Cp2TiCl-promoted isomerization of trisubstituted epoxides to exo-methylene allylic alcohols on carvone derivatives

Article abstract of DOI:10.1021/jo049358u

The ring-opening reaction of trisubstituted epoxides promoted by Cp ₂TiCl led to exo-methylene allylic alcohols as major compounds when 0.5 M solutions of the epoxides were added to 0.1 M solutions of the reagent at room temperature in THF. In most cases, the allylic alcohols were contaminated with saturated alcohols. Normal and reverse addition modes led to the alternate product being favored. The different stereochemical outcome of cis- and trans-epoxy acetates is rationalized in terms of mechanistically biased elimination processes.

Full text of DOI:10.1021/jo049358u

Cp 2TiCl-P r om oted Isom er iza tion of Tr isu bstitu ted Ep oxid es to
exo-Meth ylen e Allylic Alcoh ols on Ca r von e Der iva tives
Francisco Bermejo* and Celso Sandoval
Departamento de Qu´ımica Orga´nica, Facultad de Ciencias Qu´ımicas, Universidad de Salamanca,
Plaza de la Merced s.n., 37008 Salamanca, Spain
fcobmjo@usal.es
Received April 16, 2004
The ring-opening reaction of trisubstituted epoxides promoted by Cp2TiCl led to exo-methylene
allylic alcohols as major compounds when 0.5 M solutions of the epoxides were added to 0.1 M
solutions of the reagent at room temperature in THF. In most cases, the allylic alcohols were
contaminated with saturated alcohols. Normal and reverse addition modes led to the alternate
product being favored. The different stereochemical outcome of cis- and trans-epoxy acetates is
rationalized in terms of mechanistically biased elimination processes.
In tr od u ction
Furthermore, the titanocene-promoted isomerization of
trisubstituted epoxides to exo-methylene allylic alcohols
has been recently reported as a side reaction in the
intramolecular addition of radicals to carbonyl com-
pounds. The inability of certain intermediate radical
species to cyclize led to the isolation of the isomeric allylic
alcohols via formation of titanoxyorganotitanium inter-
mediates followed by exocyclic â-hydrogen elimination.8
It seemed reasonable to us to study the Cp2TiCl-
promoted isomerization of trisubstituted epoxides to exo-
methylene allylic alcohols in order to evaluate the scope
of this particular transformation.9
Radicals generated upon treating epoxides with para-
magnetic bis(cyclopentadienyl)titanium(III) chloride (Cp2-
TiCl) have been described as intermediates in processes
of high synthetic value: they can participate in both
intramolecular (hex-5-enyl cyclization)1 and intermolecu-
lar addition reactions.2 The radicals generated this way
can also serve as intermediates in the overall reduction
or deoxygenation of the epoxide.3 Depending on the
reactivity of the acceptor, the initially formed radical can
participate in addition processes or can be reduced
further by Ti(III) to the corresponding carbanion. In the
absence of an H-atom donor or an olefin, the resulting
â-oxido-Ti organometallic species undergoes facile elimi-
nation to give an olefin. The reaction conditions are
remarkably mild and are applicable to very sensitive
substrates.4
Resu lts a n d Discu ssion
To investigate this conjecture, several trisubstituted
epoxides were synthesized from (R)-(-)- and (S)-(+)-
carvone and treated with Cp2TiCl in an attempt to
elucidate the possible stereochemical implications of the
isomerization process.
The low-valent titanium(III) complex was readily
prepared by the in situ reduction of 2.5 equiv of Cp2TiCl2
with 5 equiv of powdered zinc in THF for 45 min at room
temperature. The reaction took place either by addition
via cannula of a 0.1 M solution of the Cp2TiCl reagent in
THF to a 0.5 M solution of the epoxide in the same
solvent (method A) or in the reverse fashion (method B)
(Table 1).
The generation of exocyclic olefins has been reported
in the course of radical cyclizations of epoxy alkenes
leading to drimanes,5 eudesmanolides,6 and different ring
synthons of paclitaxel.7 In these cases, termination of the
radical cyclization is not reductive; rather, it involves
â-hydrogen elimination providing an alkene function.
(1) Nugent, W. A.; RajanBabu, T. V. J . Am. Chem. Soc. 1988, 110,
8562-8564.
(2) RajanBabu, T. V.; Nugent, W. A. J . Am. Chem. Soc. 1989, 111,
4525-4527.
(3) RajanBabu, T. V.; Nugent, W. A.; Beattie, M. S. J . Am. Chem.
Soc. 1990, 112, 6408-6409.
The epoxides were prepared by known procedures from
(S)-(+)-carvone (1a -5a , 11a , and 12a ) or (R)-(-)-carvone
(4) (a) RajanBabu T. V.; Nugent, W. A. J . Am. Chem. Soc. 1994,
116, 986-997. (b) Gansa¨uer, A.; Rinker, B. In Titanium and Zirconium
in Organic Synthesis; Marek, I., Ed.; Wiley-VCH: Weinheim, 2002;
Chapter 12, pp 435-440. (c) Gansa¨uer, A.; Pierobon, M. In Radicals
in Organic Synthesis; Renaud, P., Sibi, M. P., Eds; Wiley-VCH:
Weinheim, 2001; Vol. 2, Chapter 3.3, pp 207-220.
(5) (a) Barrero A. F.; Cuerva, J . M.; Alvarez-Manzaneda, E. J .; Oltra,
J . E.; Chahboun, R. Tetrahedron Lett. 2002, 43, 2793-2796. (b) Barrero
A. F.; Cuerva, J . M.; Herrador, M. M.; Valdivia, M. V. J . Org. Chem.
2001, 66, 4074-4078.
(8) Ferna´ndez-Mateos, A.; Mart´ın de la Nava, E.; Pascual Coca, G.;
Ramos Silvo, A.; Rubio Gonza´lez, R. Org. Lett. 1999, 1, 607-609.
(9) A highly selective and efficient isomerization of the epoxide
moiety of a dieneoxide (E)-ester to the corresponding exo-methylene
allylic dieneol using palladium catalysis has been recently described
with occasion of the synthesis of vitamin D fluoro analogues: (a) Kabat,
M. M.; Garofalo, L. M.; Daniewski, A. R.; Hutchings, S. D.; Liu, W.;
Okabe, M.; Radinov, R.; Zhou, T. J . Org. Chem. 2001, 66, 6141-6150.
(b) Daniewski A. R.; Garofalo, L. M.; Hutchings, S. D.; Kabat, M. M.;
Liu, W.; Okabe, M.; Radinov, R.; Yiannikouros, G. P. J . Org. Chem.
2002, 67, 1580-1587.
