A new access to the 6,8-dioxabicyclo[3.2.1]octane ring system using a three-component reaction: Enantioselective synthesis of (+)-iso- exo -brevicomin

Article abstract of DOI:10.1055/s-0029-1218561

The combination of a catalytic hetero-Diels-Alder-allylboration sequence and a ruthenium-catalyzed isomerization of an allylic alcohol moiety as key steps open a new route for the asymmetric synthesis of 6,8-dioxabicyclo[3.2.1] octane subunits. The application of this strategy to the synthesis of (+)-iso-exo-brevicomin is also reported. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0029-1218561

LETTER
207
A New Access to the 6,8-Dioxabicyclo[3.2.1]octane Ring System Using a Three-
Component Reaction: Enantioselective Synthesis of (+)-iso-exo-Brevicomin
6
,8-Dioxabicyclo[3
s
.2.1]octa
m
ne RingSystem ae Bouziane,a Thomas Régnier,a François Carreaux,*a Bertrand Carboni,a Christian Bruneau,a Jean-Luc Renaudb
a
Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex, France
E-mail: francois.carreaux@univ-rennes1.fr
b
Laboratoire Chimie Moléculaire et Thioorganique, UMR CNRS 6507, 6 Bd du Maréchal Juin, 14050 Caen, France
Received 9 October 2009
R1
O
Abstract: The combination of a catalytic hetero-Diels–Alder–
allylboration sequence and a ruthenium-catalyzed isomerization of
an allylic alcohol moiety as key steps open a new route for the
asymmetric synthesis of 6,8-dioxabicyclo[3.2.1]octane subunits.
The application of this strategy to the synthesis of (+)-iso-exo-brevi-
comin is also reported.
O
R2
R3
R1 = Me, R2 = H, R3 = Et
R2 = Et, R3 = H
R1 = Et, R2 = H, R3 = Me
R2 = Me, R4 = Me
OSO3Na
O
O
Key words: natural product, asymmetric catalysis, cycloaddition,
boron, redox isomerization
O
O
insect pheromones
NaO3SO
O
O
O
Development of new approaches for the construction of
6,8-dioxabicyclo[3.2.1]octane ring system is an attractive
goal due to the number of natural products that contain
this unit, as insect pheromones1 or more complex natural
products.2 Most of them exhibited promising bioactive
profiles, such as cyclodidemniserinol trisulfate, isolated
from the Palauan Ascidian Didemnum guttatum, which is
an inhibitor of HIV-1 integrase (Figure 1).3 These proper-
ties have drawn widespread attention and Ley and co-
workers recently used this 6,8-dioxabicyclo[3.2.1]octane
ring system as scaffold for the discovery of new biologi-
cally active compounds.4
NH
NHSO3Na
O
cyclodidemniserinol trisulfate
OH
O
H
NaO3SO
O
15
O
NH2
EtO2C
didemniserinolipid B
Figure
1
Natural products containing the 6,8-dioxabi-
cyclo[3.2.1]octane ring system
Among recent strategies reported in the literature for the
construction of this fused bicyclic acetal may be men-
tioned the elegant ketalization–ring-closing metathesis
sequence5 and the cycloisomerization of alkynediols with
various metals.6 However, the synthesis of dihydroxy-
ketones followed by an intramolecular acetalization re-
mains the most widely used process for the preparation of
6,8-dioxabicyclo[3.2.1]octane skeleton.7
On the basis of these precedents, we envisioned that a-
hydroxyalkyl dihydropyran derivatives 3 could be good
precursors in an alternative strategy for the asymmetric
construction of 6,8-dioxabicyclo[3.2.1]octane ring sys-
tem. This approach can generate molecular diversity due
to the multicomponent methodology, but also because of
the presence of a double bond that can be easily further
functionalized. To illustrate the versatility of this ap-
proach, an efficient synthesis of (+)-iso-exo-brevicomin is
also presented (Scheme 1).
