Asymmetric Pauson-Khand reaction. Cobalt-mediated cycloisomerization of 1,6-enynes in carbohydrate templates: Synthesis of bis-heteroannulated pyranosides

Article abstract of DOI:10.1021/jo961138w

The Pauson-Khand reaction on the carbohydrate derived precursors 1-6 is reported. We have described for the first time the cobalt-mediated cyclization of some O-branched chain 1,6-enynes in carbohydrate templates. The resulting bis-heteroannulated pyranosides 17-22 have been obtained in diastereomerically pure form, in moderate to good yield, and in one, simple synthetic operation. These enantiomerically pure, densely functionalized carbocycles are attractive advanced intermediates for the synthesis of complex natural products.

Full text of DOI:10.1021/jo961138w

7666
J . Org. Chem. 1996, 61, 7666-7670
Articles
Asym m etr ic P a u son -Kh a n d Rea ction . Coba lt-Med ia ted
Cycloisom er iza tion of 1,6-En yn es in Ca r boh yd r a te Tem p la tes:
Syn th esis of Bis-Heter oa n n u la ted P yr a n osid es†
J ose´ Marco-Contelles
Instituto de Quı´mica Orga´nica General (CSIC), J uan de la Cierva, 3, 28006-Madrid, Spain
Received J une 17, 1996X
The Pauson-Khand reaction on the carbohydrate derived precursors 1-6 is reported. We have
described for the first time the cobalt-mediated cyclization of some O-branched chain 1,6-enynes
in carbohydrate templates. The resulting bis-heteroannulated pyranosides 17-22 have been
obtained in diastereomerically pure form, in moderate to good yield, and in one, simple synthetic
operation. These enantiomerically pure, densely functionalized carbocycles are attractive advanced
intermediates for the synthesis of complex natural products.
In tr od u ction
Cobalt-mediated inter- and intramolecular annulations
(Pauson-Khand reaction) are among the most potent
methods for cyclopentenone synthesis.1 In recent years,
several modifications have improved the utility of the
reaction; particularly useful has been the dry-state
adsorption technique,2 the inclusion of additives (DMSO,
CH3CN),3 and the discovery that tertiary amine N-oxides
accelerate the rate of cyclopentenone formation.4
F igu r e 1. Pauson-Khand reaction on pyranoside templates.
Obviously, an asymmetric version of the Pauson-
Khand reaction is highly desirable, but until 1990 no
efficient approach had been described.5 In that year
Greene at al. reported the first auxiliary-directed asym-
metric Pauson-Khand bicyclization;6 in this and the
following papers these authors extensively analyzed this
approach in the intra-7a or intermolecular version.7b The
use of chiral ligands5 has been recently reinvestigated.8
Chiral tertiary amine N-oxides have also been applied
with limited success.9 During these years homochiral
enynes have also been submitted to the Pauson-Khand
reaction, giving enantiomerically pure, differentially
substituted cyclopentenones.10 This is perhaps the most
versatile and practical approach for the asymmetric
synthesis of natural products.
In this context, in 1994, the first successful cobalt-
mediated cyclization of a 1,6-enyne functionality embod-
ied in a pyranoside substrate was reported (Figure 1).11,12
Although sugars have been used as starting materials
to prepare homochiral enynes for this annulation,10e in
our approach, the pyranoside, without disturbing the
anomeric center, was used as a chiral template for the
cyclization process. A rich and highly functionalized bis-
heteroannulated pyranoside should result from a simple
one-pot reaction. These materials are enantiomerically
pure, useful intermediates for further synthetic trans-
formations (Ferrier carbocyclization reaction,13a free radi-
cal cyclization13b) directed to the preparation of pros-
tanoids,14 polyquinanes,15 or iridoids.16 It was also
expected that the particular stereodirecting properties
† This paper is dedicated to the memory of Professor Wolfgang von
Oppolzer.
X Abstract published in Advance ACS Abstracts, October 1, 1996.
(1) For reviews, see: (a) Schore, N. E. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford,
1991; Vol. 5, p 1037. (b) Schore, N. E. Org. React. 1991, 40, 1. (c)
Pauson, P. L.; Khand, I. U. Ann. N.Y. Acad. Sci. 1977, 295, 2. (d)
Pauson, P. L. Tetrahedron 1985, 41, 5855.
(10) (a) Magnus, P.; Becker, D. P. J . Am. Chem. Soc. 1987, 109, 7495.
(b) Roush, W. R.; Park, J . C. Tetrahedron Lett. 1991, 32, 6285. (c)
Takano, S.; Inomato, K.; Ogasawara, K. Chem. Lett. 1992, 443. (d)
Stolle, A.; Becker, H.; Salau¨n, J .; de Meijere, A. Tetrahedron Lett. 1994,
35, 3521. (e) Mulzer, J .; Graske, K.-D.; Kirste, B. Liebigs Ann. Chem.
