaction mechanism and
also by 13C chemical shift correlations. In this respect, it
has been shown for related 1,2-halohydrins that the syn
isomers exhibit a consistent downfield 13C NMR shift of
about 4-5 ppm with respect to the anti isomers.3b In our
case, the same trend, albeit attenuated, was observed
with a ∆ ppm (δ syn - δ anti) value in the range 0.8-
1.6.
F igu r e 1. Proposed transition state structures that may
account for the observed stereochemical outcome of the reac-
tions involving aliphatic aldehydes (A) and aromatic aldehydes
(B).
sition state A, which nicely correlates metal enolate
geometry and the relative configuration of aldol ad-
ducts,19 fits well the metal chelating three-point coordi-
nation model previously postulated for this kind of aldol
reaction.20 If one assumes A as the lowest energy TS for
these reactions, then the major products 8 and 13 (or 14)
would arise from the attack of the aldehyde from the less
congested rear side of the chelated lithium (Z)-enolate.21
Formation of major stereoisomers 9 and 11 from aromatic
aldehydes can be better accounted for by invoking a
boatlike TS B, which would lead to the intermediate anti
halohydrins 7, 15, or 16. The formation of anti-adducts
from lithium enolates of carboxylic acid derivatives and
aromatic aldehydes has been previously observed by
The stereochemical outcome of these reactions involv-
ing aliphatic and aromatic aldehydes is consistent with
transition structures A and B, respectively, depicted in
Figure 1. The Zimmerman-Traxler type pericyclic tran-
(18) The X-ray crystal structure analyses have been performed by
one of us (A. L.) at the Organisch-Chemisches Institut der Universita¨t
Zu¨rich. Atomic coordinates, bond lengths and angles, and thermal
parameters for compounds 5, 11, 12 and 13 (R ) nPr) have been
deposited at the Cambridge Crystallographic Data Center. The coor-
dinates can be obtained, on request, from the Director, Cambridge
Crystalographic Data Center, 12 Union Road, Cambridge, CB2 1EZ,
UK. E-mail: deposit@ccdc.cam.ac.uk.
(19) (a) Zimmerman, H. E.; Traxler, M. D. J . Am. Chem. Soc. 1957,
79, 1920. (b) Evans, D. A.; Nelson, J . V.; Taber, T. T. Top. Stereochem.
1982, 13, 1.
(20) Van Draanen, N. A.; Arseniyadis, S.; Crimmins, M. T.; Heath-
cock, C. H. J . Org. Chem. 1991, 56, 2499.

9010 J . Org. Chem., Vol. 65, No. 26, 2000
Palomo et al.
Sch em e 4
responding salts 18a and 18b were isolated in yields of
60% and 66% from 10, respectively, by precipitation of
the epoxy acids as their dicyclohexylamine-derived salts
in ethyl acetate. The analysis of the mother liquors, after
evaporation of the solvent, showed no presence of the
possible trans isomerization product.
Exp er im en ta l Section
Melting points were determined with a capillary apparatus
and are uncorrected. Proton nuclear magnetic resonance (300
and 500 MHz) spectra and 13C spectra (75 MHz) were recorded
at room temperature for CDCl3 solutions, unless otherwise
stated. All chemical shifts are reported as δ values (ppm)
relative to residual CHCl3 (δH 7.26 ppm) or CDCl3 (δC 77.0
ppm) as internal standards, respectively. Optical rotations
were measured at 25 ( 0.2 °C in methylene chloride unless
otherwise stated. HPLC analyses were performed on analytical
columns (25 cm, phase Lichrosorb-Si60 and 25 cm, phase
Chiralcel OD) with flow rates using 1 mL/min and 0.5 mL/
min, respectively, using a DAD, and on preparative scale
columns (25 cm, 2.5 Ø, phase Lichrosorb-Si60). Flash chro-
matography was executed with Merck Kiesegel 60 (230-400
Mesh) using mixtures of ethyl acetate and hexane as eluents.
