Synthesis of vinyl- and alkynylcyclopentanetetraols by SmI2/Pd(0)-promoted carbohydrate ring-contraction

Article abstract of DOI:10.1021/jo0005619

A variety of vinyl- or alkynyl-substituted polyhydroxylated cyclopentanes and cyclobutanes are prepared in enantiomerically pure form from appropriate carbohydrate precursors, in a direct one-step ring-contraction procedure promoted by SmI₂ and catalytic Pd(0). This reaction is thought to proceed through intermediate ring-opened allyl- or allenylsamarium complexes that undergo ring-closure by intramolecular carbonyl addition. A predominant trans relationship is found between vinyl (or alkynyl) and hydroxyl groups at the two newly created stereogenic centers, with good to excellent levels of stereoselectivity being observed in the formation of homopropargyl cyclopentanol products. Under appropriate conditions, preparatively useful yields are realized of stereoisomers not directly available using alternative methodology.

Full text of DOI:10.1021/jo0005619

J . Org. Chem. 2000, 65, 6493-6501
6493
Syn th esis of Vin yl- a n d Alk yn ylcyclop en ta n etetr a ols by
Sm I2/P d (0)-P r om oted Ca r boh yd r a te Rin g-Con tr a ction
J ose´ M. Aurrecoechea,* Beatriz Lo´pez, and Mo´nica Arrate
Departamento de Quı´mica Orga´nica, Facultad de Ciencias, Universidad del Pa´ıs Vasco,
Apartado 644, 48080 Bilbao, Spain
qopaufem@lg.ehu.es
Received April 13, 2000
A variety of vinyl- or alkynyl-substituted polyhydroxylated cyclopentanes and cyclobutanes are
prepared in enantiomerically pure form from appropriate carbohydrate precursors, in a direct one-
step ring-contraction procedure promoted by SmI2 and catalytic Pd(0). This reaction is thought to
proceed through intermediate ring-opened allyl- or allenylsamarium complexes that undergo ring-
closure by intramolecular carbonyl addition. A predominant trans relationship is found between
vinyl (or alkynyl) and hydroxyl groups at the two newly created stereogenic centers, with good to
excellent levels of stereoselectivity being observed in the formation of homopropargyl cyclopentanol
products. Under appropriate conditions, preparatively useful yields are realized of stereoisomers
not directly available using alternative methodology.
In tr od u ction
groups capable of further synthetic transformations.
Thus, the use of allylzirconium species generated from
vinyl carbohydrate derivatives I has produced carbocycles
III by intramolecular allylation, in a direct one-pot
Besides their biological relevance,1 carbohydrates are
also becoming increasingly important in synthesis due
inter alia to a high chirality content that can be trans-
ferred into a variety of products, leading to the construc-
tion of functionalized chiral carbocyclic and heterocyclic
building blocks.2 The transformation of carbohydrate
derivatives into functionalized carbocycles has been most
commonly achieved by multistep protocols involving the
initial conversion of the carbohydrate into suitably func-
tionalized open-chain products, followed by ring closure
using conventional procedures.3 Alternatively, the cyclic
carbohydrate skeleton has been extensively used as a
template on which to build the carbocyclic structure,
using the chirality and functionalization of the carbohy-
drate both as stereocontrolling elements and versatile
synthetic tools.4 In contrast, the direct one-pot generation
of a carbocyclic structure from the carbon framework of
a carbohydrate derivative is much less common.2h,5
Furthermore, in some instances, the conversion of car-
bohydrates into carbocycles makes use of methodology
that leaves the resulting carbocycle devoid of some of the
functionality present in the original carbohydrate-derived
substrate. This last aspect acquires particular relevance
when the products need to be further elaborated into
more complex targets. Among others,2h methods based
on the intramolecular carbonyl addition of allyl-6,7 or
propargyl-8 metals overcome this problem, as the result-
ing products retain versatile and useful unsaturated
(3) See reviews 2c, 2d, 2f and recent references not included there:
(a) Grove´, J . J . C.; Holzapfel, C. W. Tetrahedron Lett. 1997, 38, 7429-
7432. (b) Boiron, A.; Zillig, P.; Faber, D.; Giese, B. J . Org. Chem. 1998,
63, 5877-5882. (c) Storch de Gracia, I.; Dietrich, H.; Bobo, S.; Chiara,
J . L. J . Org. Chem. 1998, 63, 5883-5889. (d) Ziegler, F. E.; Wang, Y.
Z. J . Org. Chem. 1998, 63, 7920-7930. (e) Keck, G. E.; Wager, T. T.;
McHardy, S. F. J . Org. Chem. 1998, 63, 9164-9165. (f) Go´mez, A. M.;
Danelo´n, G. O.; Valverde, S.; Lo´pez, J . C. J . Org. Chem. 1998, 63,
9626-9627. (g) Bennett, S. M.; Biboutou, R. K.; Zhou, Z. H.; Pion, R.
