Desymmetrization of Cyclohexadienylsilanes. Regio-, Diastereo-, and Enantioselective Access to Sugar Mimics

Article abstract of DOI:10.1021/jo991225z

Desymmetrization of cyclohexadienylsilanes available from Birch reduction of the corresponding arylsilanes is efficiently carried out using Sharpless asymmetric dihydroxylation and aminohydroxylation. Complete diastereocontrol and reasonable enantiocontrol have been attained during the preparation of the desired diols. An excellent regiocontrol has also been observed during aminohydroxylation of dienylsilanol 6b. The resulting diol 8 and hydroxycarbamate 27 have then been elaborated further, offering a straightforward access to various types of cyclitols, aminocyclitols, carbasugars, as well as the antibiotic palitantine 4. The complete functionalization of the original arylsilanes 5 is thus typically achieved in fewer than eight steps with high stereoselectivities and excellent overall yield.

Full text of DOI:10.1021/jo991225z

J . Org. Chem. 1999, 64, 9613-9624
9613
Desym m etr iza tion of Cycloh exa d ien ylsila n es. Regio-, Dia ster eo-,
a n d En a n tioselective Access to Su ga r Mim ics
Re´my Angelaud,† Odile Babot,‡ Trevor Charvat,‡ and Yannick Landais*,†,‡
Institut de Chimie Organique, Universite´ de Lausanne, Colle`ge Prope´deutique, 1015 Lausanne-Dorigny,
Switzerland, and Laboratoire de Chimie Organique et Organome´tallique, Universite´ Bordeaux-I,
33405 Talence Cedex, France
Received J uly 30, 1999
Desymmetrization of cyclohexadienylsilanes available from Birch reduction of the corresponding
arylsilanes is efficiently carried out using Sharpless asymmetric dihydroxylation and aminohy-
droxylation. Complete diastereocontrol and reasonable enantiocontrol have been attained during
the preparation of the desired diols. An excellent regiocontrol has also been observed during
aminohydroxylation of dienylsilanol 6b. The resulting diol 8 and hydroxycarbamate 27 have then
been elaborated further, offering a straightforward access to various types of cyclitols, aminocyclitols,
carbasugars, as well as the antibiotic palitantine 4. The complete functionalization of the original
arylsilanes 5 is thus typically achieved in fewer than eight steps with high stereoselectivities and
excellent overall yield.
Sch em e 1
In tr od u ction
Cyclitols and structurally related compounds have
recently received a high degree of attention due to their
wide range of biological activities.1 Their ability to mimic
the parent saccharides with respect to polarity, structure,
and conformation as well as their inertness toward
glycosidase-induced hydrolysis make them potential can-
didates as inhibitors of glycosidases, oligosaccharide-
processing enzymes.2 Small carbohydrate mimics can also
bind to protein and consequently inhibit the recognition
between cell surface carbohydrates and protein receptors,
a crucial step in viral and bacterial infection processes.3
These sugar mimics have recently been used as powerful
probes for studying the biological function of oligosac-
charides present on the cell membrane and have a
considerable potential as anticancer, antidiabetic, and
anti-HIV agents. This has made the discovery and the
total synthesis of such inhibitors a matter of considerable
interest for synthetic organic chemists.4 Among the
various synthetic strategies that have been reported, the
partial oxidation of arenes into substituted cyclohexa-
dienes is of particular interest since the six-membered
ring thus obtained has resident functionalities ready for
further elaboration.5 We have recently devised a closely
related approach that involves the desymmetrization of
cyclohexadienylsilanes I, readily available through the
“controlled” reduction (Birch) of the corresponding aryl-
silanes.6 To our surprise, functionalization of such di-
enylsilanes had never been addressed before (Scheme 1).7
Considering the double allylsilane structure of our di-
enylsilanes I, we reasoned that they could be elaborated
in the same way as simple allylsilanes. It was first
decided to submit substrates such as I to the Sharpless
asymmetric dihydroxylation8 and aminohydroxylation9
reagents, speculating that these electrophilic reagents
(E+*) would be able to differentiate the two enantiotopic
double bonds, affording in one step homochiral synthons
with three new chiral centers. We also anticipated that
the silicon group would control the diastereofacial selec-
* To whom correspondence should be addressed. Tel: 33-5-57-96-
22-89. Fax: 33-5-56-84-46-66. E-mail: y.landais@lcoo.u-bordeaux.fr.
† Universite´ de Lausanne.
‡ Universite´ Bordeaux-I.
(1) (a) Miller, T. W.; Arison, B. H.; Albers-Schonberg, G. Biotech.
Bioeng. 1973, 15, 1075. (b) Miwa, I.; Hara, H.; Okuda, J .; Suami, T.;
Ogawa, S. Biochem. Int. 1985, 11, 809. (c) Wilkox, C. S.; Gaudino, J .
J . J . Am. Chem. Soc. 1986, 108, 3102. (d) Wharton, S. A.; Weis, W.;
Skehel, J . J .; Wiley, D. C. The influenza virus; Plenum: New York,
1989.
(2) (a) Heightman, T. D.; Vasella, A. T. Angew. Chem., Int. Ed. Engl.
1999, 38, 750. (b) Winchester, B.; Fleet, G. W. J . Glycobiology 1992, 2,
199. (c) Humphries, M. J .; Matsumoto, K.; White, S. L.; Olden, K. Proc.
Natl. Acad. Sci. U.S.A. 1986, 46, 1752. (d) Legler, G. Adv. Carbohydr.
Chem. Biochem. 1990, 48, 319. (e) Sinnott, M. L. Chem. Rev. 1990,
90, 1171. (e) Carbohydrate Mimics: Concepts and Methods, Chapleur,
Y., Ed.; Wiley-VCH: Weinheim, 1998.
(3) (a) Sears, P.; Wong, C. H. Proc. Natl. Acad. Sci. U.S.A. 1996,
93, 12086. (b) Toyokuni, T.; Singhal, A. K. Chem. Soc. Rev. 1995, 24,
231. (c) Laky, L. Annu. Rev. Biochem. 1995, 64, 113. (d) Sears, P.;
Wong, C.-H. Angew. Chem., Int. Ed. Engl. 1999, 38, 2300.
(4) (a) Dalko, P. I.; Sinay¨, P. Angew. Chem., Int. Ed. Engl. 1999,
38, 773 and references therein. (b) Vogel, P.; Fattori, D.; Gasparini,
F.; Le Drian, C. Synlett 1990, 173. (c) Balci, M. Pure Appl. Chem. 1997,
69, 97.
(5) (a) Carless, H. A. J . Tetrahedron: Asymmetry 1992, 3, 795. (b)
Hudlicky, T. Chem. Rev. 1996, 96, 1. (c) Ley, S. V. Pure Appl. Chem.
1990, 62, 2031. (d) Hudlicky, T.; Entwistle, D. A.; Pitzer, K. K.; Thorpe,
A. J . Chem. Rev. 1996, 96, 1195.
(6) (a) Angelaud, R.; Landais, Y. J . Org. Chem. 1996, 61, 5202. (b)
Angelaud, R.; Landais, Y.; Schenk, K. J . Tetrahedron Lett. 1997, 38,
1407. (c) Angelaud, R.; Landais, Y. Ibid. 1997, 38, 8841. Angelaud, R.;
Landais, Y.; Parra-Rapado, L. Ibid. 1997, 38, 8845.
(7) Bennetau, B.; Dunogue`s, J . Synlett 1993, 171.
(8) Kolb, H. C.; vanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev.
1994, 94, 2483.
10.1021/jo991225z CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/02/1999

9614 J . Org. Chem., Vol. 64, No. 26, 1999
Angelaud et al.
Ta ble 1. Bir ch Red u ction of Ar ylsila n es 5a -f (Sch em e 2)
entry
substrate
products
condnsa
ratiob
yield (%)
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5c
5c
5f
6a /6b
6b/7b
6c/5c
6d /7d
6e/7e
6c/5c
6c/5c
6f/5f
A
A
A
A
A
B
C
C
50:50
100:0
2:98
60:40
30:70
100:0
100:0
100:0
80
77
88
92
89
94
87
90
F igu r e 1.
Sch em e 2
a
Conditions: (A) Li, NH3, -78 °C, 1 h; (B) Li, NH3-THF,
t-BuOH (96 equiv), -78 °C, 2.5h; (C) Al anode-stainless steel grid
cathode, THF-HMPA 8:2, t-BuOH (4 equiv), LiCl, constant
current (0.1 A), rt. Estimated ratio from 1H NMR of the crude
b
mixture obtained after aqueous workup.
overall yield after chromatography (entry 1, Table 1). The
instability of the alkoxy group in the Birch reaction
conditions prompted us to turn our attention to the
preparation of the more stable silanol 6b starting from
the commercially available phenyldimethylchlorosilane
5b.14 We were pleased to find that the use of powdered
lithium and neat NH3 provided 6b in 77% optimized yield
(entry 2, Table 1). The quantity of disiloxane (10%) that
is always formed upon hydrolysis may be minimized by
diluting the medium prior to addition of water. The
disiloxane is then easily discarded by distillation. It is
worthy of note that the Birch reduction of 5b was carried
out without addition of a proton donor (usually an
alcohol). As a comparison, 5c having no chlorine sub-
stituent at the silicon center afforded trace amount of
the diene 6c in the same conditions (entry 3, Table 1).
We assume that an aminosilane (PhMe2SiNH2) or a
disilazane (PhMe2Si)2NH)15 is formed upon addition of
the chlorosilane onto ammonia leading to the formation
of NH4Cl,16 the reduction then taking place on the
aminosilane and not on the chlorosilane. The proton
source would then be NH4Cl or the proton of the disila-
zane. When increasing the steric bulk around silicon
(entries 4 and 5, Table 1), we observed a low conversion
of the substrate into the diene, supporting the occurrence
of an aminosilane intermediate whose formation is
slowed by steric hindrance. The absence in these cases
of disiloxane after workup is also noteworthy and may
be explained by invoking again the steric demand around
silicon.
tivity of the electrophilic processes, the electrophiles
approaching the π-system anti relative to the SiR3 group
(Figure 1).10 The silicon group, which is a key element
in our strategy, could then be converted into a hydroxy
group,11 with retention of configuration at the carbon
center, allowing the incorporation of a further hydroxy
group onto the cyclohexane ring. The remaining double
bond would then be elaborated further into the desired
sugar mimics. We report here a full account of our studies
on the desymmetrization of dienylsilanes and the versa-
tility of such precursors in the total synthesis of cyclitols,
such as conduritols 1, conduramine 2, deoxyinositols 3,
and the antibiotic palitantine 4 (Scheme 1).
Discu ssion
Bir ch Red u ction of Ar ylsila n es 5. Cyclohexadienyl-
silanes 6 have been prepared through Birch reduction of
the corresponding arylsilanes 5.12 We first extended the
method originally reported by Eaborn13 to arylsilanes
possessing a silicon group that could be oxidized into a
OH group through the Tamao-Kumada-Fleming oxida-
tion.11 The mildest oxidation conditions are generally
observed with alkoxy- and fluorosilanes. We thus started
our investigations by treating the phenyldimethylethox-
ysilane 5a with Li and NH3 in THF (Scheme 2). This led
to a 1:1 mixture of the desired dienylethoxysilane 6a
along with the corresponding dienylsilanol 6b in 80%
Reduction of trialkylsilane 5c was eventually carried
out in high yield (entry 6, Table 1) by using the bulky
t-BuOH as a proton source instead of EtOH (conditions
B, Table 1) to avoid the desilylation of the dienylsilane
6c by the lithium ethanolate generated in situ.13 Finally,
the chemical Birch reduction requires a large quantity
of ammonia but can be advantageously replaced by its
electrochemical version using a sacrificial aluminum
anode (conditions C, Table 1).17 Under these conditions,
the dienylsilanes 6c and 6f were obtained in yields close
to that obtained using the chemical version (entries 7 and
8, Table 1).
(9) (a) For a review on Sharpless asymmetric aminohydroxylation,
see: O’Brien, P. Angew. Chem., Int. Ed. Engl. 1999, 38, 326. (b) Reddy,
K. L.; Sharpless, K. B. J . Am. Chem. Soc. 1998, 120, 1207. (c) Li, G.;
Chang, H.-T.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl. 1996, 35,
451. (d) Rudolph, J .; Sennhenn, P. C.; Vlaar, C. P.; Sharpless, K. B.
Ibid. 1996, 35, 2810. (e) Li, G.; Angert, H. H.; Sharpless, K. B. Ibid.
1996, 35, 2813. (f) Goossen, L. J .; Liu, H.; Ruprecht Dress, K.;
Sharpless, K. B. Ibid. 1999, 38, 1080.
(10) Fleming, I.; Dunogue`s, J .; Smithers, R. Org. React. 1989, 37,
57.
(11) For reviews on the oxidation of the C-Si bond, see: (a) Fleming,
I. ChemtractssOrg. Chem. 1996, 9, 1. (b) J ones, G. R.; Landais, Y.
Tetrahedron 1996, 52, 7599. (c) Tamao, K. Adv. Silicon Chem. 1996,
3, 1.
(12) (a) Rabideau, P. W.; Marcinow, Z. Org. React. 1992, 42, 1. (b)
Taber, D. F.; Bhamidipati, R. S.; Yet, L. J . Org. Chem. 1995, 60, 5537.
(13) (a) Eaborn, C.; J ackson, R. A.; Pearce, R. J . Chem. Soc., Perkin
Trans. 1 1975, 470. (b) Eaborn, C.; J ackson, R. A.; Pearce, R. Ibid.
1975, 2055.
(14) Available from Aldrich (no. 11, 337-9). PhMe2SiCl is also easily
prepared on 200-300 g scale from bromobenzene and Me2SiCl2:
Andrianov, K. A.; Delazari, N. V. Doklady Akad. Nauk. SSSR 1958,
122, 393; Chem. Abstr. 1959, 53, 2133.
(15) Fleming, I. Organic Silicon Chemistry; Barton, D. H. R., Ollis,
W. D., Eds.; Comprehensive Organic Chemistry Series; Pergamon
Press: New York, 1979; Vol. 3, p 576 and references therein.
(16) Addition of the chlorosilane to ammonia was accompanied by
the appearance of a white precipitate which is likely to be NH4Cl.
(17) Bordeau, M.; Biran, C.; Pons, P.; Le´ger-Lambert, M.-P.;
Dunogue`s, J . J . Org. Chem. 1992, 57, 4705.

