A concise total synthesis of dactylol via ring closing metathesis

Article abstract of DOI:10.1021/jo961600c

A straightforward total synthesis of the cyclooctenoid sesquiterpene dactylol (1) and of 3a-epi-dactylol (13) has been achieved in six synthetic operations. The unusual rearranged bicyclo[6.3.0]undecane isoprenoid skeleton of these target molecules has been formed via an initial three component coupling triggered by 1,4-addition of a methylcopper reagent (MeLi, CuI, Bu₃P) to cyclopentenone, followed by trapping of the enolate formed with 2,2-dimethyl-4-pentenal as the electrophile. The aldol 8 thus obtained was elaborated into the trans-disubstituted cyclopentanone derivative 10 which reacted with a methallylcerium reagent to afford a mixture of the tertiary alcohols 11a and 12a. Separation and O-silylation of these diastereoisomers, ring-closing metathesis (RCM) of the resulting dienes 11b and 12b to form the cyclooctene ring using Schrocks molybdenum carbene 5 as a precatalyst, and a final deprotection afforded the title compound and its epimer in excellent yields. This approach clearly surpasses previous ones in terms of efficiency, flexibility, accessibility of the substrates, number of steps, atom economy, and overall yield.

Full text of DOI:10.1021/jo961600c

8746
J . Org. Chem. 1996, 61, 8746-8749
A Con cise Tota l Syn th esis of Da ctylol via Rin g Closin g Meta th esis
Alois Fu¨rstner* and Klaus Langemann
Max-Planck-Institut fu¨r Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mu¨lheim/ Ruhr, Germany
Received August 19, 1996X
A straightforward total synthesis of the cyclooctenoid sesquiterpene dactylol (1) and of 3a-epi-
dactylol (13) has been achieved in six synthetic operations. The unusual rearranged bicyclo[6.3.0]-
undecane isoprenoid skeleton of these target molecules has been formed via an initial three-
component coupling triggered by 1,4-addition of a methylcopper reagent (MeLi, CuI, Bu3P) to
cyclopentenone, followed by trapping of the enolate formed with 2,2-dimethyl-4-pentenal as the
electrophile. The aldol 8 thus obtained was elaborated into the trans-disubstituted cyclopentanone
derivative 10 which reacted with a methallylcerium reagent to afford a mixture of the tertiary
alcohols 11a and 12a . Separation and O-silylation of these diastereoisomers, ring-closing metathesis
(RCM) of the resulting dienes 11b and 12b to form the cyclooctene ring using Schrocks molybdenum
carbene 5 as a precatalyst, and a final deprotection afforded the title compound and its epimer in
excellent yields. This approach clearly surpasses previous ones in terms of efficiency, flexibility,
accessibility of the substrates, number of steps, atom economy, and overall yield.
The synthesis of eight-membered ring systems remains
a formidable challenge despite the progress which has
been achieved in this area in recent years.1 Unfavorable
entropic and enthalpic factors impede their preparation;
once they are formed, further functionalization is difficult
due to their susceptibility to transannular reactions and
the large number of low-energy conformations. These
notions clearly emerge from many synthetic approaches
e.g. to cyclooctanoid terpenes, a rapidly growing family
of structurally diverse natural products. Among them,
dactylol (1, Figure 1) has attracted particular attention
because of its unusual rearranged trans-bicyclo[6.3.0]-
undecane isoprenoid skeleton. This compound was first
isolated from the Carribean sea hare Aplysia dactylo-
mela2 and was later found in the seaweed Laurencia
poitei.3 It seems likely that the mollusk concentrates this
metabolite while grazing on L. poitei or related Laurencia
species.3
F igu r e 1.
approach to this challenging target.9 In the following we
disclose an unprecedentedly short and efficient total
synthesis of dactylol (1) and its epimer 13 which is based
on a three-component assembly followed by ring-closing
metathesis (RCM) as the key steps.
The discovery of high-performance catalysts for RCM
of functionalized 1,ω-dienes such as the molybdenum
carbene 5 developed by Schrock et al. has substantially
upgraded this valuable process in practical terms (Scheme
1).10,11 Although most applications reported so far have
focused on the formation of five-, six-, and seven-
membered ring systems, some recent reports on success-
ful cyclizations of rather strained medium-ring sized
carbo- and heterocycles,12 together with the excellent
experiences which we have gained in RCM-based macro-
lide syntheses13 prompted us to rely upon RCM in our
approach to dactylol (Scheme 2).