Tetrahedron 1998, 54, 4761-4786. (h) Marco-Contelles, J .; Rodr´ıguez,
M. Tetrahedron Lett. 1998, 39, 6749-6750. (i) Bennett, S. M.; Biboutou,
R. K.; Salari, B. S. F. Tetrahedron Lett. 1998, 39, 7075-7078. (j)
Hyldtoft, L.; Poulsen, C. S.; Madsen, R. Chem. Commun. 1999, 2101-
2102. (k) Kapferer, P.; Sarabia, F.; Vasella, A. Helv. Chim. Acta 1999,
82, 645-656. (l) Dransfield, P. J .; Moutel, S.; Shipman, M.; Sik, V. J .
Chem. Soc., Perkin Trans. 1 1999, 3349-3355. (m) Clive, D. L. J .; He,
X.; Postema, M. H. D.; Mashimbye, M. J . J . Org. Chem. 1999, 64,
4397-4410. (n) Keck, G. E.; McHardy, S. F.; Murry, J . A. J . Org. Chem.
1999, 64, 4465-4476. (o) Matsugi, M.; Gotanda, K.; Ohira, C.;
Suemura, M.; Sano, A.; Kita, Y. J . Org. Chem. 1999, 64, 6928-6930.
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J . L. Synlett 1999, 1551-1554. (r) Marco-Contelles, J .; de Opazo, E.
Tetrahedron Lett. 1999, 40, 4445-4448. (s) Boss, O.; Leroy, E.; Blaser,
A.; Reymond, J .-L. Org. Lett. 2000, 2, 151-154. (t) Callam, C. S.;
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Go´mez, A. M.; Manteco´n, S.; Valverde, S.; Lo´pez, J . C. J . Org. Chem.
1997, 62, 6612-6614. (b) Bar, N. C.; Roy, A.; Achari, B.; Mandal, S.
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* To whom correspondence should be addressed. Phone: 34-94 601
2578; Fax: 34-94 464 8500.
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10.1021/jo0005619 CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/14/2000

6494 J . Org. Chem., Vol. 65, No. 20, 2000
Aurrecoechea et al.
Sch em e 1
Sch em e 2
carbohydrate ring-contraction (Scheme 1).7j,7k This pro-
cedure has proven very effective in the formation of
polyhydroxylated vinyl-substituted cyclopentanes and
cyclobutanes, amenable to further transformation into
biologically active substances.7j,k However, it gave poor
results when a triple bond was utilized in place of the
vinyl group.9 A general method for direct conversion of
carbohydrate-like structures into vinyl- or alkynyl-func-
tionalized enantiomerically pure carbocycles would be a
useful addition to the organic chemist synthetic reper-
toire.
We have recently reported an efficient SmI2/Pd(0)-
promoted intramolecular propargylation of carbonyl groups
using propargylic ester substrates IV (Scheme 2) as
synthetic equivalents of the propargyl anion synthon.8
This reaction is thought10 to involve the initial formation
of an allenylpalladium complex VI that is rapidly reduced
11
by SmI2 to an equilibrium mixture of allenic (VII) and
propargylic (VIII) organosamarium intermediates that
finally add to the carbonyl group. An important limitation
of this procedure is the requirement that a tethered
ketone carbonyl group must be employed to obtain good
yields of the corresponding homopropargyl cycloalkanol
products IX. When aldehydes are used, rapid SmI2-
promoted carbonyl reduction and/or reductive dimeriza-
tion prevail over formation of IX. In an effort to overcome
this limitation, we hypothesized that related substrates
V derived from the corresponding propargylic lactols,
when treated with SmI2/Pd(0), could also enter the
pathway VI-through-VII/VIII to afford the same prod-
ucts IX. It was realized that the aldehyde function, which
is masked in V, would be released into the reaction
medium simultaneously with the allenylpalladium moi-
ety. In this way, control of the amount of free aldehyde
present in the medium, exerted by the molar percentage
of catalyst used, could lead to minimization of side
reactions. We have successfully applied this procedure
to the synthesis of certain bicyclic homopropargyl alco-
hols12,13 from lactol esters V and now report the extension
of this chemistry to the direct conversion of vinyl- and
alkynylpyranosides or furanosides, derived from natu-
rally ocurring carbohydrates, into functionalized enan-
tiomerically pure cyclopentanes or cyclobutanes, respec-
tively.14
(7) Recent intramolecular allylations with allylmetals: Zinc (a)
Marshall, J . A.; McNulty, L. M.; Zou, D. J . Org. Chem. 1999, 64, 5193-
5200. Tin (b) Denmark, S. E.; Almstead, N. G. J . Org. Chem. 1994,
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1995, 299-305. (k) J enkins, D. J .; Riley, A. M.; Potter, B. V. L. J . Org.
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Chem. 1996, 61, 4496-4497. (m) Masse, C. E.; Dakin, L. A.; Knight,
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Watanabe, T.; Sakai, M.; Miyaura, N.; Suzuki, A. J . Chem. Soc., Chem.
Commun. 1994, 467-468. Samarium (o) Tabuchi, T.; Inanaga, J .;
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(8) Recent intramolecular propargylations of carbonyl compounds:
Aurrecoechea, J . M.; Fan˜ana´s, R.; Arrate, M.; Gorgojo, J . M.; Aurreko-
etxea, N. J . Org. Chem. 1999, 64, 1893-1901, and references therein.