Desymmetrization of Cyclohexadienylsilanes
J . Org. Chem., Vol. 64, No. 26, 1999 9615
Sch em e 3
Sch em e 4
Ta ble 2. Sh a r p less Asym m etr ic Dih yd r oxyla tion (AD
Rea ction ) of Dien ylsila n es 6 (Sch em es 3 a n d 4)
Sch em e 5
entry
substrate
liganda
product
ee (%)
1
2
3
4
5
6
6b
6b
6b
6b
6c
6f
(DHQD)2Phal
(DHQD)Ind
(DHQD)2Pyr
(DHQ)2Pyr
(DHQ)2Pyr
(DHQ)2Pyr
8
8
8
8
11a
11b
44b
40b
52b
65b
71c
60c
a
AD reaction: K2OsO2(OH)4, K2CO3, K3Fe(CN)6 t-BuOH-H2O
b
1:1, MeSO2NH2, 0 °C, 12 h, ligand (see above). Estimated from
the 1H NMR of the Mosher esters and H NMR of 10 with Eu(hfc)3.
1
c Estimated from the 1H NMR of the bis-Mosher ester of 11a ,b.
Asym m etr ic Dih yd r oxyla tion of Dien ylsila n es 6.
Desymmetrizations of dienylsilane 6b using either the
Sharpless18a,b or the J acobsen-Katsuki epoxidations18c
were found to be ineffective, the former leading to
recovered starting material and the latter to aromatiza-
tion of the substrate. We were finally pleased to find that
the Sharpless asymmetric dihydroxylation (AD reaction)
of 6b led to the corresponding diol 8 in 85% crude yield
(Scheme 3).19 It is noteworthy that the reaction time had
to be carefully monitored (12 h), with longer times giving
reduced yield. This was attributed to the formation of
bis-dihydroxylation products (tetrol), which are likely to
be highly soluble in water. Modest levels of enantiose-
lectivity20 were attained that agree well with literature
precedents on the AD reaction on cyclic and Z-olefins
(entries-1-3, Table 2).8 All the commercially available
Sharpless ligands were tested, and the best results were
obtained using (DHQ)2Pyr (entry 4, Table 2). Experi-
ments regarding a possible kinetic amplification effect21
have not been carried out, and therefore, such an effect
toward enantioselectivity cannot be ruled out. The crude
diol was then protected as its acetonide 9, with simul-
taneous conversion of the SiMe2OH into an SiMe2OMe
group. The C-Si bond was then oxidized using the
Tamao-Kumada-Fleming11 conditions, affording the
expected allylic alcohol 10 with retention of configuration
at the C-1 center and 50% overall yield from commercially
available chlorosilane 5b. 1H NMR studies on 9 revealed
that the process occurred, as expected, anti relative to
the silicon group.10 The AD process was also carried out
on dienylsilanes 6c and 6f affording the desired diol 11a
and 11b in quantitative and 85% yield, respectively, with
reasonable enantioselectivities (entries 5 and 6, Table 2).
Protection of the diol 11a led to the corresponding
acetonide 12a or the more robust dibenzyl ether 12b in
85% and 52% overall yield from 6c (Scheme 4).
Tota l Syn th esis of Con d u r itol E a n d Deoxyin osi-
tols. We then explored the synthetic potentialities of the
allylic alcohol 10 in the preparation of conduritols and
analogues. It was decided to introduce the required
oxygenated groups on the second double bond using the
Sharpless asymmetric epoxidation18a,b and, thus, to take
advantage of a possible kinetic resolution to improve the
enantiomeric purity of the desired products. When the
epoxidation was performed in the presence of (-)-DET,
the syn-epoxide 13 was isolated after 12 h in 75% yield
in diastereoisomerically pure form with 90% ee22 (Scheme
5). The same reaction carried out with (+)-DET gave no
reaction even after 2 days at -20 °C, demonstrating the
high epoxidation rate difference between the “matched”
and the “mismatched” pair. This result is worthy of note
if one considers the poor kinetic resolution usually
observed in Sharpless epoxidation of cyclic allylic alco-
hols. 13 was then used as a precursor of conduritols and
deoxyinositols. Thus, acid-mediated epoxide ring opening
and subsequent acetonide removal of 13 produced regi-
oselectively23 the 2-deoxy-allo-inositol 1424 in enantio-
merically pure form in 26% overall yield from PhMe2SiCl.
In a parallel manner, treatment of 13 with an excess of
LDA25 afforded the allylic alcohol 15 through a deproto-
nation-epoxide ring-opening sequence. Removal of the
acetonide and recrystallization finally afforded conduritol
(18) (a) Pfenninger, A. Synthesis 1986, 89. (b) Gao, Y.; Hanson, R.
M.; Klunder, J . M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B. J . Am.
Chem. Soc. 1987, 109, 5765. (c) J acobsen, E. N. Asymmetric Oxida-
tion: Asymmetric Catalytic Epoxidation of Unfunctionalized Olefins
in Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York,
1993; p 159.
(22) The enantiomeric excess was determined using capillary GC
(Cyclodex-B).
(23) The 1,2-trans-diaxial epoxide ring opening obeys the Fu¨rst-
Plattner rules; see: (a) Fu¨rst, A.; Plattner, P. A. Helv. Chim. Acta 1949,
32, 275. (b) Hudlicky, T.; Rouden, J .; Luna, H.; Allen, S. J . Am. Chem.
Soc. 1994, 116, 5099.
(24) (a) McCasland, G. E.; Furuta, S.; J ohnson, L. F.; Shoolery, J .
N. J . Am. Chem. Soc. 1961, 83, 2335. (b) Angyal, S. J .; Odier, L.
Carbohydr. Res. 1982, 101, 209.
(25) (a) Marshall, J . A.; Audia, V. H. J . Org. Chem. 1987, 52, 1106.
(b) Morgans, D. J ., J r.; Sharpless, K. B.; Traynor, S. G. J . Am. Chem.
Soc. 1981, 103, 462.
(19) It is noteworthy that when the dihydroxylation was carried out
with OsO4 and NMO in THF the fully aromatized silanol 6b was
formed as the sole product.
(20) Enantiomeric excesses were estimated from 1H NMR of the
Mosher ester and 1H NMR of 10 with Eu(hfc)3.
(21) Schreiber, S. L.; Schreiber, T. S.; Smith, D. B. J . Am. Chem.
Soc. 1987, 109, 1525.

9616 J . Org. Chem., Vol. 64, No. 26, 1999
Angelaud et al.
Sch em e 6
Sch em e 7
E (16) enantiomerically pure in 22% overall yield from
5b.26 It is worthy of note that this approach allows a
complete functionalization of each carbon center of the
original arylsilane 5b in only six steps.
The versatility of the strategy was further illustrated
with a short access to (+)-1-deoxy-allo-inositol 19,24a,27
an isomer of 14, starting from the acetonide 9 (Scheme
6). Osmylation of 9 followed by the protection of the diol
afforded the pseudo-C2 symmetry acetonide 17 in high
yield as a mixture of silanol and siloxane (SiMe2X).28
Surprisingly, it appears that the dihydroxylation occurred
exclusively anti relative to the acetonide, suggesting that
the two methyl groups probably hinder the top face of
the allylsilane forcing the osmium reagent to approach
the π-system syn relative to the silicon moiety. The C-Si
bond of 17 was then oxidized as above to give the pentitol
18, which after removal of the acetonide led to the desired
deoxyinositol 19 in 40% overall yield from 9. The optical
rotation of 19 was unfortunately found not to match that
of the enantiomerically pure product27 even after several
recrystallizations. Considering the different processes
involved in our approach, we thus assume that 19
possesses at least the same optical purity as the starting
diol 9 (65% ee).
Tota l Syn th esis of (-)-P a lita n tin e. (+)-Palitantine
4 is a metabolite isolated from Penicillum palitans that
exhibits antifungal and antibiotic activities.29 Several
total syntheses of 4 have been reported to date, but only
two have been carried out in the asymmetric series with
overall yield not exceeding 10%.29 The biological activity
and the attractive structure of palitantine prompted us
to devise a synthesis based on our desymmetrization
approach. The precursor 10 was found to be particularly
attractive for our purpose since a simple oxidation of the
allylic alcohol would afford an R,â-unsaturated ketone
that could be elaborated further into palitantine through
a one-pot cupration-aldolization sequence (Scheme 7).
10 was first oxidized using Swern conditions30 to afford
the desired ketone 20 in 76% yield. 1,4-Addition of the
(E,E)-dienylcyanocuprate 21 (prepared from the corre-
sponding (E,E)-1-bromohepta-1,3-diene) onto 20 occurred
anti relative to the acetonide group31 to afford the enolate
intermediate, which was directly treated with monomeric
formaldehyde, leading to a 6:4 mixture of the cis isomer
22a and trans isomer 22b, respectively. Compounds
22a ,b were separated by chromatography and treated
separately. The acetonide group of 22b was cleanly
removed to afford unnatural (-)-palitantine 4 in 97%
yield. In a parallel manner, the primary hydroxy group
of 22a was tritylated to afford the known ether 23,32
which was isomerized using a catalytic amount of DBU
and then converted to (-)-palitantine 4 using the re-
ported deprotection procedure.32 Recrystallization of the
material obtained from both routes afforded enantio-
merically pure unnatural (-)-4 in 15% overall yield
starting from PhMe2SiCl.
Syn th esis of Am in ocyclitols: Asym m etr ic Am i-
n oh yd r oxyla tion of Cycloh exa d ien ylsila n es. Ami-
nocyclitols represent another class of potent glycosidase
inhibitors that possess a structure close to that of cyclitols
and are found as a constituent of the aglycon part of some
complex antibiotics such as streptomycins and fortimy-
cins (i.e., 2, Scheme 1).33 We first focused our attention
on their syntheses starting from the enantiopure epoxide
13, assuming that the ring opening of the epoxide with
an amine would be as regioselective as that observed with
oxygenated nucleophiles (Scheme 5).23 Unfortunately,
treatment of 13 with BnNH2 in CHCl3 or NaN3 in DME-
EtOH furnished a mixture of the corresponding aminocy-
clitols with regioselectivity not exceeding 9:1. As the
regioisomers were finally found to be inseparable, we
reasoned that much better regioselectivity could be
achieved by tethering the nucleophile onto the allylic
hydroxy group of a precursor such as 10 (Scheme 8). This
was easily accomplished by treating 10 with TsNCO,
which produced the desired carbamate.34 Carbamates are
known to be ambident nucleophiles, and the presence of
(26) Takano, S.; Yoshimitsu, T.; Ogasawara, K. J . Org. Chem. 1994,
59, 54. (b) Hudlicky, T.; Luna, H.; Olivo, H. F.; Andersen, C.; Nugent,
T.; Price, J . D. J . Chem. Soc., Perkin Trans. 1 1991, 2907.
(27) Angyal, S. J .; Odier, L. Carbohydr. Res. 1982, 100, 43.
(28) The siloxane and the silanol are probably formed through
hydrolysis of the Si-OMe function during the osmylation with OsO4-
NMO‚H2O.
(29) Isolation of (+)-palitantine: Bowden, K.; Lythgoe, B.; Marsden,
D. J . S. J . Chem. Soc. 1959, 1662. Total asymmetric syntheses of (+)-
palitantine: (a) Deruyttere, X.; Dumortier, L.; Van der Eycken, J .;
Vandewalle, M. Synlett 1992, 51. (b) Hanessian, S.; Sakito, Y.; Dhanoa,
D.; Baptistella, L. Tetrahedron 1989, 45, 6623.
(32) Ichichara, A.; Ubukata, M.; Sakamura, S. Tetrahedron 1980,
36, 1547.
(33) (a) Hooper, I. R. Aminoglycoside Antibiotics; Umezawa, U.,
Hooper, I. R., Eds.; Springer: Berlin, 1982; p, 7. (b) Rinehart, K. L.;
Suami, T. Aminocyclitol antibiotics; Symposium Series no. 125;
American Chemical Society: Washington D.C., 1980. (c) McAuliffe, J .
C.; Hindsgaul, O. Chem. Ind. 1997, 170.
(30) Mancuso, A. J .; Swern, D. Synthesis 1981, 165.
(31) Hydrolysis of the enolate directly after the cupration afforded
the addition product as a unique diastereomer having the trans
relationship between the acetonide and the dienyl chain at C-3.
(34) Hirama, M.; Iwashita, M.; Yamazaki, Y.; Ito, S. Tetrahedron
Lett. 1984, 25, 4963.