THF was distilled over sodium. MeOH was dried over mag-
nesium metal and iodine.
several authors, who have proposed boatlike models to
justify the results.22
Once the R,â-epoxy ketone adducts were available in
a diastereoselective way, the question of the oxidative
cleavage of the ketol moiety to form the corresponding
carboxylic acids still remained. For instance, the treat-
ment of either compounds 9, 10, or 13 with sodium
periodate in a mixture of MeOH/water gave in all cases
tested either a complex mixture of unidentified products
(reaction conducted at reflux) or unmodified starting
adducts (reaction at room temperature). No improvement
was observed when mCPBA was employed as the oxi-
dazing agent instead. Better results were obtained when
adducts 13 (R ) Et) and 11 were first reduced to the
corresponding alcohol with NaBH4 and then subjected
to treatment with Pb(OAc)4 in benzene. In both examples,
a mixture of camphor and the corresponding R,â-epoxy
aldehyde was obtained, albeit in yields lower than 40%.
Furthermore, purification of the thus obtained epoxy
aldehyde proved to be troublesome. Finally, conversion
of the epoxy adducts into the corresponding epoxy acids
was accomplished satisfactorily by treatment with ceric-
(IV) ammonium nitrate (CAN).23 For instance, treatment
of 10e and 10f in a mixture of CH3CN/water with 6 equiv
of CAN for 5 min at room temperature afforded the
corresponding epoxy acids 17a and 17b along with
camphor (Scheme 4). From the crude mixture, (+)-
camphor was easily recovered in high yields either by
column chromatography or extractions with n-hexane.
However, the free epoxy acids 17a and 17b proved to be
very difficult to purify. Neither the methyl esters, ob-
tained by direct treatment with trimethylsilyl diazo-
methane, were purified satisfactorily. Instead, the cor-
(1R)-2-en d o-Br om oa cetyl-2-exo-tr im eth ylsilyloxy-1,7,7-
tr im eth ylbicyclo[2.2.1]h ep ta n e (3). A mixture of diisopro-
pylamine (1.6 mL, 12 mmol) in THF (20 mL) was cooled to
-78 °C and n-BuLi (1.6 M in hexanes, 7.5 mL, 12 mmol) was
added dropwise. After stirring for 30 min, a solution of
trimethylsilyl chloride (2.2 mL, 16.7 mmol) in THF (12 mL)
and methyl ketone 211 (1.0 g, 5.0 mmol) in THF (12 mL) were
successively added. The reaction mixture was allowed to stir
for 1 h at -78 °C and warmed to room temperature, and the
solvent was evaporated in vacuo at room temperature. The
residue was extracted with pentane, filtered through a sintered
glass funnel, and the solvent evaporated under reduced
pressure at room temperature. The resulting viscous oil was
dissolved in THF (25 mL), and to this solution, cooled to -78
°C, was added NBS (1 g, 5.6 mmol) in portions over a period
of 10 min. The reaction mixture was stirred at -78 °C for a
further period of 20 min, quenched with water (50 mL), and
extracted with CH2Cl2. The combined organics were dried over
MgSO4, and the solvent was evaporated under reduced pres-
sure to give 3 as a viscous oil which was purified to a clear oil
by column chromatography (silica gel, eluent ethyl acetate:
hexane 1:100): yield 1.62 g (93%); [R]25D ) -20.7 (c ) 1.0, CH2-
1
Cl2); IR (neat) 1724 cm-1 (CO); H NMR (CDCl3, δ) 4.34 (d, J
) 14.3 Hz, 1H), 4.07 (d, J ) 14.3 Hz, 1H), 2.54 (d, J ) 13.0
Hz, 1H), 1.30-1.90 (m, 4H), 1.04-1.18 (m, 1H), 1.02, 0.99 and
0.82 (s, 3H), 0.67-0.78 (m, 1H), 0.09 (s, 9H); 13C NMR (CDCl3,
δ) 202.7, 91.8, 52.3, 51.4, 45.7, 41.2, 34.3, 31.0, 26.4, 21.5, 20.8,
11.8, 2.2.
(21) Formation of the Z-enolate, which was experimentally sup-
ported by trapping of it with TMSCl and isolation of the corresponding
Z-silyl enol ester (see Supporting Information for details), can be
rationalized according to Ireland’s transition state model, assuming
that the depicted intermolecular Br-L interaction is largely over-
whelmed by the intramolecular Br-H interaction. For pertinent
information on this topic, see: (a) R. E. Ireland, R. H. Mueller, A. K.