(9) Yoshida, Y.; Nakagawa, T.; Sato, F. Synlett 1996, 437-438.
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2275-2278.
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Imamoto, T. Lanthanides in Organic Synthesis; Academic Press:
London, 1994. (b) Molander, G. A. In Organic Reactions; Paquette, L.
A., Ed.; J ohn Wiley & Sons: New York, 1994; Vol. 46, pp 211-367. (c)
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Resu lts
Syn th esis of 6-En o- a n d 6-Yn op yr a n osid es. The
substrates used in this study were synthesized from
(12) Aurrecoechea, J . M.; Fan˜ana´s-San Anto´n, R. J . Org. Chem.
1994, 59, 702-704.
(13) Aurrecoechea, J . M.; Fan˜ana´s, R.; Lo´pez, B. Arkivoc 2000, 1
(2), 124-139.
(14) A part of these results has been previously communicated: (a)
Aurrecoechea, J . M.; Lopez, B. Tetrahedron Lett. 1998, 39, 2857-2860.
For other recent SmI2-promoted carbohydrate to carbocycle conver-
sions, see: (b) Enholm, E. J .; Trivellas, A. J . Am. Chem. Soc. 1989,
111, 6463-6465. (b) Enholm, E. J .; Satici, H.; Trivellas, A. J . Org.
Chem. 1989, 54, 5841-5843. (c) Tadano, K.; Isshiki, Y.; Minami, M.;
Ogawa, S. J . Org. Chem. 1993, 58, 6266-6279. (d) Enholm, E. J .;
Trivellas, A. Tetrahedron Lett. 1994, 35, 1627-1628. (e) Chiara, J . L.;
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Synlett 1995, 277-279. (g) Grove, J . J . C.; Holzapfel, C. W.; Williams,
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Ferna´ndez-Mayoralas, A.; J aramillo, C. J . Org. Chem. 1997, 62, 1916-
1917. (i) Marco-Contelles, J .; Gallego, P.; Rodr´ıguez-Ferna´ndez, M.;
Khiar, N.; Destabel, C.; Bernabe´, M.; Mart´ınez-Grau, A.; Chiara, J . L.
J . Org. Chem. 1997, 62, 7397-7412. See also 2h, 3b, 3c, 3 g, 3i, 3p, 3q,
and 5d.

Synthesis of Vinyl- and Alkynylcyclopentanetetraols
J . Org. Chem., Vol. 65, No. 20, 2000 6495
Sch em e 3
Sch em e 4
promoted elimination of a C4-alkoxide from an anion
intermediate 7 (Scheme 4). The same problem was
encountered in the attempted direct one-step alkynyla-
tion of 2d with dimethyl 1-diazo-2-oxopropylphospho-
nate,28 that yielded the corresponding enyne 8 (P1 ) Bn;
P ) H) in very good yield (83%), instead of the expected
5d . The alternative use of lithium trimethylsilyldiaz-
omethane29 was essayed with 2a but this did not signifi-
cantly improve the yield of the Corey-Fuchs procedure,
and purification of the product was more troublesome.
Treatment of acetals 3 or 5 with Ac2O/H2SO430 led to the
corresponding acetates 4 or 6, respectively (56-90%
yields). These were generally obtained as diastereomeric
mixtures at C1, where the R-anomer predominated.
Rea ction s of 6-En op yr a n osid es w ith Sm I2/P d (0).
Substrates 3 and 4 were reacted under a variety of
conditions with SmI2 (3 equiv) and a catalytic amount of
a Pd(0) complex (5-10 mol %) to afford in all cases the
expected cyclopentanols 9 as diastereomeric mixtures
(Table 1). In a control experiment, treatment of 3c with
SmI2 alone yielded recovered starting material. In gen-
eral, acetals 3 required refluxing in THF for conversion
into 9, whereas, as expected based on leaving group
abilities, acetates 4 were more reactive and afforded 9
already at room temperature. In all reactions run under
refluxing conditions with Pd(Ph3P)4 as catalyst (entries
1, 3, 6, 9), the major diastereoisomer of 9 had a trans
relationship between substituents at the two new ste-
reogenic centers (C1, C5) created upon cyclization, while
the relative orientation of these with respect to the
resident substituents was substrate dependent. Thus, the
major diastereoisomer of 9a and 9b, derived from glucose
and mannose, respectively, had a free hydroxyl group on
the face of the molecule opposite to that occupied by the
adjacent OBn, whereas the reverse was true for the
galactose-derived 9c and 9d . The second most abundant
product in these high-temperature reactions displayed
in all cases a cis relationship between the OH and vinyl
groups, while the relative orientation of OH and adjacent
OBn in these isomers was always trans. In contrast,
reactions run at room temperature with the same cata-
lyst had a tendency to yield increasing amounts of cis
products (entries 5, 7, 8), the exception being the reaction
of acetate 4a (entry 2) where the trans selectivity actually
increased at room temperature. Surprisingly, the galac-
tose-derived substrate 3c (â-anomer) was found to be
much more reactive than the corresponding glucose- and
mannose-derived 3a ,b (R-anomers), and it could be
converted into cyclopentane 9c in very high yield already
at room temperature (Table 1, entry 7). However, this
also resulted in a significant decrease of diastereoselec-
tivity, as nearly equal amounts of cis- and trans-products
were obtained.