Desymmetrization of Cyclohexadienylsilanes
J . Org. Chem., Vol. 64, No. 26, 1999 9617
Ta ble 3. Sh a r p less Asym m etr ic Am in oh yd r oxyla tion
(AA Rea ction ) of Dien ylsila n es 6 (Sch em es 9 a n d 11)
Sch em e 8
entry
substrate
liganda
product
regio
ee (%)
1
2
3
4
6b
6c
6c
6c
(DHQ)2Pyr
(DHQ)2Pyr
quinuclidine
i-Pr2NEt
27
>98%
92:8
7:3
68b
31a /31b
31a /31b
31a /31b
81c,d
1:1
a
AA reaction: K2OsO2(OH)4, t-BuOCl, NaOH, EtO2CNH2
b
n-PrOH-H2O 1:1, rt, 1.5 h, ligand (see above). Estimated from
the 1H NMR of the Mosher ester of 29. c Estimated from the 1H
d
NMR of the Mosher ester of 31a . 31b: ee 12% (from Mosher ester
of 31b).
an N-tosyl group increases the nucleophilicity of the
nitrogen center. Iodocarbamation then afforded the crude
iodide, which on treatment with DBU led to the elimina-
tion product 24 as a unique diastereomer having the
expected cis relative configuration between the C1-O and
C2-N bonds. Having installed the amino and hydroxy
groups onto the cyclohexane ring, we then removed
selectively the protective groups. The tosyl function was
cleanly removed using Na-naphthalene35 leading to the
free oxazolidine, which was directly saponified (KOH) to
afford the amino alcohol, which on acidic treatment led
to the conduramine E 25 (as its hydrochloride).36 The
latter was finally isolated as its tetraacetate 26 in 48%
overall yield from 10. Unfortunately, whereas the ef-
ficiency of the sequence was rather satisfying, the optical
rotation of 26 was found not to match that of the reported
enantiomerically pure material even after recrystalliza-
tion of 24 and 26.36
Sch em e 9
Sch em e 10
Fortunately, a more satisfactory answer to the problem
of regio- and enantioselectivity described above was
provided by the recent asymmetric aminohydroxylation
(AA) process discovered by Sharpless et al.9 We reasoned
that the desymmetrization of dienylsilanes 6 using this
new reagent would be particularly attractive, offering a
more straightforward access to aminocyclitols. We as-
sumed that, analogously to the dihydroxylation process,
the aminohydroxylation reagent would approach the
π-system anti relative to the silicon group. However, this
AA process was even more challenging than the AD
process since nothing was known at that time concerning
the regioselectivity of aminohydroxylation of allylsilanes.
Preliminary attempts on dienylsilane 6b were made
using the Sharpless AA mixture with chloramine T
(NaClNTs) or benzylcarbamate (H2NCO2Bn) as nitrogen
sources. Unfortunately, using these reagents, 6b was
recovered unchanged, probably owing to the steric hin-
drance of the groups on nitrogen. We were finally pleased
to find that repeating the reaction under the same
conditions with H2NCO2Et as the nitrogen source and
(DHQ)2Pyr as a chiral ligand provided the aminohy-
droxylation product 27 in good yield and more impor-
tantly with complete regio- and diastereocontrol (to the
expected, the aminohydroxylation had taken place anti
relative to the bulky silicon group, with the amino group
located on the carbon center the closest to the silicon
group. The enantioselectivity of the process was esti-
mated to be 68% based on the 19F NMR spectrum of the
Mosher ester of 29. It is noteworthy that, owing to the
presence of carbamate rotamers, this determination was
achieved by recording the spectrum at 80 °C in toluene-
d8.37 Importantly, we then found that a single recrystal-
lization of 29 in ether-hexane finally provided the allylic
alcohol in optically pure form, thus preventing the
problems of enantiomeric purity encountered above. The
absolute configuration of 29 (1R,2S,6S), determined by
conversion of 27 into the known intermediate 30,9c
confirmed that the reaction using (DHQ)2Pyr as a chiral
ligand had occurred with the same topicity as the
dihydroxylation (Scheme 10). We also observed that the
regioselectivity of the aminohydroxylation was substrate
and ligand dependent (Table 3). AA reaction on dienyl-
silane 6c thus afforded a 92:8 mixture of the chromato-
graphically separable regioisomers 31a and 31b, respec-
tively (entry 2, Table 3, Scheme 11). The enantiomeric
1
excesses, estimated from the H NMR of the correspond-
ing Mosher esters, were found to be 81% and 12%,
respectively, indicating a striking parallel between the
enantio- and the regioselectivity. We also studied the
influence of the nitrogen ligand structure on the regi-
oselectivity of the AA reaction on 6c (entries 2-4, Table
3). It was found that the best regioselectivities were
encountered with chiral ligand (DHQ)2Pyr and that other
1
limit of detection of H NMR) (entry 1, Table 3, Scheme
9).
The oxidation of the C-Si bond with retention of
configuration gave the diol 28. The cis carbamate and
OH groups were selectively protected as the acetonide
29. The diastereofacial selectivity and the regioselectivity
of the AA reaction on dienylsilane 6b were finally secured
with the X-ray structure determination of 29.6b As
(37) 13C NMR studies in CDCl3 showed that at room temperature
29 is a 9:1 mixture of the cis- and trans-carbamate rotamers. 19F NMR
studies of the Mosher ester of 29 in toluene-d8 produced four signals
at room temperature. Upon raising the temperature to 80 °C, these
signals finally coalesced into one signal for each diastereomer. For
similar observations, see: Garner, P.; Park, J . M. J . Org. Chem. 1987,
52, 2361.
(35) Chmielewski, M.; Zegrocka, O. Carbohydr. Res. 1994, 256, 319.
(36) The optical rotation of 26: [R]25D ) + 123 (c 1, CH2Cl2) [lit. [R]25
D
) +151 (c 1.4, CH2Cl2)]: Trost, B. M.; Pulley, S. R. Tetrahedron Lett.
1995, 36, 8737.

9618 J . Org. Chem., Vol. 64, No. 26, 1999
Angelaud et al.
Sch em e 12
F igu r e 2.
Sch em e 11
carbamate function allows for further elaboration of the
cyclohexene skeleton. For instance, 31a was protected in
acidic conditions as an acetonide 32 and in basic condi-
tions as an oxazolidinone 33 through nucleophilic dis-
placement of the ethyl group of the carbamate followed
by N-benzylation (Scheme 11).
We then demonstrated that the functionalization of the
enantiopure allylic alcohol 29 offered an efficient entry
to a large variety of aminocyclitols. We first developed a
straightforward access to an advanced precursor of
fortamine,41 the aglycon moiety of the antibiotic fortimy-
cins. 29 was thus treated with m-CPBA, affording the
epoxide 34 as a unique diastereomer. The epoxide was
then treated as before with an excess of LDA to provide
the fortamine precursor 35, diastereo- and enantiomeri-
cally pure in 23% overall yield (six steps) from PhMe2-
SiCl (Scheme 12). It is worthy of note that the epoxidation
occurred with complete diastereofacial selectivity, syn
relative to the allylic hydroxy group.42 Such a directing
effect may also rationalize the stereochemical outcome
of the osmylation of 29, which provides the syn-diol 36
as a unique diastereomer (Scheme 12). The methyl
groups of the oxazolidine that point above the plane of
the olefin 29 may also force the electrophile to approach
anti, thus reinforcing the syn directing effect of the allylic
hydroxy group.
The versatility of our strategy was further illustrated
by a straightforward access to the 1,3-aminocyclitol
skeleton found in the aglycon moiety of streptomycin
antibiotics.33a The second amino group was introduced
through iodocarbamation of the allylic double bond of 29.
The carbamate intermediate easily prepared from the
precursor 29 was treated with I2 to produce the iodide
37 as a unique diastereomer (Scheme 13). As described
for the preparation of conduramine E 25, iodocarbama-
achiral amines led to a larger amount of the other
regioisomer. This may indicate that, as suggested re-
cently by Han and J anda,38 the (DHQ)2Pyr-osmium
catalytic species adopts a binding pocket conformation
that imposes the positioning of the substrate and conse-
quently the regioselectivity of the process. The regiose-
lectivity would thus be controlled by the way the olefin
binds to the catalyst. The nitrogen atoms of the RNd
OsO3 moiety and that of the quinuclidine ring would
occupy the apical positions, the binding of the olefin then
initiating the [3 + 2] cycloaddition through the axial NR
groups and one of the equatorial oxygen as illustrated
in Figure 2.38 In our case, it is reasonable to assume that
the more favorable diene binding mode would be that in
which the sterically demanding silicon group (i.e., SiMe2-
t-Bu) is located outside the pocket (the length of a C-Si
is 1.9 Å). The other regioisomer 31b would then be
formed through a nonregio- and nonenantioselective
process occurring outside the cavity (the formation of 31b
inside the pocket would imply large steric interactions
between the SiR3 group and the spacer). Similarly, the
absence of such a binding pocket in quinuclidine and
i-PrEt2N would explain the poor regioselectivity (entries
3-4, Table 3). It is interesting to notice that in this model
the polar SiMe2OH group of 6b is ideally placed in a more
hydrophilic environment outside the cavity (H2O-n-
PrOH), explaining the higher regioselectivity in this case
(entry 1, Table 3). This parallels previous observations9
that ligands such as (DHQ)2Pyr not only induce high
enantioselectivities but also largely improve the regiose-
lectivity of the AA process compared to that of the
racemic version.39,40 Finally, protection of the hydroxy-
(40) Investigations about the regioselectivity of the AA process were
also carried out in acyclic series. As illustrated below, it appears that
with terminal olefins, the bulky carbamate group prefers the less
substituted end of the olefin regardless of the steric or electronic nature
of the substituents at the allylic centre.With disubstituted Z-olefins,
the picture is not so clear-cut and is more difficult to rationalize.
(38) For a recent study about the control of the regioselectivity of
AA-process, see: Han, H.; Cho, C.-W.; J anda, K. D. Chem. Eur. J . 1999,
5, 1565 and references therein.
(39) (a) Sharpless, K. B.; Chong, A. O.; Oshima, K. J . Org. Chem.
1976, 41, 177. (b) Herranz, E.; Sharpless, K. B. Ibid. 1978, 43, 2544.
(c) Herranz, E.; Biller, S. A.; Sharpless, K. B. J . Am. Chem. Soc. 1978,
100, 3596. (d) Herranz, E.; Sharpless, K. B. J . Org. Chem. 1980, 45,
2710.
(41) Schubert, J .; Schwesinger, R.; Knothe, L.; Prinzbach, H. Liebigs
Ann. Chem. 1986, 2009.
(42) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993, 93,
1307 and references therein.