(6) Barrero, A. F.; Olatra, J . E.; Cuerva J . M.; Rosales, A. J . Org.
Chem. 2202, 67, 2566-2571.
(7) Nakai, K.; Kamoshita, M.; Doi, T.; Yamada, H.; Takahashi, T.
Tetrahedron Lett. 2001, 42, 7855-7857.
10.1021/jo049358u CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/03/2004
J . Org. Chem. 2004, 69, 5275-5280
5275

Bermejo and Sandoval
TABLE 1. Rin g-Op en in g Rea ction s of Ep oxid e Der iva tives of (R)-(-)- a n d (S)-(+)-Ca r von e P r om oted by Cp 2TiCl
a
Isolated yields obtained by flash chromatography.
5276 J . Org. Chem., Vol. 69, No. 16, 2004

Cp2TiCl-Promoted Isomerization of Trisubstituted Epoxides
SCHEME 1. Rin g-Op en in g Rea ction s of cis- a n d
tr a n s-Ep oxy Aceta tes u n d er Cp 2TiCl P r om otion
(6a -10a ). In most cases, the overall yields of the desired
exo-methylene allylic alcohols were acceptable, although
they were always contaminated with the saturated
alcohols. The chromatographic resolution of the resulting
products, however, proved satisfactory in most cases.
Vinyl oxirane 1a 10 led to a 1:1 mixture of the deoxy-
genated product 1b and the allylic alcohol 1c. Formation
of the hydroxy compound 1c may arise by formation of
the allylic radical, further reduction to the titanium
enolate, and hydrolysis during the workup. This result
is similar to that obtained by Molander and co-workers11
upon reducing vinyl oxiranes of the enantiomeric series
with samarium diiodide.
X-ray analysis was grown from diisopropyl ether, and the
correct stereochemistry of 3c was established. We assume
that, first, radical addition to the carbonyl takes place
and then the alkoxytitanium species promotes lacton-
ization. Both methods afforded the allylic alcohol 3b as
the minor component of the reaction mixture.
Starting from (-)-trans-carveol,12 the homologated
epoxide 2a was obtained by application of a four-step
synthetic sequence with 52% overall yield: ortho ester
Claisen rearrangement, saponification, bromolactoniza-
tion, and methanolysis. The oxidative degradation of the
isopropenyl chain allowed us to prepare the epoxides 3a -
5a by sequential ozonolysis, Baeyer-Villiger oxidation,
saponification, and either acetylation or silyl protection
processes.13
Under Cp2TiCl promotion, the epoxy esters 2a -5a
undergo epoxide ring opening to yield the desired allylic
alcohols 2b-5b with the exocyclic double bond in all
cases. These products are major components of the
reaction mixture obtained by addition of the epoxide
solution to the reagent solution (method B) except for 3a .
Normal addition led to the saturated products 2c-5c as
major products (method A).
The cis-epoxy acetate 6a was easily prepared from (R)-
(-)-carvone by alkaline hydrogen peroxide epoxidation
followed by L-Selectride reduction15 and further alcohol
protection. Again, the oxidative degradation of the un-
saturated chain allowed us to sequentially isolate the
epoxides 7a and 8a following the above-mentioned pro-
cedure. The trans-epoxy acetates 9a and 10a were
prepared from (R)-(-)-carvone by epoxidation followed by
triisobutylaluminum reduction,16 acetylation, and oxida-
tive degradation of the isopropenyl chain.
When method B was applied, the cis-epoxy acetates 6a ,
7a , and 8a yielded the â-elimination products 6b, 7b, and
8b, respectively. Only in the case of 6a was the presence
of saturated acetate 6c detected as a major product by
normal addition (method A).
It is known that under an excess of the reagent
(method B) the reduction of alkoxytitanium radicals to
alkoxytitanium carbanions takes place, after which these
species undergo â-hydrogen elimination to yield the
allylic alcohols. At low Ti(III) concentrations, however,
the radicals are not reduced to carbanions but instead
abstract hydrogens atoms from the solvent (THF) leading
to the formation of the saturated alcohols (method A).
The stereochemistry of the saturated alcohols 2c, 4c,
and 5c was demonstrated by spectroscopic analysis
However, the trans-epoxy acetates 9a and 10a yielded
the allylic alcohols 9b and 10b, respectively, as major
components when method B was used. In addition, the
saturated hydroxy derivative 9c or the â-elimination
product 8b were isolated as minor components of the
reaction mixture. These two latter products were ob-
tained as major components of the reaction mixture when
method A was applied.
1
including HNMR NOE studies. Thus, in all cases there
are sizable NOE effects (5-8%) at the secondary methyl
groups upon irradiation at the vicinal methine protons
of the corresponding secondary alcohols.14
In the case of the epoxide 3a , the addition of the radical
species to the carbonyl functionality takes place. Both
methods (A and B) yielded the tricyclic lactone 3c, mp
125-127 °C, as the major product. A single crystal for
To explain the different chemical behavior of the cis-
and trans-epoxy acetates, in the cis case the reductive
opening of the epoxide takes place by cleavage of the axial
CO bond of the most likely starting conformation (Scheme
1). We assume that the oxyanionic group would be
coordinated with the titanocene that attacks the radical
and that the ring Ti thus ends up on the same side as
the acetate group. The elimination can then easily be
envisioned as a concerted cis-elimination via a six-
membered ring transition state with minimum charge
development.
(10) (a) Baggiolini, E. G.; Iacobelli, J . A.; Hennessy, B. M.; Uskokovic,
M. R. J . Am. Chem. Soc. 1982, 104, 2945-2948. (b) Baggiolini, E. G.;
Iacobelli, J . A.; Hennessy, B. M.; Batcho, A. D.; Sereno, J . F.; Uskokovic,
M. R. J . Org. Chem. 1986, 51, 3098-3108.
(11) Molander, G. A.; La Belle, B. E.; Hahn, G. J . Org. Chem. 1986,
51, 5259-5264.
(12) (a) J ohnston, R. G.; Read, J . J . Chem. Soc. 1934, 233-237 (b)
Klein, E.; Ohloff, G. Tetrahedron. 1963, 19, 1091-1099 (c) Schroeter,
S. Liebigs Ann. 1964, 118-121 (d) Schroeter, S.; Eliel, E. L. J . Org.
Chem. 1965, 30, 1-7.
(13) Experimental procedures for the preparation of 2a -5a , 11a ,
and 12a are provided in the Supporting Information. Similar trans-
formations have been reported in the enantiomeric series starting from
(R)-(-)-carvone: (a) Bermejo, F.; Rico-Ferreira, R.; Bamidele-Sanni,
S.; Garc´ıa-Granda, S. J . Org. Chem. 2001, 66, 8257-8260. (b) Rico,
R.; Zapico, J .; Bermejo, F. Tetrahedron: Asymmetry 1998, 9, 293-303.
