Efficient synthesis of enantiopure conduritols by ring-closing metathesis

Article abstract of DOI:10.1021/jo0101297

Two short synthetic approaches to enantiopure conduritols are described starting from the chiral pool. In both cases, the cyclohexene ring is assembled via ring-closing olefin metathesis. The terminal diene precursers for the metathesis reaction are prepared either from octitols or from tartaric acids. The former route involves a new method for selective bromination of the primary positions in long-chain carbohydrate polyols. Subsequent reductive elimination with zinc then generates the diene. The latter route uses a highly diastereoselective addition of divinylzinc to tartaric dialdehydes for preparation of the dienes.

Full text of DOI:10.1021/jo0101297

4630
J . Org. Chem. 2001, 66, 4630-4634
Efficien t Syn th esis of En a n tiop u r e Con d u r itols by Rin g-Closin g
Meta th esis
Morten J ørgensen, Erik H. Iversen, Andreas L. Paulsen, and Robert Madsen*
Department of Organic Chemistry, Technical University of Denmark, DK-2800 Lyngby, Denmark
rm@kemi.dtu.dk
Received February 1, 2001
Two short synthetic approaches to enantiopure conduritols are described starting from the chiral
pool. In both cases, the cyclohexene ring is assembled via ring-closing olefin metathesis. The terminal
diene precursers for the metathesis reaction are prepared either from octitols or from tartaric acids.
The former route involves a new method for selective bromination of the primary positions in long-
chain carbohydrate polyols. Subsequent reductive elimination with zinc then generates the diene.
The latter route uses a highly diastereoselective addition of divinylzinc to tartaric dialdehydes for
preparation of the dienes.
In tr od u ction
by Schrock and Grubbs, the area of olefin metathesis has
emerged as a very effective new tool for C-C bond
formation.10 The area of carbohydrate chemistry has also
taken advantage of olefin metathesis mainly by the use
of catalyst 1.11 However, carbohydrate derivatives are
generally not very reactive toward metathesis due to the
electron-withdrawing oxygen substituents. This problem
has very recently been circumvented by the use of newly
developed N-heterocyclic carbene catalysts 212 and 3,13
which are more reactive than 1 for metathesis of
carbohydrates.9a,b In particular, complex 3 appears to be
the catalyst of choice as it is more reactive than 2 and
very recently has become commercially available.14
Cyclohex-5-ene-1,2,3,4-tetrols are an important class
of cyclitols known as the conduritols. A total of 10
different stereoisomers exist of which six are diastereo-
mers (conduritols A-F).1 They display diverse biological
activities, e.g., as insulin modulators2 and glycosidase
inhibitors.3 In addition, many synthetic analogues of the
conduritols have attracted significant attention.4 Due to
the carbocyclic structure, the conduritols are also valu-
able starting materials for synthesis of natural products.5
Only conduritol A6 and (+)-conduritol F7 have been
found in nature and only in small amounts. All 10
stereoisomers have been prepared in nonracemic form
by chemical synthesis.1,8 However, many of the previous
synthetic approaches require a significant number of
steps, particularly for manipulation of protecting groups,
e.g., benzyl groups. Recently, the method of ring-closing
olefin metathesis (RCM) was introduced as a powerful
technique for formation of the cyclohexene ring in the
conduritols.9 Since the pionering catalyst developments
Herein, we report convenient routes to conduritols from
higher carbon sugars and tartaric acids by the use of ring-
closing metathesis catalyst 3. We also demonstate a new
reaction for selective bromination of the terminal posi-
tions in carbohydrate polyols.
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10.1021/jo0101297 CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/01/2001

Synthesis of Enantiopure Conduritols
J . Org. Chem., Vol. 66, No. 13, 2001 4631
Sch em e 1
Sch em e 2a
Resu lts a n d Discu ssion
Retr osyn th esis. Inspection of the carbon skeleton in
the conduritols gives rise to the retrosynthetic analysis
outlined in Scheme 1. A major task is to find short and
efficient methods for preparation of the diene precursers
for the RCM reaction. These eight-carbon dienes can
originate either from the corresponding octitols by elimi-
nation or from four-carbon dialdehydes by addition of two
vinyl groups. The octitols can be prepared from higher
carbon sugars while the dialdehydes are available from
tartaric acids. The higher carbon sugar route is a new
approach to conduritols while the tartaric acid route has
previously been explored for preparation of a (+)-con-
duritol E derivative.9d
Dien es fr om High er Ca r bon Su ga r s. The one-pot
Wittig/dihydroxylation transformation gives easy access
to several higher carbon sugars from simple aldoses.15
Subjecting the reaction to D-glucose gives D-erythro-L-
galacto-octonolactone, which on reduction with sodium
borohydride gives octitol 4 (Scheme 2). The same elonga-
tion on D-galactose gives D-threo-L-galacto-octonolactone,
which on reduction provides octitol 5.