Recently, we and Hall’s group have simultaneously de-
scribed an efficient three-component cycloaddition–
allylboration sequence using Jacobsen’s chiral Cr(III) cat-
alyst 2,8 to give a-hydroxyalkyl dihydropyrans 3.9 This
sequence begins by an inverse electron-demand hetero-
[4+2] cycloaddition that affords a cyclic allylboronate,
which is then able to react with an aldehyde to give the
six-membered adducts with two contiguous asymmetric
centers. The efficiency of this methodology in terms of
stereoselectivity and yields has been validated by the syn-
thesis of various natural products.10
The a-hydroxyalkyl dihydropyran derivatives 3a–d were
prepared using our previously described tandem reaction
with a high enantio- and diastereoselectivity.9c Formation
of the 6,8-dioxabicyclo[3.2.1]octane ring system from 3a
under aqueous acidic conditions led to the desired product
in the presence of substantial quantity of starting material
(6 M HCl–THF, 4a: 50%). Transformation of acetals 3
into 4 were found to be cleaner and more efficient using
boron trifluoride etherate as Lewis acid (Scheme 2). For
example, reaction of 3d with 1.1 equivalents of BF3·OEt2
in CH2Cl2 for 10 minutes at 0 °C provided 4d in 95% yield
after purification.11
SYNLETT 2010, No. 2, pp 0207–0210
x
x.
x
x.
2
0
1
0
Advanced online publication: 10.12.2009
DOI: 10.1055/s-0029-1218561; Art ID: G34409ST
© Georg Thieme Verlag Stuttgart · New York

208
A. Bouziane et al.
LETTER
O
OH
R2
R3
a
c
O
O
H
H
O
H
R1
O
H
R1
H
H
H
O
O
O
OH
O
OEt
R
R
R
O
5c
4
7d
OBn
R1
OH
Ph
R = H
Ph
Ph
12, R1 = Me
3
R = OTBDPS
b
d
O
O
H
OH
OH
H
N
O
HO
Cr
O
H
H
Cl
O
O
(+)-iso-exo-brevicomin
B(OR4)2
H
R
O
O
(1S,2R)-2
R
1
6c
8d
+
+
R CHO
Ph
Ph
OEt
O
R = H
R = OTBDPS
1
Scheme 3 Reagents and conditions: a) H2 (1 atm), 10% Pd(C),
Et2O, r.t., 2 h, 98%; b) cat. OsO4 (0.3 mol%), NMO (1.5 equiv), ace-
tone–H2O, r.t., 12 h, 70%; c) MCPBA (3 equiv), CH2Cl2, 0 °C to r.t.,
Scheme 1 Retrosynthetic analysis
With these structurally diverse bicyclic acetals in hand, 93%; d) LiAlH4 (3 equiv), THF, 0 °C to r.t., 87%.
our next aim was to show that the double bond present in
these units is a point of chemical diversification. Hydro-
ple pest in the timber regions of west coast of North Amer-
genation of 4c using palladium on charcoal in Et2O led to
the formation of the expected product 5c (Scheme 3). On
the other hand, the double bond of 4c was subjected to the
usual dihydroxylation conditions using a catalytic amount
of osmium tetroxide and N-methylmorpholine N-oxide as
a co-oxidant, to afford the desired diol 6c as a single dias-
tereomer. In light of this result, we envisaged the installa-
tion of the C2 axial alcohol, present on 6,8-
dioxabicyclo[3.2.1]octane nucleus of numerous natural
products, using an epoxidation–LAH reduction protocol.
The olefin of bicyclic acetal 4d underwent a stereoselec-
tive epoxidation with MCPBA at room temperature in
CH2Cl2 to afford 7d in 93% yield as a unique diastereo-
mer. It is interesting to note that the epoxide 7d can be also
obtained from 3d with a 60% yield, using a 2:1 mixture of
MCPBA and BF3·OEt2 reagents in a ‘one-pot’ process.