1988, 891.
(2) Smit, W. A.; Kireev, S. L.; Nefedov, O. M.; Tarasov, V. A.
Tetrahedron Lett. 1989, 30, 4021.
(3) Chung, Y. K.; Lee, B. Y.; J eong, N.; Hudecek, M.; Pauson, P. L.
Organometallics 1993, 12, 220.
(4) Shambayati, S.; Crowe, W. E.; Schreiber, S. L. Tetrahedron Lett.
1990, 31, 5289.
(5) For some previous marginally successful efforts, see: Bladon,
P.; Pauson, P. L.; Brunner, H.; Eder, R. J . Organomet. Chem. 1988,
355, 449.
(6) (a) Castro, J .; So¨rensen, H.; Riera, A.; Morin, C.; Moyano, A.;
Perica´s, M. A.; Greene, A. E. J . Am. Chem. Soc. 1990, 112, 9388.
(7) (a) Castro, J .; Moyano, A.; Perica´s, M. A.; Riera, A.; Greene, A.
E. Tetrahedron: Asymmetry 1994, 5, 307 and references cited therein.
(b) Fonquerna, S.; Moyano, A.; Perica´s, M. A.; Riera, A. Tetrahedron
1995, 51, 4239, and references cited therein.
(8) (a) Brunner, H.; Niederhuber, A. Tetrahedron: Asymmetry 1990,
1, 711. (b) Hay, A. M.; Kerr, W. J .; Kirk, G. G.; Middlemiss, D.
Organometallics 1995, 14, 4986.
(11) (a) Marco-Contelles, J . Tetrahedron Lett. 1994, 35, 5059. For
our continued interest in the synthesis of heteroannualted sugars,
see: (b) Marco-Contelles, J .; Ruiz-Ferna´ndez, P.; Sa´nchez, B. J . Org.
Chem. 1993, 58, 2894 and references cited therein.
(12) Lindsell, W. E.; Preston, P. N.; Rettie, A. B. Carbohydr. Res.
1994, 254, 311 (in this paper the first synthesis and characterization
of a hexacarbonyldicobalt complexes derived from 2-O-propynyl and
3-O-butynyl 4,6-dideoxy-R-D-erythro-hex-2-enopyranosides have been
described; unfortunately, these authors were unable to transform them
into the annulated cyclopentenones).
(13) (a) Ferrier, R. J . J . Chem. Soc., Perkin Trans. 1 1979, 1455. (b)
Clive, D. L. J .; Cole, D. C.; Tao, Y. J . Org. Chem. 1994, 59, 1396.
(14) Kraft, M. E.; Wright, C. Tetrahedron Lett. 1992, 33, 151.
(15) Casalnuovo, J . A.; Scott, R. W.; Harwood, E. A.; Schore, N. E.
Tetrahedron Lett. 1994, 35, 1153.
(9) Kerr, W. J .; Kirk, G. G.; Middlemiss, D. Synlett 1995, 1085.
S0022-3263(96)01138-3 CCC: $12.00 © 1996 American Chemical Society

Asymmetric Pauson-Khand Reaction
J . Org. Chem., Vol. 61, No. 22, 1996 7667
Sch em e 1a
and conformational bias of these sugar derivatives offer
potentially high degrees of stereochemical control in the
formation of the new stereocenters. After our initial
report11 other authors, using our strategy, have described
interesting results on this subject.17
Resu lts a n d Discu ssion
In this report, the results that have been obtained
using some selected and representative 1,6-enynes in the
D-glucopyranoside series are described in full. These
substrates have been designed to determine general
structure-reactivity trends and explore the different
possibilities for the location on the functional groups on
the 1,6-enyne moiety. A pyranoid nucleus allows the
ideas to be examined. We have synthesized the carbo-
hydrate-derived precursors 1-6.
a
Reagents: (a) ClSi-t-BuMe2, imidazole, DMF (49%); (b)
(Bu3Sn)2O, propargyl bromide (52%); (c) Ph3P, I2 (48%).
Sch em e 2a
a
Reagents: (a) ClSi-t-BuMe2, imidazole, DMF; (b) NaH, pro-
pargyl bromide (57% from 12; 96% from 16); (c) NaMeO, MeOH
(90%); (d) ClSi-t-BuPh2, imidazole, DMF (66%).
O-propargylation (77% yield). Compound 4 is a glucal
with the double bond at C-1 and C-2; the O-propargyl
arm is â-orientated in C-3. Finally, structures 5 and 6
have been obtained following similar synthetic sequences
starting from tri-O-acetyl-D-glucal 11 (Scheme 2), using
as intermediates the already known sugars 1220 or 14.21
In glycosides 5 and 6 the O-propargyl branch is R
orientated in C-4, and the double bond is now at C-2 and
C-3.