(14) In case of the epoxy ester 2a , the isolation of the saturated
alcohol 2c was more easily achieved by treatment of the reaction
mixture with MnO2 and fractionation of the reaction mixture by flash
chromatography.
In the trans case, the titanocene chloride attacks the
radical from the same side as the oxyanionic group; the
ring Ti is thus on the opposite side from the acetate
group, thus precluding a concerted cis elimination involv-
(15) Hatakeyama, S.; Numata, H.; Shimada, J .; Osanai, K.; Takano,
S. J . Org. Chem. 1989, 54, 3515-3517.
(16) (a) Roberts, M. R.; Parsons, W. H.; Schlessinger, R. H. J . Org.
Chem. 1978, 43, 3970-3972. (b) Gemal, A. L.; Luche, J .-L. J . Am.
Chem. Soc. 1981, 103, 5454-5459. (c) Kirsch, S.; Bach, T. Synthesis
2003, 1827-1836.
J . Org. Chem, Vol. 69, No. 16, 2004 5277

Bermejo and Sandoval
Wor k u p . When the reaction mixture turned from deep
green to red saturated solutions of NaPO4H2 (5 mL) and NaCl
(5 mL) were added. Stirring was maintained for 1 h, and the
reaction mixture was then diluted with ether and filtered. The
filtrate was extracted with ether (3 × 25 mL), washed with a
saturated NaCl solution, and dried over Na2SO4. Evaporation
of the solvent at reduced pressure led to the isolation of the
reaction product. Isolation of the reaction products was suc-
cessfully achieved by flash chromatography on silica gel.20
Cp 2TiCl-P r om oted Rin g-Op en in g Rea ction of Ep oxid e
1a . Eth yl (E)-[(5S)-2-m eth yl-5-(2-p r op en yl)cycloh ex-2-en -
ing minimum charge development. Instead, â-hydride
elimination occurs, presumably in a cis mode.17
Silyl-protected epoxy esters 11a and 12a were avail-
able by anionic [2,3]-Wittig rearrangement18 of (-)-trans-
carvyloxyacetic acid and subsequent transformations
similar to those described for the preparation of 2a -4a .
The epoxide opening of epoxides 11a and 12a led to
the allylic alcohols 11b and 12b, respectively, which were
contaminated with the saturated alcohols 11c and 12c
when method A was used; however, optimal conversion
of 12a into 12b was achieved when we made use of the
reverse addition (method B).
1-ylid en e]a ceta te 1b: Rf ) 0.4 (hexane/EtOAc 98:2); [RD]20
D
+99.5 (c 0.9, CHCl3); IR (neat) ν 2972, 1711, 1607, 1167, 1042,
887 cm-1; MS (EI) m/z 220 (M+, 15), 205 (5), 191 (10), 175 (20),
147 (40), 119 (40), 105 (100), 91 (70), 77 (60), 55 (50); 1H NMR
(CDCl3) δ 1.25 (t, J ) 7 Hz, 3H), 1.73 (s, 3H), 1.82 (s, 3H),
2.1-2.4 (m, 4H), 3.71 (m, 1H), 4.13 (q, J ) 7 Hz, 2H), 4.74 (s,
2H), 5.71 (s, 1H), 6.04 (t, J ) 4 Hz, 1H); 13C NMR (CDCl3) δ
14.3 (CH3), 19.5 (CH3), 20.6 (CH3), 31.3 (CH2), 31.6 (CH2), 41.2
(CH), 59.5 (CH2), 109.6 (CH2), 112.2 (CH), 132.6 (C), 135.1
(CH), 148.3 (C), 154.8 (C), 167.2 (CO). Anal. Calcd for
Con clu sion s
The ring-opening reaction of trisubstituted epoxides
promoted by Cp2TiCl yielded the isomeric exo-methylene
allylic alcohols with good yields. In most cases, the allylic
alcohols were contaminated with the saturated alcohols
although they can be separated by flash chromatography.
Different modes of reactant addition led to the alternate
product being favored. The different stereochemical
outcome of the ring-opening reaction of cis- and trans-
epoxy acetates is rationalized in terms of mechanistically
biased processes: â-acetate elimination (cis-epoxy ace-
tates) or â-hydride elimination (trans-epoxy acetates).
C
14H20O2: C, 76.33; H, 9.15. Found: C, 76.41; H, 9.19.
Eth yl [(3S,5R)-3-h yd r oxy-2-m eth yl-5-(2-p r op en yl)-1-cy-
cloh exen yl]a ceta te 1c: Rf ) 0.3 (hexane/EtOAc 98:2); [RD]20
D
-130.6 (c 0.9, CHCl3); IR (neat) ν 3461, 2980, 2936, 1732, 1645,
1443, 1370, 1167, 1030, 889 cm-1; MS (EI) m/z 238 (M+, 10),
1
220 (60), 121 (100), 105 (70), 91 (50), 77 (45); H NMR (Cl3-
CD) δ 1.23 (t, J ) 7 Hz, 3H), 1.72 (s, 3H), 1.79 (s, 3H), 1.4-2.5
(m, 5H), 3.04 (s, 2H), 4.02 (m, 1H), 4.11 (q, J ) 7 Hz, 2H),
4.72 (s, 2H); 13C NMR (Cl3CD) δ 14.4 (CH3), 17.1 (CH3), 21.0
(CH3), 35.9 (CH), 36.2 (CH2), 36.7 (CH2), 39.2 (CH2), 60.8 (CH2),
69.9 (CH), 109.3 (CH2), 128.0 (C), 131.5 (C), 149.8 (C), 171.7
(CO). Anal. Calcd for C14H22O3 C: 70.56; H, 9.30. Found: C,
70.63; H, 9.34.
Exp er im en ta l Section
Gen er a l P r oced u r e for Red u ctive Op en in g of Ep -
oxid es 1a -12a .19 Solu tion a . Titanocene dichloride Cp2TiCl2
(548 mg, 2.2 mmol) and powdered Zn (431 mg, 6.6 mmol) were
placed in a two-necked 50 mL round-bottomed flask under an
argon atmosphere. Anhydrous fresh distilled and deoxygenated
THF (2.2 mL) was added, and stirring was maintained for 1 h
at room temperature (deep green color appeared after 15-30
min).
Solu tion b. The epoxide (1 mmol) was placed in a two-
necked round-bottomed flask, and anhydrous freshly distilled
and deoxygenated THF (10 mL) was added under an argon
atmosphere.