Reductive trans-diaxial opening of epoxide 7d was ac-
complished by treatment of LiAlH4 at 0 °C. This proce-
dure was successfully reported in the literature on similar
structures.5b Under these nonoptimized conditions, the de-
sired axial alcohol 8d was obtained in 87% yield.12
ica.13 To the best of our knowledge, several syntheses of
iso-exo-brevicomin were reported,13,14 but only one for
the dextrogyre enantiomer14d in which stereochemical
centers are generated by carbon–carbon bond formation.
Our work began by the preparation of the new dihydro-
pyran 3e possessing the requisite configuration, using the
asymmetric catalyzed hetero-Diels–Alder–allylboration
sequence (Scheme 4). After completion of the cycloaddi-
tion step which led to the formation of cyclic allylbor-
onate, freshly distilled acetaldehyde was added. The
mixture was then warmed at 40 °C for 5 hours to furnish
intermediate 3e in 70% yield as a single diastereomer in a
>95% enantiomeric excess.15 Hydrogenation of the dou-
ble bond in presence of Pd/C, followed by benzylation of
the hydroxy group using standard conditions, afforded the
benzyl ether 10 with a 69% overall yield for the two steps.
As mentioned in the retrosynthetic analysis, our plan was
to install the ketone function via a redox isomerization of
allylic alcohol 12. It was important to note that few exam-
ples of this reaction have been employed in total synthe-
sis.16 For this purpose, hydrolysis of ethyl lactol 10 was
carried out with camphorsulfonic acid in an aqueous mix-
ture at room temperature to give the compound 11, which
was converted into a mixture of diastereomers of allylic
alcohol 12 by addition of vinylmagnesium chloride
(Scheme 5). Considerable effort was devoted to the trans-
position of allylic alcohols into saturated carbonyls medi-
In order to show also the interest of this approach for ac-
cessing molecules possessing a central 6,8-dioxabicyc-
lo[3.2.1]octane core with two appended alkyl chains, we
decided to synthesize (+)-iso-exo-brevicomin. This natu-
ral product is an aggregation pheromone produced by the
Western pine beetle Dendroctonus ponderosae, a princi-
Bpin
R
O
O
O
H
a
ref. 9c
R
+
+
RCHO
H
O
OEt
O
OEt
O
R
OH
H
1
3
4
4a, R = 4-O2NC6H4
4b, R = 4-ClC6H4
4c, R = Bn
4d, R = (2R)-PhCH(OTBDPS)
pin = pinacolate
Scheme 2 Reagents and conditions: a) BF3·OEt2 (1.1 equiv), CH2Cl2, r.t.; 4a: 92%, 4b, 93%, 4c: 87%, 4d: 95%.
Synlett 2010, No. 2, 207–210 © Thieme Stuttgart · New York

LETTER
6,8-Dioxabicyclo[3.2.1]octane Ring System
209
Bpin
OH
Bpin
O
a
a
b
+
O
OEt
10
OEt
O
b
OH
OH
OEt
c
O
OH
O
3e
1
OBn
12
OBn
OBn
OBn
11
O
OEt
O
OEt
OH
OBn
OH
+
9
10
O
H
13
c
d
Scheme 4 Reagents and conditions: a) 2 (0.01 equiv), 4 Å MS, r.t.,
2 h then MeCHO (10 equiv), 40 °C, 5 h, 70%; b) H2 (1 atm), 10% Pd/
C, Et2O, r.t., 2 h, 96%; c) NaH (1.3 equiv), BnBr (1.5 equiv), Bu4N+I–
(0.1 equiv), THF, r.t., 24 h, 72%.