Desymmetrization of Cyclohexadienylsilanes
J . Org. Chem., Vol. 64, No. 26, 1999 9619
Sch em e 13
Sch em e 15
Sch em e 14
essentially turned our attention toward electrophilic
desymmetrization processes, but the scope of the utiliza-
tion of such dienes can certainly be explored further. As
an example, hydrosilylation was used to functionalize the
diene system. A reactive silane function (i.e., SiMe2H)
was tethered onto the allylic hydroxy group of 6b to give
silane 41 in quantitative yield (Scheme 15). Hydrosily-
lation using Speier’s catalyst45 then led to the cyclic
siloxane, which was directly submitted to the Tamao-
Kumada oxidation affording the racemic diol 4246 in 43%
overall yield from 6b. Attempts to repeat this hydrosi-
lylation in nonracemic series have failed so far, but this
short sequence demonstrates that dienylsilanols may be
very useful synthons for organic chemistry. Further
investigations aimed at developing more in depth this
chemistry are now underway in our laboratory.
tion occurred syn relative to the allylic alcohol with the
nitrogen and the iodide groups, adding anti across the
double bond. 37 was then directly treated with DBU as
above (Scheme 8) to afford in 30% overall yield (calcu-
lated from 29) the 1,3-diamino cyclitol 38 possessing two
orthogonally protected amino alcohol functions.
Finally, we considered a stereocontrolled access to
amino carbasugar through the introduction of the CH2-
OH substituent at C-6 using a tin-mediated 5-exo-trig
radical cyclization of a bromomethylsilyl ether.43 The
silylmethyl ether precursor 39 was prepared by silylation
of 29 with ClSiMe2CH2Br (Scheme 14). The radical
cyclization of 39 then led to the formation of the cyclic
siloxane as one diastereomer (cis) that was directly
oxidized to the desired amino carbasugar 40. The sugar
skeleton having four stereogenic centers was thus elabo-
rated in only seven steps and 21% overall yield from
chlorosilane 5b.
Exp er im en ta l Section
1H NMR and 13C NMR were recorded using CDCl3 as
internal reference unless otherwise indicated. The chemical
shifts (δ) and coupling constants (J ) are expressed in ppm and
Hz, respectively. Elemental analyses were performed by the
I. Beetz laboratory, W-8640 Kronach (Germany). Melting
points were not corrected. Silica gel 60 (70-230 mesh) and
(230-400 mesh ASTM) were used for flash chromatography.
CH2Cl2, NEt3, and (i-Pr)2NH were distilled from CaH2. THF
was distilled from potassium. Benzene, toluene, ether, hexane,
and HMPA were distilled from sodium. Chlorosilanes were
distilled over magnesium. Li powder (Fluka no. 62365) and
anhydrous NH3 (Fluka no. 09684) were used for the Birch
reduction.
Bir ch Red u ction of Siloxa n e (5a ). In a dry 150 mL three-
necked flask equipped with a magnetic stirrer, an inlet for
argon, and a thermometer was condensed NH3 (50 mL) at -80
°C under argon in THF (10 mL). 5a (0.25 g, 1.4 mmol) was
then added slowly. Lithium powder (0.3 g, 43 mmol) was then
introduced, and the solution turned immediately blue. This
solution was stirred at -80 °C for 1.5 h, and anhydrous NH4-
Cl was added until the blue coloration disappeared. Ether (30
mL) and water (20 mL) were then added successively, and
ammonia was evaporated at room temperature. The aqueous
layer was extracted with ether. The combined extracts were
washed with water (2×) and brine and dried over MgSO4, and
the solvents were evaporated in vacuo. The residue was then
purified by flash chromatography through Florisil (petroleum
ether/EtOAc 98:2) to afford dienylsilane 6a (0.11 g, 40%): 1H
NMR δ 5.85-5.52 (4H, m), 3.72 (2H, q, J ) 7 Hz), 2.62 (2H,
m), 2.43 (1H, m), 1.20 (3H, t, J ) 7 Hz), 0.16 (6H, s). 6b (0.09
g, 40%): 1H NMR δ 5.75-5.57 (4H, m), 2.72 (2H, m), 2.36 (1H,
Con clu sion
We have described a new and efficient route to biologi-
cally relevant cyclitols, aminocyclitols, and analogues
using the desymmetrization of readily available cyclo-
hexadienylsilanes. The silicon group is a key element of
our strategy that first controls the diastereofacial selec-
tivity of the electrophilic processes before serving as a
masked hydroxy group. Four to five chiral centers can
thus be generated in a stereocontrolled manner in a
limited number of steps (<8) from an aromatic precursor
available in multigram quantities. One limitation of our
approach remains the efficiency of the Sharpless dihy-
droxylation and aminohydroxylation processes on our
substrates. Nevertheless, the enantiomeric purity of the
final products has been in most cases raised through
crystallization. More efficient chiral ligands are, however,
required to avoid such a limitation.44 We have so far
m), 0.18 (6H, s); IR (film) 3300 cm-1
.
Gen er a l P r oced u r e for th e P r ep a r a tion of Dien ylsil-
a n ols 6 (Con d ition s A): 6b. In a dry 250 mL three-necked
flask equipped with a magnetic stirrer, an inlet for argon, and
a thermometer was condensed NH3 (80 mL) at -80 °C under
argon. The chlorosilane 5b (1 mL, 6 mmol) was then slowly
added, and a white precipitate appeared. After 5 min, lithium
powder (0.3 g, 42 mmol) was introduced, and the solution
(43) (a) Pingli, L.; Vandewalle, M. Tetrahedron 1994, 50, 7061 and
references therein. (b) Bols, M.; Skrydstrup, T. Chem. Rev., 1995, 95,
1253.
(44) Asymmetric aminohydroxylation of 6c using recently discovered
(AQN)2PYR ligand unfortunately led to recovered starting material.
(AQN)2PYR: Eecker, H.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl.
1996, 35, 448.
(45) Benkeser, R. A.; Kang, J . J . Organomet. Chem. 1980, C9.
(46) Banwell, M. G.; Lambert, J . N.; Richards, L. Aust. J . Chem.
1991, 44, 939.