Dactylol is biosynthetically derived from humulene (4)
and structurally closely related to poitediol (2)3 and
precapnelladiene (3).4 The known entries into this class
of compounds, although they elegantly exploit either
sigmatropic rearrangements5,6 or cycloaddition strate-
gies,7,8 are rather lengthy with the overall yield being <
1% in all cases. This also holds true for a biomimetic
X Abstract published in Advance ACS Abstracts, November 15, 1996.
(1) Reviews: (a) Petasis, N. A.; Patane, M. A. Tetrahedron 1992,
48, 5757-5821. (b) Rousseau, G. Tetrahedron 1995, 51, 2777-2849.
(2) Schmitz, F. J .; Hollenbeak, K. H.; Vanderah, D. J . Tetrahedron
1978, 34, 2719-2722.
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Djerassi, C. Tetrahedron 1979, 35, 1035-1039. Syntheses: (b) Kinney,
W. A.; Coghlan, M. J .; Paquette, L. A. J . Am. Chem. Soc. 1985, 107,
7352-7360. (c) Mehta, G.; Murty, A. N. J . Chem. Soc.; Chem. Commun.
1984, 1058-1060.
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Res. 1995, 28, 446-452. (b) Schmalz, H.-G. Angew. Chem. 1995, 107,
1981-1984. (c) Koert, U. Nachr. Chem. Techn. Lab. 1995, 43, 809-
814. (d) Grubbs, R. H.; Pine, S. H. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 5, pp
1115-1127.
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3025-3036. (b) Paquette, L. A.; Ham, W. H.; Dime, D. S. Tetrahedron
Lett. 1985, 4983-4986.
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1990, 112, 8490-8496. (b) Feldman, K. S.; Wu, M.-J .; Rotella, D. P. J .
Am. Chem. Soc. 1989, 111, 6457-6458.
(11) For the preparation of the molybdenum carbene 5, see: Schrock,
R. R.; Murdzek, J . S.; Bazan, G. C.; Robbins, J .; DiMare, M.; O’Regan,
M. J . Am. Chem. Soc. 1990, 112, 3875-3886.
(8) Molander, G. A.; Eastwood, P. R. J . Org. Chem. 1995, 60, 4559-
4565.
S0022-3263(96)01600-3 CCC: $12.00 © 1996 American Chemical Society

Total Synthesis of Dactylol
Sch em e 1
J . Org. Chem., Vol. 61, No. 25, 1996 8747
Sch em e 2a
glandin synthesis.14 We made use of such a one-pot
“three component coupling process” developed by Noyori
et al.15 for the expeditious assembly of the carbon
skeleton of 1 from cyclopentenone 6 as the starting
material. Specifically, reaction of 6 with the organo-
copper reagent formed in situ from MeLi, CuI, and Bu3P
at low temperature, followed by addition of commercially
available 2,2-dimethyl-4-pentenal in order to trap the
kinetically defined, nonequilibrating enolate 7, gave
compound 8 in 77% yield. Its dehydration afforded enone
9 as a single isomer which underwent chemo- and
diastereoselective hydrogenation on treatment with
Bu3SnH in the presence of ZnCl2 and catalytic amounts
of Pd(PPh3)4.16 The 1,2-trans arrangement in ketone 10
thus formed clearly emerged from the analysis of the 13C
NMR spectrum of this compound by comparison with
literature data.17 Thus, the stage was set for the forma-
tion of the tertiary alcohol group bearing a methallyl side
chain. Best results were obtained upon reaction of the
readily enolizable ketone 10 with a highly nucleophilic
but only weakly basic organocerium reagent.18 Hence,
methallylbromide was first converted into the corre-
sponding Grignard reagent without Wurtz coupling
interfering on treatment with highly activated Mg-
graphite in THF.19 Its transmetalation with anhydrous
a
Total synthesis of (()-dactylol (1) and its 3a-epimer 13. Only
one antipode of the racemates is depicted: [a] MeLi (1 equiv), CuI
(1 equiv), Bu3P (2.2 equiv), Et2O, -78 °C (1 h) f -40 °C (2.5 h);
[b] 2,2-dimethyl-4-pentenal, -78 °C f rt, 77%; [c] methanesulfonyl
chloride, DMAP, CH2Cl2, 35 °C, 18 h, 85%; [d] Bu3SnH (1.2 equiv),
ZnCl2 (1.5 equiv), Pd(PPh3)4 (1.6 mol %), THF, rt, 20 min, 83%;
[e] (i) methallyl bromide, Mg-graphite (4.3 equiv), THF, 65 °C,
30 min; (ii) CeCl3, -78 °C, 2 h, 80% combined yield, 11a :12a )
1:1.2; [f] (Me3Si)2NH (1.25 equiv), acetyl chloride (1.25 equiv),
DMAP (1.33 equiv), 93% (11a f 11b), 95% (12a f 12b); [g] (i)
molybdenum carbene 5 (3 mol %), hexane, 55 °C, 3 h; (ii) aqueous
TBAF, THF, 50 °C, 3 h, 92% (11b f 1), 85% (12b f 13).