O
O
(+)-iso-exo-brevicomin
OH
14
ated by transition-metal catalysts.17 Recently, we reported
that ruthenium (II) complex [RuCp*(MeCN)3][PF6] is
able to catalyze this transformation of functionalized sub-
strates under smooth conditions.18 In a first experiment for
the transformation of 12 into carbonyl compound 13, we
used reaction conditions similar to those previously de-
scribed (acetonitrile as solvent, potassium carbonate as
base, and 2 mol% of catalyst). After one hour at reflux, the
desired product was not detected by 1H NMR analysis of
the crude reaction mixture. The best conditions were
found in changing the solvent and increasing the quantity
of catalyst to 20 mol%. In toluene at room temperature,
the carbonyl compound 13 was obtained in the presence
of a,b-unsaturated carbonyl 14 in a ratio 7:3, respectively,
with 75% overall yield.19 This result clearly confirms our
postulated mechanism in which the catalyst
[RuCp*(MeCN)3][PF6] reacts firstly by a b-hydride elim-
ination, followed in a second time by the 1,4-addition of
the ruthenium monohydride species on the a,b-unsaturat-
ed ketone. We did not seek to improve the ratio in favor of
saturated carbonyl compound taking into account that the
hydrogenation reaction of the mixture, in presence of pal-
ladium on charcoal and a trace of acid, could lead to the
formation of the same product.
Scheme 5 Reagents and conditions: a) CSA (1.5 equiv), MeCN–
H2O (1:1), r.t., 18 h, 90%; b) vinylmagnesium chloride (2.2 equiv),
THF, 0 °C, 63%; c) [RuCp*(MeCN)3][PF6] (20 mol%), K2CO3 (1.2
equiv), toluene, r.t., 24 h, 75%; d) H2 (1 atm), 10% Pd/C, MeOH, 3 M
HCl, r.t., 18 h, 60%.
Acknowledgment
T. Régnier thanks the CNRS for a postdoctoral fellowship. The
CNRS and the University of Rennes 1 are gratefully acknowledged
for financial support.
References and Notes
(1) (a) Mori, K. Tetrahedron 1989, 45, 3233. (b) Francke, W.;
Schröder, W. Curr. Org. Chem. 1999, 3, 407.
(2) Some examples: (a) For palytoxin, see: Moore, R. E. Prog.
Chem. Org. Nat. Prod. 1985, 48, 81. (b) For pinnatoxin A,
see: Uemura, D.; Chou, T.; Haino, T.; Nagatsu, A.;
Fukuzawa, S.; Zheng, S. Z.; Chen, H. S. J. Am. Chem. Soc.
1995, 117, 1155. (c) For attenol A, see: Takada, N.;
Suenaga, K.; Yamada, K.; Zheng, S.-Z.; Chen, H.-S.;
Uemura, D. Chem. Lett. 1999, 1025. (d) For pteriatoxins,
see: Takada, N.; Umemura, N.; Suenaga, K.; Uemura, D.
Tetrahedron Lett. 2001, 42, 3495. (e) For trichodermatide
A, see: Sun, Y.; Tian, L.; Huang, J.; Ma, H.-Y.; Zheng, Z.;
Lv, A.-L.; Yasukawa, K.; Pei, Y.-H. Org. Lett. 2008, 10,
393.
(3) Mitchell, S. S.; Rhodes, D.; Bushman, F. D.; Faulkner, D. J.
Org. Lett. 2000, 2, 1605.
(4) (a) Milroy, L.-G.; Zintalla, G.; Prencipe, G.; Michel, P.; Ley,
S.; Gunaratnam, M.; Beltran, M.; Neidle, S. Angew. Chem.
Int. Ed. 2007, 46, 2493. (b) Milroy, L.-G.; Zintalla, G.;
Loiseau, F.; Qian, Z.; Prencipe, G.; Pepper, C.; Fegan, C.;
Ley, S. V. ChemMedChem 2008, 3, 1922.