It was decided to introduce bromine at the primary
positions that would then set the stage for a reductive
elimination in the presence of zinc. However, regioselec-
tive bromination of the terminal positions in these
unprotected polyols is not trivial. Simple reaction with
triphenylphosphine and carbontetrabromide16 caused
cyclization to derivatives of tetrahydrofuran. Acetyl
bromide, which has been developed for bromination of
smaller polyols,17 was not suitable either due to compet-
ing cyclization and epimerization reactions. Tosylation
was not sufficiently regioselective to be synthetically
useful. To circumvent the problem of an intramolecular
cyclization when the primary position is activated, it was
decided to tritylate these positions. This was easily
achieved in a hot pyridine solution with 2.5 equiv of trityl
chloride. The same reaction mixture could be used for a
subsequent benzoylation of the remaining six secondary
hydroxy groups after cooling to room temperature. By
pouring the reaction mixture into ethanol-ice, protected
octitols 6 and 7 crystallized in high yields.
a
Key: (a) TrCl, pyridine, 90 °C; then BzCl, rt; (b) HBr in AcOH,
rt; (c) Zn, AcOH/EtOAc/H2O (6:3:1), ultrasound.
with this highly acidic mixture affected bromination of
the primary positions to give 8 and 9. Under these
conditions, the trityl groups are cleaved immediately and
yellow trityl bromide precipitates. Presumably, 1,2-
benzoxonium ions are then formed which undergo ring-
opening at the least sterically hindered position. Minor
byproducts were also isolated containing bromine at a
secondary position or acetate at the primary position. The
best results were obtained when the reaction was allowed
to proceed for 7 days apparently because some primary
acetate is slowly converted into bromide. This bromina-
tion procedure constitutes a new method for the selective
introduction of bromine in longer chain alditols. It has
the additional advantage that the products are set up
directly for a reductive elimination with zinc to give
dienes 10 and 11 in high yields.
To further explore the versatility of this bromination
reaction, heptitols 1219 and 13 were also prepared
(Scheme 2). Tritylation and benzoylation of these pro-
ceeded as described above to give crystalline 14 and 15,
which on bromination with hydrogen bromide in acetic
acid gave dibromides 16 and 17. Treatment of these with
zinc and deprotection give dienes that we have previously
cyclized to trihydroxycyclopentenes by RCM.9a On the
other hand, the corresponding acetylated R,ω-ditrityl
heptitols and octitols did not undergo clean bromination
at the primary positions with hydrogen bromide in acetic
acid. Fairly complex mixtures of epimers were obtained
in these cases, presumably due to migration of the 1,2-
acetoxonium ions.20
Dien es fr om Ta r ta r ic Acid s. Preparation of condu-
ritols from tartaric acids is a particularly short and
efficient strategy. In a recent synthesis of a (+)-conduritol
E derivative from protected L-tartaric acid, the first step
involved reduction with Dibal-H to the corresponding
A saturated solution of hydrogen bromide in acetic acid
is a frequently applied brominating agent in carbohy-
drate chemistry.18 Indeed, direct treatment of 6 and 7
(15) J ørgensen, M.; Iversen, E. H.; Madsen, R. J . Org. Chem. 2001,
66, 4625.
(16) Castro, B. R. Org. React. 1983, 29, 1.
(17) Crombez-Robert, C.; Benazza, M.; Fre´chou, C.; Demailly, G.
Carbohydr. Res. 1997, 303, 359.
(19) Wolfrom, M. L.; Thompson, A. Methods Carbohydr. Chem. 1963,
2, 65.
(20) For other examples of acetoxonium ion migrations in carbohy-
drate chemistry, see: Paulsen, H. Methods Carbohydr. Chem. 1972,
6, 142.
(18) Lundt, I. Top. Curr. Chem. 1997, 187, 118.

4632 J . Org. Chem., Vol. 66, No. 13, 2001
J ørgensen et al.
Ta ble 1. F or m a tion of Con d u r itols by RCMa
Sch em e 3
dialdehyde followed by vinyl Grignard addition.9d The
major diastereomer 19 was obtained in this case in a ratio
of 3:1 (19/other two diastereomers).9d However, we ob-
served that by using divinylzinc this ratio could be
improved to greater than 10:1 (Scheme 3). This is in
accordance with addition reactions in similar systems
where divinylzinc gives significantly better diastereo-
selectivity than vinyl Grignard.9a,21 Furthermore, vinyl
Grignard can act as a reducing agent, and more reduction
of the intermediate dialdehyde to alcohol was observed
with this reagent than when using divinylzinc. It is
important for the chemoselectivity in the Dibal-H reduc-
tion that this reaction is carried out at -78 °C. This could
only be performed with Dibal-H in toluene as severe
precipitation occurred when Dibal-H in hexane was used.