CeCl3 followed by addition of 10 gave alcohols 11a and
12a in a 1:1.2 ratio. These compounds can be readily
separated by flash chromatography and were processed
independently.
Attempted cyclization of these alcohols by RCM with
the Schrock carbene 5 as the precatalyst11 completely
failed and led to quantitative recovery of the starting
(12) For the formation of medium-sized rings by RCM see: (a) Miller,
S. J .; Kim, S.-H.; Chen, Z.-R.; Grubbs, R. H. J . Am. Chem. Soc. 1995,
117, 2108-2109. (b) Miller, S. J .; Grubbs, R. H. J . Am. Chem. Soc.
1995, 117, 5855-5856. (c) Martin, S. F.; Chen, H.-J .; Courtney, A. K.;
Liao, Y.; Pa¨tzel, M.; Ramser, M. N.; Wagman, A. S. Tetrahedron 1996,
52, 7251-7264. (d) Martin, S. F.; Wagman, A. S. Tetrahedron Lett.
1995, 1169-1170. (e) Martin, S. F.; Liao, Y.; Wong, Y.; Rein, T.
Tetrahedron Lett. 1994, 691-694. (f) Visser, M. S.; Heron, N. M.;
Didiuk, M. T.; Sagal, J . F.; Hoveyda, A. H. J . Am. Chem. Soc. 1996,
118, 4291-4298. (g) Winkler, J . D.; Stelmach, J . E.; Axten, J .
Tetrahedron Lett. 1996, 4317-4318.
(13) (a) Fu¨rstner, A.; Langemann, K. J . Org. Chem. 1996, 61, 3942-
3943. (b) Fu¨rstner, A.; Kindler, N. Tetrahedron Lett. 1996, 7005-7008.
(14) For pertinent reviews, see: (a) Noyori, R. Asymmetric Catalysis
in Organic Synthesis; Wiley: New York, 1994; pp 298-322. (b) Noyori,
R.; Suzuki, M. Angew. Chem. 1984, 96, 854-882.
(15) Suzuki, M.; Kawagishi, T.; Suzuki, T.; Noyori, R. Tetrahedron
Lett. 1982, 4057-4060.
(18) (a) Imamoto, T.; Takiyama, N.; Nakamura, K. Tetrahedron Lett.
1985, 4763-4766. (b) Review: Molander, G. A. Chem. Rev. 1992, 92,
29-68. (c) Imamoto, T. Lanthanides in Organic Synthesis; Academic
Press: New York, 1994. (d) A better diastereoselectivity was obtained
with a titanium ate complex formed in situ from methallylmagnesium
bromide and Ti(O-iPr)4 (11a :12a ) 2.3:1), cf.: Reetz, M. T.; Wester-
mann, J .; Steinbach, R.; Wenderoth, B.; Peter, R.; Ostarek, R.; Maus,
S. Chem. Ber. 1985, 118, 1421-1440; however, the conversion was low
and the products formed were difficult to separate from the unreacted
starting material.
(19) (a) For the preparation of Mg-graphite and applications in
pinacol coupling reactions, see: Fu¨rstner, A.; Csuk, R.; Rohrer, C.;
Weidmann, H. J . Chem. Soc., Perkin Trans. 1 1988, 1729-1734. (b)
Reviews on activated metal systems: Fu¨rstner, A. Angew. Chem. 1993,
105, 171-197; Angew. Chem., Int. Ed. Engl. 1993, 32, 164-189. (c)
Active Metals. Preparation, Characterization, Applications; Fu¨rstner,
A., Ed.; VCH: Weinheim, 1996. (d) The solution of anhydrous MgCl2
in THF was prepared from Mg and dichloroethane according to:
Nu¨tzel, K. in Houben-Weyl, Methoden der Organischen Chemie; Mu¨ller,
E., Ed.; Thieme: Stuttgart, 1973; Vol. XIII/2a, p 176.
(16) Keinan, E.; Gleize, P. A. Tetrahedron Lett. 1982, 477-480.