9620 J . Org. Chem., Vol. 64, No. 26, 1999
Angelaud et al.
turned immediately blue. This solution was then stirred at -80
°C for 45 min, and anhydrous NH4Cl was added until the blue
coloration disappeared. Ether (30 mL) and water (20 mL) were
then added successively, and ammonia was evaporated at room
temperature. The aqueous layer was extracted with ether. The
combined extracts were washed with water (2×) and then with
a saturated NaCl solution and dried over MgSO4, and the
solvents were evaporated in vacuo. The residue was then
purified by Kugelrohr distillation (70 °C, 0.4 mbar) or by flash
chromatography through Florisil (petroleum ether/EtOAc 95:
5) to give dienylsilanol 6b as a colorless oil (0.72 g, 77%).
Spectroscopic data were identical in many respects with those
described above.
of p-TsOH was added, and the solution was stirred for 2 h at
room temperature. The solvents were then evaporated in vacuo
and a saturated Na2CO3 solution was added. The aqueous
layer was extracted with ether, then the combined extracts
were washed with brine and dried over MgSO4. Evaporation
of the solvent afforded the crude acetonide 9 (3 g) as a colorless
1
liquid. H NMR δ 5.74-5.67 (2H, m), 4.48-4.37 (2H, m), 3.46
(3H, s), 2.25 (2H, m), 2.02 (1H, m), 1.43 (3H, s), 1.35 (3H, s),
0.17 (3H, s), 0.16 (3H, s). 9 was then oxidized following the
general Tamao-Kumada procedure: To a solution of 9 (3 g,
12.4 mmol) in DMF (5 mL) were added at 0 °C KF (2.16 g,
37.2 mmol), KHCO3 (3.72 g, 37.2 mmol), and H2O2 (35%
solution in water, 21 mL, 0.248 mol). The reaction mixture
was then stirred at 60 °C overnight. The mixture was
quenched with solid Na2S2O3 and dried over MgSO4 and the
solvent was evaporated in vacuo. The resulting yellow oil was
purified by chromatography through silica gel (petroleum
ether/EtOAc 7:3) to afford 10 as a colorless oil (1.4 g, 65%,
three steps) (65% ee, measured from 1H NMR with Eu(hfc)3):
1H NMR δ 5.86-5.72 (2H, m), 4.36 (1H, ddd, J ) 7.5, 5.5, 5
Hz), 4.18 (1H, br s), 4.01 (1H, dd, J ) 7.5, 6 Hz), 2.65 (1H,
ddd, J ) 17, 5.4, 5 Hz), 2.5 (1H, br s), 2.18 (1H, dddd, J ) 17,
7.9, 5.5, 2.5 Hz), 1.47 (3H, s), 1.37 (3H, s); 13C NMR δ 130.5,
125.2, 108.2, 80.5, 71.6, 69.8, 28.4, 27.2, 24.8; IR (film) 3440,
Gen er a l P r oced u r e for th e P r ep a r a tion of Dien ylsi-
la n es 6 (Con d ition s B): 6c. In a dry 1 L three-necked flask
equipped with a magnetic stirrer, an inlet for argon, and a
thermometer was condensed NH3 (350 mL) in dry THF (80
mL) at -80 °C under argon. t-BuOH (182 mL, 1.95 mol) and
arylsilane 5c (3.9 g, 20.3 mmol) were then slowly added. After
2 min, lithium powder (2.84 g, 0.4 mol) was introduced, and
the solution immediately turned blue. This solution was then
stirred at -80 °C for 2.5 h, and anhydrous NH4Cl was added
until the blue coloration disappeared. Ether (60 mL) and water
(50 mL) were then added successively, ammonia was evapo-
rated at room temperature, and the aqueous layer was
extracted with ether. The combined extracts were washed
twice with water and then with a saturated NaCl solution and
dried over MgSO4, and the solvents were evaporated in vacuo.
The residue was then purified by filtration over Celite (petro-
leum ether), affording the diene 6c as a colorless oil (3.7 g,
1654 cm-1; MS m/z 171 (M•+ + 1, 8), 112 (100); [R]25 + 54 (c
D
0.46, CHCl3). Anal. Calcd for C9H14O3: C, 63.49; H, 8.30.
Found: C, 63.39; H, 8.45.
Sh a r p less Dih yd r oxyla tion of Dien ylsila n e 6f (11b).
Following the general procedure described above, dienylsilane
6f gave after Sharpless dihydroxylation and purification by
chromatography through silica gel (petroleum ether/EtOAc 95:
5) the diol 11b as a colorless oil (85%) (60% ee measured from
the 1H NMR of the bis-Mosher’s ester of the corresponding
diol): 1H NMR δ 5.51-5.39 (2H, m), 3.89-3.87 (1H, m), 3.77-
3.70 (1H, m), 2.42 (2H, br s), 2.32-2.06 (2H, m), 1.80-1.78
(1H, m), 0.01 (9H, s); 13C NMR δ 129.0, 125.2, 120.7, 70.4, 68.4,
1
94%): H NMR δ 5.78-5.50 (4H, m), 2.68 (2H, m), 2.40 (1H,
m), 0.93 (s, 9H), 0.00 (6H, s); IR (film) 3028 cm-1. Anal. Calcd
for C12H22Si: C, 74.17; H, 11.42; Si, 14.41. Found: C, 74.20;
H, 11.48; Si, 14.32.
Gen er a l P r oced u r e for th e P r ep a r a tion of Dien ylsi-
la n es 6 (Con d ition s C): 6c. In a one-compartment cell fitted
with a sacrificial anode of aluminum and a cylindrical stainless
grid were introduced, under nitrogen, the supporting electro-
lyte LiCl (3.53 g, 83.3 mmol), t-BuOH (6 mL, 62.3 mmol),
anhydrous THF (90 mL), HMPA (15 mL), and the arylsilane
5c (4 g, 20.8 mmol). Electrolysis (constant current 0.1 A) was
then initiated and was maintained until the starting material
had disappeared (∼17 h) (monitored by GC). A solution of HCl
10% (50 mL) and pentane (30 mL) was then added to the
reaction mixture, and the organic layer was decanted. The
aqueous layer was extracted with pentane (3 × 20 mL), the
combined extracts were washed with brine and dried over
MgSO4, and the solvents were evaporated in vacuo to afford
the diene 6c as a colorless oil used in the next step without
further purifications (3.5 g, 87%). GC (5 min at 80 °C then 6
°C/min): tR (6c) 12.7 min; tR (5c) 11.6 min. Spectroscopic data
for 6c prepared according procedure C were identical with
those described above.
Dien ylsila n e (6f). Following the general procedure C, the
dienylsilane 6f was obtained from arylsilane 5f as a colorless
oil (90%). Spectroscopic data were all identical in many
respects with those described in the literature.13 GC (5 min at
80 °C then 6 °C/min): tR (6f) 5.13 min; tR (5f) 5.05 min.
Gen er a l P r oced u r e for th e Sequ en ce Sh a r p less Dih y-
d r oxyla tion -Diol P r otection -Ta m a o-Ku m a d a Oxid a -
tion of Dien ylsila n es 6 (10). In a 250 mL flask were placed
AD-mix [(K3FeCN6 (12.8 g, 39 mmol), K2CO3 (5.4 g, 39 mmol),
(DHQ)2Pyr (0.11 g, 0.13 mmol), K2OsO2‚2H2O (0.048 g, 0.13
mmol)], H2O (65 mL), and t-BuOH (65 mL). The solution was
stirred for 5 min, and methanesulfonamide (1.23 g, 13 mmol)
was added. The orange solution was cooled to 0 °C, and 6b (2
g, 13 mmol) was introduced under vigorous stirring. After 12
h at 0 °C, sodium sulfite (19.5 g) was added, and the solution
was allowed to stir at room temperature for 45 min. The
aqueous layer was extracted with EtOAc (5 ×), the combined
extracts were washed with a 10% NaOH solution, dried over
MgSO4, and the solvents were evaporated in vacuo to give the
crude diol 8, which was directly protected as an acetonide
following the general procedure: 8 was dissolved in acetone
(20 mL) and dimethoxypropane (15 mL). A catalytic amount
35.8, 30.1, -2.4; IR (film) 3382, 1643 cm-1; MS m/z 186 (M•+
,
3), 73 (100); HRMS (C9H18O2Si) calcd 186.1076, found 186.1074.
Sh a r p less Dih yd r oxyla tion of Dien ylsila n e 6c (12a ).
Following the general procedure described above, dienylsilane
6c (3 g, 15.5 mmol) gave after Sharpless dihydroxylation, diol
protection, and purification by chromatography through silica
gel (petroleum ether/EtOAc 95:5) the acetonide 12a as a
colorless oil (3.5 g, 85%, 2 steps) (71% ee measured from the
1H NMR of the bis-Mosher ester of the corresponding diol):
1H NMR δ 5.77 (1H, m), 5.63 (1H, m), 4.46 (1H, m), 2.22 (2H,
m), 2.09 (1H, m), 1.43 (3H, s), 1.34 (3H, s), 0.95 (9H, s), 0.04
(3H, s), -0.03 (3H, s); 13C NMR δ 127.3 (d, J ) 160 Hz), 120.7
(d, J ) 162 Hz), 107.4, 74.5, 72.7, 28.5, 28.4, 27.3, 26.9, 25.4,
17.4, -6.0, -6.3; IR (film) 3034 cm-1; MS m/z 269 (M•+ + 1,
1), 115 (12), 73 (100); [R]25 +132.5 (c 1.08, CHCl3).
D
(1S,2S,3S)-1,2-Dib en zyloxy-3-ter t-b u t yld im et h ylsilyl-
cycloh ex-4-en e (12b). Sharpless dihydroxylation of dienyl-
silane 6c (4.7 g, 24.2 mmol), following the general procedure,
afforded the crude diol 11a , which was then added to a solution
of NaH (2.9 g, 0.12 mol) in anhydrous THF (150 mL) at 0 °C.
Benzyl bromide (6 mL, 50 mmol) and KI (8.4 g, 50 mmol) were
then added successively. The solution was stirred overnight
at room temperature, then quenched with an aqueous satu-
rated solution of NH4Cl, extracted with ether, and dried over
MgSO4, and the solvent was evaporated. The crude product
was purified by chromatography through silica gel (petroleum
ether/ EtOAc 95:5) to give 12b as a colorless oil (5.1 g, 52%,
two steps): 1H NMR δ 7.43-7.25 (10H, m), 5.58-5.50 (2H, m),
4.78 (2H, 2 d, J ) 12.5 Hz), 4.57 (2H, s), 3.99 (1H, m), 3.59
(1H, ddd, J ) 10, 6 and 1.7 Hz), 2.55-2.32 (2H, m), 2.19 (1H,
m), 0.86 (9H, s), -0.15 (3H, s), -0.19 (3H, s); 13C NMR δ 139.3,
138.7, 128.3, 128.2, 127.5, 127.3, 126.2, 121.2, 75.4, 74.5, 71.5,
70.1, 31.7, 27.3, 26.8, 17.2, -6.2, -6.7; IR (film) 3063 cm-1
;
MS m/z 426 (M•+ + 1 + NH3, 100); [R]25D +68.2 (c 0.73, CHCl3).
Anal. Calcd for C26H36O2Si: C, 76.42; H, 8.89; Si, 6.85.
Found: C, 76.49; H, 8.86; Si, 6.88.
Ep oxid e 13. In a dry 100 mL three-necked flask equipped
with a thermometer, an inlet for argon, and a septum was
introduced under argon Ti(O-i-Pr)4 (0.7 mL, 2.3 mmol) at -30

Desymmetrization of Cyclohexadienylsilanes
J . Org. Chem., Vol. 64, No. 26, 1999 9621
°C in CH2Cl2 (10 mL). (-)-Diethyl-D-tartrate (0.48 mL, 2.8
mmol) was then added under stirring. The resulting pale
yellow solution was then stirred for 15 min, and allylic alcohol
10 (0.4 g, 2.3 mmol) in CH2Cl2 (5 mL) was added. A 3 M
t-BuOOH solution in toluene (1.6 mL, 4.8 mmol) was then
slowly introduced, and the reaction mixture was kept at -25
°C for 7 h. A saturated solution of Na2SO3 was then added,
and a vigorous stirring was maintained for 45 min at 0 °C.
The resulting orange gelatinous mixture was filtered through
Celite, thoroughly washed with CH2Cl2, and dried over MgSO4.
After evaporation of the solvent under vacuum, the crude
product was purified by chromatography through silica gel
(petroleum ether/EtOAc 7:3) to afford the epoxide 13 as a
IR (film) 3464, 1265 cm-1; MS m/z 245 (M•+ + 1, 1); [R]25D +30.6
(c 0.52, CHCl3). Anal. Calcd for C12H20O5: C, 58.98; H, 8.26.
Found: C, 58.86; H, 8.39.
(+)-1-Deoxy-a llo-in ositol (19). Bis-acetonide 18 (0.14 g,
0.57 mmol) was dissolved in a 1:1 mixture of 80% AcOH (5
mL) and THF (5 mL) and heated under reflux for 12 h.
Evaporation of the solvents under vacuum afforded the crude
pentol 19 as a white solid (0.9 g, 96%): mp 246-248 °C (EtOH)
[lit.27 mp 246-248 °C (EtOH)]; 13C NMR (D2O) δ 73.7, 71.3,
70.6, 68.7, 66.7, 33.1; [R]25D + 34 (c 0.75, H2O) [lit.27 [R]21D +62
(c 0.5, H2O)].
Cycloh ex-2-en on e (20). To a solution of (COCl)2 (0.4 mL,
4.7 mmol) in dry CH2Cl2 (10 mL) at -50 °C were added DMSO
(0.67 mL, 9.4 mmol) and, after 5 min, the allylic alcohol 10
(0.4 g, 2.35 mmol). The solution was allowed to warm to -10
°C over 20 min, and NEt3 (3.3 mL, 23.5 mmol) was added.
Water was then added at room temperature and the organic
layer extracted with CH2Cl2. The combined extracts were dried
over MgSO4 and the solvents evaporated in vacuo. The residue
was purified by chromatography through silica gel (petroleum
ether/EtOAc 6:4) to afford the ketone 20 as a white solid (0.3
1
colorless oil (0.33 g, 75%) (90% ee, GC, Cyclodex-B): H NMR
δ 4.29 (1H, ddd, J ) 11.6, 11, 6.2 Hz), 4.09 (2H, m), 3.32 (2H,
m), 2.61 (1H, ddd, J ) 15, 11, 7.6 Hz), 2.03 (1H, ddd, J ) 15,
7.5, 6.2 Hz), 1.46 (3H, s), 1.31 (3H, s); 13C NMR δ 107.5, 78.9,
70.9, 70.8, 54.5, 50.7, 27.7, 27.2, 24.3; IR (film) 3447, 1267 cm-1
;
MS m/z 187 (M•+ + 1, 5), 171 (100); [R]25D +67.3 (c 0.79, CHCl3).
Anal. Calcd for C9H14O4: C, 58.04; H, 7.58. Found: C, 58.10;
H, 7.41.
1
(-)-2-Deoxy-a llo-in ositol (14). Epoxide 13 (0.2 g, 1.07
mmol) was dissolved in a 1:1 mixture of 10% AcOH (5 mL)
and THF (5 mL) and then heated under reflux for 48 h.
Evaporation of the solvents under vacuum afforded the pentol
14 (0.14 g, 80%), optically pure after one recrystallization from
MeOH/ether (0.12 g, 70%). Spectroscopic data were all identi-
cal in many respects with those described in the literature:
mp 256-257 °C (MeOH/ether) [lit.27 mp 254-255 °C (H2O/
EtOH)]; 13C NMR (D2O) δ 72.97, 72.74, 72.54, 68.63, 67.14,
34.30; [R]25 -50 (c 0.5, H2O) [lit.27 [R]20 +50 (c 1.4, H2O)].
g, 76%): mp 79 °C (hexane/ether); H NMR δ 6.83-6.78 (1H,
m), 6.09-6.05 (1H, m), 4.60 (1H, m), 4.25 (1H, d, J ) 5.1 Hz),
2.88-2.73 (2H, m), 1.35 (3H, s), 1.30 (3H, s); 13C NMR δ 196.2,
146.3, 128.1, 109.0, 75.4, 72.8, 27.6, 27.3, 25.8; IR (CHCl3) 1690
cm-1; MS m/z 186 (M•+ + NH3, 83), 169 (M•+ + 1, 100); [R]25
D
+76.3 (c 0.94, CHCl3). Anal. Calcd for C9H12O3: C, 64.26; H,
7.20. Found: C, 64.31; H, 7.19.
Cu p r a tion -Ald oliza tion of Keton e 20 (22a ,b). In a dry
100 mL three-necked flask equipped with a thermometer, an
inlet for nitrogen, and a septum was introduced (E,E)-1-
bromohepta-1,3-diene47 (1.04 g, 5.9 mmol) in ether (40 mL)
under nitrogen. A 1.5 M solution of t-BuLi in pentane (7.9 mL,
11.9 mmol) was then added slowly at -90 °C. After 1.5 h at
-90 °C, CuCN (0.27 g, 3 mmol) was added, and the resulting
pale yellow solution was warmed to -20 °C over 40 min and
then cooled to -80 °C. Ketone 20 (0.5 g, 3 mmol) in ether (10
mL) was added, and after 5 min at -80 °C, a 0.5 M solution of
monomeric formaldehyde48 in THF (24 mL, 12 mmol) was
added. The black mixture was then quenched with a saturated
solution of NH4Cl, extracted with EtOAc, and dried over
MgSO4, and the solvents were evaporated. The crude mixture
was purified by chromatography through silica gel (petroleum
ether/EtOAc 6:4) to afford a 6:4 mixture of diastereomers
22a ,b. 22a eluted first and was obtained as a colorless oil (0.32
g, 37%): 1H NMR δ 6.08 (1H, dd, J ) 14.9, 10.3 Hz), 5.97 (1H,
dd, J ) 14.9, 10.3 Hz), 5.64 (1H, dt, J ) 14.9, 7 Hz), 5.44 (1H,
dd, J ) 14.9, 7.5 Hz), 4.58 (1H, m), 4.43 (1H, d, J ) 5.6 Hz),
3.89-3.77 (2H, m), 3.00 (1H, m), 2.77 (1H, m), 2.20-2.00 (5H,
m), 1.43-1.35 (8H, m), 0.89 (3H, t, J ) 7.3 Hz); 13C NMR δ
210.2, 134.8, 132.0, 129.6, 129.4, 109.8, 78.3, 76.0, 59.3, 55.8,
D
D
(+)-Con d u r itol E (16). In a dry 50 mL three-necked flask
equipped with a thermometer, an inlet for nitrogen, and a
septum was introduced 13 (0.2 g, 1.07 mmol) in THF (10 mL)
under nitrogen. LDA (3.7 mmol) in THF (10 mL) was then
added at -80 °C. After 5 h at 0 °C, the resulting yellow solution
was quenched with a saturated solution of NH4Cl, and the
aqueous layer was extracted with EtOAc. The combined
extracts were washed with brine and dried over MgSO4, and
the solvents were evaporated under vacuum. The crude
product was purified by chromatography through silica gel
(petroleum ether/EtOAc 6:4) to afford the diol 15 as a white
solid (0.15 g, 75%), used directly in the next step without
further purifications: mp 65 °C (hexane/ether); 1H NMR δ 5.92
(2H, d, J ) 2.3 Hz), 4.66 (1H, dd, J ) 5.8, 1.8 Hz), 4.36 (1H,
dd, J ) 6.7, 1.8 Hz), 4.29 (1H, br s), 3.96 (1H, dd, J ) 6.7, 3.7
Hz), 3.30 (1H, br s), 3.12 (1H, br s), 1.44 (3H, s), 1.38 (3H, s);
[R]25 +126 (c 0.67, CHCl3). The diol 15 (65 mg, 0.35 mmol)
D
was dissolved in a 1:1 mixture of 10% AcOH (3 mL) and THF
(3 mL) and then heated under reflux for 6 h. Evaporation of
the solvents in vacuo afforded the (+)-conduritol E (16) (50
mg, 99%) obtained optically pure after one recrystallization
(41 mg, 80%). Spectroscopic data were all identical in many
respects with those described in the literature: mp 191-192
°C (MeOH/ether) [lit.26 mp 192-194 °C (MeOH)]; 1H NMR
37.2, 34.6, 29.6, 27.1, 25.8, 22.3, 13.6; IR (film) 3485, 1726 cm-1
;
MS m/z 295 (M•+ + 1, 15). The minor diastereomer 22b (0.21
g, 24%) was obtained as a white solid: mp 93-95 °C (hexane/
1
ether); H NMR δ 6.11 (1H, dd, J ) 14.9, 10.3 Hz), 5.99 (1H,
(D2O) δ 5.82 (2H, br s), 4.25 (2H, br s), 3.88 (2H, br s); [R]25
dd, J ) 14.9 10.3 Hz), 5.67 (1H, dt, J ) 14.9 7 Hz), 5.35 (1H,
dd, J ) 14.9 9 Hz), 4.58 (1H, m), 4.32 (1H, d, J ) 5.3 Hz), 3.76
(2H, m), 2.67 (1H, m), 2.47 (1H, t, J ) 7.2 Hz), 2.36 (1H, m),
2.28 (1H, m), 2.05 (2H, q, J ) 7 Hz), 1.45-1.39 (8H, m), 0.91
(3H, t, J ) 7.3 Hz); 13C NMR δ 210.3, 135.3, 132.7, 130.2, 129.3,
109.9, 79.1, 76.3, 59.9, 54.9, 38.6, 34.7, 33.0, 27.0, 26.0, 22.3,
D
+ 327 (c 0.55, H2O) [lit.26 [R]20 +326 (c 0.22, H2O)].
D
Bis-a ceton id e (18). Allylsilane 9 (0.8 g, 2 mmol) and NMO‚
H2O (0.49 g, 2.2 mmol) were dissolved in THF (20 mL), and
then a 0.05 M solution of OsO4 in THF (2 mL, 0.1 mmol) was
introduced dropwise at room temperature. The solution was
stirred overnight, the solution was quenched with 10% Na2-
SO3, and the aqueous layer was extracted with EtOAc. The
organic layer was dried over MgSO4, and the solvents were
evaporated under vacuum to afford the crude diol, which was
protected as the acetonide 17 and submitted to the Tamao-
Kumada oxidation following the general procedure described
above. The crude mixture was purified by chromatography
through silica gel (petroleum ether/EtOAc 7:3) to give the
alcohol 18 as a colorless oil (0.3 g, 40%, three steps): 1H NMR
δ 4.53-4.47 (2H, m), 4.37 (1H, dd, J ) 7.8, 3.5 Hz), 4.30 (1H,
dd, J ) 7.6, 6 Hz), 3.83 (1H, m), 2.49 (1H, d, J ) 4.2 Hz), 2.25
(1H, ddd, J ) 14.1, 6, 4.6 Hz), 1.91 (1H, ddd, J ) 14.1, 7, 4.6
Hz), 1.48 (3H, s), 1.45 (3H, s), 1.35 (3H, s), 1.33 (3H, s); 13C
NMR δ 108.1, 75.1, 73.9, 71.5, 71.4, 29.7, 26.7, 26.1, 23.7, 23.5;
13.7; IR (CHCl3) 3583, 1719 cm-1; MS m/z 294 (M•+, 0.3); [R]25
D
+34.8 (c 0.95, CHCl3). Anal. Calcd for C17H26O4: C, 69.34; H,
8.91. Found: C, 69.48; H, 9.01.
Tr ityl Keton e (23). To a solution of the alcohol 22a (0.2 g,
0.7 mmol) in pyridine (2 mL) was added Ph3CCl (0.28 g, 1
mmol) at room temperature. The reaction mixture was stirred
for 2 days at room temperature and then quenched with a
saturated solution of NH4Cl, and the aqueous layer was
extracted with ether. The combined extracts were dried over
MgSO4, and the solvent was evaporated in vacuo. The crude
(47) Williams, D. R.; Nishitani, K.; Bennett, W.; Sit, S. Y. Tetrahe-
dron Lett. 1981, 38, 3745.
(48) Schlosser, M.; J enny, T.; Guggisberg, Y. Synlett, 1990, 704.