The reactions could also be performed on meso tartaric
acid 20 where the diastereoselectivity with divinylzinc
was about 3:1. In this case, the vinyl Grignard reagent
was rather unselective and gave a quite complex mixture.
The structures of 19 and 21 were verified after the RCM
reaction. The formation of these as the major products
with divinylzinc is in accordance with the predictions
from the Felkin-Anh model.22
Rin g-Closin g Olefin Metath esis. The obtained dienes
were then converted into the conduritols by RCM. Initial
experiments revealed that benzoylated diene 10 or the
corresponding unprotected tetrol gave low yields and
significant decomposition in the metathesis reaction.
Therefore, the benzoyl groups were replaced with acetyl
groups to give diene 22, which was well suited for
metathesis in accordance with our previous experience.9a
As anticipated,9a,10 complex 3 was the best catalyst for
the ring-closure giving a near-quantitative yield of the
natural (+)-conduritol F tetraacetate 23 (Table 1, entries
1 and 2). A similar result was obtained for (+)-conduritol
E tetraacetate 25 (entry 3). Diene tetraacetate 24 is
available either from D-galactose (Scheme 2) or from
L-tartaric acid (Scheme 3), the latter route being the
shortest. Meso diene 21 could be cyclized directly to
conduritol D acetonide 26 without changing the protect-
ing group (entry 4) presumably aided by the Thorpe-
Ingold effect from the isopropylidene group.23
a
b
All reactions were carried out in CH2Cl2 at 40 °C. 18% of 22
was recovered.
sugars or tartaric acids. These syntheses complement our
previously developed preparation of conduritol B and C
using a zinc-mediated tandem reaction.9a In all cases, the
cyclohexene ring has been prepared by RCM with cata-
lyst 3. Hereby, we have now prepared five of the six
diastereomeric conduritols in few steps from the chiral
pool. These strategies should also be promising for
synthesis of analogues and other natural products.
Exp er im en ta l Section
For general procedures, see the preceding paper in this
issue.15
D-er yth r o-L-ga la cto-Octitol (4). D-erythro-L-galacto-Octo-
nolactone15 (5.36 g, 22.5 mmol) was dissolved in H2O (100 mL),
and acidic ion-exchange resin (12 mL, Amberlite IR-120-H+)
was added. The mixture was cooled in ice and stirred while
NaBH4 (1.15 g, 30.4 mmol) was added at such a rate that the
pH was maintained around 5. An additional amount of NaBH4
(1.40 g, 37.0 mmol) was then added, increasing the pH to about
9. After the mixture was stirred at 0 °C for 1 h, more ion-
exchange resin (125 mL, Amberlite IR-120-H+) was added
decreasing the pH to 3. The mixture was stirred overnight.
The resin was removed by filtration and washed with H2O.
The filtrate was concentrated and co-concentrated with MeOH
(4 × 100 mL) to give a white solid. Recrystallization from
EtOH/H2O yielded 4.01 g (74%) of 4. Mp: 148-150 °C (lit.24
mp 153-154 °C). 13C NMR (D2O, 75 MHz): δ 74.4, 72.7, 72.0,
70.8, 70.4, 68.9, 64.0, 63.3.
D-th r eo-L-ga la cto-Octitol (5). D-threo-L-galacto-Octono-
lactone15 (25.0 g) was reduced with NaBH4 as described above
to give after recrystallization from H2O 20.8 g (82%) of 5. Mp:
216-218 °C (lit.25 mp 230 °C). 13C NMR (D2O, 75 MHz): δ
70.5 (2C), 69.6 (2C), 68.5 (2C), 63.5 (2C).
D-glycer o-D-ga la cto-H ep t it ol (13). D-glycero-D-galacto-
Heptonolactone15 (17.8 g) was reduced with NaBH4 as de-
scribed above to give after recrystallization from MeOH/H2O
15.8 g (87%) of 13. Mp: 178-182 °C (lit.26 mp 187-188 °C).
13C NMR (D2O, 75 MHz): δ 73.1, 72.4, 71.4, 71.3, 70.4, 65.4
(2C).
In conclusion, we have developed a convenient synthe-
sis of conduritols D-F starting from either higher carbon
Gen er a l P r oced u r e for Tr it yla t ion /Ben zoyla t ion
(Sch em e 2). Trityl chloride (7.0 g, 25.0 mmol) was added in
(21) Boschetti, A.; Nicotra, F.; Panza, L.; Russo, G. J . Org. Chem.
1988, 53, 4181.