Willard J . Am. Chem. Soc. 1976, 98, 2868. (b) L. Xie, K. M. Isenberg,
G. Held, L. M. Dahl J . Org. Chem. 1997, 62, 7516.
(1R)-2-en d o-Br om oa cetyl-1,7,7-tr im eth ylbicyclo[2.2.1]-
h ep ta n -2-ol (4). Silica gel 60 (230-400 mesh, 0.5 g) was added
to a solution of 3 (0.347 g, 1 mmol) in a mixture of MeOH (4
mL) and 1 N HCl (2 mL), and the resulting slurry mixture
was stirred at room temperature for 44 h. Then the mixture
was diluted with CH2Cl2 and filtered, the organic layer was
separated, washed with an aqueous saturated solution of
NaHCO3, and dried over MgSO4, and the solvent was evapo-
rated under reduced pressure. The solid thus obtained was
purified by crystallization from a mixture of CH2Cl2/hexane
(1:1): yield 0.245 g (89%); mp 77 °C; [R]25 ) -11.3 (c ) 1.0,
D
CH2Cl2); IR (film) 3423 (OH), 1705 cm-1 (CO); 1H NMR (CDCl3,
δ) 4.44 (d, J ) 14.2 Hz, 1H), 4.18 (d, J ) 14.2 Hz, 1H), 2.36 (d,
J ) 12.8 Hz, 1H), 1.94-1.60 (m, 3H), 1.53-1.14 (m, 2H), 1.11,
1.01 and 0.86 (s, 3H), 0.89-0.99 (m, 1H); 13C NMR (CDCl3, δ)
204.7, 89.2, 53.1, 51.3, 45.6, 43.2, 35.1, 31.0, 26.9, 21.4, 21.2,
11.4. Anal. Calcd for C12H10NO2Br (275.18): C, 52.38; H, 6.96.
Found: C, 52.63; H, 7.72.
(22) For a detailed information on this topic, see: (a) ref 3b. (b)
Evans, D. A.; Takacs, J . M.; Mcgee, L. R.; Ennis, M. D.; Mathre, D. J .;
Bartoli, J . J . Pure Appl. Chem. 1981, 53, 1109. (c) Nerz-Stormes, M.;
Thornton, E. R. J . Org. Chem. 1991, 56, 2489.
(23) (a) Ho, T.-L. In Organic Syntheses by Oxidation with Metal
Compounds; Mijs, W. J ., De J onge, C. R. H. I., Eds.; Plenum Press:
New York, 1996; p.569. (b) Ho, T.-L. Synthesis 1973, 347.
(1R)-2-en d o-Ch lor oa cetyl-2-exo-tr im eth ylsilyloxy-1,7,7-
tr im eth ylbicyclo[2.2.1]h ep ta n e (5). A mixture of diisopro-

Camphor-Based R-Bromo Ketones
J . Org. Chem., Vol. 65, No. 26, 2000 9011
pylamine (5.2 mL, 37.5 mmol) in THF (30 mL) was cooled to
-78 °C and n-BuLi (2.5 M in hexanes, 15.0 mL, 37.5 mmol)
was added dropwise. After stirring for 30 min, a solution of
trimethylsilyl chloride (7.6 mL, 60 mmol) in THF (30 mL) and
methyl ketone 2 (3.0 g, 15 mmol) in THF (30 mL) were
successively added. The reaction mixture was allowed to stir
for 1 h at -78 °C and then warmed to room temperature over
a 30 min period. The reaction mixture was cooled to 0 °C and
a solution of mCPBA (13 g, 37.5 mmol) in THF (30 mL) was
then added. The resulting mixture was allowed to stir at room
temperature for 15 min. The solid was filtered off and the
filtrate was diluted with CH2Cl2 and washed sucesively with
saturated Na2SO3 and saturated NaHCO3. The organic phase
was dried over MgSO4 and the solvent evaporated under
reduced pressure to give 5 as a viscous oil which solidified on
standing. It was purified by crystallization from a mixture of
with CH2Cl2. The combined organics were dried over MgSO4,
and the solvent was evaporated under reduced pressure.
Purification of the product was effected by flash column
chromatography, using a 1:50 EtOAc:hexane mixture as the
eluent. In some cases, the major isomer was separated by
preparative HPLC (eluent EtOAc:hexane 10:90).