Meth od A. Solution a was added dropwise via cannula to
solution b under argon at room temperature. The reaction
mixture was stirred at room temperature for 3-5 h.
Meth od B. Solution b was added dropwise via cannula to
solution a at room temperature under an argon atmosphere.
The reaction mixture was stirred at room temperature for 3-5
h.
Cp 2TiCl-P r om oted Rin g-Op en in g Rea ction of Ep oxid e
2a . Meth yl [(1S,3S,5R)-3-h yd r oxy-2-m eth ylen e-5-(2-p r o-
p en yl)cycloh exyl]a ceta te 2b: Rf ) 0.3 (hexane/EtOAc 8:2);
[R]20 -6.9 (c 1.4 CHCl3); IR (neat) ν 3461, 2951, 1738, 1439,
D
1024, 897 cm-1; MS (EI) m/z 224 (M+, 1), 206 (10), 191 (20),
146 (30), 132 (100), 117 (40), 105 (65), 91 (60), 67 (50), 55 (70);
1H NMR (CDCl3) δ 1.5-1.7 (m, 4H), 1.72 (s, 3H), 1.93 (m, 1H),
2.51 (m, 2H), 2.86 (m, 1H), 3.65 (s, 3H), 4.36 (t, J ) 4 Hz, 1H),
4.75 (s, 2H), 4.78 (1s, 1H), 4.94 (s, 1H); 13C NMR (CDCl3) δ
21.1 (CH3), 33.7 (CH), 36.5 (CH2), 38.2 (CH), 38.8 (CH2), 39.7
(CH2), 51.4 (CH3), 72.1 (CH), 109.4 (CH2), 111.5 (CH2), 148.0
(C), 150.1 (C), 173.6 (CO); HRMS (EI) calcd for C13H20O3 (M+)
224.1412, found 224.1423.
Meth yl [(1S,2S,3S,5R)-3-h yd r oxy-2-m eth yl-5-(2-p r op e-
n yl)cycloh exyl]a ceta te 2c: Rf ) 0.2 (hexane/EtOAc 8:2);
[R]20 -23.0 (c 0.9 CHCl3); IR (neat) ν 3503, 2934, 1738, 1437,
D
1260, 1165, 1024, 889 cm-1; MS (EI) m/z 226 (M+, 2), 208 (10),
135 (15), 168 (10), 154 (20), 134 (75), 119 (65), 105 (30), 93
(50), 74 (100); 1H NMR (CDCl3) δ 0.97 (d, J ) 7 Hz, 3H), 1.35-
1.71 (m, 4H), 1.72 (s, 3H), 1.73 (m, 1H), 2.24 (m, 1H), 2.40 (m,
1H), 2.51-2.54 (m, 2H), 3.66 (s, 3H), 3.91 (m, 1H), 4.76 (s, 1H),
4.80 (s, 1H); 13C NMR (CDCl3) δ 13.0 (CH3), 21.3 (CH3), 33.7
(CH2), 34.0 (CH), 34.4 (CH), 35.2 (CH2), 37.1 (CH2), 37.9 (CH),
51.3 (CH3), 70.9 (CH), 109.2 (CH2), 148.9 (C), 174.5 (CO);
HRMS (EI) calcd for C13H22O3 (M+) 226.1569, found 226.1574.
Cp 2TiCl-P r om oted Rin g-Op en in g Rea ction of Ep oxid e
3a . Meth yl (1S,3S,5R)-5-a cetyl-3-h yd r oxy-2-m eth ylen ecy-
cloh exyl a ceta te 3b: Rf ) 0.4 (hexane/EtOAc 1:1); [R]20D -6.5
(c 0.4 CHCl3); IR (neat) ν 3445, 2928, 1738, 1715, 1653, 1437,
1362, 1262, 1167, 909 cm-1; MS (EI) m/z 226 (M+, 15), 210
(20), 183 (55), 152 (95), 109 (95), 98 (85), 71 (100), 59 (90); 1H
NMR (CDCl3) δ 1.5-1.9 (m, 4H), 2.20 (s, 3H), 2.4-2.6 (m, 3H),
3.02 (m, 1H), 3.67 (s, 3H), 4.37 (t, J ) 5.3 Hz, 1H), 4.79 (s,
1H), 5.00 (s, 1H); 13C NMR(CDCl3) δ 28.4 (CH3), 33.7 (CH2),
36.1 (CH2), 37.5 (CH), 39.4 (CH2), 42.5 (CH), 51.9 (CH3), 71.3
(17) If the titanium chloride attacks the radical (2) from the trans
side, the resulting product has the Ti ring group and the acetate in a
trans diequatorial conformation (3) that cannot lead to elimination.
In order for the latter to occur, the ring would have to flip to a
conformation with three axial groups, two of which are strongly
eclipsed (4). It is likely that elimination in the direction of the methyl
will occur instead in clear contradiction with our results. We are greatly
indebted to the reviewer who suggested the cis elimination pathway
to us prior to publication of this paper.
(18) Nakai, T.; Mikami, K. In Organic Reactions; Paquette, L. A.,
Ed.; J ohn Wiley & Sons, Inc.: New York, 1994; Vol. 46, p 105.
(19) See the Supporting Information for experimental details on the
preparation of epoxides 1a -12a (Table 1).
(20) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923-
2925.
5278 J . Org. Chem., Vol. 69, No. 16, 2004

Cp2TiCl-Promoted Isomerization of Trisubstituted Epoxides
(CH), 110.8 (CH2), 149.5 (C), 175.8 (CO), 211.5 (CO); HRMS
Meth yl (1S,2S,3S,5R)-5-ter t-bu tyld im eth ylsilyloxy-3-
h yd r oxy-2-m eth ylcycloh exyl a ceta te 5c: Rf ) 0.3 (hexane/
EtOAc 1:1); [R]20D -7.1 (c 1.43 CHCl3); IR (neat) ν 3437, 2930,
2857, 1742, 1472, 1437, 1256, 1051, 835, 775 cm-1; MS (EI)
m/z 316 (M+, 4), 259 (100), 227 (20), 183 (30), 153 (20), 107
(EI) calcd for C12H18O4 (M+) 226.1205, found 226.1193.