Briefly, these substrates have been designed in order
to have the O-propargyl arm at C-1, C-2, C-3, and C-4
and the necessary double bond at different suitable
positions for the preparation of the annulated bicyclo-
[3.3.0]cyclopentenones. As a consequence, the resulting
Pauson-Khand molecules are annulated branched-chain
sugars (or C-glycosides for compound 4) at different
positions in the pyranoside ring.
Th e P a u son -Kh a n d Rea ction . In the standard
conditions for the Pauson-Khand reaction (see Experi-
mental Section), after cobalt complex formation and in
situ decomposition with NMO, the 1,6-enynes 1-6 gave
the cyclopentenones 17-22, in moderate to good yield,
in one synthetic operation (see Figure 2). The moderate
overall yield in the Pauson-Khand reaction is compen-
Syn th esis of En yn es for th e P a u son -Kh a n d Re-
a ction . Compounds 1 and 212 are known and have been
prepared by the described protocols. In these products,
the endo-double bond is in positions C-2/C-3 and the
O-propargyl or O-butynyl function has been located at
C-1; the Ferrier glycosylation reaction18 with tri-O-acetyl-
D-glucal and the corresponding alcohol allowed prepara-
tion of an inseparable mixture of the anomers at C-1, the
major isomer being the R-glycoside. Compound 3 has
been obtained as shown in Scheme 1 by routine manipu-
lations from commercial methyl R-D-glucopyranoside (7).
In methyl glycoside 3 the O-propargyl branch is R
orientated in C-2 and the endo-double bond is in positions
C-3 and C-4. Product 4 has been prepared from 6,4-O-
isopropylidene-3-O-propargyl-D-glucal (10)19 by simple
(16) J eong, N.; Lee, B. Y.; Lee, S. M.; Chung, Y. K.; Lee, S.-G.
Tetrahedron Lett. 1993, 34, 4023.
(17) (a) Naz, N.; Al-Tel, T. H.; Al-Abed, Y.; Voelter, W. Tetrahedron
Lett. 1994, 35, 8581. (b) Naz, N.; Al-Tel, T. H.; Al-Abed, Y.; Voelter,
W.; Ficker, R.; Hiller, W. J . Org. Chem. 1996, 61, 3250. (c) Borodkin,
V.; Shpiro, N. A.; Azov, V. A.; Kochetkov, N. K. Tetrahedron Lett. 1996,
37, 1489.
(18) (a) Ferrier, R. J . Adv. Carbohydr. Chem. Biochem. 1969, 24,
199. (b) Ferrier, R. J .; Prasad, N. J . Chem. Soc. C 1969, 570.
(19) Fraser-Reid, B.; Walker, D. L.; Tam, S. Y.-K.; Holder, N. L. Can.
J . Chem. 1973, 51, 3950.
(20) Xiong, Y.; Xia, H.; Moore, H. W. J . Org. Chem. 1995, 60, 6462.
(21) Koreeda, M.; Houston, T. A.; Shull, B.; Klemke, E.; Tuinman,
R. J . Synlett 1995, 90.

7668 J . Org. Chem., Vol. 61, No. 22, 1996
Marco-Contelles
signal pattern in the NMR spectra (see Experimental
Section). Compounds 17-22 were diastereomerically
1
pure as we observed by H NMR analysis. In fact, the
observed vicinal coupling constants in the 1H NMR
spectra of products 17-22 (17: J 1,2 ) 6.2 Hz, J 2,3 ) 6.7
Hz; 18: J 1,2 ) 4.2 Hz, J 2,3 ) J 3,4 ) 6.0 Hz; 19: J 1,2 ) 5.2
Hz, J 2,3 ) 9.1 Hz, J 3,4 ) 6.6 Hz; 20 J 1,2 ) 5.1 Hz, J 2,3
)
J 3,4 ) 8.4 Hz; 21: J 1,2 ) 7.7 Hz, J 2,3 ) 7.5 Hz, J 3,4 ) 8.7
Hz; 22: J 1,2 ) 7.6 Hz, J 2,3 ) 7.1 Hz) suggested that the
absolute configurations at the carbons where the fused-
cyclopentenones are anchored are determined by the
stereochemistry of the carbon linked to the O-propargyl
branch. The carbonylative acetylenic insertion always
takes place from the same side where the propargyl
moiety is located. The cyclization of precursor 4 is
particularly interesting because it gives
a stereo-
controlled C-glycosyl derivative in a one-pot reaction and
complements another reported free radical based strategy
for a similar transformation.22
Con clu sion s
The results reported here give a new insight in the
cobalt-mediated cycloisomerization of chiral 1,6-enynes.
The versatility of these pyranoside templates open many
synthetic possibilities in the preparation of different types
of 1,6-enyne precursors: carbon-carbon-branched chain
sugars, azapropargyl chains, etc. In addition, other
different transition metals (Pd,23 Cr,24 Zr,25 etc.) could be
applied with success to these substrates, giving rise to
new types of useful synthetic intermediates. These
endeavors are being pursued and will be reported in due
course.