Com p ou n d 13 (R ) Et): yield 0.292 g (72%); colorless oil;
[R]25 ) -58.9 (c ) 1.0, CH2Cl2); IR (film) 3500 (OH), 1697
D
cm-1 (CO); H NMR (CDCl3, δ) 4.96 (bs, 1H), 3.56-3.67 (m,
1
1H), 3.48 (d, J ) 2.3 Hz, 1H), 2.50 (d, J ) 13 Hz, 1H), 1.97-
0.72 (m, 9H), 1.06 and 0.98 (s, 3H), 0.96 (t, J ) 7.3 Hz, 3H),
0.85 (s, 3H), 0.22 (s, 9H); 13C NMR (CDCl3, δ) 209.1, 92.2, 70.5,
52.9, 51.9, 50.7, 45.6, 42.4, 31.1, 29.0, 26.4, 21.7, 20.9, 12.1,
10.3, 3.0.
Com p ou n d 13 (R )n P r ): yield 0.373 g (89%); mp 106-
108 °C; [R]25 ) -60.8 (c ) 1.0, CH2Cl2); IR (KBr) 3509 (OH),
D
ethyl acetate/hexane: yield 4.23 g (94%); mp 43-45 °C; [R]25
1
1699 cm-1 (CO); H NMR (CDCl3, δ) 4.91 (s, 1H), 3.62-3.76
D
) -19.8 (c ) 1.0, CH2Cl2); IR (film) 1724.5 cm-1 (CO); 1H NMR
(CDCl3, δ) 4.56 (d, J ) 15.8, Hz 1H), 4.18 (d, J ) 15.8 Hz,
1H), 2.57 (d, J ) 13.0 Hz, 1H), 1.95-0.70 (m, 6H), 1.05, 1.01
and 0.84 (s, 3H), 0.12 (s, 9H); 13C NMR (CDCl3, δ) 202.3, 91.0,
51.7, 50.9, 46.3, 45.1, 40.5, 30.2, 25.7, 20.8, 20.2. Anal. Calcd
for C15H27O2SiCl (302.92): C, 59.48; H, 8.98. Found: C, 59.10;
H, 8.92.
(m, 1H), 3.44 (d, 1H, J ) 2.3 Hz), 2.52 (d, 1H, J ) 13.1 Hz),
1.95-1.10 (m, 6H), 1.04, 0.96 and 0.83 (s, 3H), 0.96-0.91 (m,
7H), 0.21 (s, 9H); 13C NMR (CDCl3, δ) 208.5, 91.5, 68.2, 52.3,
51.3, 50.8, 44.9, 41.7, 37.6, 30.5, 25.8, 21.0, 20.2, 18.4, 14.0,
11.5, 2.4. Anal. Calcd for C19H35O3BrSi (419.48): C, 54.40; H,
8.41. Found: C, 54.40; H, 7.90.
Com p ou n d 13 (R ) n Bu ): yield 0.295 g (68%); mp 63-65
Gen er a l P r oced u r e for th e Ald ol Rea ction s of 4. A
mixture of diisopropylamine (0.33 mL, 2.4 mmol) and anhy-
drous LiCl (0.25 g, 6 mmol) in dry THF (10 mL) was cooled to
-78 °C under a nitrogen atmosphere and n-butyllithium (1.6
M in hexane, 1.50 mL, 2.4 mmol) was added dropwise. After
stirring for 30 min at the same temperature, a solution of 4
(0.275 g, 1 mmol) in THF (5 mL) was added dropwise. The
resulting mixture was allowed to stir for 1 h at -78 °C and
then a precooled (-78 °C) solution of the corresponding
aldehyde (1.5 mmol) in THF (10 mL) was added dropwise. The
reaction was allowed to stir for 1.5-2.5 h at -78 °C and then
was quenched with 5 mL of a saturated aqueous solution of
NaHCO3. The resulting mixture was allowed to warm to room
temperature, after which the layers were separated, and the
aqueous layer was extracted twice with CH2Cl2. The combined
organics were dried over MgSO4, and the solvent was evapo-
rated under reduced pressure. The crude product was purified
by flash column chromatography, using a 1:50 EtOAc:hexane
mixture as the eluent, except for compounds 9a and 9c, which
were eluted with a EtOAc:hexane:Et3N 2:100:0.2 mixture.