commercially available carbohydrate derivatives as shown
in Scheme 3. Thus, methyl gluco-, manno-, and galacto-
pyranosides were transformed into alcohols 1 using
conventional protection-deprotection protocols.15 Swern
oxidation of 1, according to the procedure described by
Sinay¨,23 afforded aldehydes 2. After azeotropic removal
of water of hydration, these were submitted to olefination
or alkynylation procedures to yield vinyl- or ethynyl-
carbohydrate derivatives 3 or 5, respectively, as outlined
in Scheme 3. Thus, the standard Wittig olefination
conditions with Ph3PdCH2 gave good overall yields (46-
76%, two steps from 1) of 6-enopyranosides 3. For the
synthesis of alkynes 5, modified Corey-Fuchs24 proce-
dures25-27 were applied, the best overall results being
obtained with the use of CBr4/Ph3P/Et3N at room tem-
perature26 for initial dibromoolefin formation, and LDA
at -78 °C27 in the final elimination step. Slow addition
of LDA and careful monitoring of the progress of the
reaction were found important. This procedure avoided
the presence of excess base in the reaction mixture, which
otherwise led to the formation of enynes 8 by base-
(15) Benzyl-protected methyl gluco-,16 manno-17 and galacto-18 pyra-
nosides 1a -c were prepared according to the three-step procedure
described in ref 19. tert-Butyldimethylsilylation of the primary alcohol
in methyl 3, 4-O-isopropylidene-â-D-galactopyranoside,20 followed by
benzylation and desilylation afforded alcohol 1d .
(16) Bernet, B.; Vasella, A. Helv. Chim. Acta 1979, 62, 1990-2016.
(17) Boren, H. B.; Eklind, K.; Garegg, P. J .; Lindberg, B.; Pilotti, A.
Acta Chem. Scand. 1972, 26, 4143-4146.
(18) Gorin, P. A. Carbohydr. Res. 1982, 101, 13-20.
(19) J aramillo, C.; Chiara, J . L.; Mart´ın-Lomas, M. J . Org. Chem.
1994, 59, 3135-3141.
(20) Flowers, H. M. Carbohydr. Res. 1975, 39, 245-251. Prepared
following the procedure described for its R-anomer.21,22
(21) Buchanan, J . G.; Saunders, R. M. J . Chem. Soc. 1964, 1796-
1803.
(22) Umezawa, S.; Okazaki, Y.; Tsuchiya, T. Bull. Chem. Soc. J pn.
1972, 45, 3619-3624.
(23) Chenede, A.; Pothier, P.; Sollogoub, M.; Fairbanks, A. J .; Sinay¨,
P. J . Chem. Soc., Chem. Commun. 1995, 1373-1374.
(24) Corey, E. J .; Fuchs, P. L. Tetrahedron Lett. 1972, 3769-3772.
(25) Goekjian, P. G.; Wu, T. C.; Kang, H. Y.; Kishi, Y. J . Org. Chem.
1991, 56, 6422-6434.
(26) Marshall, J . A.; Bartley, G. S.; Wallace, E. M. J . Org. Chem.
1996, 61, 5729-5735.
(27) Mourin˜o, A.; Torneiro, M.; Vitale, C.; Ferna´ndez, S.; Pe´rez-
Sestelo, J .; Anne, S.; Gregorio, C. Tetrahedron Lett. 1997, 38, 4713-
4716.
(28) Muller, S.; Liepold, B.; Roth, G. J .; Bestmann, H. J . Synlett
1996, 521-522.
(29) Miwa, K.; Aoyama, T.; Shioiri, T. Synlett 1994, 107-108.
(30) Sondheimer, S. J .; Eby, R.; Schuerch, C. Carbohydr. Res. 1978,
60, 187-192.

6496 J . Org. Chem., Vol. 65, No. 20, 2000
Ta ble 1. Rea ction s of Vin ylp yr a n osid es 3 a n d 4 w ith Sm I2/P d (0)a
Aurrecoechea et al.
a
b
Unless otherwise indicated, 3 equiv of SmI2 and 5 mol % of Pd(0) were used. A ) Pd(Ph3P)4; B ) Pd(OAc)2‚4Bu3P; C ) Pd(OAc)2‚Bu3P.
c Where several diastereoisomers were obtained, only structures for the two major isomers are displayed, along with their overall relative
d
amounts within brackets. Isolated total yield of 9. Diastereomeric ratios determined by weight of isolated diastereoisomers after
chromatographic separation. e Trans and cis refer to relative orientation of vinyl and hydroxy groups. f Bath temperature. (R:â ) 4.3:1).
g
h
i
j
k
Yield based on recovered starting material. â-OMe. R:â ) 3.8:1. A second portion of Pd(Ph3P)4 (5 mol %) was added after 2 h (total
reaction time 15 h).