(5) (a) Burke, S. D.; Müller, N.; Beaudry, C. M. Org. Lett. 1999,
1, 1827. (b) Marvin, C. C.; Voight, E. A.; Suh, J. M.;
Paradise, C. L.; Burke, S. D. J. Org. Chem. 2008, 73, 8452.
(6) For the formation of dioxabicyclo[3.2.1]octane structure via
catalyzed cycloisomerization, see: (a) Antoniotti, S.; Genin,
E.; Michelet, V.; Genet, J. P. J. Am. Chem. Soc. 2005, 127,
9976. (b) Liu, B.; De Brabander, J. K. Org. Lett. 2006, 8,
4907. (c) Ramana, C. V.; Patel, P.; Gonnade, R. G.
Tetrahedron Lett. 2007, 48, 4771. (d)Diéguez-Vasquez, A.;
Tzschuscke, C. C.; Lam, W. Y.; Ley, S. V. Angew. Chem.
Int. Ed. 2008, 47, 209. (e) Ramana, C. V.; Induvadana, B.
Tetrahedron Lett. 2009, 50, 271.
Indeed, the (+)-iso-exo-brevicomin was obtained in 60%
25
yield after purification on silica gel20 {[a]D +53 (c 0.3,
CHCl3); lit.14d [a]D +54 (c 0.5, CHCl3)} and with an over-
all yield of 12.3% starting from the (2E)-3-(4,4,5,5-
tetramethyl-1,3,2-dioxaborolan-2-yl)prop-2-enal (1,21
7
steps).
In conclusion, we reported in this paper a new approach
for the asymmetric synthesis of the 6,8-dioxabicyclo-
[3.2.1]octane ring system based on a three component
hetero-Diels–Alder–allylboration sequence. This strategy
was validated by the total synthesis of (+)-iso-exo-brevi-
comin including a redox isomerization of an allylic alco-
hol among the key steps. Use of this new route for the
synthesis of more complex molecules comprising a 6,8-
dioxabicyclo[3.2.1]octane skeleton is currently under way
in our laboratory.
Synlett 2010, No. 2, 207–210 © Thieme Stuttgart · New York

210
A. Bouziane et al.
LETTER
(14) (a) Mori, K.; Takikawa, H.; Nishimura, Y.; Horikiri, H.
(7) For some reviews on synthesis of bridged bicyclic ketals,
see: (a) Kotsuki, H. Synlett 1992, 97. (b) Kiyota, H. Top.
Heterocycl. Chem. 2006, 5, 65.
Liebigs Ann./Recl. 1997, 327. (b) Taniguchi, T.; Takeuchi,
M.; Ogasawara, K. Tetrahedron: Asymmetry 1998, 9, 1451.
(c) De Sousa, A. L.; Resck, I. S. J. Braz. Chem. Soc. 2002,
13, 233. (d) Prasad, K. R.; Anbarasan, P. Tetrahedron:
Asymmetry 2007, 18, 1419.
(8) Gademan, K.; Chavez, D. E.; Jacobsen, E. N. Angew. Chem.
Int. Ed. 2002, 41, 3059.
(9) (a) Deligny, M.; Carreaux, F.; Toupet, L.; Carboni, B. Adv.
Synth. Catal. 2003, 345, 1215. (b) Gao, X.; Hall, D. G.
J. Am. Chem. Soc. 2003, 125, 9308. (c) Gao, X.; Hall,
D. G.; Deligny, M.; Favre, A.; Carreaux, F.; Carboni, B.
Chem. Eur. J. 2006, 12, 3132.
(10) (a) Deligny, M.; Carreaux, F.; Carboni, B. Synlett 2005,
1462. (b) Gao, X.; Hall, D. G. J. Am. Chem. Soc. 2005, 127,
1628. (c) Carreaux, F.; Favre, A.; Carboni, B.; Rouaud, I.;
Boustie, J. Tetrahedron Lett. 2006, 47, 4545. (d) Favre, A.;
Carreaux, F.; Deligny, M.; Carboni, B. Eur. J. Org. Chem.