°C; [R]25D ) -56.6 (c ) 1.0, CH2Cl2); IR (KBr) 3528, 3506 (OH),
1
1698 cm-1 (CO); H NMR (CDCl3, δ) 4.92 (s, 1H), 3.76-3.61
(m, 1H), 3.46 (d, 1H, J ) 1.9 Hz), 2.50 (d, 1H, J ) 13.2 Hz),
1.95-1.10 (m, 6H), 1.05, 0.97 and 0.84 (s, 3H), 0.92-0.89 (m,
9H), 0.22 (s, 9H); 13C NMR (CDCl3, δ) 209.1, 92.2, 69.1, 52.9,
51.9, 51.5, 45.6, 42.4, 35.8, 31.1, 27.9, 26.4, 23.2, 21.7, 20.9,
14.6, 12.2, 3.0. Anal. Calcd for C20H37O3BrSi (433.50): C, 55.41;
H, 8.60. Found: C, 55.53; H, 8.10.
i
Com p ou n d 13 (R ) Bu ): yield 0.351 g (81%); mp 72-73
°C; [R]25D ) -54.7 (c ) 1.0, CH2Cl2); IR (KBr) 3479 (OH), 1689
cm-1 (CO); 1H NMR (CDCl3, δ) 4.87 (s, 1H), 3.85-3.75 (m, 1H),
3.34 (s, 1H), 2.50 (d, 1H, J ) 13.0 Hz), 1.95-0.78 (m, 9H),
1.06 and 0.97 (s, 3H), 0.96 (d, 3H, J ) 4.4 Hz), 0.93 (d, 3H, J
) 6.04 Hz), 0.85 (s, 3H), 0.22 (s, 9H); 13C NMR (CDCl3, δ) 208.2,
91.5, 66.4, 52.3, 52.0, 51.4, 45.9, 44.9, 41.7, 30.5, 25.8, 24.0,
23.5, 22.0, 21.1, 20.2, 11.4, 2.4. Anal. Calcd for C20H37O3BrSi
(433.50): C, 55.41; H, 8.60. Found: C, 55.56; H, 8.22.
Com p ou n d 13 (R ) P h CH2CH2): yield 0.240 g (53%); mp
60-62 °C; [R]25 ) -67.6 (c ) 1.0, CH2Cl2); IR (KBr) 3503
D
(OH), 1699 cm-1 (CO); 1H NMR (CDCl3, δ) 7.40-7.18 (m, 5H),
4.90 (d, 1H, J ) 0.73 Hz), 3.76-3.64 (m, 1H), 3.42 (d, 1H, J )
1.65 Hz), 3.06-2.64 (m, 2H), 2.51 (d, 1H, J ) 1.32 Hz), 2.32-
2.10 (m, 1H), 1.98-1.84 (m, 1H), 1.82-1.54 (m, 3H), 1.39-
1.10 (m, 2H), 1.06, 0.84, and 0.76 (s, 3H), 0.80-0.65 (m, 1H),
0.24 (s, 9H); 13C NMR (CDCl3, δ) 208.7, 141.3, 129.2, 129.1,
126.7, 92.1, 67.8, 52.9, 51.9, 45.5, 42.3, 38.1, 31.9, 31.0, 26.5,
21.7, 20.9, 11.8, 3.0. Anal. Calcd for C24H37O3BrSi (453.46):
C, 59.86; H, 7.74. Found: C, 60.30; H, 7.76.
Com p ou n d 9a . yield 0.274 g (91%); mp 138-139 °C; [R]25
D
) +161.4 (c ) 1.0, CH2Cl2); IR (KBr) 3436 (OH), 1716 cm-1
1
(CO); H NMR (CDCl3, δ) 7.20-7.41 (m, 5H), 4.03 (d, J ) 1.7
Hz, 1H), 3.93 (d, J ) 1.7 Hz, 1H), 2.37 (d, J ) 13.0 Hz, 1H),
1.95-1.20 (m, 7H), 1.13, 1.09 and 0.88 (s, 3H); 13C NMR
(CDCl3, δ) 206.3, 136.3, 129.5, 126.5, 88.9, 61.3, 60.4, 53.1, 51.6,
46.5, 45.7, 42.9, 30.9, 26.8, 21.4, 21.2, 11.7. Anal. Calcd for
C
19H24O3 (300.40): C, 75.97; H, 8.05. Found: C, 76.16; H, 8.43.