(22) Che´rest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968,
2199. Anh, N. T. Top. Curr. Chem. 1980, 88, 145.
(23) Forbes, M. D. E.; Patton, J . T.; Myers, T. L.; Maynard, H. D.;
Smith, D. W., J r.; Schulz, G. R.; Wagener, K. B. J . Am. Chem. Soc.
1992, 114, 10978.
(24) Hann, R. M.; Merrill, A. T.; Hudson, C. S. J . Am. Chem. Soc.
1944, 66, 1912.
(25) Maclay, W. D.; Hann, R. M.; Hudson, C. S. J . Am. Chem. Soc.
1938, 60, 1035.
(26) Richtmyer, N. K. Methods Carbohydr. Chem. 1963, 2, 90.

Synthesis of Enantiopure Conduritols
J . Org. Chem., Vol. 66, No. 13, 2001 4633
portions to a slurry of the polyol (10.0 mmol) in redistilled
pyridine (35 mL) at 90 °C over 2-5 h. The solution was then
cooled to 0 °C before benzoyl chloride (10.5 mL, 90.0 mmol)
was added. After the solution was stirred for 48 h at room
temperature, the crude product was poured into a mixture of
EtOH (60 mL) and ice (30 mL) and stirred for 2 h to provide
a solid that was filtered off.
131.2, 129.7-128.2 (20C), 120.9, 120.8, 73.6, 73.4, 71.4, 71.2.
Anal. Calcd for C36H30O8: C, 73.21; H, 5.12. Found: C, 73.36;
H, 5.47.
3,4,5,6-Tet r a -O-b en zoyl-1,2,7,8-t et r a d eoxy-L-m a n n o-
octa -1,7-d ien itol (11). Prepared from dibromide 9 as de-
scribed above for 10. Rf ) 0.50 (hexane/EtOAc ) 3:1). [R]D:
1
-80.0 (c 2, CHCl3). H NMR (CDCl3, 300 MHz): δ 8.08 (dd, J
) 7.4, 0.6 Hz, 4H), 7.96 (dd, J ) 7.3, 1.5 Hz, 4H), 7.55 (dt, J
) 7.6, 1.5 Hz, 2H), 7.50 (dd, J ) 8.0, 0.6 Hz, 2H), 7.41 (dd, J
) 7.6, 7.4 Hz, 4H), 7.32 (dd, J ) 8.0, 7.3 Hz, 4H), 6.06 (ddd, J
) 17.3, 10.4, 6.9 Hz, 2H), 5.96 (d, J ) 5.2 Hz, 2H), 5.87 (m,
2H), 5.55 (d, J ) 17.4 Hz, 2H), 5.38 (d, J ) 10.4 Hz, 2H). 13C
NMR (CDCl3, 75 MHz): δ 165.2 (2C), 165.0 (2C), 133.1 (2C),
132.9 (2C), 131.3 (2C), 129.7 (4C), 129.6 (6C), 129.5 (2C), 128.3-
(4C), 128.2 (4C), 121.0 (2C), 73.5 (2C), 70.9 (2C). Anal. Calcd
for C36H30O8: C, 73.21; H, 5.12. Found: C, 72.86; H, 5.00.
2,3,4,5,6-P en ta -O-ben zoyl-1,7-d i-O-tr ip h en ylm eth yl-D-
glycer o-D-gu lo-h ep titol (14). Rf ) 0.42 (hexane/EtOAc ) 7:2).
2,3,4,5,6,7-Hexa -O-ben zoyl-1,8-d i-O-tr ip h en ylm eth yl-D-
er yth r o-L-ga la cto-octitol (6). Rf ) 0.47 (hexane/EtOAc )
2:1). Mp: 98-100 °C (CHCl3/EtOH). [R]D: +3.5 (c 2, CHCl3).
1H NMR (CDCl3, 300 MHz): δ 8.25-6.85 (m, 60H), 6.16 (dd,
J ) 8.2, 4.1 Hz, 1H), 6.09 (dd, J ) 6.6, 3.9 Hz, 1H), 6.05 (dd,
J ) 6.4, 3.0 Hz, 1H), 5.99 (t, J ) 4.0 Hz, 1H), 5.81 (ddd, J )
8.8, 5.8, 3.2 Hz, 1H), 5.58 (ddd, J ) 7.7, 4.3, 2.7 Hz, 1H), 3.40-
3.05 (m, 4H). 13C NMR (CDCl3, 75 MHz): δ 165.1, 165.0 (2C),
164.8 (2C), 164.6, 143.2 (6C), 132.7-132.5 (6C), 129.8-126.6
(60C), 86.8, 86.5, 71.6, 70.9, 70.8, 70.0 (2C), 69.2, 62.1, 61.9.