(1S ,5S ,7R ,8R ,9S )-8,9-Dim e t h yl-3-oxo-2-oxa t r icyclo-
[5.2.1.05,9]d eca n -8-ol 3c: Rf ) 0.3 (hexane/EtOAc 1:1); mp
125-127 °C (diisopropyl ether); [R]20 +19.3 (c 1.29, CHCl3);
D
1
IR (KBr) ν 3466, 2957, 1703, 1378, 1235, 1026, 941, 814 cm-1
;
(35), 93 (85), 75 (62); H NMR (CDCl3) δ 0.02 (s, 3H), 0.05 (s,
MS (EI) m/z 196 (M+, 2), 178 (5), 152 (100), 109 (20), 94 (25),
71 (15); 1H NMR (CDCl3) δ 1.05 (s, 3H), 1.22 (s, 3H), 1.29 (dd,
J 1 ) 14.4 Hz, J 2 ) 2.7 Hz, 1H), 1.57 (m, 1H), 1.90 (t, J ) 4.4
Hz, 1H), 2.28 (m, 1H), 2.45 (m, 2H), 2.58 (m, 2H), 4.47 (dt, J 1
) 10 Hz, J 2 ) 2.5 Hz, 1H); 13C NMR (CDCl3) δ 11.3 (CH3),
19.0 (CH3), 31.3 (CH2), 34.6 (CH), 35.4 (CH2), 37.7 (CH2), 42.9
(CH), 44.9 (C), 84.5 (C), 84.7 (CH), 169.9 (CO); HRMS (EI)
calcd for C11H16O3 (M+) 196.1099, found 196.1112.
3H), 0.78 (d, J ) 7 Hz, 3H), 0.87 (s, 9H), 1.36 (m, 1H), 1.52
(m, 1H), 1.65 (m, 2H), 2.00 (m, 1H), 2.24 (ddd, J 1 ) 15 Hz, J 2
) 8.5 Hz, J 3 ) 6.8 Hz, 2H), 2.49 (m, 1H), 3.64 (s, 3H), 4.08 (dt,
J 1 ) 3.2 Hz, J 2 ) 6.5 Hz 1H), 4.14 (m, 1H); 13C NMR (CDCl3)
δ: -4.9 (2CH3), 5.1 (CH3), 17.9 (C) 25.7 (3CH3), 31.1 (CH), 33.5
(CH2), 36.7 (CH2), 38.2 (CH), 38.3 (CH2), 51.3 (CH3), 60.8 (CH),
68.6 (CH), 173.3 (CO). Anal. Calcd for C16H32O4Si: C, 60.72;
H, 10.19. Found: C, 60.82; H, 10.28.
Cp 2TiCl-P r om oted Rin g-Op en in g Rea ction of Ep oxid e
6a . The spectroscopic properties obtained for 6b are identical
to those described for (+)-trans-carveol.12a,b,d,21 (1R,2S,3S,5R)-
3-Acetoxy-2-m eth yl-5-(2-p r op en yl)cycloh exa n ol 6c: Rf )
0.5 (hexane/EtOAc 8:2) 0.5; [R]20D +32.5 (c 0.4 CHCl3). IR (neat)
ν 3592, 3470, 2936, 1645, 1449, 1375, 1256, 1063, 1020, 889
cm-1; MS (EI) m/z 212 (M+, 4), 181 (5), 152 (35), 134 (100),
119 (65), 105 (20), 93 (35), 79 (25); 1H NMR (CDCl3) δ 1.08 (d,
J ) 7 Hz, 3H), 1.37-1.49 (m, 2H), 1.72 (s, 3H), 1.73 (m, 1H),
2.01 (m, 1H), 2.05 (m, 1H), 2.10 (s, 3H), 2.42 (tt, J 1 ) 12.8 Hz,
J 2 ) 3.2 Hz, 1H), 3.85 (m, 1H), 4.71 (s, 1H), 4.75 (s, 1H), 5.17
(m, 1H); 13C NMR (CDCl3) δ 14.2 (CH3), 20.9 (CH3), 21.2 (CH3),
32.1 (CH), 35.1 (CH2), 37.4 (CH), 38.7 (CH2), 71.2 (CH), 74.9
(CH), 109.4 (CH2), 148.5 (C), 169.7 (CO); HRMS (EI) calcd for
X-r a y Da ta . The X-ray data have been deposited at the
Cambridge Crystallographic Data Centre (deposition no. CCDC
223320). An ORTEP diagram and crystallographic information
in CIF format are available as Supporting Information.
(1S ,5S ,7R ,8S ,9S )-8,9-Dim e t h yl-3-oxo-2-oxa t r icyclo-
[5.2.1.05,9]d eca n -8-ol 3d : Rf ) 0.3 (hexane/EtOAc 1:1); [R]20
D
+23.9 (c 0.30 CHCl3); IR (neat) ν 3447, 2963, 1701, 1456, 1389,
1231, 1109, 1059, 1028, 937 cm-1; MS (EI) m/z 196 (M+, 8),
178 (17), 152 (100), 109 (35), 94 (35), 71 (25); 1H NMR (CDCl3)
δ 1.06 (s, 3H), 1.26 (s, 3H), 1.28 (m, 1H), 1.9 (t, J ) 4.4 Hz,
1H), 2.0-2.2 (m, 2H), 2.4-2.7 (m, 4H), 4.77 (dt, J 1 ) 10 Hz,
J 2 ) 2.5 Hz, 1H); 13C NMR (CDCl3) δ 11.3 (CH3), 18.6 (3H, s,
CH3), 31.7 (CH2), 34.2 (CH), 34.6 (CH2), 38.0 (CH2), 42.8 (CH),
44.5 (C), 85.8 (C), 86.5 (CH), 169.8 (CO); HRMS (EI) calcd for
C
12H20O3 (M+) 212.1412, found 212.1418.
C
11H16O3 (M+) 196.1099, found 196.1104.
Cp 2TiCl-P r om oted Rin g-Op en in g Rea ction of Ep oxid e
Cp 2TiCl-P r om oted Rin g-Op en in g Rea ction of Ep oxid e
7a . (1R,5S)-5-Acetyl-2-m eth ylcycloh ex-2-en -1-ol 7b: Rf )
4a . Met h yl (1S,3S,5R)-5-a cet oxy-3-h yd r oxy-2-m et h yl-
en ecycloh exyl a ceta te 4b: Rf ) 0.4 (hexane/EtOAc 1:1);
0.4 (hexane/EtOAc 7:3); [R]20 +186.2 (c 1.2 CHCl3); IR (neat)
D
ν 3414, 2918, 1709, 1443, 1356, 1244, 1173, 1057, 1034, 808
[R]20 -42.9 (c 0.6 CHCl3); IR (neat) ν 3495, 2955, 1734, 1437,
D
cm-1; MS (EI) m/z 154 (M+, 6), 136 (15), 121 (24), 111 (100),
1375, 1260, 1020, 903, 804 cm-1; MS (EI) m/z 242 (M+, 4), 224
(4), 182 (18), 108 (100), 77(45); 1H NMR (CDCl3) δ 1.40 (dt, J 1
) 14 Hz, J 2 ) 2.8 Hz, 1H), 1.59 (dt, J 1 ) 14 Hz, J 2 ) 2.8 Hz,
1H), 1.95 (dt, J 1 ) 14 Hz, J 2 ) 1.5 Hz, 1H), 2.08 (s, 3H), 2.23
1
93 (42), 77 (28); H NMR (CDCl3) δ 1.61 (dt, J 1 ) 13.2 Hz, J 2
) 4 Hz, 2H), 1.76 (s, 3H), 2.01-2.24 (m, 2H), 2.16 (s, 3H), 2.80
(m, 1H) 4.01 (s, 1H), 5.52 (s, 1H); 13C NMR (CDCl3) δ 20.7
(CH3), 27.1 (CH2), 28.1 (CH3), 33.6 (CH2), 42.0 (CH), 67.3 (CH),
123.7 (CH), 134.4 (C), 211.4 (CO). Anal. Calcd for C9H14O2: C,
70.10; H, 9.15. Found: C, 70.21; H, 9.12.