Com p ou n d 9c. yield 0.311 g (93%); mp 144-145 °C; [R]25
D
) +164.2 (c ) 1.0, CH2Cl2); IR (KBr) 3430 (OH), 1705 cm-1
(CO); H NMR (CDCl3, δ) 7.33 (d, J ) 8.6 Hz, 2H), 7.23 (d, J
Com p ou n d s 11/12. The general procedure for aldol reac-
tions with 3 was followed, except that the reaction mixture
was allowed to rise to room temperature over a period of 1 h,
before quenching. After usual workup and purification of the
product by column chromatography, both diastereomers were
separated by preparative HPLC (eluent EtOAc:hexane 1:50).
1
) 8.6 Hz, 2H), 3.98 (d, J ) 1.8 Hz, 1H), 3.91 (d, J ) 1.8 Hz,
1H), 2.34 (d, J ) 12.9 Hz, 1H), 1.95-1.05 (m, 7H), 1.13, 1.08
and 0.88 (s, 3H); 13C NMR (CDCl3, δ) 205.9, 135.4, 134.9, 129.4,
127.8, 89.0, 61.2, 59.7, 53.1, 51.7, 45.7, 43.0, 30.9, 26.9, 21.5,
21.2, 11.8. Anal. Calcd for C19H23O3Cl (334.84): C, 68.15; H,
6.92. Found: C, 67.81; H, 7.03.
Gen er a l P r oced u r e for th e Ald ol Rea ction s of 3/5. A
mixture of diisopropylamine (0.196 mL, 1.4 mmol) in dry THF
(10 mL) was cooled to -78 °C under a nitrogen atmosphere
and n-butyllithium (1.6 M in hexane, 0.88 mL, 1.4 mmol) was
added dropwise. After stirring for 30 min at the same tem-
perature, a solution of either 3 or 5 (1 mmol) in THF (5 mL)
was added dropwise. The resulting mixture was allowed to stir
for 1 h at -78 °C, and then a precooled (-78 °C) solution of
the corresponding aldehyde (1.5 mmol) in THF (10 mL) was
added dropwise. The reaction was allowed to stir for 1.5-2.5
h at -78 °C and then was quenched with 5 mL of a saturated
aqueous solution of NaHCO3. The resulting mixture was
allowed to warm to room temperature, after which the layers
were separated, and the aqueous layer was extracted twice
Compound 11: yield 0.052 g (30%); mp 110 °C; [R]25
)
D
-161.6 (c ) 1.0, CH2Cl2); IR (KBr) 1715 cm-1 (CO); H NMR
(CDCl3, δ) 7.25-7.34 (m, 5H), 4.07 (d, J ) 1.7 Hz, 1H), 3.95
(d, J ) 1.7 Hz, 1H), 2.55 (d, J ) 13.0 Hz, 1H), 1.95-1.10 (m,
6H), 1.07 (s, 3H), 0.82 (s, 6H), 0.70-0.85 (m, 1H), 0.17 (s, 9H);
13C NMR (CDCl3, δ) 204.9, 136.4, 129.5, 129.4, 126.2, 91.5,
61.9, 61.8, 59.9, 59.8, 52.8, 51.5, 45.9, 40.6, 31.1, 26.5, 21.4,
21.0, 11.9, 2.4. Anal. Calcd for C12H32O3Si (372.58): C, 70.92;
H, 8.66. Found: C, 71.31; H, 8.49.
1
Compound 12: yield 0.064 g (37%); mp 70 °C; [R]25
)
D
+154.2 (c ) 1.0, CH2Cl2); IR (KBr), 1715 cm-1 (CO); 1H NMR
(CDCl3, δ) 7.26-7.41 (m, 5H), 4.08 (d, J ) 1.7 Hz, 1H), 4.00
(d, J ) 1.7 Hz, 1H), 2.47 (d, J ) 12.8 Hz, 1H), 1.95-1.15 (m,
6H), 1.14, 1.07 and 0.87 (s, 3H), 0.90-1.00 (m, 1H); 13C NMR
(CDCl3, δ) 205.9, 136.3, 129.5, 129.3, 126.4, 91.4, 60.8, 60.6,
60.4, 60.3, 53.0, 51.0, 46.1, 41.2, 31.0, 26.3, 21.5, 20.9, 12.2,

9012 J . Org. Chem., Vol. 65, No. 26, 2000
Palomo et al.