In summary, we have described for the first time the
successful cobalt-mediated cyclization of some 1,6-enynes
embodied in O-branched-chain D-glucopyranosides. The
reaction conditions are very mild, the yields are modest,26
and no special experimental conditions have to be
observed. Finally, the Pauson-Khand compounds are
valuable and advanced intermediates in the synthesis of
some natural products.
Exp er im en ta l Section
Gen er a l Meth od s. See ref 11b.
F igu r e 2. Pauson-Khand annulation of enynes 1 and 3-6.
Gen er a l P r oced u r e for O-Silyla tion . To a solution of
the alcohol in anhydrous DMF (0.4 M), were added imidazole
(2.2 equiv) and tert-butyldimethylsilyl chloride or tert-butyl-
diphenylsilyl chloride (1.1 equiv). The mixture was stirred at
room temperature overnight. When the reaction was complete
(TLC analysis), the mixture was diluted with methylene
chloride, washed with saturated aqueous ammonium chloride
solution, and extracted again with methylene chloride. The
combined organic layers were back-washed with water, dried
over sodium sulfate, and concentrated in vacuo.
Gen er a l P r oced u r e for O-P r op a r gyla tion . To a solution
of the alcohol in freshly distilled THF (0.12 M) was added
sodium hydride (1.5 equiv, 60% oil suspension) in portions;
gas evolution was observed. The mixture was stirred at room
temperature for 3 h, and then propargyl bromide (2 equiv, 80%
in toluene) was added at 0 °C. The mixture was stirred at
room temperature overnight. The resulting suspension was
quenched with saturated ammonium chloride and extracted
sated for by the efficiency of the one-pot process and the
highly functionalized final products obtained, which are
difficult to synthesize by other methodologies. Com-
pounds 17-20 have been obtained using dry NMO, but
in the case of enynes 5 and 6 we used NMO‚H2O; from
the observed chemical yields it appears that each form
of the reagent gives good results. Substrate 1 was
submitted to cyclization as an inseparable mixture of R
and â anomers; after annulation we could separate the
corresponding Pauson-Khand reaction products (17 and
18) derived from each anomer; major isomer 17 comes
from the R-glycoside. Enyne 2 afforded the hexacar-
bonyldicobalt complex, but after the usual treatment,
only decomposition was observed and no annulated
compound could be detected; this observation means that
the use of O-butynyl side chains in order to prepare the
annulated bicyclo[4.3.0] systems in these substrates are
less favored than the formation of the analogous bicyclo-
[3.3.0] structures, easily obtained from the O-propargyl
derivatives. All the new Pauson-Khand reaction com-
pounds showed the expected IR bands and the typical
(22) Lo´pez, J . C.; Fraser-Reid, B. J . Am. Chem. Soc. 1989, 111, 3450.
(23) Trost, B. M. Acc. Chem. Res. 1990, 23, 34.
(24) Kim, O. K.; Wulff, W. D.; J iang, N. J . Org. Chem. 1993, 58,
5571.
(25) Negishi, E. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 5, p 1163.
(26) The rest of the mass was polar, unidentified material.

Asymmetric Pauson-Khand Reaction
J . Org. Chem., Vol. 61, No. 22, 1996 7669
with diethyl ether. The combined organic layers were washed
with brine, dried over sodium sulfate, and concentrated in
vacuo.
hexanes-ethyl acetate) we finally obtained the propargylated
product 5 (2.1 g, 57% overall yield from 12) as an oil: IR (film)
ν
max 3300, 2120 cm-1; 1H NMR (200 MHz, CDCl3) δ 6.03 (br d,
J ) 10.3 Hz, 1 H), 5.71 (ddd, J ) 2.0, 2.7 Hz, 1 H), 4.81 (m, 1
H), 4.19 (d, J ) 2.4 Hz, 2 H), 4.07 (ddd, J ) 9.1, 3.3, 1.6 Hz,
1 H), 3.69-3.88 (m, 3 H), 3.38 (s, 3 H), 2.38 (t, J ) 2.4 Hz, 1
H), 0.91 (s, 9 H), 0.12 (s, 6 H); 13C NMR (50 MHz, CDCl3) δ
130.1, 126.6, 95.0, 76.1, 74.2, 70.2, 69.9, 62.5, 56.1, 55.3, 25.7,
18.1, -5.3; MS (70 eV) m/z 295 (M+ - 1, 3), 281 (M+ - 15,
100). Anal. Calcd for C16H28O4Si: C, 61.49; H, 9.03. Found:
C, 61.25; H, 8.87.
Gen er a l P r oced u r e for th e P a u son -Kh a n d Rea ction .