Anal. Calcd for C88H70O14: C, 78.21; H, 5.22. Found: C, 77.99;
H, 5.24.
1
Mp: 111-112 °C (CHCl3/EtOH). H NMR (CDCl3, 250 MHz):
δ 7.87-6.96 (m, 55H), 6.33 (dd, J ) 7.6, 4.4 Hz, 2H), 5.96 (t,
J ) 4.4 Hz, 1H), 5.56 (ddd, J ) 7.6, 4.7, 3.4 Hz, 2H), 3.45 (dd,
J ) 10.5, 4.7 Hz, 2H), 3.29 (dd, J ) 10.5, 3.4 Hz, 2H). 13C NMR
(CDCl3, 75 MHz): δ 165.0, 164.9 (2C), 164.8 (2C), 143.2 (6C),
132.8-126.6 (60C), 86.6 (2C), 71.4 (2C), 69.6 (2C), 69.5, 61.9
(2C). Anal. Calcd for C80H64O12: C, 78.93; H, 5.30. Found: C,
78.79; H, 5.45.
2,3,4,5,6-P en ta -O-ben zoyl-1,7-d i-O-tr ip h en ylm eth yl-D-
glycer o-D-ga la cto-h ep titol (15). Rf ) 0.62 (hexane/EtOAc )
2:1). Mp: 173-176 °C (CHCl3/EtOH). [R]D: +21.4 (c 1.7,
CHCl3). 1H NMR (CDCl3, 500 MHz): δ 7.91-7.82 (m, 10H),
7.55-7.42 (m, 5H), 7.35-7.24 (m, 22H), 7.05-6.95 (m, 18H),
6.20 (dd, J ) 7.8, 1.8 Hz, 1H), 6.04 (dd, J ) 6.9, 1.8 Hz, 1H),
5.94 (dd, J ) 6.9, 2.9 Hz, 1H), 5.79 (m, 1H), 5.53 (m, 1H), 3.40
(dd, J ) 10.8, 3.2 Hz, 1H), 3.36 (dd, J ) 9.8, 6.9 Hz, 1H), 3.24
(dd, J ) 9.9, 5.5 Hz, 1H), 3.21 (dd, J ) 10.9, 5.3 Hz, 1H). 13C
NMR (CDCl3, 75 MHz): δ 165.1 (2C), 165.0, 164.7, 164.5, 143.3
(6C), 132.9, 132.8 (2C), 132.7, 132.6, 129.8-126.6 (55C), 86.8,
86.6, 71.1, 70.7, 70.1, 69.2, 69.1, 62.0 (2C). Anal. Calcd for
2,3,4,5,6,7-Hexa -O-ben zoyl-1,8-d i-O-tr ip h en ylm eth yl-D-
th r eo-L-ga la cto-octitol (7). Rf ) 0.51 (hexane/EtOAc ) 2:1).
Mp: 118-120 °C (CHCl3/EtOH). [R]D: -12.5 (c 2.0, CHCl3).
1H NMR (CDCl3, 300 MHz): δ 7.89 (d, J ) 7.6 Hz, 4H), 7.82
(d, J ) 7.5 Hz, 4H), 7.68 (d, J ) 7.4 Hz, 4H), 7.49-7.35 (m,
6H), 7.30-7.17 (m, 24H), 7.03-6.98 (m, 18H), 6.04 (d, J ) 5.2
Hz, 2H), 5.98 (dd, J ) 5.2, 2.6 Hz, 2H), 5.78 (ddd, J ) 6.4, 6.1,
2.6 Hz, 2H), 3.27 (dd, J ) 9.4, 6.4 Hz, 2H), 3.12 (dd, J ) 9.4,
6.1 Hz, 2H). 13C NMR (CDCl3, 75 MHz): δ 165.0 (4C), 164.7
(2C), 143.2 (6C), 132.8 (2C), 132.6 (2C), 132.5 (2C), 129.9-
126.6 (60C), 86.7 (2C), 70.8 (2C), 70.7 (2C), 70.4 (2C), 61.6 (2C).
Anal. Calcd for C88H70O14: C, 78.21; H, 5.22. Found: C, 77.98;
H, 5.22.
Gen er a l P r oced u r e for Br om in a tion (Sch em e 2). The
ditrityl compound (1.5 mmol) was treated with 32% HBr in
AcOH (20 mL) in a closed flask for 7 days. The mixture was
diluted with CH2Cl2 (50 mL) and washed with H2O (200 mL)
and 5% aqueous NaHCO3 (3 × 200 mL). The organic phase
was dried and concentrated and the residue purified by flash
chromatography.
C
80H64O12: C, 78.93; H, 5.30. Found: C, 78.67; H, 5.42.