2.1. Anal. Calcd for C22H32O3Si (372.58): C, 70.92; H, 8.66.
Found: C, 70.82; H, 8.78.
Desilyla tion of 12. The general desilylation procedure,
method B, was followed starting from compound 12 to yield
0.147 g (98%) of a product, which exhibited identical physical
and spectroscopic data to that of compound 9a , obtained as
previously described.
Cycliza t ion of H a loh yd r in s 13/14 t o E p oxid es 10.
Meth od A. The corresponding halohydrin (0.5 mmol) was
dissolved in a mixture of MeOH (2 mL) and 1 N HCl (1 mL),
silica gel 60 (230-400 mesh, 0.25 g) was added to the solution,
and the mixture was stirred at room temperature for 4-5 days.
After dilution with CH2Cl2 (10 mL), an aqueous solution of
NaHCO3 (saturated, 5 mL) was added, the organic layer was
separated and dried over MgSO4, and the solvent was evapo-
rated under reduced pressure. The resulting crude product was
dissolved in MeOH (5 mL), the solution cooled to 0 °C, and
then Na2CO3 (0.265 g, 2.5 mmol) was added. The reaction was
allowed to warm to room temperature and stirred at this
temperature for 3 h. Then the solvent was evaporated under
reduced pressure and CH2Cl2 (10 mL) was added. The result-
ing solution was washed with an aqueous saturated solution
of NH4Cl and NaHCO3. The organic solution was dried over
MgSO4 and the solvent evaporated under reduced pressure.
The corresponding epoxide was obtained as a white solid.
Meth od B. To a solution of the corresponding halohydrin
(0.5 mmol) in THF (10 mL) was added TBAF (1 M solution in
THF, 1 mL, 1 mmol), and the reaction mixture was stirred at
room temperature for 20 min. The solvent was evaporated
under reduced pressure, and the residue was dissolved in CH2-
Cl2 (20 mL) and washed with water (2 × 25 mL). The organic
layer was dried over MgSO4 and the solvent was evaporated
under reduced pressure. The crude product was purified by
column chromatography (silica gel, eluent EtOAc:hexane 1:50).
Ep oxid e 10e. Method B was followed: yield from 13, 0.122
Gen er a l P r oced u r e for F or m a tion of Ep oxy Acid Sa lts
18. To a solution of the corresponding epoxide 10 (1.5 mmol)
in CH3CN (18 mL) was added dropwise at room temperature
a solution of CAN (4.11 g, 7.5 mmol) in H2O (9 mL). The
resulting yellowish solution was stirred for 5 min at room
temperature and then diluted with H2O and extracted twice
with CH2Cl2. The organic layer was dried over MgSO4 and the
solvent evaporated under reduced pressure to give an oil. The
NMR analysis of the crude reaction product showed the
presence of the corresponding epoxy acid 17 along with (+)-
camphor in equimolar ratios. The thus obtained oily product
was dissolved in EtOAc (10 mL), and dicyclohexylamine (0.363
g, 2 mmol) was added dropwise via syringe. From the resulting
solution a precipitate slowly appeared which was filtered off
after 14 h of standing. From the mother liquors, additional
crops were obtained and combined.
Com p ou n d 18a : yield 0.268 g (60%); mp 149-150 °C; [R]25
D
) -8.8 (c ) 1.0, CH2Cl2); IR (film) 3416.0, 1602.4 cm-1 (CO);
1H NMR (CDCl3, δ) 3.42 (d, J ) 4.77 Hz, 1H), 3.10-2.75 (m,
3H), 2.10-2.0 (m, 4H), 1.85-1.60 (m, 8H), 1.60-1.45 (m, 4H),
1.30-1.10 (m, 8H), 1.06 (t, J ) 7.7 Hz, 3H); 13C NMR (CDCl3,
δ) 173.0, 58.1, 55.6, 52.7, 29.3, 29.0, 25.2, 24.79, 24.76, 21.6,
10.5. Anal. Calcd for C17H31O3N (297.44): C, 68.65; H, 10.50;
N, 4.71. Found: C, 68.12; H, 10.47; N, 4.70.