(17) The CR-atoms of substituents in trans-disubstituted cyclopen-
tanes resonate at significantly lower field than that in the correspond-
ing cis-disubstituted ones, cf.: Kalinowski, H.-O.; Berger, S.; Braun,
S. 13C-NMR Spektroskopie; Thieme: Stuttgart, 1984.

8748 J . Org. Chem., Vol. 61, No. 25, 1996
Fu¨rstner and Langemann
2-cyclopentenone (6, 677 mg, 691 µL, 8.25 mmol) in Et2O (20
mL). The yellow suspension is stirred for 1 h at -78 °C and
2.5 h at -40 °C. After the suspension is recooled to -78 °C,
2,2-dimethyl-4-pentenal (923 mg, 1.119 mL, 8.23 mmol) is
added via syringe. The reaction mixture is allowed to warm
to rt and is quenched with saturated aqueous NH4Cl (50 mL).
The organic layer is separated, the aqueous phase is extracted
twice with diethyl ether (30 mL each); the combined extracts
are dried over Na2SO4, filtered, and evaporated to dryness.
The residue is purified by column chromatography (hexane/
ethyl acetate 30:1f2:1) to give 8 as a colorless liquid (1.328 g,
77%) which is admixed with ≈15% of the dehydration product
material. Although such carbene species were reported
to tolerate unprotected -OH groups in the substrates,10
we reasoned that an interaction of this functionality with
the electrophilic metal center might inhibit the desired
metathetic conversion. Therefore these compounds were
O-silylated using N,O-bis(trimethylsilyl)acetamide20
formed in situ from (Me3Si)2NH, acetyl chloride, and
DMAP. Analysis (13C NMR, NOESY) of the fairly stable
silyl ethers 11b and 12b formed clearly established the
mutual trans relationship of the carbon side chains in
the former compound. Most gratifyingly, however, both
dienes cyclized smoothly to the corresponding cyclooctene
derivatives in 0.03 M hexane solution in the presence of
the molybdenum carbene 5 (3 mol %).11 The crude
products formed were desilylated by means of TBAF.
Thus, dactylol (1) and 3a-epi-dactylol (13) were obtained
in 92% and 85% isolated yield, respectively. The spec-
troscopic and analytical data of 1 are in full accordance
with those reported in the literature.2,5-8 The 13C NMR
spectrum of its epimer 13 features a characteristic
broadening of the signals of the cyclooctene ring, indicat-
ing a slow equilibration of different conformers of this
cis-fused [6.3.0] framework, which is considerably more
strained than that of the natural product 1.21
In summary we have achieved a straightforward
synthesis of the cyclooctenoid sesquiterpene dactylol (1)
and its epimer 13 based on a three-component coupling
for the functionalization of the cyclopentane entity fol-
lowed by an efficient cyclization of the eight-membered
ring via ring closing metathesis. This approach which
affords these structurally demanding target molecules in
17% and 19% overall yield, respectively, in only six
synthetic operations clearly surpasses previous ones in
terms of efficiency and practicability. We now try to
implement this flexible concept into the synthesis of
related natural and nonnatural products.
1
9: Rf 0.62 (hexane/ethyl acetate 2:1); H NMR (300 MHz) δ
5.92-5.65 (m, 1H), 5.09-4.99 (m, 2H), 3.36 (s, 1H), 2.52 (s,
1H), 2.38-2.12 (m, 5H), 2.04-1.92 (m, 2H), 1.47-1.41 (m, 1H),
1.16-1.13 (m, 3H), 0.91 (s, 3H), 0.87 (s, 3H); 13C NMR (75
MHz) δ 220.3, 135.2, 117.5, 77.8, 57.2, 43.4, 38.8, 38.6, 37.9,
29.3, 23.5, 22.8, 19.3; IR (neat) 3531, 3074, 2959, 2930, 2872,
1729, 1639, 1465, 1406, 1292, 1154, 1095, 1053, 997, 913 cm-1
;
MS (EI) m/ z (rel intensity) 192 ([M+ - H2O], 2), 151 (28), 109
(41), 98 (27), 69 (48), 55 (100); MS (CI) 228 ([M + NH4+], 2).