2,3,4,5,6-P en t a -O-b en zoyl-1,7-d ib r om o-1,7-d id eoxy-D-
2,3,4,5,6,7-Hexa -O-ben zoyl-1,8-d ibr om o-1,8-d id eoxy-D-
er yth r o-L-ga la cto-octitol (8). Rf ) 0.46 (hexane/EtOAc )
glycer o-D-gu lo-h ep titol (16). Rf ) 0.64 (hexane/EtOAc ) 2:1).
Mp: 158-160 °C (Et2O). 1H NMR (CDCl3, 300 MHz): δ 7.96-
7.82 (m, 10H), 7.56-7.38 (m, 5H), 7.37-7.22 (m, 10H), 6.16-
6.04 (m, 3H), 5.68 (dd, J ) 10.9, 5.1 Hz, 2H), 3.79 (dd, J )
11.4, 4.4 Hz, 2H), 3.63 (dd, J ) 11.4, 5.3 Hz, 2H). 13C NMR
(CDCl3, 75 MHz): δ 165.1, 164.9 (4C), 133.2 (5C), 129.8 (4C),
129.7, 128.3-128.0 (20C), 70.9 (4C), 68.5, 30.0 (2C). Anal.
Calcd for C42H34O10Br2: C, 58.76; H, 3.99. Found: C, 58.80;
H, 3.86.
1
2:1). [R]D: +5.58 (c 1, CHCl3). H NMR (CDCl3, 250 MHz): δ
8.21-7.10 (m, 30H), 6.20-6.00 (m, 4H), 5.68 (dt, J ) 6.4, 2.3
Hz, 1H), 5.59 (ddd, J ) 6.9, 4.4, 4.1 Hz, 1H), 3.71 (dd, J )
11.5, 4.1 Hz, 1H), 3.65-3.38 (m, 3H). 13C NMR (CDCl3, 75
MHz): δ 165.1, 165.0 (4C), 164.8, 133.5, 133.2 (2C), 133.0 (3C),
130.1-127.8 (30C), 71.0, 70.8 (2C), 70.6, 69.0, 68.7, 30.1, 29.0.
Anal. Calcd for C50H40O12Br2: C, 60.50; H, 4.06; Br, 16.10.
Found: C, 60.95; H, 4.20; Br, 15.94.
2,3,4,5,6-P en t a -O-b en zoyl-1,7-d ib r om o-1,7-d id eoxy-D-
glycer o-D-ga la cto-h ep titol (17). Rf ) 0.60 (hexane/EtOAc )
2,3,4,5,6,7-Hexa -O-ben zoyl-1,8-d ibr om o-1,8-d id eoxy-D-
th r eo-L-ga la cto-octitol (9). Rf ) 0.53 (hexane/EtOAc ) 3:1).
Mp: 152-155 °C (hexane/EtOAc). [R]D: +12.7 (c 1.5, CHCl3).
1H NMR (CDCl3, 300 MHz): δ 7.96-7.83 (m, 12H), 7.54-7.41
(m, 6H), 7.36-7.22 (m, 12H), 6.07 (d, J ) 6.6 Hz, 2H), 6.03
(dd, J ) 6.6, 2.6 Hz, 2H), 5.67 (ddd, J ) 6.6, 6.2, 2.6 Hz, 2H),
3.56 (dd, J ) 10.8, 6.2 Hz, 2H), 3.50 (dd, J ) 10.8, 6.6 Hz,
2H). 13C NMR (CDCl3, 75 MHz): δ 165.1 (2C), 164.9 (4C), 133.2
(4C), 133.0 (2C), 129.8-128.1 (30C), 71.2 (2C), 70.7 (2C), 69.5
(2C), 28.9 (2C). Anal. Calcd for C50H40O12Br2: C, 60.50; H, 4.06;
Br, 16.10. Found: C, 60.18; H, 4.13; Br, 16.05.
3,4,5,6-Tetr a -O-ben zoyl-1,2,7,8-tetr a d eoxy-D-gu lo-octa -
1,7-d ien itol (10). Dibromide 8 (0.33 g, 0.33 mmol) was
dissolved in a mixture of EtOAc (3 mL), H2O (1 mL), and AcOH
(6 mL). Activated zinc9a (1.00 g, 15.3 mmol) was added and
the mixture sonicated for 3 h. The precipitate was filtered off
and washed with H2O and CH2Cl2. The filtrate was diluted
with CH2Cl2 (60 mL) and washed with H2O (25 mL) and 5%
aqueous NaHCO3 (50 mL). The organic layer was dried and
concentrated and the residue purified by flash chromatography
(hexane/EtOAc ) 3:1) to provide 0.20 g (99%) of 10 as a foam.