The substrate was placed in a round-bottomed flask that was
then flushed with argon for 5-10 min. Methylene chloride
was added, and Co2(CO)8 (1.1 equiv) was tipped inside. The
resulting solution was stirred for 2-3 h at room temperature
and cooled at 0 °C, and NMO‚H2O or dry NMO (6 equiv) was
added. The cooling bath was removed and the mixture stirred
at room temperature for the indicated time. The solvent was
evaporated and the residue processed as indicated in each
experiment.
Allyl 2,3-Did eoxy-4,6-d ih yd r oxy-r-D-er yth r o-h ex-2-
en op yr a n osid e (15). Allyl 4,6-di-O-acetyl-R-D-erythro-hex-
2-enopyranoside (14)21 (837 mg, 3.1 mmol) was treated with
sodium methoxide (cat.) in methanol (15 mL) at room tem-
perature (2 h). The solvent was removed, and the residue was
submitted to flash chromatography (1:4 hexanes-ethyl ace-
Meth yl 6-O-(ter t-Bu tyld im eth ylsilyl)-r-D-glu cop yr a n o-
sid e (8). Methyl R-D-glucopyranoside (7, 1.95 g, 10 mmol),
submitted to the general procedure, after flash chromatogra-
phy (4:6 hexanes-ethyl acetate) gave the silylated compound
tate) to give compound 15 (660 mg, 90%) as an oil: [R]25 +69
8 (1.2 g, 49% yield) as a solid: mp 88-90 °C; [R]25 +85 (c
D
D
0.75, CHCl3); IR (film) νmax 3400 cm-1
;
1H NMR (200 MHz,
(c 1.1, CHCl3); IR (film) νmax 3600-3100, 3080, 3060, 1640
cm-1; 1H NMR (200 MHz, CDCl3) δ 5.75-6.00 (m, 3 H), 5.19-
5.35 (m, 2 H), 5.02 (s, 1 H), 3.80-4.40 (m, 6 H), 2.32 (d, J )
6.9 Hz, 1 H), 1.74 (br s, 1 H). Anal. Calcd for C9H14O4: C,
58.05; H, 7.58. Found: C, 57.90; H, 7.81.
CDCl3) δ 4.71 (d, J ) 3 Hz, 1 H), 3.31-4.00 (m, 9 H), 3.40 (s,
3 H), 0.91 (s, 9 H), 0.12 (s, 6 H). Anal. Calcd for C13H28O6Si:
C, 50.62; H, 9.15. Found: C, 50.73; H, 9.11.
Meth yl 6-O-(ter t-Bu tyld im eth ylsilyl)-3-O-p r op a r gyl-r-
D-glu cop yr a n osid e (9). Compound 8 (476 mg, 1.5 mmol) was
dissolved in toluene (15 mL), and dibutyltin oxide (400 mg,
1.65 mmol) was added. The suspension was stirred and
warmed at reflux for 3 h. Then, the solution was cooled, and
propargyl bromide (0.48 mL, 3.3 mmol, 80% toluene solution)
and tetrabutylammonium iodide (590 mg, 1.6 mmol) were
added, and the reaction was stirred at room temperature
overnight. The solvent was removed and the residue submit-
ted to chromatography (1:1 hexanes-ethyl acetate) to give
Allyl 2,3-Did eoxy-6-O-(ter t-b u t yld ip h en ylsilyl)-4-h y-
dr oxy-r-D-er yth r o-h ex-2-en opyr an oside (16). Starting from
compound 15 (660 mg, 3.5 mmol) and following the general
procedure the silylated product 16 (1.07 g, 66% yield) was
obtained as an oil: [R]25 +12 (c 1.3, CHCl3); IR (film) νmax
D
3600-3100, 3080, 3060, 1640 cm-1; 1H NMR (200 MHz, CDCl3)
δ 7.35-7.50 and 7.65-7.72 (m, 10 H), 5.94 (br d, J ) 1.1 Hz,
1 H), 5.82 (m, 1 H), 5.75 (ddd, J ) 10.3, 2.1, 2.6 Hz, 1 H), 5.24
(dq, J ) 9.1, 1.7 Hz, 1 H), 5.14 (dq, J ) 17.2, 1.7 Hz, 1 H),
4.97 (dd, J ) 2.6, 1.1 Hz, 1 H), 3.70-4.30 (m, 6 H), 2.56 (d, J
) 4.6 Hz, 1 H), 0.89 (s, 9H). Anal. Calcd for C25H32O4Si: C,
70.72; H, 7.59. Found: C, 70.59; H, 7.77.