(dt, J 1 ) 14 Hz, J 2 ) 1.5 Hz, 1H), 2.37 (dd, J 1 ) 15 Hz, J 2
)
7 Hz, 1H), 2.69 (dd, J 1 ) 15 Hz, J 2 ) 7 Hz, 1H), 2.87 (m, 1H),
3.68 (s, 3H), 4.40 (dd, J 1 ) 10.5 Hz, J 2 ) 4.4 Hz, 1H), 4.75 (s,
1H), 5.09 (s, 1H), 5.23 (m, 1H); 13C NMR (CDCl3) δ: 21.3 (CH3),
34.0 (CH), 37.2 (CH2), 37.6 (CH2), 40.5 (CH2), 51.6 (CH3), 68.8
(CH), 69.3 (CH), 103.7 (CH2), 152.3 (C), 170.3 (CO), 172.8 (CO);
HRMS (EI) calcd for C12H18O5 (M+) 242.1154, found 242.1159.
Cp 2TiCl-P r om oted Rin g-Op en in g Rea ction of Ep oxid e
8a . (1R,5S)-5-Acetoxy-2-m eth ylcycloh ex-2-en -1-ol 8b: Rf
) 0.4 (hexane/EtOAc 8:2); [R]20D +92.7 (c 0.56 CHCl3); IR (neat)
ν 3453, 2961, 1738, 1437, 1370, 1244, 1036, 795 cm-1; MS
(FAB) m/z 171 (M+ + 1, 5), 154 (35), 111 (40), 93 (70), 73 (100);
1H NMR (CDCl3) δ 1.79 (s, 3H), 1.81-1.99 (m, 2H), 2.03 (s,
3H), 2.39 (m, 2H), 4.14 (s, 1H), 5.10 (m, 1H), 5.40 (s, 1H); 13C
NMR (CDCl3) δ 20.0 (CH3), 21.3 (CH3), 31.1 (CH2), 37.0 (CH2),
67.1 (CH), 68.5 (CH), 121.6 (CH), 135.4 (C), 170.6 (CO); HRMS
(FAB) calcd for C9H14O3 (M+ + 1) 171.0943, found 171.0951.
Cp 2TiCl-P r om oted Rin g-Op en in g Rea ction of Ep oxid e
9a . (1R,3R,5R)-3-Acetoxy-2-m eth ylen e-5-(2-p r op en yl)cy-
Met h yl (1S,2S,3S,5R)-5-a cet oxy-3-h yd r oxy-2-m et h yl-
cycloh exyl a ceta te 4c: Rf ) 0.3 (hexane/EtOAc 1:1); [R]20
D
-21.45 (c 0.42 CHCl3); IR (neat) ν 3447, 2957, 1734, 1717,
1437, 1373, 1262, 1022, 909, 801 cm-1; MS (EI) m/z 244 (M+,
4), 184 (18), 166 (25), 111 (100), 93 (55), 74 (100); 1H NMR
(CDCl3) δ 0.83 (d, J ) 7 Hz, 3H), 1.45 (dt, J 1 ) 14 Hz, J 2 ) 2.8
Hz, 1H), 1.55 (m, 3H), 1.85 (m 1H), 2.04 (s, 3H), 2.1-2.4 (m,
3H), 3.68 (s, 3H), 4.08 (m, 1H), 5.13 (m, 1H); 13C NMR (CDCl3)
δ 5.1 (CH3), 21.2 (CH3), 30.1 (CH2), 31.7 (CH), 33.1 (CH2), 37.5
(CH), 37.6 (CH2), 51.5 (CH3), 68.7 (CH), 69.4 (CH), 170.2 (CO),
173.0 (CO); HRMS (EI) calcd for C12H20O5 (M+) 244.1311, found
244.1298.
cloh exa n ol 9b: Rf ) 0.5 (hexane/EtOAc 1:1); [R]20 -91.6 (c
D
1.40 CHCl3); IR (film) ν 3461, 2940, 1738, 1645, 1435, 1375,
1248, 1099, 1053, 1028, 891 cm-1; MS (EI) m/z 210 (M+, 2),
150 (82), 132 (85), 108 (100), 91 (50), 77 (65), 67 (45); 1H NMR
(CDCl3) δ 1.17-1.50 (m, 2H), 1.71 (s, 3H), 1.97-2.82 (m, 3H),
2.15 (s, 3H), 4.53 (t, J ) 2.8 Hz, 1H), 4.71 (s, 2H), 4.87 (s, 1H),
4.96 (s, 1H), 5.61 (m, 1H); 13C NMR (CDCl3) δ 20.7 (CH3), 21.0
(CH3), 37.2 (CH), 38.3 (CH2), 38.5 (CH2), 71.0 (CH), 73.3 (CH),
107.6 (CH2), 109.5 (CH2), 147.8 (C), 170.1 (CO); HRMS (EI)
calcd for C12H18O3 (M+) 210.1256, found 210.1271.