2-(2,2-Dim e t h ylp e n t -4-e n -1-ylid e n e )-3-m e t h ylcyclo-
p en ta n on e (9). DMAP (580 mg, 4.75 mmol) and methane-
sulfonyl chloride (272 mg, 184 µL, 2.37 mmol) in CH2Cl2 (10
mL) are added to a stirred solution of 8 (200 mg, 0.95 mmol)
in CH2Cl2 (10 mL). The mixture is refluxed for 18 h, cooled to
rt, and filtered through a plug of silica, which is washed several
times with CH2Cl2. The solvent is removed, and the resulting
oil is purified by flash chromatography (hexane/ethyl acetate
5:1) to give 9 as a colorless syrup (155 mg, 85%): Rf 0.64
1
(hexane/ethyl acetate 2:1); H NMR (300 MHz) δ 6.44 (d, 1H,
J ) 1.6), 5.79-5.65 (m, 1H), 5.06-5.00 (m, 2H), 3.39-3.34 (m,
1H), 2.38-2.15 (m, 4H), 1.98-1.87 (m, 1H), 1.77-1.74 (m, 1H),
1.17-1.15 (m, 9H); 13C NMR (75 MHz) δ 208.4, 143.8, 140.2,
134.7, 117.7, 47.7, 37.1, 34.1, 32.9, 27.9, 27.4, 27.1, 21.6; UV
λmax (log ꢀ) 238 (4.36), 359 (1.76), 345 (1.90), 332 (1.87); IR
(neat) 3076, 2964, 2931, 2872, 1724, 1640, 1462, 1414, 1203,
1178, 997, 914, 799 cm-1; MS m/ z (rel intensity) 192 ([M+],
3), 151 (69), 109 (100), 93 (9), 81 (14), 67 (29); HR-MS (C13H20O)
calcd 192.1514, found 192.1512; C13H20O (192.3) calcd C 81.20,
H 10.48; found C 81.15, H 10.54.
tr a n s-2-(2,2-Dim et h ylp en t -4-en -1-yl)-3-m et h ylcyclo-
p en ta n on e (10). (n-Bu)3SnH (716 mg, 662 µL, 2.46 mmol) is
added within 5 min via syringe to a stirred mixture of enone
9 (394 mg, 2.05 mmol), Pd(PPh3)4 (46 mg, 0.004 mmol), and
ZnCl2 (409 mg, 3 mmol) in THF (5 mL) at ambient tempera-
ture. The yellow solution is stirred for an additional 20 min
and then quenched with saturated aqueous NH4Cl (10 mL).
A standard extractive workup (Et2O) followed by flash chro-
matography (hexane/ethyl acetate 20:1) affords the title com-
pound as a single diastereomer (330 mg, 83%); Rf 0.63 (hexane/
Exp er im en ta l Section
Gen er a l. All reactions were carried out under Ar using
Schlenk techniques. The Schrock carbene 5 was purchased
from Strem Chemical Inc. and used as received.11 Anhydrous
CeCl3: the commercially available CeCl3‚7H2O (Aldrich, 99.9%)
was flame-dried in vacuo; the crystals obtained were rapidly
pulverized in a mortar and redried for 24 h at 150 °C at 10-2
Torr. The pyrophoric potassium-graphite laminate (C8K)
used for the preparation of activated Mg-graphite was
prepared and handled as described in the literature.19 Bu3P
and 2-cyclopentenone were distilled under Ar prior to use. All
other commercially available substrates (Aldrich) were used
as received. The solvents were dried by distillation over the
following drying agents prior to use and were transferred
under Ar: Et2O (Na/K), CH2Cl2 (P4O10), THF (Mg-anthra-
cene), and hexane (Na/K). Flash chromatography: For this
procedure Merck silica gel 60 (230-400 mesh) was used with
n-hexane/ethyl acetate in various proportions as eluents,
unless stated otherwise. For the instrumentation used see the
Supporting Information. Elemental analyses: Dornis & Kolbe,
Mu¨lheim.
1
ethyl acetate 10:1); H NMR (200 MHz) δ 5.86 (ddt, 1H, J )
16.3, 10.8, 7.4), 5.05-4.95 (m, 2H), 2.42-2.26 (m, 1H), 2.19-
1.94 (m, 4H), 1.78-1.39 (m, 4H), 1.15-1.12 (m, 4H), 0.87 (s,
3H), 0.86 (s, 3 H); 13C NMR (50 MHz) δ 220.9 (s), 135.6 (d),
116.9 (t), 53.1 (d), 47.3 (t), 40.4 (t), 39.4 (d), 37.1 (t), 33.4 (s),
29.3 (t), 26.7 (q), 26.6 (q), 19.4 (q); IR (neat) 3462, 3075, 3003,
2958, 2928, 2878, 1742, 1639, 1466, 1367, 1154, 995, 912, 806
cm-1; MS m/ z (rel intensity) 194 ([M+], 18), 179 (31), 153 (100),
135 (36), 111 (39), 97 (57), 83 (50); C13H22O (194.3) calcd C
80.35, H, 11.41, found C 80.19, H 11.26.