Rf ) 0.35. [R]D: -27.2 (c 1, CHCl3). 1H NMR (CDCl3, 300
MHz): δ 8.15-7.88 (m, 8H), 7.66-7.27 (m, 12H), 6.09-5.81
(m, 6H), 5.53-5.27 (m, 4H). 13C NMR (CDCl3, 75 MHz): δ
165.3, 165.2, 165.1, 164.9, 133.3, 133.1, 132.9 (2C), 131.5,
1
2:1). Mp: 138-142 °C (EtOH). [R]D: +3.3 (c 1.7, CHCl3). H
NMR (CDCl3, 500 MHz): δ 8.08-7.79 (m, 10H), 7.59-7.19 (m,
15H), 6.08-6.02 (m, 3H), 5.71 (dt, J ) 6.3, 2.1 Hz, 1H), 5.64
(dt, J ) 6.1, 4.9 Hz, 1H), 3.79 (dd, J ) 11.4, 4.5 Hz, 1H), 3.62-
3.53 (m, 3H). 13C NMR (CDCl3, 125 MHz): δ 165.1-164.9 (5C),
133.5, 133.4 (2C), 133.2, 133.1, 130.0-128.1 (25C), 71.1, 70.8,
70.2, 70.0, 68.6, 29.8, 28.9. Anal. Calcd for C42H34O10Br2: C,
58.76; H, 3.99; Br, 18.61. Found: C, 59.02; H, 3.83; Br, 18.39.
4,5-O-Isop r op ylid en e-1,2,7,8-tetr a d eoxy-L-m a n n o-octa -
1,7-d ien itol (19). To a solution of L-tartrate 18 (2.5 g, 11.5
mmol) in toluene (20 mL) at -78 °C was added a 1.2 M solution
of Dibal-H in toluene (22 mL, 26.4 mmol) over 5 min. The
mixture was stirred at -78 °C for 2 h followed by dropwise
addition of a 0.5 M solution of divinylzinc9a in THF (92 mL,
46 mmol) over 20 min. The stirring was continued for 1 h at
-78 °C, and the solution was then allowed to warm to room
temperature. The mixture was carefully quenched with H2O
(10 mL) followed by addition of a saturated aqueous solution
of Rochelle salt (100 mL) and EtOAc (100 mL). After the
mixture was stirred for 30 min, the phases were separated
and the aqueous phase was extracted with EtOAc (3 × 100
mL). The combined organic phases were dried and concen-
trated. The residue was purified by flash chromatography
(hexane/EtOAc ) 2:1) to afford 2.03 g (83%) of 19 as a syrup.

4634 J . Org. Chem., Vol. 66, No. 13, 2001
J ørgensen et al.
1
Rf ) 0.50. [R]D: -44.9 (c 2.1, CHCl3). H and 13C NMR are in
3,4,5,6-Tetr a -O-a cetyl-1,2,7,8-tetr a d eoxy-L-m a n n o-octa -
1,7-d ien itol (24). A solution of diene 19 (2.03 g, 11.4 mmol)
in 80% aqueous AcOH (50 mL) was stirred at 50 °C for 22 h.
The solvent was removed in vacuo to leave a solid. This was
treated with Ac2O (7.2 mL, 76.3 mmol), Et3N (10.7 mL, 76.8
mmol), and a crystal of DMAP in CH2Cl2 (75 mL) at room
temperature for 20 h. The mixture was washed with H2O (50
mL) and the aqueous layer extracted with CH2Cl2 (20 mL).
The combined organic phases were dried and concentrated,
and the residue was purified by flash chromatography (hexane/
EtOAc ) 2:1) to give 2.73 g (83%) of 24 as a syrup. Rf ) 0.63.
accordance with literature data.9b
4,5-O-Isop r op ylid en e-1,2,7,8-tetr a d eoxy-a llo-octa -1,7-
d ien itol (21). Prepared from meso-tartrate 20 as described
above for 19. Rf ) 0.50 (hexane/EtOAc ) 2:1). 1H NMR (CDCl3,
300 MHz): δ 6.04 (ddd, J ) 17.4, 10.6, 5.7 Hz, 2H), 5.39 (dt,
J ) 17.4, 1.6 Hz, 2H), 5.28 (dt, J ) 10.6, 1.4 Hz, 2H), 4.36
(ddd, J ) 7.1, 5.7, 1.5 Hz, 2H), 4.03 (dd, J ) 7.2, 1.5 Hz, 2H),
1.41 (s, 3H), 1.32 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ 137.8
(2C), 117.0 (2C), 109.1, 80.4 (2C), 70.7 (2C), 28.1, 25.7. Anal.
Calcd for C11H18O4: C, 61.66; H, 8.47. Found: C, 61.07; H,
8.67.