compound 9 (275 mg, 52% yield) as an oil: [R]25 +62 (c 1.6,
D
CHCl3); IR (film) νmax 3400, 3300, 2120 cm-1
;
1H NMR (200
MHz, CDCl3) δ 4.91 (d, J ) 3.4 Hz, 1 H), 4.36 (d, J ) 2.2 Hz,
2 H), 3.50-4.00 (m, 5 H), 3.41 (s, 3 H), 3.16 (br s, 1 H), 2.79
(br s, 1 H), 2.48 (t, J ) 2.2 Hz, 1 H), 1.75 (br s, 1 H), 0.91 (s,
9 H), 0.12 (s, 6 H). Anal. Calcd for C16H30O6Si: C, 55.46; H,
8.72. Found: C, 55.30; H, 8.61.
Allyl 2,3-Did eoxy-6-O-(ter t-b u t yld ip h en ylsilyl)-4-O-
p r op a r gyl-r-D-er yth r o-h ex-2-en op yr a n osid e (6). Starting
from compound 16 (1.07 g, 2.5 mmol) and following the general
procedure the propargylated product 6 (1.09 g, 96% yield) was
Met h yl 6-O-(ter t-Bu t yld im et h ylsilyl)-3-O-p r op a r gyl-
3,4-d id eoxy-r-D-er yth r o-h ex-2-en op yr a n osid e (3). Diol 9
(275 mg, 0.79 mmol) was dissolved in toluene (10 mL) and
treated with triphenylphosphine (602 mg, 2.3 mmol), imidazole
(210 mg, 3.1 mmol), and iodine (584 mg, 2.3 mmol) at reflux
for 40 min. The mixture was diluted with ethyl acetate and
washed with 10% aqueous sodium thiosulfate and brine. The
organic layers were washed with water, dried with sodium
sulfate, filtered, and evaporated. Flash chromatoghraphy (4:1
hexanes-ethyl acetate) gave compound 3 (121 mg, 48% yield)
obtained as a solid: mp 41-43 °C; [R]25 +31(c 1.2, CHCl3);
D
IR (film) νmax 3300, 3080, 3060 cm-1
;
1H NMR (200 MHz,
CDCl3) δ 7.35-7.50 and 7.65-7.72 (m, 10 H), 6.08 (br d, J )
1.1 Hz, 1 H), 5.92 (m, 1 H), 5.80 (ddd, J ) 10.3, 2.1, 2.6 Hz, 1
H), 5.24 (dq, J ) 9.1, 1.7 Hz, 1 H), 5.14 (dq, J ) 17.2, 1.7 Hz,
1 H), 5.07 (dd, J ) 2.6, 1.1 Hz, 1 H), 3.70-4.30 (m, 8 H), 2.34
(t, J ) 2.4 Hz, 1 H), 0.89 (s, 9H); 13C NMR (50 MHz, CDCl3) δ
135.8, 135.6, 134.5, 133.8, 133.5, 130.4, 129.5, 127.6, 127.5,
126.9, 117.1, 93.3, 79.8, 74.4, 70.5, 70.2, 68.7, 63.4, 56.4, 26.8,
19.3. Anal. Calcd for C28H34O4Si: C, 72.68; H, 7.40. Found:
C, 72.49; H, 7.27.
as an oil: [R]25 +5 (c 1.5, CHCl3); IR (film) νmax 3300, 2120
D
cm-1; H NMR (200 MHz, CDCl3) δ 5.85 (dt, J ) 1.5, 1.8 Hz,
1
P a u son -Kh a n d P r od u cts 17 a n d 18. Starting from
compound 1 (87 mg, 0.3 mmol; as a mixture of anomers R:â/
85:15) and following the general procedure (2 h 30 min for the
formation of the complex and 5 h 30 min for the NMO
treatment), after flash chromatography (2:3 hexanes-ethyl
acetate) compounds 17 (49 mg, 55% yield) and 18 (10 mg, 11%
1 H), 5.78 (dq, J ) 10.7, 1.5 Hz, 1 H), 4.99 (d, J ) 3.9 Hz, 1
H), 4.32 (m, 1 H), 4.28 (d, J ) 2.4 Hz, 2 H), 4.15 (m, 1 H), 3.71
(dd, J ) 5.6 Hz, J ) 10.3 Hz, 1 H), 3.60 (dd, J ) 10.3 Hz, J )