2-(2,2-Dim eth ylp en t-4-en -1-yl)-3-m eth yl-1-(2-m eth yl-2-
p r op en -1-yl)cyclop en ta n ols (11a a n d 12a ). A solution of
MgCl2 in THF (10.72 mL, 0.3844 M, 4.12 mmol)19d is added at
rt to a stirred suspension of C8K (1.114 g, 8.24 mmol) in THF
(20 mL). The mixture is refluxed for 30 min and stirred at rt
for another 2 h. 3-Bromo-2-methyl-1-propene (556 mg, 415
µL, 4.12 mmol) is then added dropwise, and stirring is
continued for 2 h at that temperature. The Grignard solution
is transferred via cannula to a cooled (-78 °C) suspension of
anhydrous CeCl3 (1.016 g, 4.12 mmol) in THF (20 mL). After
the resulting yellow suspension was stirred for 2 h at -78 °C,
a solution of 10 (186 mg, 0.96 mmol) in THF (10 mL) is added,
and the reaction is allowed to warm to ambient temperature
overnight. Treatment with 30 mL of aqueous saturated NH4Cl
followed by a standard extractive workup and a final flash
2-(1-H yd r oxy-2,2-d im e t h ylp e n t -4-e n -1-yl)-3-m e t h yl-
cyclop en ta n on e (8). To a stirred suspension of CuI (1.651
g, 8.67 mmol) in Et2O (60 mL) is added P(n-Bu)3 (4.75 mL,
19.07 mmol) at ambient temperature. After stirring for 10 min
the colorless solution is cooled to -78 °C and MeLi (1.14 M in
diethyl ether, 7.61 mL, 8.67 mmol) is added, causing the
formation of a white suspension. Stirring is continued for
another 20 min at that temperature prior to the addition of
(20) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 2nd ed.; Wiley: New York, 1991; and literature cited.
(21) For details see the Supporting Information.

Total Synthesis of Dactylol
J . Org. Chem., Vol. 61, No. 25, 1996 8749
chromatography (hexane/diethyl ether 30:1) gives pure 11a (86
mg, 36%) and pure 12a (105 mg, 44%) as a colorless syrup
each. Analytical data for 11a : Rf 0.30 (hexane/diethyl ether
30:1), 1H NMR (600 MHz, C6D6) δ 5.85 (ddt, 1H, J ) 17.1,
10.0, 7.4), 5.06-5.01 (m, 2H), 4.85-4.84 (m, 1H), 4.75 (m, 1H),
2.36 (d, 1H, J ) 13.0), 1.97-1.86 (m, 4H), 1.82 (d, 1H, J )
13.0), 1.76 (s, 3H), 1.70 (dd, 1H , J ) 15.0, 3.2), 1.56 (ddd, 1H,
J ) 13.2, 9.4, 8.0), 1.47 (ddd, 1H, J ) 13.2, 8.3, 4.0), 1.18 (dd,
1H, J ) 15.0, 5.9), 1.18 (s, 1H), 1.11-1.05 (m, 1H), 0.99 (d,
3H, J ) 6.7), 0.97 (ddd, 1H, J ) 8.4, 5.9, 3.0), 0.86 (s, 3H),
0.84 (s, 3H); 13C NMR (100 MHz) δ 143.3 (s), 135.8 (d), 116.8
(t), 114.5(t), 82.5 (s), 51.9 (d), 48.4 (t), 48.1 (t), 41.0 (t), 39.9
(d), 37.9 (t), 33.2 (s), 31.1 (t), 27.4 (q), 24.7 (q), 21.0 (q); MS
m/ z (rel intensity) 232 (1), 217 (2), 195 (4), 177 (28), 153 (31),
135 (30), 121 (18), 107 (28), 97 (41), 83 (39), 69 (37), 55 (100),
41 (58). Analytical data for 12a : Rf 0.39 (hexane/diethyl ether
30:1); 1H NMR (600 MHz, C6D6) δ 5.86 (ddt, 1H, J ) 16.8,
10.3, 7.4), 5.07-5.02 (m, 2H), 4.87-4.86 (m, 1H), 4.74 (m, 1H),
2.26 (d, 1H, J ) 13.4), 2.00 (dd, 2H, J ) 7.4, 1.1), 1.91 (d, 1H,
J ) 13.4), 1.77 (s, 3H), 1.69-1.61 (m, 2H), 1.47 (dd, 1H, J )
14.3, 4.9), 1.44-1.40 (m, 3H), 1.30-1.24 (m, 2H), 1.05 (d, 3H,
J ) 6.4), 0.95 (dd, 1H, J ) 14.3, 4.3), 0.93 (s, 3H), 0.91 (s, 3H);
13C NMR (100 MHz) δ 143.5 (s), 135.9 (d), 116.7 (t), 114.6 (t),
82.3 (s), 53.9 (d), 47.8 (t), 44.6 (t), 41.6 (t), 40.3 (d), 38.2 (t),
33.5 (s), 30.8 (t), 27.4 (q), 27.3 (q), 24.9 (q), 21.5 (q); IR (neat)
3475, 3074, 2956, 2870, 1639, 1453, 1386, 1375, 1367, 1097,
1072, 1020, 912, 888 cm-1; MS m/ z (rel intensity) 232 (1), 217
(3), 191 (8), 177 (26), 153 (13), 135 (25), 121 (17), 107 (24), 97
(38), 83 (39), 69 (36), 55 (100), 41 (53).