2008, 4900. (e) Penner, M.; Rauniyar, V.; Kaspar, L. T.;
Hall, D. G. J. Am. Chem. Soc. 2009, 131, 14216.
(15) The ee was measured by GC analysis using a chiral
stationary phase (Varian WCOT Fused Silica 25 × 0.25 mm
coated CP Chirasil-dex CB DF = 0.25).
(16) (a) Using isomerization of allylic alcohols, see: Ito, M.;
Kitahara, S.; Ikariya, T. J. Am. Chem. Soc. 2005, 127, 6172.
(b) Using isomerization of propargylic alcohols, see: Trost,
B. M.; Livingston, R. C. J. Am. Chem. Soc. 2008, 130,
11970.
(17) For reviews, see: (a) Uma, R.; Crévisy, C.; Grée, R. Chem.
Rev. 2003, 103, 27. (b) Cadierno, V.; Crochet, P.; Gimeno,
J. Synlett 2008, 1105.
(11) General Procedure and Selected Characterization Data
To a stirred solution of 3 (0.3 mmol) in CH2Cl2 (3 mL) at
0 °C was added BF3·OEt2 (0.33 mmol). After 10 min, the
resulting solution was warmed to r.t. and stirred for 90 min
(excepted in the case of 3d). The reaction mixture was
quenched with sat. aq NaHCO3 (1 mL), and the aqueous
phase was extracted with Et2O (2 × 2 mL). The combined
organic phases were washed with brine, dried over MgSO4,
filtrated, and concentrated under reduced pressure.
Compounds 4 were purified by flash chromatography on
silica gel (210–400 mesh).
(18) Bouziane, A.; Carboni, B.; Bruneau, C.; Carreaux, F.;
Renaud, J.-L. Tetrahedron 2008, 64, 11745.
(19) 1-Phenylpropan-1-one can be obtained from the
corresponding allylic alcohol in 97% yield with only 2 mol%
of [RuCp*(MeCN)3][PF6] in toluene at r.t. These new
conditions represent an improvement of the previously
described process with this catalyst.
(20) Characterization Data for Key Synthetic Intermediates
Compound 3e was obtained from 1 in 70% yield as a
colorless oil. [a]D25 +72 (c 0.59, CH2Cl2). 1H NMR (300
MHz, CDCl3): d = 1.18–1.25 (m, 6 H), 2.19–2.22 (m, 2 H),
2.72 (br s, 1 H), 3.53 (dq, 1 H, J = 7.1, 9.3 Hz), 3.69–3.72 (m,
1 H), 3.96 (dq, 1 H, J = 7.1, 9.3 Hz), 3.98–4.03 (m, 1 H), 4.72
(dd, 1 H, J = 4.8, 6.1 Hz), 5.60–5.63 (m, 1 H), 5.78–5.80 (m,
1 H). 13C NMR (75 MHz, CDCl3): d = 15.2, 18.6, 31.1, 64.4,
69.6, 78.8, 98.5, 124.9, 126.1. HRMS (EI): m/z [M –
·OCH2CH3]+ calcd for C7H11O2: 127.0759; found: 127.0755.
Compound 12 was obtained as colorless oil (mixture of
diastereomers, 63%). 1H NMR (300 MHz, CDCl3): d = 1.20
(d, 3 H, J = 5.9 Hz), 1.35–1.70 (m, 6 H), 1.81 (br s, 1 H), 2.68
(br s, 1 H), 3.40–3.43 (m, 2 H), 4.09–4.12 (m, 1 H), 4.43 (d,
1 H, J = 11.5 Hz), 4.68 (d, 1 H, J = 11.5 Hz), 5.11 (dd, 1 H,
J = 1.2, 10.4 Hz), 5.23 (d, 1 H, J = 17.2 Hz), 5.88 (ddd, 1 H,
J = 6.2, 10.4, 17.2 Hz), 7.26–7.43 (m, 5 H). 13C NMR (75
MHz, CDCl3): d = 15.5, 21.3, 21.4, 32.5, 32.6, 36.9, 71.0,
73.0, 73.1, 74.8, 74.9, 78.3, 78.4, 114.5, 114.6, 127.7, 127.8,
128.5, 138.3, 141.1, 141.2. ESI-HRMS: m/z [M + Na]+ calcd
for C16H24O3Na: 287.1623; found: 287.1623.