In reactions of allylic acetates, the use of equimolar
amounts of Pd(OAc)2 and n-Bu3P, Pd(OAc)2‚Bu3P, as an
in situ source of Pd(0), has been shown to give improved
results in terms of yield and diastereoselectivity.31-34
However, in the two cases where we have applied this
catalyst system, there was in fact a drop in stereoselec-
tivity, and starting materials were partially recovered
(Table 1, entries 4 and 11). Alternatively, the use of a
1:4 ratio of Pd(OAc)2 to n-Bu3P, Pd(OAc)2‚4Bu3P, which
proved beneficial with 5 and 6 (vide infra), led to a further
drop in reactivity, as 3b was recovered unchanged,
whereas 4a and 4b underwent extensive decomposition,
and only 3d afforded the desired product, albeit in low
yield and with poor stereoselectivity (Table 1, entry 10).
Rea ction s of 6-Yn op yr a n osid es w ith Sm I2/P d (0).
The corresponding use of the alkynyl derivatives 5 and
6 resulted in the obtention of homopropargyl cyclopen-
tanols 10. Reaction conditions, yields, and diastereomeric
ratios are collected in Table 2. These reactions displayed
some significantly different features with respect to their
vinylic counterparts. Thus, under appropriate conditions,
the use of pyranosyl acetates in place of methyl pyrano-
sides led invariably to higher yields and diastereoselec-
tivities.35 Also beneficial was the incorporation of n-Bu3P
as Pd ligand (entries 3, 7, 12). Moreover, the levels of
trans selectivity (ethynyl and OH groups) were much
higher in these series, to the exclusion of cis products in
some cases.
In common with the vinyl series, diastereoselectivity
was again substrate-dependent. Thus, while the man-
nose-derived cyclopentanol 10b was formed preferentially
with the same trans configuration (1S,5S) as the corre-
sponding major vinylic product 9b, opposite trans con-
figurations were obtained for the major vinyl- (9a , 1R,5R)
and alkynyl- (10a , 1S,5S) diastereoisomers in the gluco-
series, and the galacto-derivatives displayed a mixed
behavior that was dependent on both the peripheral
protecting groups and the ligands used in the Pd catalyst.
Thus, the reactions of the benzyl-protected substrates 5c
and 6c with SmI2 and Pd(Ph3P)4 afforded preferentially
the 10c diastereoisomer with (1R, 5R) configuration,
which is opposite to that obtained from the corresponding
vinyl derivatives, whereas the use of Pd(OAc)2‚4Bu3P led
predominantly to the (1S, 5S)-isomer. This was the
(31) Mandai, T.; Matsumoto, T.; Kawada, M.; Tsuji, J . J . Org. Chem.
1992, 57, 1326-1327.
(32) Mandai, T.; Matsumoto, T.; Kawada, M.; Tsuji, J . J . Org. Chem.
1992, 57, 6090-6092.
(33) Mandai, T.; Matsumoto, T.; Tsuji, J . Tetrahedron Lett. 1993,
34, 2513-2516.
(35) However, acetates 6 underwent slow degradation when reacted
at temperatures that presumably did not lead to efficient oxidative
additions. See, for example, entries 6 and 7 in Table 2.
(34) Oppolzer, W.; Flachsmann, F. Tetrahedron Lett. 1998, 39,
5019-5022.

Synthesis of Vinyl- and Alkynylcyclopentanetetraols
J . Org. Chem., Vol. 65, No. 20, 2000 6497
Ta ble 2. Rea ction s of Alk yn ylp yr a n osid es 5 a n d 6 w ith Sm I2/P d (0)a
a
b
Unless otherwise indicated, 3 equiv of SmI2 and 5 mol % of Pd(0) were used. A ) Pd(Ph3P)4; B ) Pd(OAc)2‚4Bu3P. c Where several
diastereoisomers were obtained, only structures for the two major isomers are displayed, along with their overall relative amounts within
d
brackets. Isolated total yield of 10. Diastereomeric ratios determined by weight of isolated diastereoisomers after chromatographic
separation. e Trans and cis refer to relative orientation of ethynyl and hydroxy groups. f Bath temperature. g Also obtained was cyclobutanol
h
i
18 (7%) (see Scheme 6). The two isomers of undetermined stereochemistry were isolated in relative amounts of 17% and 7%. One other
isomer (stereochemistry not determined) was isolated in 9% relative amount. Also isolated were lactol 5b-OH (X ) H) (30%), benzyl
alcohol (29%), and benzyl acetate. Substrate degradation. â-OMe. R:â ) 71:29.
j
k
l
m
Sch em e 5
with moderate yield and trans-stereoselectivity at the
vinyl- and hydroxy-bearing stereogenic centers. However,
analogous Bn-protected substrates only reacted under
refluxing conditions, and this led to substrate degrada-
tion and formation of benzyl alcohol as the only identifi-
able product. The reaction of the propargylic substrate
13 at room temperature led to a low yield of the
corresponding homopropargyl alcohol 14.
Ster eoch em ica l Elu cid a tion . In most cases the dia-
stereoisomers were readily separated by liquid chroma-
tography. Vinylcyclopentanols (1R,5S)-9a , (1S,5R)-9b,
and (1S,5R)-9c were characterized by direct comparison
of their 1H and 13C NMR spectra with data previously
reported in the literature for the same compounds.37 The
stereochemical elucidation of the rest of isolated cycloal-
kanol products was made unambiguously with the aid
of NOE effects. As a general rule, for pairs of protons on
adjacent ring carbons, a percent NOE g 9 was taken as
almost exclusive configuration obtained for acetonide 10d
with both catalyst systems.