Cp 2TiCl-P r om oted Rin g-Op en in g Rea ction of Ep oxid e
5a . Meth yl (1S,3S,5R)-5-ter t-bu tyld im eth ylsilyloxy-3-h y-
d r oxy-2-m eth ylen ecycloh exyl a ceta te 5b: Rf ) 0.5 (hexane/
EtOAc 1:1); [R]20D -20.0 (c 0.27 CHCl3); IR (neat) ν 3252, 2926,
2857, 1740, 1437, 1252, 1086, 1028, 835, 775, 694 cm-1; MS
(EI) m/z 314 (M+, 12), 293 (5), 257 (100), 225 (35), 181(28),
(1R,2R,3R,5R)-3-Acetoxy-2-m eth yl-5-(2-p r op en yl)cyclo-
1
h exa n ol 9c: Rf ) 0.5 (hexane/EtOAc 1:1); [R]20 -83.2 (c 1.4
105 (85), 91(29), 75(95). H NMR (CDCl3) δ 0.06 (s, 3H), 0.07
D
(s, 3H), 0.90 (s, 9H), 1.31 (m, 1H), 1.46 (dt, J 1 ) 13.2 Hz, J 2
)
CHCl3); IR (neat) ν 3488, 2934, 1734, 1645, 1456, 1373, 1244,
1026, 891 cm-1; MS (EI) m/z 212 (M+, 2), 194 (5), 152 (53),
2.4 Hz, 1H), 1.77 (m, 1H), 2.09 (m, 1H), 2.33 (dd, J 1 ) 15 Hz,
J 2 ) 6.5 Hz, 1H), 2.69 (dd, J 1 ) 15 Hz, J 2 ) 6.5 Hz, 1H), 2.97
(m, 1H), 3.67 (s, 3H), 4.19 (m, 1H), 4.48 (dd, J 1 ) 10.5 Hz, J 2
) 4.4 Hz, 1H), 4.68 (s, 1H), 5.02 (s, 1H); 13C NMR (CDCl3) δ
-5.0 (CH3), -4.9 (CH3), 17.9 (C), 25.7 (3CH3), 33.3 (CH), 37.5
(CH2), 41.3 (CH2), 44.4 (CH2), 51.5 (CH3), 66.3 (CH), 69.2 (CH),
102.1 (CH2), 153.9 (C), 170.0 (CO). Anal. Calcd for C16H30O4-
Si: C, 61.11; H, 9.61. Found: C, 61.49; H, 9.65.
1
124 (100), 119 (68), 105 (15), 93 (10); H NMR (CDCl3) δ 1.01
(d, J ) 7 Hz, 2H), 1.2 (m, 1H), 1.42 (ddd, J 1 ) 14 Hz, J 2
)
(21) (a) Naves, Y. R. Helv. Chim. Acta, 1964, 47, 1617-1621 (b)
Barton, D. H. R.; Motherwell, R. S. H.; Motherwell W. B. J . Chem.
Soc., Perkin Trans. 1 1981, 2363-2367 (c) Yasui, K.; Fugami, K;
Tanaka, S.; Tamaru, Y. J . Org. Chem. 1995, 60, 1365-1380.
J . Org. Chem, Vol. 69, No. 16, 2004 5279

Bermejo and Sandoval
12.8 Hz, J 3 ) 2.5 Hz, 1H), 1.6 (m, 1H), 1.72 (s, 3H), 1.9 (m,
1H), 2.05 (s, 3H), 2.1 (m, 1H), 2.53 (tt, J 1 ) 12.8 Hz, J 2 ) 2.5
(CH2), 147.2 (C), 173.8 (CO); HRMS (EI) calcd for C19H36O4Si
(M+) 356.2383, found 356.2371.
Hz, 1H), 4.03 (m, 1H), 4.70 (s, 1H), 4.72 (s, 1H), 4.90 (dt, J 1
)
Cp 2TiCl-P r om oted Rin g-Op en in g Rea ction of Ep oxid e
12a . (2R*,1′R*,3′S*,5′R*)-2-(5′-Acetoxy-3′-h yd r oxy-2′-m e-
t h yle n e cycloh e xyl)-2-t er t -b u t yld im e t h yld im e t h ylsil-
yloxya cetic a cid m eth yl ester 12b: Rf ) 0.5 (hexane/EtOAc
1:1); IR (neat) ν 2953, 2859, 1738, 1439, 1373, 1246, 1157, 1022,
841, 779, 706 cm-1; MS (EI) m/z 372 (M+, 3), 315 (5), 237 (17),
195 (75), 163 (100), 121 (200), 75 (70); 1H NMR (CDCl3) δ 0.07
(s, 3H), 0.12 (s, 3H), 0.93 (s, 9H), 1.74 (m, 1H), 1.86 (m, 3H),
2.03 (s, 3H), 2.97 (m, 1H), 3.68 (s, 3H), 4.27 (t, J ) 5.2 Hz,
1H), 4.36 (d, J ) 3.8 Hz, 1H), 4.99 (s, 1H), 5.09 (s, 1H), 5.35
(m, 1H); 13C NMR (CDCl3) δ -5.5 (CH3), -5.3 (CH3), 18.2 (C),
21.2 (CH3), 25.6 (3CH3), 34.9 (CH2), 40.1 (CH2), 43.1 (CH), 51.7
(CH3), 67.9 (CH), 69.9 (CH), 75.8 (CH), 111.5 (CH2), 146.1 (C),
170.2 (CO), 172.5 (CO). Anal. Calcd for C18H32O6Si: C, 58.03;
H, 8.66. Found: C, 58.22; H, 8.81.
(2R*,1′R*,2′S*,3′S*,5′R*)-2-(5′-Acetoxy-3′-h ydr oxy-2′-m e-
t h ylcycloh exyl)-2-ter t-b u t yld im et h yld im et h ylsilyloxy-
a cetic a cid m eth yl ester 12c: Rf ) 0.3 (hexane/EtOAc 3:1);
IR (neat) ν 3478, 2953, 2859, 1738, 1250, 839, 779 cm-1; MS
(EI) m/z 374 (M+, 2), 315 (15), 299 (40), 239 (70), 165 (90), 133
(35), 75 (100); 1H NMR (CDCl3) δ 0.03 (s, 3H), 0.05 (s, 3H),
0.90 (d, J ) 7 Hz, 3H), 0.91 (s, 9H), 1.36 (m, 1H), 1.57-1.65
(m, 2H), 1.84 (m, 1H), 2.02 (s, 3H), 2.23 (m, 2H), 3.72 (s, 3H),
4.00 (m, 1H), 4.08 (d, J ) 7 Hz, 1H), 5.15 (m, 1H); 13C NMR
(CDCl3) δ -5.4 (CH3), -5.1 (CH3), 5.0 (CH3), 18.1 (C), 21.2
(CH3), 25.6 (3CH3), 26.3 (CH2), 32.6 (CH2), 34.8 (CH), 38.6
(CH), 51.7 (CH3), 68.5 (CH), 69.5 (CH), 74.5 (CH), 170.2 (CO),
173.5 (CO). Anal. Calcd for C18H34O6Si: C, 57.72; H, 9.15.
Found: C, 57.98; H, 9.27.