6.0 Hz, 1 H), 3.51 (s, 3 H), 2.44 (t, J ) 2.4 Hz, 1 H), 0.91 (s, 9
H), 0.12 (s, 6 H). Anal. Calcd for C16H28O4Si: C, 61.49; H,
9.03. Found: C, 61.35; H, 8.97.
yield) were obtained. 17: oil; [R]25 -17 (c 2.3, CHCl3); IR
D
6,4-O-Isopr opylid en e-3-O-p r op a r gyl-D-glu ca l (4). Start-
ing from 6,4-O-isopropylidene-3-O-propargyl-D-glucal (10)19 (66
mg, 0.35 mmol) and following the general procedure, after flash
chromatoghraphy (85:15 hexanes-ethyl acetate) we obtained
(film) νmax 1760-1720 cm-1; 1H NMR (300 MHz, CDCl3) δ 5.59
(d, J ) 6.2 Hz, 1 H), 4.97 (dd, J ) 8.9, 10.3 Hz, 1 H), 4.84 (d,
J ) 14.6 Hz, 1 H), 4.59 (d, J ) 14.6 Hz, 1 H), 4.17 dd, J )
11.7, 4.1 Hz, 1 H), 4.10 (dd, J ) 11.7, 2.7 Hz, 1 H), 3.70 (ddd,
J ) 2.7, 4.1, 10.3 Hz, 1 H), 3.50 (d, J ) 6.2, 6.7 Hz, 1 H), 3.35
(m, 1 H), 2.08, 2.05 (s, s, 3 H, 3 H), 1.82 (br s, 3 H); 13C NMR
(75 MHz, CDCl3) δ 205.2, 172.3, 170.5, 169.8, 134.6, 96.2, 66.6,
66.1, 65.1, 62.7, 45.4, 44.9, 20.6, 9.1. Anal. Calcd for
compound 4 (61 mg, 77% yield) as an oil: [R]25 +8 (c 2.7,
D
CHCl3); IR (film) νmax 3300, 2120, 1640 cm-1
;
1H NMR (200
MHz, CDCl3) δ 6.32 (dd, J ) 16.1 Hz, J ) 1.4 Hz, 1 H), 4.78
(dd, J ) 16.1, 2.0 Hz, 1 H), 4.37 (dd, J ) 15.6, 2.5 Hz, 1 H),
4.29 (dd, J ) 15.6, 2.5 Hz, 1 H), 4.25 (ddd, J ) 7.3, 2.0, 1.4
Hz, 1 H), 3.65-4.05 (m, 4 H), 2.44 (t, J ) 2.5 Hz, 1 H), 1.53 (s,
3 H), 1.42 (s, 3 H). Anal. Calcd for C12H16O4: C, 64.27; H,
7.19. Found: C, 64.44; H, 7.39.
Met h yl 2,3-Did eoxy-4-O-p r op a r gyl-6-O-(ter t-b u t yld i-
m eth ylsilyl)-r-D-er yth r o-h ex-2-en op yr a n osid e (5). Start-
ing from methyl 2,3-dideoxy-4,6-dihydroxy-R-D-erythro-hex-2-
enopyranoside (12)20 (1.89 g, 11.81 mmol) and following the
general procedure, we obtained the silylated compound 13, as
a crude that was pure enough for further transformation.
Using the general procedure, after flash chromatography (4:1
C15H18O7: C, 58.06; H, 5.85. Found: 57.85; H, 6.10. 18: oil;
1
[R]25 +6 (c 0.69, CHCl3); IR (film) νmax 1760-1720 cm-1; H
D
NMR (300 MHz, CDCl3) δ 5.43 (d, J ) 4.2 Hz, 1 H), 4.83-4.68
(m, 3 H), 4.11 (dd, J ) 12.0 Hz, J ) 5.7 Hz, 1 H), 4.00 (dd, J
) 12.0 Hz, J ) 3.0 Hz, 1 H), 3.70 (ddd, J ) 5.7, 3.0, 2.8 Hz, 1
H), 3.28 (m, 1 H), 3.02 (t, J ) 6.0 Hz, 1 H), 2.11, 2.04 (s, s, 3
H, 3 H), 1.82 (br s, 3 H); 13C NMR (75 MHz, CDCl3) δ 207.1,
170.4, 169.4, 169.3, 133.3, 98.4, 74.1, 66.2, 65.8, 63.1, 50.6, 46.3,
20.7, 20.55, 9.2. Anal. Calcd for C15H18O7: C, 58.06; H, 5.85.
Found: 57.95; H, 6.08.
P a u son -Kh a n d P r od u ct 19. Starting from compound 3

7670 J . Org. Chem., Vol. 61, No. 22, 1996
Marco-Contelles
(121 mg, 0.38 mmol) and following the general procedure (2 h
30 min for the formation of the complex and 2 h for the NMO
treatment), after flash chromatography (2:3 hexanes-ethyl
for the formation of the complex and overnight for the NMO
treatment), after flash chromatography (4:1 hexanes-ethyl
acetate) compound 21 (204 mg, 62% yield) was obtained: oil;
[R]25D +160 (c 1.16, EtOH); IR (film) νmax 1760-1720 cm-1; 1H
NMR (300 MHz, CDCl3) δ 5.70 (br s, 1 H), 4.79 (d, J ) 7.7 Hz,
1 H), 3.99 (s, 2 H), 3.90-3.86 (m, 2 H), 3.66 (dd, J ) 11.1, 6.5
Hz, 1 H), 3.41 (m, 1 H), 3.09 (s, 3 H), 2.87 (dd, J ) 7.7, 7.5 Hz,
1 H), 2.67 (m, 1 H), 0.89, 0.087 (s, s, 9 H, 6 H); 13C NMR (75
MHz CDCl3) δ 206.9, 178.6, 125.1, 96.5, 70.6, 66.6, 65.2, 63.0,
55.2, 51.7, 45.4, 25.8, 18.3, -5.4. Anal. Calcd for C17H28O5Si:
C, 59.96; H, 8.28. Found: C, 59.75; H, 8.02.