Rea ction s w ith F u r a n ose Der iva tives. The corre-
sponding transformations using furanose substrates were
also investigated (Scheme 5). The ring-contraction pro-
cedure using SmI2/Pd(0) led to the formation of cyclobu-
tane products, but the reaction does not appear to be of
general application. Thus, vinylacetonide 1136 afforded
at room temperature the homoallylic cyclobutanol 12
(36) Ryan, K. J .; Arzoumanian, H.; Acton, E. M.; Goodman, L. J .
Am. Chem. Soc. 1964, 86, 2503-2508. Prepared by Wittig olefination
with Ph3PdCH2 of the corresponding aldehyde precursor, itself pre-
pared according to: Barrett, A. G. M.; Lebold, S. A. J . Org. Chem. 1990,
55, 3853-3857.
(37) Ito, H.; Motoki, Y.; Taguchi, T.; Hanzawa, Y. J . Am. Chem. Soc.
1993, 115, 8835-8836.

6498 J . Org. Chem., Vol. 65, No. 20, 2000
Aurrecoechea et al.
Sch em e 6
capable of reaction at room temperature (Table 1, entry
7). The reason for this enhanced reactivity resides likely
in the less-hindered SN2′ approach of the palladium
catalyst when the C4 substituent is axial, rather than
in an inherently higher reactivity of the equatorially
disposed leaving group.39 This effect was not observed
in the corresponding propargylic substrate 5c, which is
expected to be intrinsically less reactive.40
Always latent in these reactions is the possibility of
unwanted elimination of a samarium alkoxide41 between
the organosamarium moiety and an adjacent alkoxy
substituent in intermediates analogous to VII, VIII
(Scheme 2). Indeed, a small amount (7%) of the allenyl
cyclobutanol 18 was isolated from the reaction of acetal
5a . This product may have formed by SmI2/Pd(0)-medi-
ated ring-opening and reduction, followed by elimination
and SmI2-promoted 4-exo-trig intramolecular addition42
of an enyne samarium ketyl radical 17. Remarkably, out
of all of the cyclopentane-forming reactions tested, this
was the only instance that such a kind of product was
observed. It is therefore concluded that, if organosamari-
ums analogous to 15 are indeed intermediates in these
reactions, their cyclization is faster than the alternative
competing elimination.
The reactions reported here are related to the
“Cp2Zr”/BF3-promoted ring contraction of 6-enopyrano-
sides37 that affords the same vinylcyclopentanols through
the intermediacy of allylzirconium species II (Scheme 1).
However, the corresponding reactions with 6-ynopyra-
nosides have not been reported, and attempts to carry
out an analogous transformation on non-carbohydrate
substrates gave poor results.9 Alternatively, the synthesis
of simple alkynylcyclopentanols has been possible using
allenyltitanium intermediates in a related ring-contrac-
tion method.9 Comparison of our reactions with these
precedents shows remarkable differences in stereochem-
ical trends. Thus, while the SmI2/Pd(0) reaction gives a
high incidence of trans products, the “Cp2Zr”/BF3-
promoted ring contraction of 6-enopyranosides affords the
corresponding cis-vinylcyclopentanols, and the titanation
of related non-carbohydrate alkynyl substrates with Ti-
(Oi-Pr)4/i-PrMgCl also leads to cis products predomi-
nantly. Therefore, this SmI2/Pd(0)-promoted reaction and
the existing methods are stereochemically complemen-
tary. Also worthy of note, with the exception of 9a , the
cis isomers obtained from substrates 3 using the “Cp2Zr”/
BF3 method37 are not the same as those afforded by the
SmI2/Pd(0) reaction.
an indication of a cis relationship between those protons,
whereas values of NOE e 5 led normally to a trans
assignment. For pairs of protons on nonadjacent ring
carbons, the observation of NOE effects was interpreted
as indicative of cis relationships. All observed effects were
consistent with the assigned structures. A chart with the
most significant NOE data is included with the Support-
ing Information.
Discu ssion
The SmI2/Pd(0)-mediated direct conversion of 6-eno-
and 6-ynopyranosides into functionalized carbocycles is
a practical procedure for the preparation of enantiomeri-
cally pure functionalized carbocyclic building blocks.
Substrates are simply made in a few steps, with reliable
reactions, and the major carbocyclic products are in most
cases readily separated by liquid chromatography in
preparatively useful yields. For a given configuration of
the starting carbohydrate, different stereochemical out-
comes are possible depending mainly on (i) type of
substrate (allylic or propargylic); (ii) reaction conditions;
and (iii) palladium ligands. As a consequence, the method
gives ready access to stereoisomers which are not directly
available using alternative methodology.