9622 J . Org. Chem., Vol. 64, No. 26, 1999
Angelaud et al.
mixture was purified by chromatography through silica gel
(petroleum ether/EtOAc 8:2), affording 23 (0.3 g, 80%). Spec-
troscopic data were all identical in many respects with those
described in the literature:32 1H NMR δ 7.40-7.18 (15 H, m),
5.96 (1H, dd, J ) 15.1, 10.2 Hz), 5.84 (1H, dd, J ) 15.0, 10.2
Hz), 5.57 (1H, dt, J ) 15.0, 6.9 Hz), 5.20 (1H, dd, J ) 15.1, 7.9
Hz), 4.45 (1H, m), 4.26 (1H, d, J ) 5.5 Hz), 3.38 (1H, dd, J )
9.5, 5.8 Hz), 3.28 (1H, dd, J ) 9.5, 7.4 Hz), 2.96 (1H, m), 2.82
(1H, m), 2.06-1.99 (4H, m), 1.44 (3H, s), 1.39 (2H, q, J ) 7.3
Hz), 1.34 (3H, s), 0.90 (3H, t, J ) 7.3 Hz).
residue was dissolved in EtOAc and the organic layer washed
with a saturated solution of Na2CO3 and with brine then dried
over MgSO4. The solvent was then evaporated and the residue
purified by chromatography on silica gel (petroleum ether/
EtOAc 2:8), affording pure pentaacetyl conduramine E 26 (0.23
g, 77%): mp 178-180 °C (CH2Cl2/petroleum ether) [lit.36 mp
1
182-184 °C]; H NMR δ 6.35-6.30 (1H, m), 5.80-5.71 (2H,
m), 5.54-5.53 (1H, m), 5.32-5.27 (2H, m), 5.02-5.00 (1H, m),
2.01 (3H, s), 2.00 (3H, s), 1.99 (3H, s), 1.94 (3H, s); 13C NMR
δ 170.2, 169.8, 130.2, 125.7, 67.3, 66.8, 66.0, 45.4, 22.8, 20.7,
20.6; [R]25 +123 (c 1, CH2Cl2) [lit.36 [R]25 +151 (c 1.4, CH2-
(-)-P a lita n tin e (4). The alcohol 22b (0.1 g, 0.34 mmol) was
dissolved in methanol (3 mL) and then treated with a 2 M
solution of HCl (3 mL). The mixture was stirred for 8 h at room
temperature, and the solvents were evaporated under vacuum
to afford a yellow solid that was recrystallized to give (-)-
D
D
Cl2)].
Gen er a l P r oced u r e for th e Sh a r p less Am in oh yd r oxy-
la tion of Dien ylsila n e 6 (Hyd r oxyca r ba m a te 27). In a 500
mL flask equipped with a magnetic stirrer and a thermometer,
H2NCO2Et (3.6 g, 40 mmol) was dissolved in n-propanol (50
mL). To this solution was added a freshly prepared solution
of NaOH (1.6 g, 40 mmol) in water (100 mL), followed by
t-BuOCl (5.8 g, 52.6 mmol) and a solution of the ligand
(DHQ)2Pyr (0.57 g, 0.6 mmol) in n-propanol (50 mL). The flask
was then immersed in a water bath (15 °C), and after the
mixture was stirred for a few minutes, the osmium catalyst
(K2OsO2(OH)4, 0.12 g, 0.5 mmol) was added, followed by the
diene 6b (2 g, 12.9 mmol). The green reaction mixture was
stirred for 1.5 h and then treated with sodium sulfite (5 g),
followed by water (30 mL) and EtOAc (50 mL). After being
stirred for 15 min, the organic layer was decanted and the
aqueous layer extracted with EtOAc (4 × 50 mL). The
combined extracts were dried over MgSO4 and the solvent was
evaporated in vacuo to give a residue that was purified by
chromatography through silica gel (EtOAc/petroleum ether
8:2), affording the aminohydroxylation product 27 as a color-
palitantine 4 (88 mg, 97%): mp 162-164 °C (H2O); [R]25
546
-4.33 (c 0.6, CHCl3) [lit.29a [R]25
-4.4 (c 0.8, CHCl3)].
546
Spectroscopic data were all identical in many respects with
those described in the literature.29a,b
Tosyloxa zolid in on e (24). To a solution of alcohol 10 (0.3
g, 1.8 mmol) in dry THF (5 mL) was added tosyl isocyanate
(0.28 mL, 1.8 mmol), and the mixture was stirred for 3 h at
room temperature. The solvent was evaporated in vacuo and
the resulting carbamate poured into CCl4 (10 mL). A solution
of KHCO3 (0.7 g, 7.2 mmol) in water (10 mL) was then added
followed by I2 (0.9 g, 3.6 mmol), and the reaction mixture was
stirred for 2 h at room temperature. The solution was diluted
with CH2Cl2 and then quenched with a saturated solution of
Na2S2O3. The aqueous layer was extracted with CH2Cl2, and
the solvents were evaporated in vacuo to afford the crude iodo
intermediate, which was directly used in the next step without
purification. The iodide was dissolved in CH3CN (20 mL), and
DBU (0.53 mL, 3.6 mmol) was added. The mixture was stirred
overnight at room temperature, and then the solvent was
evaporated in vacuo. The crude oil was diluted in ether and
quenched with a saturated solution of NH4Cl and the aqueous
layer extracted with ether. The combined extracts were washed
with brine and dried over MgSO4, and the solvents were
evaporated under vacuum to give a residue that was purified
by chromatography through silica gel (petroleum ether/EtOAc
7:3) affording 24 as a white solid (0.4 g, 62%, three steps): mp
134-136 °C (petroleum ether/CH2Cl2); 1H NMR δ 7.95 (2H, d,
J ) 8.4 Hz), 7.36 (2H, d, J ) 8 Hz), 5.95 (2H, m), 4.93 (2H, br
s), 4.53 (2H, br s), 2.45 (3H, s), 1.37 (3H, s), 1.36 (3H, s); 13C
NMR δ 150.3, 145.8, 135.0, 130.1, 129.8, 128.5, 121.4, 110.3,
1
less oil (2.5 g, 75%): H NMR δ 5.63-5.49 (2H, m), 5.35 (1H,
m), 4.07 (4H, m), 3.09 (1H, br s), 2.41-2.10 (2H, m), 1.23 (3H,
t, J ) 7.1 Hz), 0.19 (3H, s), 0.16 (3H, s); 13C NMR δ 155.7,
125.7, 121.3, 67.4, 61.2, 50.8, 34.2, 31.0, 14.5, -0.9, -1.7; IR
(film) 3385, 1694 cm-1; MS m/z 259 (M•+, 3), 75 (100); [R]25
+44.5 (c 0.47, CHCl3).
D
(1S,2S,3S)-2-N-E t h oxyca r b on ylcycloh ex-4-en e-1,3-d i-
ol (28). To a solution of allylsilane 27 (2.2 g, 8.5 mmol) in DMF
(35 mL) were added at 0 °C KHCO3 (2.6 g, 26 mmol) and KF
(1.5 g, 26 mmol). A 30% H2O2 solution (18.6 mL, 0.27 mol) was
then added dropwise over 30 min (exothermic!). After 18 h at
60 °C, the reaction mixture was cooled to 0 °C, and Na2S2O3
was added. After filtration, the solvent was removed in vacuo
to afford a pale yellow oil that was purified by chromatography
through silica gel (EtOAc), affording the diol 28 as a colorless
oil (1.2 g, 70%): 1H NMR δ 5.75-5.66 (2H, m), 5.55 (1H, br s),
4.27 (1H, m), 4.17-4.10 (3H, m), 3.69 (1H, m), 3.34 (1H, br s),
3.00 (1H, br s), 2.51-2.22 (2H, m), 1.25 (3H, t, J ) 7.2 Hz);
13C NMR δ 157.8, 128.3, 125.4, 68.9, 67.6, 61.4, 57.4, 32.6, 14.5;
IR (film) 3382, 1682 cm-1; MS m/z 183 (M•+ - OH, 2).
Allylic Alcoh ol (29). The diol 28 (1 g, 5 mmol) was
dissolved in dry benzene (35 mL), and then dimethoxypropane
(10 mL) and p-TsOH (50 mg, 0.26 mmol) were added. The
reaction mixture was heated under reflux for 0.5 h, cooled to
room temperature, and washed with a saturated solution of
Na2CO3. The organic layer was decanted and the aqueous layer
extracted with ether. The combined extracts were dried over
MgSO4, and the solvent was evaporated in vacuo to give a
residue that was purified by chromatography through silica
gel (EtOAc/petroleum ether 8:2), affording the allylic alcohol
71.5, 70.6, 68.8, 53.0, 27.8, 26.6, 21.7; IR (CHCl3) 1791 cm-1
;
MS m/z 383 (M•+ + 1 + NH3, 100), 366 (M•+ + 1, 27); [R]25
D
+82.3 (c 0.48, CHCl3). Anal. Calcd for C17H19NO6S: C, 55.88;
H, 5.24; N, 3.84; S, 8.76. Found: C, 55.96; H, 5.19; N, 3.89; S,
8.77.
(-)-P en ta a cetylcon d u r a m in e E (26). To a solution of
naphthalene (0.74 g, 5.8 mmol) in anhydrous DME (0.25 mL)
was added Na (0.15 g, 6.72 mmol) under argon. The green
mixture was stirred for 0.5 h at room temperature and then
cooled to -30 °C, and a solution of 24 (0.35 g, 0.96 mmol) in
DME (1 mL) was added. After 20 min at -20 °C, the reaction
mixture was quenched with H2O and the aqueous layer
extracted with EtOAc. The combined extracts were dried over
MgSO4, and the solvents were evaporated under vacuum. The
crude product was purified by chromatography through silica
gel (petroleum ether/EtOAc 1:1) to give the tosyl-free carbam-
ate (0.2 g, 98%): 1H NMR δ 6.33 (1H, br s), 5.87-5.80 (1H,
m), 5.62-5.57 (1H, m), 5.01 (1H, m), 4.60 (2H, m), 4.18 (1H,
m), 1.39 (3H, s), 1.36 (3H, s). The preceding carbamate was
then dissolved in a 1:1 mixture of THF (15 mL) and 2 M KOH
(15 mL) and then heated under reflux for 5 h. The organic
layer was decanted and the aqueous layer extracted with
EtOAc. The combined extracts were dried over MgSO4 and the
solvents evaporated in vacuo to afford a residue that was
diluted in a 1:1 mixture of 2 M HCl (5 mL) and THF (5 mL)
and heated under reflux for 2 h. The solution was evaporated
to dryness, affording the crude conduramine E-HCl 25, which
was dissolved in pyridine (10 mL) and acetic anhydride (5 mL,
52 mmol). The reaction mixture was stirred at room temper-
ature for 2 h, and the solvents were evaporated in vacuo. The
29 as a white solid (0.9 g, 75%), [R]25 -19.3 (c 0.71, CHCl3).
D
Recrystallization from ether/hexane gave the pure alcohol: mp
80 °C; [R]25 -23.3 (c 0.79, CHCl3); 1H NMR δ 5.77-5.63 (2H,
D
m), 4.91 (1H, br s), 4.34 (1H, m), 4.19 (3H, m), 3.75 (1H, t, J
) 6.3 Hz), 2.67-2.27 (2H, m), 1.58 (3H, s), 1.53 (3H, s), 1.31
(3H, t, J ) 7.1 Hz); 13C NMR δ 156.0, 129.0, 123.2, 92.8, 71.0,
69.9, 63.0, 62.0, 27.6, 27.5, 24.4, 14.4; IR (film) 3450, 1659 cm-1
;
MS m/z 242 (M•+ + 1, 2). Anal. Calcd for C12H19NO4: C, 59.72;
H, 7.94; N, 5.81. Found: C, 59.60; H, 7.81; N, 5.64.
Deter m in a tion of th e Absolu te Con figu r a tion of 27.
N-Mesyla m in ocycloh exa n -2-ol (30). The allylsilane 27 (0.65
g, 2.5 mmol) was dissolved in THF (10 mL), and a 1 M solution
of TBAF in THF (3.8 mL, 3.75 mmol) was added dropwise.