g (97%); from 14, 0.119 g (94%); mp 63-64 °C; [R]25 ) -42.5
Com p ou n d 18b: yield 0.285 g (61%); mp 133-135 °C;
D
(c ) 1, CH2Cl2); IR (KBr) 3484 (OH), 1707 cm-1 (CO); 1H NMR
(CDCl3, δ) 3.98 (d, J ) 5.0 Hz, 1H), 3.25 (dt, J ) 5.0 Hz, J ′ )
6.0 Hz, 1H), 2.27 (d, J ) 13.2 Hz, 1H), 1.89-0.80 (m, 8H), 1.12
and 1.05 (s, 3H), 0.99 (t, J ) 7.4 Hz, 3H), 0.87 (s, 3H); 13C
NMR (CDCl3, δ) 206.4, 88.5, 60.7, 58.1, 52.4, 50.9, 45.0, 42.6,
29.9, 26.1, 20.8, 20.6, 19.9, 11.1, 10.3. Anal. Calcd for C15H24O3
(252.35): C, 71.39; H, 9.59. Found: C, 71.66; H, 9.16.
[R]25 ) -5.5 (c ) 1.0, CH2Cl2); IR (film) 3425.6, 1602.4 cm-1
D
(CO); 1H NMR (CDCl3, δ) 3.41 (d, J ) 4.77 Hz, 1H), 3.10-
3.05 (m, 1H), 3.05-2.90 (m, 2H), 2.10-1.95 (m, 4H), 1.85-
1.75 (m, 4H), 1.70-1.60 (m, 4H), 1.60-1.40 (m, 6H), 1.35-
1.10 (m, 8H), 0.94 (t, J ) 7.34 Hz, 3H); 13C NMR (CDCl3, δ)
173.0, 56.7, 55.5, 52.7, 30.5, 29.6, 29.3, 25.2, 24.8, 24.7, 19.8,
14.0. Anal. Calcd for C18H33O3N (311.46): C, 69.41; H, 10.68;
N, 4.50. Found: C, 69.28; H, 10.25; N, 4.38.
Ep oxid e 10f. Method A was followed: yield from 13. 0.124
g (93%); from 14, 0.123 g (92%); mp 62-64 °C; [R]25 ) -42.7
D
(c ) 1, CH2Cl2); IR (KBr) 3437 (OH), 1701 cm-1 (CO); 1H NMR
(CDCl3, δ) 3.97 (d, 1H, J ) 4.96 Hz), 3.35-3.20 (m, 1H), 2.34
(s, 1H), 2.28-2.20 (m, 1H), 1.83-1.14 (m, 6H), 1.11, 1.04 and
0.85 (s, 3H), 0.95-0.88 (m, 7H); 13C NMR (CDCl3, δ) 207.2,
89.4, 60.1, 58.6, 53.2, 51.7, 45.8, 43.4, 30.7, 29.3, 26.9, 21.6,
21.3, 20.4, 14.6, 11.8. Anal. Calcd for C16H26O3 (266.38): C,
72.14; H, 9.84. Found: C, 71.94; H, 10.01.
Ack n ow led gm en t. This work was financially sup-
ported by Gobierno Vasco (Project EX-1998-124) and in
part by Universidad del Pa´ıs Vasco (Project UPV
170.215-G47/98). Grants from Gobierno Vasco to A. K.
S. and to M. C. G.-R. are gratefully acknowledged.
Ep oxid e 10g. Method A was followed: yield from 13, 0.129
g (92%); mp 76-78 °C; [R]25D ) -40.9 (c ) 1, CH2Cl2); IR (KBr)
3438 (OH), 1699 cm-1 (CO); 1H NMR (CDCl3, δ) 3.98 (d, 1H, J
) 4.94 Hz), 3.33-3.25 (m, 1H), 2.32-2.24 (m, 1H), 2.21 (s, 1H),
1.86-1.01 (m, 12H), 1.14, 1.06 and 0.88 (s, 3H), 1.09-0.85 (m,
3H); 13C NMR (CDCl3, δ) 207.1, 84.3, 60.3, 58.6, 53.2, 51.7,
45.8, 43.4, 30.6, 30.4, 29.1, 26.9, 23.0, 21.5, 21.3, 14.6, 11.8.
Anal. Calcd for C17H28O3 (280.40): C, 72.82; H, 10.06. Found:
C, 71.24; H, 10.02.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedure for the trapping of the trimethylsilylenol ether deriva-
tive of the enolate of 3, ORTEP representations of 5, 11, 12,
and 13 (R ) nPr), and NMR spectra of representative com-
pounds are provided. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O001031F