The formation of cycloalkanol products is readily
rationalized as the result of a Pd(0)-promoted ring-
opening of 3-6, 11, 13, followed by reduction of an
intermediate π-allyl- or allenylpalladium complex (see,
for example, VI in Scheme 2 for allenyl case), and
carbonyl addition of the resulting organosamarium (eg
VII, VIII). The initial oxidative addition leading to VI
may be facilitated by coordination of the endocyclic or
exocyclic acetal-type oxygens of V to Lewis-acidic Sm-
(III) species, formed in the reduction step, or to SmI2
itself.38 Additionally, in six-membered cyclic substrates,
both axial and equatorial orientations of the exocyclic
leaving group are tolerated. While a higher degree of
concertedness is possible when the leaving group is
equatorial (e.g., 3c, 3d , 5c, 5d ), stereoelectronic as-
sistance provided by the endocyclic oxygen to an axially
oriented leaving group may also be beneficial, providing
oxocarbenium-like character during ring-opening. Inter-
estingly, out of all of the acetal derivatives 3 or 5, the
vinylic 3c, with an equatorial OMe, was the only one
For ring-closure reactions that proceed through allyl-
6,7f,37 or allenyl-propargyl organometallic intermediates,43
(39) Another factor that could play a role here is the electronic
interaction between the axially oriented C4 substituent in 3c and the
axial lone pair of ring oxygen. This has been shown to lead to higher
rates in the acid hydrolysis of certain galactopyranosides when
compared with the corresponding gluco-analogues. However, it should
be pointed out that these data apply to R-anomers that react with
substantial development of oxocarbenium-like character. See MiljKovic,
M.; Yeagley, D.; Deslongchamps, P.; Dory, Y. L. J . Org. Chem. 1997,
62, 7597-7604.
(40) Tsuji, J .; Mandai, T. Angew. Chem., Int. Ed. Engl. 1995, 34,
2589-2612.
(41) Previous examples of elimination of samarium alkoxides from
allenyl-propargyl intermediates: (a) Okamura, W. H.; Aurrecoechea,
J . M.; Gibbs, R. A.; Norman, A. W. J . Org. Chem. 1989, 54, 4072-
4083. (b) Aurrecoechea, J . M.; Solay-Ispizua, M. Heterocycles 1994, 37,
223-226. (c) Marco-Contelles, J.; Destabel, C.; Chiara, J. L. Tetrahedron-
Asymmetry 1996, 7, 105-108.
(42) The SmI2-promoted intramolecular 4-exo-trig addition of ketyl
radicals has been described: J ohnston, D.; McCusker, C. M.; Procter,
D. J . Tetrahedron Lett. 1999, 40, 4913-4916.
(38) Curran, D. P.; Gu, X.; Zhang, W.; Dowd, P. Tetrahedron 1997,
53, 9023-9042.

Synthesis of Vinyl- and Alkynylcyclopentanetetraols
J . Org. Chem., Vol. 65, No. 20, 2000 6499
the formation of cis products is usually interpreted in
terms of chelated “cyclic” transition states, whereas the
corresponding “open” transition states would lead to
trans products. High Lewis acidities of the organometallic
species involved in C-C bond formation favor the former
whereas weakly acidic organometallics and the presence
of strong external Lewis acids facilitate attainment of the
latter. In a close precedent, the intramolecular addition
of an oxyallylsamarium, generated from a vinyloxirane,
to an appended ketone at -30 °C affords a cyclized
product with cis stereochemistry, presumably through a
chelated transition state.7p Thus, in our case, the ob-
served stereochemical trends could be interpreted as the
result of competing chelated (X, XI) and nonchelated (XII,
XIII) transition structures originated from intermediate
(iii) palladium ligands. For vinylcyclopentanols 9, the
stereocontrolling element appears to be the tendency of
the free hydroxyl group to be oriented trans (probably
for steric reasons) to the adjacent alkoxy substituent.45
However, the opposite trend is frequently observed in the
formation of alkynylcyclopentanols 10 and, in one case,
the tendency is reversed with a change in Pd ligands.46
Clearly, the mechanistic aspects of these SmI2/Pd(0)-
promoted reactions appear to be somewhat more complex
than the simple picture just outlined, and a convincing
explanation for these observations cannot be given at this
point. Additional factors that would need to be considered
may include (i) the configuration and configurational
stability of the organometallic species involved in cy-
clization48 and (ii) the stereoelectronic impact6 of sub-
stituents upon the stereochemistry of cyclization. Par-
ticularly intriguing is the close similarity between the
stereochemical trends observed for reactions of vinyl
substrates 3 and those reported for SmI2-promoted radi-
cal cyclizations of carbohydrate-derived ω-unsaturated
aldehydes.49 To address these points, it would be helpful
to study simpler substrates to isolate the effect of each
individual substituent. At the same time, further changes
in the catalyst ligands and in the nature (e.g., Lewis
acidity) of the metal involved in cyclization might help
to better define the characteristics of the cyclization step.
Efforts toward these goals are under way and will be
reported in due course.
allylic or propargylic organosamariums in the ring-
closure step. In light of the foregoing precedent, the high
incidence of trans products observed in the SmI2-
promoted ring-contractions may be surprising. Thus, the
formation of cis products through chelates X, XI is
expected to be favored by the known high oxophilicity
associated to Sm(III) species. However, the alternative
XII, XIII, that leads to the corresponding trans products,
is similarly favored by coordination of the carbonyl group
to bulky solvated Sm(III) resulting from SmI2-promoted
reductions. Incidentally, these SmX3 species are expected
to be more Lewis acidic than the nucleophilic organosa-
mariums (RSmX2) directly involved in bond formation.