25
Compound 4d was obtained as a colorless oil (95%). [a]D
+33.5 (c 1.75, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d = 1.03 (s, 9 H), 1.91–1.97 (m, 1 H), 2.33–2.42 (m, 1 H),
4.26 (d, 1 H, J = 8.4 Hz), 4.44 (d, 1 H, J = 8.8 Hz), 4.47 (d,
1 H, J = 4.9 Hz), 5.50–5.52 (m, 1 H), 5.60–5.63 (m, 1 H),
5.98–6.04 (m, 1 H), 7.20–7.28 (m, 7 H), 7.35–7.49 (m, 6 H),
7.66–7.71 (m, 2 H). 13C NMR (75 MHz, CDCl3): d = 19.4,
26.9, 33.8, 72.0, 75.0, 88.7, 100.9, 124.3, 127.4, 127.5,
127.6, 127.7, 128.0, 128.9, 129.7, 129.8, 133.0, 134.0,
135.9, 136.0, 141.4. Anal. Calcd for C29H32O3Si: C, 76.28;
H, 7.06. Found: C, 76.35; H, 7.01.
25
(12) Compound 8 was obtained as colorless oil (87%). [a]D
+20.3 (c 1.30, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d = 1.03 (s, 9 H), 1.45–1.88 (m, 4 H), 2.29 (br s, 1 H), 3.60–
3.63 (m, 1 H), 4.04 (d, 1 H, J = 7.3 Hz), 4.20–4.25 (m, 1 H),
4.49 (d, 1 H, J = 7.3 Hz), 5.32 (br s, 1 H), 7.21–7.33 (m, 7
H), 7.35–7.48 (m, 6 H), 7.61–7.69 (m, 2 H). 13C NMR (75
MHz, CDCl3): d = 19.4, 23.8, 26.8, 26.9, 66.7, 76.1, 77.2,
78.9, 81.5, 102.5, 127.4, 127.6, 127.8, 128.1, 129.6, 129.8,
133.1, 133.8, 135.9, 136.0, 140.9. Anal. Calcd for
(+)-Iso-exo-brevicomin was obtained as a colorless oil
(highly volatile, 60%): [a]D25 +53 (c 0.3, CHCl3); lit.14d [a]D
+54 (c 0.5, CHCl3). 1H NMR (300 MHz, CDCl3): d = 0.96 (t,
3 H, J = 7.9 Hz), 1.18 (d, 3 H, J = 6.5 Hz), 1.43–1.95 (m, 8
H), 4.06 (br s, 1 H), 4.22 (q, 1 H, J = 6.5 Hz). 13C NMR (75
MHz, CDCl3): d = 7.3, 17.1, 21.6, 28.0, 30.6, 33.5, 75.5,
79.9, 109.5. Anal. Calcd for C9H16O2: C, 69.19; H, 10.32.
Found: C, 69.27; H, 10.41.
C29H34O4Si: C, 73.38; H, 7.22. Found: C, 73.37; H, 7.11.
(13) Francke, W.; Schröder, F.; Philipp, P.; Meyer, H.; Sinnwell,
V.; Gries, G. Bioorg. Med. Chem. 1996, 4, 363.
(21) Gravel, M.; Touré, B. B.; Hall, D. G. Org. Prep. Proced. Int.
2004, 36, 573.
Synlett 2010, No. 2, 207–210 © Thieme Stuttgart · New York

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