Com p ou n d 12b . DMAP (40 mg, 0.32 mmol) and acetyl
chloride (24 mg, 21 µL, 0.30 mmol) are added to a stirred
solution of 12a (60 mg, 0.24 mmol) and hexamethyldisilazane
(48 mg, 62 µL, 0.30 mmol) in CH2Cl2 (10 mL). The resulting
solution is stirred at rt for 24 h until TLC shows complete
conversion of the starting material. The mixture is filtered
through a short pad of silica, which is washed several times
with hexane. Evaporation of the solvent and flash chroma-
tography (hexane) gives 12b (74 mg, 95%) as a colorless
syrup: Rf 0.95 (hexane/ethyl acetate 40:1); 1H NMR (400 MHz)
δ 5.85 (ddt, 1H, J ) 16.7, 10.5, 7.4), 4.87-4.82 (m, 2H), 4.71-
4.70 (m, 1H), 4.52-4.51 (m, 1H), 2.23 (d, 1H, J ) 13.5), 2.01-
1.98 (m, 2H), 1.91-1.86 (m, 2H), 1.78 (s, 3H), 1.69 (m, 1H),
1.66 (dt, 1H, J ) 12.8, 3.4), 1.59-1.49 (m, 2H), 1.51-1.46 (m,
1H), 1.24 (m, 1H), 1.06 (m,1H), 1.02 (d, 3H, J ) 6.6), 0.90 (s,
3H), 0.89 (s, 3H), 0.09 (s, 9H); 13C NMR (100 MHz) δ 144.0
(s), 133.3 (d), 116.4 (t), 113.6 (t), 85.8 (s), 54.7 (d), 47.8 (t), 43.1
(t), 41.1 (t), 38.0 (d), 35.4 (t), 33.4 (s), 30.0 (t), 27.7 (q), 24.9
(q), 22.1 (q), 2.5 (q); IR (neat) 3074, 2954, 2872, 1641, 1467,
1453, 1414, 1385, 1374, 1321, 1306, 1261, 1251, 1106, 1093,
1051, 1038, 961, 912, 888, 865, 839, 751 cm-1; MS m/ z (rel
intensity) 322 ([M+], 9), 307 (9), 267 (84), 183 (100), 177 (16),
170 (13), 155 (14), 135 (23), 121 (14), 95 (25), 73 (78), 55 (23);
HR-MS (C20H38OSi) calcd 322.2692, found 322.2701.
(t), 48.6 (t), 42.6 (t), 40.4 (d), 37.7 (t), 33.4 (s), 31.7 (t), 27.7 (q),
27.4 (q), 25.1 (q), 21.1 (q), 2.5 (q); IR (KBr) 3075, 2955, 2870,
1932, 1829, 1793, 1640, 1466, 1385, 1375, 1366, 1310, 1260,
1250, 1114, 1071, 994, 963, 912, 890, 864, 838, 752, 685 cm-1
;
MS m/ z (rel intensity) 322 (M+, 6), 307 (8), 267 (100), 191 (15),
183 (82), 177 (21), 170 (11), 155 (14), 135 (38), 121 (19), 107
(13), 95 (29), 73 (73), 55 (25); HR-MS (C20H38OSi) calcd
322.2692, found 322.2695.