Desymmetrization of Cyclohexadienylsilanes
J . Org. Chem., Vol. 64, No. 26, 1999 9623
The reaction mixture then turned red and was stirred over-
night at room temperature. The solvent was evaporated in
vacuo, and the residue was dissolved in EtOAc (30 mL). Pd/C
(10%, 200 mg) was added to the reaction mixture, and the flask
was flushed with hydrogen (3×) and then left under vigorous
stirring overnight. After filtration of the catalyst, the solvent
was evaporated and the residue purified by chromatography
through silica gel (petroleum ether/EtOAc 4:6) to give the
desired cyclohexanol (0.35 g, 75%, two steps) directly used in
the next step. A mixture of hexamethyldisilazane (0.24 mL,
1.2 mmol) and iodine (0.15 g, 0.58 mmol) was refluxed until
the solution became colorless. Then the preceding cyclohexanol
(0.1 g, 0.53 mmol) in CH2Cl2 (3 mL) was added, and the yellow
mixture was refluxed for 3 h and then stirred at room
temperature overnight. MeOH (3 mL) was added, the solution
was stirred for 10 min, and then the solvent was evaporated
to give a yellow solid (0.13 g) that was dissolved in CH2Cl2 (5
mL). NEt3 (0.21 mL, 1.6 mmol) and MeSO2Cl (0.038 mL, 0.53
mmol) were then added, and the reaction mixture was stirred
at room temperature for 2 h. The solvent was evaporated under
vacuum and the residue purified by chromatography through
silica gel (petroleum ether/EtOAc 2:8) to give 30 (0.06 g, 60%,
two steps): [R]25 +13.4 (c 0.8, EtOH 95%) [lit.9c [R]25 +18.8
3.5 Hz), 2.17 (1H, dd, J ) 17.5, 5.8 Hz), 2.06 (1H, m), 0.77
(9H, s), -0.12 (3H, s), -0.21 (3H, s); IR (film) 1750, 1640 cm-1
.
Ep oxid e 34. The alcohol 29 (0.27 g, 1.12 mmol) was
dissolved in CH2Cl2 (10 mL), m-CPBA (0.6 g, 2.24 mmol) and
Na2HPO4 (0.43 g, 3 mmol) were added, and the resulting white
suspension was stirred for 56 h at room temperature. After
addition of a saturated solution of Na2S2O3, the aqueous layer
was extracted with CH2Cl2. The combined extracts were
washed with a saturated solution of Na2CO3 and dried over
MgSO4. The solvent was evaporated in vacuo and the crude
oil purified by chromatography through silica gel (petroleum
ether/EtOAc 4:6), affording the epoxide 34 as a colorless oil
(0.24 g, 84%): 1H NMR δ 5.29 (1H, s), 4.25-4.02 (5H, m), 3.38
(1H, m), 3.29 (1H, m), 2.65 (1H, ddd, J ) 16, 8.6 and 2 Hz),
2.07 (1H, m), 1.56 (3H, s), 1.47 (3H, s), 1.30 (3H, t, J ) 7.2
Hz); 13C NMR δ 156.2, 92.4, 71.2, 69.6, 62.3, 60.8, 56.0, 51.0,
27.6, 24.2, 14.4; IR (film) 3392, 1662 cm-1; MS m/z 258 (M•+
+
1, 13), 242 (100); [R]25 -44.6 (c 0.112, CHCl3). Anal. Calcd
D
for C12H19NO5: C, 56.00; H, 7.45; N, 5.45. Found: C, 55.98;
H, 7.42; N, 5.48.
Allylic Diol 35. To a solution of epoxide 34 (0.19 g, 0.74
mmol) in dry THF (10 mL) was added, at -80 °C, a solution
of LDA (2.6 mmol) in THF (5 mL), and the resulting mixture
was stirred overnight at 0 °C. The reaction mixture was then
quenched with a saturated solution of NH4Cl and the aqueous
layer extracted with EtOAc. The combined extracts were
washed with brine and dried over MgSO4. The solvents were
evaporated under vacuum, and the resulting crude oil was
purified by chromatography through silica gel (petroleum
ether/EtOAc 4:6), affording the diol 35 as a colorless oil (0.17
g, 89%): 13C NMR δ 156.3 (s), 130.7, (d, J ) 165 Hz), 126.4 (d,
J ) 165 Hz), 94.1 (s), 72.9 (d, J ) 146 Hz), 70.7 (d, J ) 147
Hz), 65.3 (d, J ) 146 Hz), 62.3 (t, J ) 144 Hz), 58.0 (d, J )
145 Hz), 27.5 (q, J ) 128 Hz), 24.2 (q, J ) 127 Hz), 14.2 (q, J
) 127 Hz); IR (film) 3405, 1666 cm-1; MS m/z 258 (M•+ + 1,
D
D
(c 1, EtOH 95%)]. Spectroscopic data (1H, NMR, IR) were all
identical with those described in the literature.
Sh a r p less Am in oh yd r oxyla t ion of Dien ylsila n e 6c
(31a ,b). Following the general procedure described above,
dienylsilane 6c (2.2 g, 11.3 mmol) afforded after purification
by chromatography through silica gel (EtOAc/petroleum ether
6:4) a 92:8 mixture of the regioisomers 31a and 31b (65%).
31a (2 g): 81% ee measured from the 1H NMR of the
corresponding Mosher ester; 1H NMR δ 5.57-5.47 (2H, m),
4.96 (1H, d, J ) 6 Hz), 4.15-4.09 (3H, m), 3.92 (1H, m), 3.05
(1H, br s), 2.43-2.39 (1H, m), 2.17-2.03 (1H, m), 1.25 (3H, t,
J ) 6.9 Hz), 0.94 (9H, s), 0.07 (3H, s), -0.02 (3H, s); 13C NMR
δ 157.8, 126.4, 121.3, 67.9, 61.1, 52.4, 31.7, 30.3, 26.9, 17.3,
13); [R]25 +24.5 (c 0.67, CHCl3). Anal. Calcd for C12H19NO5:
D
C, 56.00; H, 7.45; N, 5.45. Found: C, 55.98; H, 7.40; N, 5.36.
Tr iol 36. Allylic alcohol 29 (0.15 g, 0.62 mmol) was dissolved
in THF (5 mL), and then NMO‚H2O (0.09 g, 0.68 mmol) and a
0.05 M solution of OsO4 in THF (0.62 mL, 0.03 mmol) were
successively added. The reaction mixture was stirred overnight
at room temperature and was quenched with a 10% solution
of Na2SO3. The organic layer was decanted and the aqueous
layer extracted with EtOAc. The combined extracts were
washed with brine and dried over MgSO4, and the solvents
were evaporated in vacuo to give the crude triol, which was
recrystallized from MeOH/ether affording 36 as a white solid
(0.1 g, 60%): mp 152-153 °C (MeOH/ether); 1H NMR δ 4.35-
4.18 (3H, m), 4.06 (1H, m), 4.01-3.88 (2H, m), 3.72 (1H, m),
2.30-2.10 (2H, m), 1.57 (3H, s), 1.51 (3H, s), 1.35 (3H, t, J )
14.5, -6.09, -6.59; IR (film) 3439, 1698 cm-1; MS m/z 299 (M•+
,
11), 73 (100); [R]25D +108.8 (c 1.5, CHCl3); HRMS (C15H29NO3-
Si) calcd 299.1917, found 299.1912. 31b (0.2 g): 12% ee
measured from the 1H NMR of the corresponding Mosher ester;
1H NMR δ 5.55-5.47 (2H, m), 5.27 (1H, d, J ) 8.7 Hz), 4.10-
3.99 (3H, m), 3.77 (1H, m), 2.55 (1H, br s), 2.31-2.27 (1H, m),
2.05-1.98 (1H, m), 1.20 (3H, t, J ) 7 Hz), 0.91 (9H, s), 0.06
(3H, br s), -0.02 (3H, s);13C NMR δ 156.2, 126.0, 121.0, 69.8,
60.6, 48.8, 33.9, 27.2, 26.9, 17.2, 14.5, -6.3, -6.8; IR (film)
3396, 1703 cm-1; MS m/z 299 (M•+,1), 73 (100); [R]25 -1.5 (c
D
0.66, CHCl3).
Sh a r p less Am in oh yd r oxyla t ion of Dien ylsila n e 6c
(32). Hydroxy carbamate 31a (2 g, 6.7 mmol) was dissolved
in dry benzene (60 mL), and dimethoxypropane (40 mL) and
then p-TsOH (100 mg, 0.52 mmol) were added. The reaction
mixture was heated under reflux for 0.75 h, cooled to room
temperature, and washed with a saturated solution of Na2-
CO3. The organic layer was decanted and the aqueous layer
extracted with ether. The combined extracts were washed with
brine and dried over MgSO4, and the solvents were evaporated
in vacuo to give a crude oil that was purified by chromatog-
raphy through silica gel (EtOAc/petroleum ether 95:5), afford-
ing the acetonide 32 as a pale yellow oil (1.8 g, 80%): 1H NMR
(toluene-d8, 80 °C) δ 6.09-6.05 (1H, m), 5.81-5.77 (1H, m),
4.53-4.48 (2H, m), 4.31-4.23 (2H, dq, J ) 7.1, 3.3 Hz), 2.43
(1H, ddd, J ) 16.6, 6.9, 2 Hz), 2.16-2.09 (1H, m), 1.83 (3H, s),
1.70 (3H, s), 1.32 (3H, t, J ) 7.1 Hz), 1.17 (9H, s), 0.42 (3H, s),
0.16 (3H, s); IR (film) 1703 cm-1; MS m/z 339 (M•+, 10), 73
(100); [R]25D +62.8 (c 0.81, CHCl3). Anal. Calcd for C18H33NO3-
Si: C, 63.67; H, 9.80; N, 4.13; Si, 8.25. Found: C, 63.67; H,
9.73; N, 4.05; Si, 8.16.
7 Hz); IR (CDCl3) 3583, 3400, 1657 cm-1; MS m/z 276 (M•+
+
1, 100); [R]25 -7 (c 0.68, MeOH). Anal. Calcd for C12H21NO6:
D
C, 52.35; H, 7.69; N, 5.09. Found: C, 52.44; H, 7.66; N, 5.07.
1,3-Dia m in ocyclitol (38). To a solution of allylic alcohol
29 (0.2 g, 0.83 mmol) in dry THF (5 mL) was added tosyliso-
cyanate (0.13 mL, 1 mmol), and the mixture was stirred for 3
h at room temperature. The solvent was evaporated under
vacuum, and the crude tosyl carbamate was poured into CCl4
(10 mL). A solution of NaHCO3 (0.28 g, 3.32 mmol) in water
(10 mL) was then added followed by I2 (0.44 g, 1.7 mmol). The
reaction mixture was stirred for 2 h at room temperature,
diluted with CH2Cl2, and quenched with a saturated solution
of Na2S2O3. The organic layer was decanted and the aqueous
layer extracted with CH2Cl2. The combined extracts were
washed with brine and dried over MgSO4, and the solvent was
evaporated in vacuo. The crude oil was purified by chroma-
tography through silica gel (CH2Cl2), affording the iodide 37
(0.28 g, 60%, two steps). This intermediate was then dissolved
in CH3CN (10 mL), and DBU (0.2 mL, 1.7 mmol) was added.
The mixture was stirred overnight at room temperature and
the solvent evaporated in vacuo. The crude oil was diluted in
ether and quenched by a saturated solution of NH4Cl, and the
aqueous layer was extracted with ether. The combined extracts
were washed with brine and dried over MgSO4. The solvents
were evaporated under vacuum to give an oil that was purified
Sh a r p less Am in oh yd r oxyla t ion of Dien ylsila n e 6c
(33). Following the benzylation procedure described for 12b,
amino alcohol 31a (1.2 g, 4 mmol) gave, after chromatography
through silica gel (petroleum ether/EtOAc 8:2), the benzylated
oxazolidinone 33 as a colorless oil (1.12 g, 82%): 1H NMR δ
7.33-7.23 (5H, m), 5.71 (2H, m), 4.86-4.83 (1H, m), 4.72 (1H,
d, J ) 15.6 Hz,), 4.07-4.00 (2H, m), 2.41 (1H, dd, J ) 17.5,