11.2 Hz, J 2 ) 4 Hz, 1H); 13C NMR (CDCl3) δ 14.1 (CH3), 20.8
(CH3), 21.2 (CH3), 36.8 (CH2), 36.8 (CH), 38.0 (CH2), 40.9 (CH),
71.6 (CH), 73.9 (CH), 109.2 (CH2), 148.4 (C), 170.7 (CO); HRMS
(EI) calcd for C12H20O3 (M+) 212.1412, found 212.1398.
Cp 2TiCl-P r om oted Rin g-Op en in g Rea ction of Ep oxid e
10a . (1R,3R,5R)-3,5-bisa cetoxy-2-m eth ylen ecycloh exa n ol
10b: Rf ) 0.3 (hexane/EtOAc 8:2); [R]20D -32.2 (c 1.60 CHCl3);
IR (neat) νmax 3482, 2936, 1748, 1723, 1653, 1437, 1260, 1063,
1026, 982, 918 cm-1; MS (EI) m/z 228 (M+, 4), 211 (10), 129
(12), 109 (60), 91 (72), 81 (48), 69 (72); 1H NMR (CDCl3) δ 1.6-
2.4 (m, 4H), 2.01 (s, 3H), 2.07 (s, 3H), 4.57 (t, J ) 4.3 Hz, 1H),
4.93 (s, 1H), 5.06 (s, 1H), 5.28 (m, 1H), 5.57 (dd, J 1 ) 9.6 Hz,
J 2 ) 4.6 Hz, 1H); 13C NMR (CDCl3) δ 20.9 (CH3), 21.1 (CH3),
37.2 (CH2), 38.9 (CH2), 67.8 (CH), 69.9 (CH), 70.1 (CH), 109.1
(CH2), 146.4 (C), 169.8 (CO), 170.1 (CO); HRMS (EI) calcd for
C
11H16O5 (M+) 228.0998, found 228.1013.
10c. The spectroscopic properties obtained for 10c are
identical to those described for 8b.
Cp 2TiCl-P r om oted Rin g-Op en in g Rea ction of Ep oxid e
11a . (2R*,1′R*,3′S*,5′R*)-2-ter t-Bu tyld im eth yld im eth yl-
silyloxy-2-[3′-h yd r oxy-2′-m eth ylen e-5′-(2-p r op en yl)cyclo-
h exyl]a cetic a cid m eth yl ester 11b: Rf ) 0.4 (hexane/EtOAc
8:2); IR (neat) ν 3461, 2951, 2859, 1740, 1647, 1474, 1437, 1258,
1119, 839, 781 cm-1; MS (EI) m/z 354 (M+, 3), 295 (10), 239
1
(35), 205 (75), 133 (80), 73 (100); H NMR (CDCl3) δ 0.08 (s,
3H), 0.11 (s, 3H), 0.96 (s, 9H), 1.37 (dt, J 1 ) 13.2 Hz, J 2 ) 2.8
Hz, 1H), 1.68 (m, 1H), 1.70 (s, 3H), 1.76 (m, 1H), 1.99 (dq, J 1
) 13.2 Hz, J 2 ) 2.4 Hz, 1H), 2.78 (tt, J 1 ) 13.2 Hz, J 2 ) 3.6
Hz, 1H), 2.97 (t, J ) 5 Hz, 1H), 3.69 (s, 3H), 4.23 (t, J 2 ) 2.4
Hz, 1H), 4.49 (d, J ) 5 Hz, 1H), 4.69 (s, 1H), 4.72 (s, 1H), 4.80
(s, 1H), 5.0 (s, 1H); 13C NMR (CDCl3) δ -5.5 (CH3), -5.4 (CH3),
18.0 (C), 20.7 (CH3), 25.6 (3CH3), 34.0 (CH), 34.5 (CH2), 39.5
(CH2), 44.7 (CH), 51.6 (CH3), 71.1 (CH), 77.9 (CH), 109.1 (CH2),
116.3 (CH2), 146.0 (C), 149.2 (C), 172.2 (CO); HRMS (EI) calcd
for C19H34O4Si (M+) 354.2226, found 354.2216.
Ack n ow led gm en t. Financial support of this work
by the Direccion General de Investigacio´n Cient´ıfica y
Te´cnica, Spain (DGICYT PPQ2002-00290), and the
J unta de Castilla y Leo´n (SA 027/03) is gratefully
acknowledged.
(2R*,1′R*,2′S*,3′S*,5′R*)-2-ter t-Bu tyld im eth yld im eth yl-
silyloxy-2-[3′-h ydr oxy-2′-m eth yl-5′-(2-pr open yl)cycloh exyl]-
a cetic a cid m eth yl ester 11c: Rf ) 0.3 (hexane/EtOAc 8:2);
IR (neat) ν 3422, 2951, 2859, 1740, 1458, 1260, 1105, 839, 779
cm-1; MS (EI) m/z 356 (M+, 2), 323 (6), 297 (12), 281 (92), 207
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for the preparation of the epoxides 2a -5a , 11a , and
12a and the intermediates 13-16, 17a ,b , 18, 20, and 21;
spectroscopic data (1H NMR and 13C NMR) of compounds 1a -
12a , 1b-12b, 1c-6c, 9c, 11c, and 12c, and intermediates 13-
21; NOE or ROESY experiments for 2c, 4c, 5c, 6c, 9c, 11c,
12c, and 20; ORTEP diagram and tables of the crystal data,
bond lengths, angles, atomic coordinates, and anisotropic
thermal parameters obtained for the tricyclic lactone 3c. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
(62), 147 (70), 107 (40), 75 (100); H NMR (CDCl3) δ 0.04 (s,
3H), 0.08 (s, 3H), 0.90 (d, J ) 7 Hz, 3H), 0.92 (s, 9H), 1.48 (m,
1H), 1.54 (m, 1H), 1.70 (s, 3H), 1.72 (m, 1H), 2.15 (m, 1H),
2.32 (m, 1H), 2.50 (t, J ) 5 Hz, 1H), 3.71 (s, 3H), 3.82 (m, 1H),
4.13 (d, J ) 6.7 Hz, 1H), 4.75 (s, 1H), 4.83 (s, 1H); 13C NMR
(CDCl3) δ -5.4 (CH3), -5.2 (CH3), 8.5 (CH3), 18.1 (C), 21.9
(CH3), 25.7 (3CH3), 29.3 (CH2), 29.6 (CH2), 36.0 (CH), 36.2 (CH),
36.9 (CH), 39.9 (CH), 51.6 (CH3), 69.2 (CH), 75.2 (CH), 110.2
J O049358U
5280 J . Org. Chem., Vol. 69, No. 16, 2004