acetate) compound 19 (51 mg, 41% yield) was obtained: oil;
1
[R]25 -57 (c 1.9, CHCl3); IR (film) νmax 1760-1720 cm-1; H
D
NMR (300 MHz, CDCl3) δ 5.95 (br s, 1 H), 4.78 (d, J ) 5.2 Hz,
1 H), 4.76 (d, J ) 15.8 Hz, 1 H), 4.71 (d, J ) 15.8 Hz, 1 H),
4.33 (dd, J ) 5.2, 9.1 Hz, 1 H), 3.91 (dd, J ) 11.2, 2.2 Hz, 1
H), 3.74 (dd, J ) 11.2, 6.7 Hz, 1 H), 3.48 (ddd, J ) 2.2, 6.7 Hz,
10.5 Hz, 1 H), 3.41 (m, 1 H), 3.29 (s, 3 H), 2.79 (dd, J ) 10.5,
6.6 Hz, 1 H), 0.89, 0.087 (s, s, 9 H, 6 H); 13C NMR (75 MHz
CDCl3) δ 209.1, 182.6, 121.5, 98.3, 71.7, 65.4, 67.4, 64.5, 55.4,
47.5, 44.9, 25.8, 18.3, -5.4. Anal. Calcd for C17H28O5Si: C,
59.96; H, 8.28. Found: C, 59.77; H, 8.47.
P a u son -Kh a n d P r od u ct 22. Starting from compound 6
(289 mg, 0.62 mmol) and following the general procedure (1 h
for the formation of the complex and 4 h for the NMO
treatment), after flash chromatography (4:1 hexanes-ethyl
acetate) compound 22 (166 mg, 53% yield) was obtained: oil;
P a u son -Kh a n d P r od u ct 20. Starting from compound 4
(31 mg, 0.13 mmol) and following the general procedure (3 h
for the formation of the complex and 3 h for the NMO
treatment), after flash chromatography (1:1 hexanes-ethyl
acetate) compound 20 (10 mg, 30% yield) was obtained as a
[R]25 +136 (c 1.08, CHCl3); IR (film) νmax 1760-1720 cm-1
;
D
1H NMR (300 MHz, CDCl3) δ 7.70-7.30 (m, 10 H), 5.90 (br s,
1 H), 5.76 (m, 1H), 5.06 (d, J ) 7.6 Hz, 1 H), 5.15-5.00 (m, 2
H), 4.59 (d, J ) 15.8 Hz, 1 H), 4.50 (d, J ) 15.8 Hz, 1 H), 4.42
(ddd, J ) 15.7, 1.5, 1.5 Hz, 1 H), 4.38 (ddd, J ) 15.7 Hz, J )
1.5, 1.5 Hz, 1 H), 3.98 (m, 1 H), 3.76 (dd, J ) 11.3, 6.5 Hz, 1
H), 3.62 (dd, J ) 11.3, 2.2 Hz, 1 H), 3.40 (ddd, J ) 6.5, 2.2, 9.1
Hz, 1 H), 3.26 (m, 1 H), 3.16 (dd, J ) 7.6, 7.1 Hz, 1 H), 0.89 (s,
9H); 13C NMR (75 MHz CDCl3) δ 206.7, 178.3, 133.5, 135.6,
133.4, 129.6, 127.6, 125.1, 116.4, 94.3, 70.7, 66.8, 67.8, 65.2,
63.9, 51.6, 45.5, 26.7, 19.1. Anal. Calcd for C29H34O5Si: C,
70.98; H, 6.98. Found: C, 70.65; H, 6.77.
solid: mp 145-148 °C; [R]25 -190 (c 0.13, CHCl3); IR (film)
D
1
νmax 1760-1720 cm-1; H NMR (300 MHz, CDCl3) δ 6.07 (br
s, 1 H), 4.76 (br s, 2 H), 4.40 (d, J ) 5.1 Hz, 1 H), 4.36 (d, J )
8.4 Hz, 1 H), 3.91 (dd, J ) 11.1, 6.0 Hz, 1 H), 3.62 (dd, J )
11.1, 9.9 Hz, 1 H), 3.49-3.43 (m, 2 H), 3.27 (ddd, J ) 6.0, 9.9,
5.7 Hz, 1 H), 1.42, 1.47 (s, s, 3 H, 3 H); 13C NMR (75 MHz
CDCl3) δ 203.5, 179.0, 121.8, 99.6, 77.1, 76.5, 71.7, 68.9, 65.4,
61.6, 47.9, 28.9, 18.3. Anal. Calcd for C13H16O5: C, 61.89; H,
6.39. Found: C, 61.57; H, 6.11.
P a u son -Kh a n d P r od u ct 21. Starting from compound 5
(302 mg, 0.97 mmol) and following the general procedure (3 h
J O961138W