1
[R]D: -27.0 (c 1, CHCl3). H NMR (CDCl3, 300 MHz): δ 5.71
3,4,5,6-Tet r a -O-a cet yl-1,2,7,8-t et r a d eoxy-D-gu lo-oct a -
1,7-d ien itol (22). Diene 10 (1.00 g, 1.69 mmol) was dissolved
in a mixture of MeOH (10 mL) and CH2Cl2 (1 mL). Sodium
(25 mg) was added and the solution stirred at room temper-
ature for 20 h. The solvent was removed in vacuo and the
residue purified by flash chromatography (Et2O f acetone)
to give 261 mg of a syrup. To a solution of this in CH2Cl2 (25
mL) were added Ac2O (0.85 mL, 9.0 mmol), Et3N (1.6 mL, 11.5
mmol), and a crystal of DMAP. The mixture was stirred at
room temperature for 20 h and then concentrated and purified
by flash chromatography (hexane/EtOAc ) 2:1) to afford 438
mg (76%) of 22 as a syrup. Rf ) 0.55. [R]D: -16.0 (c 2.2, CHCl3).
1H NMR (CD3OD, 300 MHz): δ 5.80 (ddd, J ) 16.5, 10.6, 5.1
Hz, 1H), 5.78 (ddd, J ) 15.4, 10.6, 5.1 Hz, 1H), 5.42-5.20 (m,
8H), 2.06 (s, 3H), 2.06, (s, 3H), 2.04 (s, 3H), 2.00 (s, 3H). 13C
NMR (CD3OD, 75 MHz): δ 171.4, 171.3 (2C), 171.2, 133.1,
132.9, 121.4, 120.3, 74.0, 73.7, 71.9 (2C), 20.9, 20.8, 20.7, 20.6.
Anal. Calcd for C16H22O8: C, 56.14; H, 6.48. Found: C, 56.19;
H, 6.47.
(ddd, J ) 17.0, 10.1, 7.5 Hz, 2H), 5.38 (dd, J ) 17.0, 0.2 Hz,
2H), 5.34 (dd, J ) 10.1, 0.2 Hz, 2H), 5.32-5.20 (m, 4H), 2.06
(s, 6H), 2.04 (s, 6H). 13C NMR (CDCl3, 75 MHz): δ 169.7 (2C),
169.4 (2C), 132.3 (2C), 120.7 (2C), 71.6 (2C), 69.5 (2C), 20.9
(2C), 20.7 (2C). Anal. Calcd for C16H22O8: C, 56.14; H, 6.48.
Found: C, 56.20; H, 6.43.
(+)-Con d u r itol E Tetr a a ceta te (25). Rf ) 0.26 (hexane/
EtOAc ) 2:1). [R]D: +199.3 (c 1, MeOH). 1H and 13C NMR are
in accordance with literature data.28
Con d u r itol D Aceton id e (26). Rf ) 0.49 (EtOAc). Mp:
123-124 °C (hexane/EtOAc). 1H NMR (CDCl3, 300 MHz): δ
5.76 (s, 2H), 4.53 (m, 2H), 4.04 (bs, 2H), 1.41 (s, 3H), 1.38 (s,
3H). 13C NMR (CDCl3, 75 MHz): δ 131.4 (2C), 75.4 (2C), 66.3
(2C), 26.0, 25.0. Anal. Calcd for C9H14O4: C, 58.05; H, 7.58.
Found: C, 58.09; H, 7.71. Removal of the isopropylidene group
with 80% aqueous AcOH gave conduritol D as a syrup with
1H and 13C NMR in accordance with literature data.29
Gen er a l P r oced u r e for Rin g-Closin g Olefin Meta th e-
sis (Ta ble 1). The catalyst was added to a deoxygenated
solution of the diene (100 mg) in CH2Cl2 (5 mL) under a
nitrogen atmosphere. The solution was stirred at 40 °C until
TLC revealed full conversion (about 4 h). The mixture was
concentrated and the residue purified by flash chromatogra-
phy.
Ack n ow led gm en t. We thank the Danish Natural
Science Research Council for financial support.
J O0101297
(27) Le Drian, C.; Vionnet, J .-P.; Vogel, P. Helv. Chim. Acta 1990,
73, 161.
(28) Carpintero, M.; Ferna´ndez-Mayoralas, A.; J aramillo, C. J . Org.
Chem. 1997, 62, 1916.
(29) Donohoe, T. J .; Moore, P. R.; Beddoes, R. L. J . Chem. Soc.,
Perkin Trans. 1 1997, 43.
(+)-Con d u r itol F Tetr a a ceta te (23). Rf ) 0.27 (hexane/
EtOAc ) 2:1). [R]D: +47.1 (c 1, CHCl3) (lit.27 [R]25 +45.6 (c
D
1.12, CHCl3)). 1H and 13C NMR are in accordance with
literature data.27