9624 J . Org. Chem., Vol. 64, No. 26, 1999
Angelaud et al.
by chromatography through silica gel (petroleum ether/EtOAc
6:4), affording 38 as an amorphous solid (0.11 g, 30% overall
yield from 29): 1H NMR (toluene-d8, 80 °C) δ 7.13 (2H, d, J )
8.2 Hz), 6.28 (1H, dd, J ) 10.3, 2.8 Hz), 5.92 (1H, dd, J ) 10.3,
4.1 Hz), 5.06 (1H, br s), 4.88 (1H, d, J ) 6.8 Hz), 4.35 (1H, m),
4.27-4.15 (3H, m), 2.23 (3H, s), 1.71 (3H, s), 1.63 (3H, s), 1.29
(3H, t, J ) 7.1 Hz); 13C NMR (toluene-d8, 80 °C) δ 152.9, 150.3,
95.2, 74.9, 68.2, 61.2, 55.7, 54.2, 27.5, 24.9, 20.8, 14.0; IR (film)
21.9 (t, J ) 130 Hz), 20.2 (t, J ) 131 Hz), 14.2 (q, J ) 127 Hz);
IR (film) 3420, 1666 cm-1; MS m/z 274 (M•+ + 1, 6), 258 (100);
[R]25 -15.3 (c 0.32, CHCl3). Anal. Calcd for C13H23NO5: C,
D
57.13; H, 8.48. Found: C, 57.20; H, 8.52.
cis-Cycloh ex-3-en e-1,2-d iol (42). A solution of silanol 6b
(1 g, 6.5 mmol) in tetramethyldisilazane (4 mL) was refluxed
overnight. Excess disilazane was then evaporated in vacuo to
give quantitatively the crude siloxane 41, which was used in
the next step without further purifications: 1H NMR δ 5.70-
5.55 (4H, m), 4.70 (1H, sext, J ) 1.5 Hz), 2.80-2.62 (2H, m),
2.32 (1H, m), 0.19 (3H, s), 0.18 (3H, s), 0.11 (6H, s); IR (film)
3027, 2960, 2824, 2163, 1624, 1486, 1255, 1067, 911, 801, 768,
689, 661 cm-1. Siloxane 41 (0.2 g, 1.3 mmol) and H2PtCl6‚6H2O
(33 mg, 0.06 mmol) in toluene (5 mL) were refluxed for 1 h.
The solvent was then evaporated in vacuo, and the crude cyclic
siloxane was directly submitted to Tamao-Kumada oxidation,
following the general procedure. The resulting yellow oil was
purified by chromatography through silica gel (CH2Cl2/ether
3:2), affording the pure racemic diol 42 (64 mg, 43%, three
steps). Spectroscopic data were all identical in many respects
with those described in the literature.46
1800 cm-1; MS m/z 437 (M•+ + 1, 1), 421 (100); [R]25 +81.1 (c
D
0.68, CHCl3). Anal. Calcd for C20H24N2O7S: C, 55.04; H, 5.54;
N, 6.42; S, 7.35. Found: C, 55.05; H, 5.63; N, 6.37; S, 7.23.
Siloxa n e 39. To a solution of alcohol 29 (0.3 g, 1.25 mmol)
in dry ether (20 mL) were added NEt3 (0.3 mL, 1.88 mmol)
and (bromomethyl)dimethylchlorosilane (0.19 mL, 1.34 mmol).
The solution was stirred at room temperature overnight. The
resulting white slurry was then filtered and the solvent
evaporated under vacuum. The resulting oil was purified by
chromatography through silica gel (petroleum ether/EtOAc 9:1)
to afford the siloxane 39 as a colorless oil (0.46 g, 94%): 1H
NMR δ 5.78 (2H, m), 4.39 (1H, m), 4.33-3.88 (4H, m), 2.61-
2.31 (4H, m), 1.66-1.45 (6H, m), 1.29 (3H, t, J ) 8 Hz), 0.28
(6H, s); IR (film) 1698 cm-1; MS m/z 392 (M•+, 0.2), 171 (100).
Anal. Calcd for C15H26BrNO4Si: C, 45.92; H, 6.68; Br, 20.36;
N, 3.57; Si, 7.16. Found: C, 45.99; H, 6.74; Br, 20.28; N, 3.42;
Si, 7.01.
Am in oca r ba su ga r 40. To a solution of the siloxane 39 (0.4
g, 1.02 mmol) in dry and degassed benzene (30 mL) was added
via a syringe pump a mixture of Bu3SnH (0.45 g, 1.53 mmol)
and AIBN (cat.) in benzene (8 mL) under reflux over a 2 h
period. The reaction mixture was then heated for an additional
1 h, and the solvent was evaporated under vacuum. The crude
oil was then submitted to the general Tamao-Kumada oxida-
tion procedure described above. The pale yellow oil thus
obtained was purified by chromatography through silica gel
(petroleum ether/EtOAc 2:8), affording the aminocarbasugar
40 as a colorless oil (0.25 g, 74%, two steps): 13C NMR δ 155.7
(s), 92.8 (s), 75.9 (d, J ) 152 Hz), 72.1 (d, J ) 147 Hz), 62.3 (t,
J ) 140 Hz), 61.9 (t, J ) 148 Hz), 61.3 (d, J ) 148 Hz), 38.8
(d, J ) 128 Hz), 27.2 (q, J ) 127 Hz), 24.3 (q, J ) 127 Hz),
Ackn owledgm en t. R.A and Y.L. gratefully acknowl-
edge the Swiss National Science Foundation (CHiral 2
program), the Office Fe´de´ral de L’Education et de la
Science (OFES), and the Fondation Agassiz for generous
support. T.C. thanks the NHL for a summer grant.
Special thanks goes to Dr. K. J . Schenk (University of
Lausanne) for the X-ray structure determination and
Prof. P. Dumy (University of Grenoble, France) for his
help concerning the NMR studies.
Su p p or tin g In for m a tion Ava ila ble: Spectroscopic data
for compounds (-)-4, 10, 12a ,b, 13, 15, 18, 20, 22a ,b, 24, 26-
29, 31a ,b, 34, and 41. Preparation of (E,E)-1-bromohepta-1,3-
diene. Crystal structure of 29. This material is available free
of charge via the Internet at http://pubs.acs.org.
J O991225Z