(1r,3a r,9a r)-1,2,3,4,7,8,9,9a -Oct a h yd r o-1,5,8,8-t et r a -
m eth yl-3a H-cyclop en ta cycloocten -3â-ol (13). To a stirred
solution of 12b (80 mg, 0.25 mmol) in hexane (5 mL) at 55 °C
is added the molybdenum carbene 5 (6 mg, 0.0076 mmol, 3
mol %) dissolved in hexane (2 mL) via cannula. The reddish
mixture is stirred at that temperature for 2.5 h, cooled to rt,
and aerated for 15 min. The solvent is evaporated and the
residue is flashed through a pad of silica with hexane. The
solvent is removed, and the remaining oil dissolved in THF
(20 mL) and desilylated upon treatment with Bu4NF (0.5 mL,
1 M solution in THF) at 50 °C for 4.5 h. Quenching with H2O
(20 mL) followed by a standard extractive workup and flash
chromatography (hexane/ethyl acetate 20:1) affords product
13 as a colorless syrup (47 mg, 85%): Rf 0.27 (hexane/ethyl
acetate 10:1); 1H NMR (400 MHz) δ 5.44 (t, 1H, J ) 6.1), 2.36
(d, 1H, J ) 11.6), 2.13 (d, 1H, J ) 11.6), 2.07 (bs, 1H), 1.79 (s,
3H), 1.70-1.57 (m, 4H), 1.45-1.32 (m, 5H), 1.05 (d, 1H, J )
9.0), 1.03 (d, 3H, J ) 4.6), 0.87 (s, 6H); 13C NMR (100 MHz) δ
136.0, 123.8, 85.7, 54.4, 46.8, 44.7, 43.1, 39.5, 36.2, 32.2, 31.3,
27.3, 26.2, 20.7; IR (KBr) 3466, 3039, 2951, 2868, 1669, 1459,
1364, 1374, 1285, 1264, 1203, 1121, 1002, 987, 882, 856, 840,
758 cm-1; MS m/ z (rel intensity) 222 ([M+], 6), 204 (51), 189
(19), 161 (15), 153 (100), 148 (21), 135 (43), 111 (57), 97 (43),
81 (36), 69 (57), 55 (40), 41 (37). HR-MS (C15H26O) calcd
222.1984, found 222.1954.
Da ctylol (1) is prepared according to the procedure de-
scribed above using 11b (60 mg, 0.19 mmol) and carbene 5 (5
mg, 0.0065 mmol, 3 mol %). Dactylol was obtained as colorless
crystals (39 mg, 92%): Rf 0.33 (hexane/ethyl acetate 10:1); mp
1
48-50 °C (lit.2 mp 50.3-51.5 °C); H NMR (300 MHz) δ 5.53
(t, 1H, J ) 8.6), 2.40 (d, 1H, J ) 13.5), 2.18 (d, 1H, J ) 13.5),
2.02 -1.86 (m, 2H), 1.84 (s, 3H), 1.76-1.70 (m, 3H), 1.59 (dd,
1H, J ) 12.7, 6.3), 1.40 (dd, 2H, J ) 14.4, 8.1), 1.22-1.07 (m,
2H), 0.96 (d, 3H, J ) 6.6), 0.92 (s, 3H), 0.91 (s, 3H), 0.83 (d,
1H, J ) 14.1); 13C NMR (50 MHz) δ 135.3 (s), 124.9 (d), 83.2
(s), 52.8 (d), 42.8 (t), 39.9 (t), 39.1 (t), 36.4 (t), 35.1 (s), 29.2
(q), 28.7 (q), 27.7 (q), 19.0 (q); IR (neat) 3488, 3030, 2952, 2910,
2867, 1469, 1383, 1375, 1364, 1339, 1259, 1204, 1046, 1015,
859, 735 cm-1; MS m/ z (rel intensity) 222 ([M+], 18), 207 (7),
153 (100), 135 (17), 110 (40), 97 (27), 81 (17), 69 (34), 55 (23),
41 (21); HR-MS (C15H26O) calcd 222.1984, found 222.1960.
Ack n ow led gm en t. K.L. thanks the Fonds der Che-
mischen Industrie for a Kekule´ Stipendium.
Com p ou n d 11b. Prepared as described above in 93%
isolated yield as a colorless syrup: Rf 0.70 (hexane); 1H NMR
(400 MHz) δ 5.84 (ddt, 1H, J ) 16.9, 10.3, 7.4), 5.01-4.98 (m,
2H), 4.96-4.94 (m, 1H), 4.84-4.82 (m, 1H), 2.28 (d, 1H, J )
13.4), 2.09 (d, 1H, J ) 13.4), 1.95 (d, 2H, J ) 7.4), 1.89-1.80
(m, 2H), 1.78 (s, 3H), 1.74-1.61 (m, 3H), 1.26-1.22 (m, 1H),
1.13-1.02 (m, 1H), 0.99 (d, 3H, J ) 6.8), 0.98-0.95 (m, 1H),
0.85 (s, 3H), 0.84 (s, 3H), 0.08 (s, 9H); 13C NMR (100 MHz) δ
143.4 (s), 136.2 (d), 116.4 (t), 114.4 (t), 86.8 (s), 51.1 (d), 49.4
Su p p or tin g In for m a tion Ava ila ble: Copies of the 1H,
13C, and 2D NMR spectra of all new compounds; compilation
of the instrumentation used (31 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
J O961600C