In this scenario, chelated structures would be more easily
attained from allylsamariums than from the linear
allenic-propargylic species, thus leading to the higher
trans selectivity observed for the latter. Also consistent
with this reasoning, in the allylic series, the formation
of trans products is observed to be favored by high
temperatures,44 that probably cause the rupture of the
samarium chelate. Conversely, the reported7p cyclization
of an oxyallylsamarium at -30 °C leads, as mentioned
above, to the exclusive formation of a cis product.
Con clu sion
The SmI2/Pd(0)-promoted carbohydrate ring-contrac-
tion provides easy access to a variety of stereochemically
defined enantiomerically pure carbocycles while preserv-
(45) The exception is the formation of 9c and 9d , where the
formation of the major isomer under refluxing conditions could be
explained by the intermediacy of the chelate i.
(46) The use of n-Bu3P ligands in place of Ph3P was initially
prompted by the apparent need for a more reactive Pd(0) in reactions
of acetates 6a and 6b, that were sluggish with Pd(Ph3P)4 (Table 2,
compare entries 2 and 5 with 3 and 7, respectively). The additional
observation of changes in diastereoselectivity with changes in the
Pd(0) ligands is interesting. It could be interpreted as an indication
that phosphane ligands are incorporated in the coordination sphere
of the Sm(III) species involved in cyclization. Alternatively, it has been
recently suggested47 that the SmI2/Pd(0)-promoted in situ generation
of allylsamarium intermediates may proceed through an oxidative
transmetalation pathway that would presumably involve bimetallic
species ii (R ) allyl). If ii rather than iii were also the nucleophilic
species involved in cyclization, changes in the palladium ligands could
bring about diastereoselectivity differences through changes in the
Lewis acidity and the electron-donating ability of the metallic moiety.
More difficult to explain is the relationship between
the configuration of C1, C5 and that of their respective
adjacent stereogenic centers in the formation of cyclo-
pentanols 9 and 10. This is found to be dependent on (i)
configuration and structural features of starting carbo-
hydrate, (ii) type of substrate (allylic or propargylic), and
(47) Marshall, J . A.; Grant, C. M. J . Org. Chem. 1999, 64, 8214-
8219.
(43) Kadota, I.; Hatakeyama, D.; Seki, K.; Yamamoto, Y. Tetrahe-
dron Lett. 1996, 37, 3059-3062.
(48) For example, the Pd(0)-mediated oxidative addition of propar-
gylic esters is kwown to take place with inversion of configuration and
the resulting allenylpalladium complexes appear to be configurationally
stable. However, no data are available on the preferred stereochemical
pathway of the ensuing reductive transmetalation to Sm. In any case,
the diastereoisomer distribution in most SmI2/Pd(0) ring-contraction
reactions indicates that, at least to some extent, stereochemical
scrambling takes place, probably at the organosamarium level.
(44) Examples of chelate-related, temperature-dependent stereose-
lectivity abound in SmI2 chemistry. See, for example: (a) Sturino, C.
F.; Fallis, A. G. J . Am. Chem. Soc. 1994, 116, 7447-7448. (b)
Kawatsura, M.; Dekura, F.; Shirahama, H.; Matsuda, F. Synlett 1996,
373-376. (c) Concello´n, J . M.; Bernad, P. L.; Pe´rez-Andre´s, J . A. J .
Org. Chem. 1997, 62, 8902-8906. (d) Matsuda, F.; Kawatsura, M.;
Hosaka, K.; Shirahama, H. Chem. Eur. J . 1999, 5, 3252-3259.

6500 J . Org. Chem., Vol. 65, No. 20, 2000
Aurrecoechea et al.
ture, and saturated NH4Cl (20 mL) was added. The aqueous
phase was extracted with Et2O, and the combined organic
extracts were dried (Na2SO4). The crude after evaporation was
purified by flash chromatography to yield alkenes 3. Purifica-
tion and characterization data are given in the Supporting
Information.
ing useful and versatile functionality in the final prod-
ucts. These features will enable their use as functional-
ized building blocks suitable for further elaboration into
more complex targets. A trans relationship between the
two newly created stereogenic centers is observed in
many cases and this nicely complements related existing
methodology for direct carbohydrate to carbocycle conver-
sion. In most cases, an appropriate choice of substrate
structural features and reaction conditions allows the
selective preparation of one stereoisomer out of four
possible, in preparatively useful yields.
Gen er a l P r oced u r es for Dibr om om eth ylen a tion of
Ald eh yd es 2. Method A: In a typical experiment, to a solution
of CBr4 (4.87 g, 14.7 mmol) in CH2Cl2 (8 mL) at 0 °C was added
dropwise a solution of Ph3P (7.74 g, 29.5 mmol) in CH2Cl2 (20
mL). The resulting slurry was allowed to reach rt and was
stirred further 20 min. The mixture was cooled to 0 °C, and a
solution of the appropriate aldehyde 2 (6.85 mmol) in CH2Cl2
(5 mL) was added dropwise. The mixture was allowed to reach
rt and, after 20 min, the resulting slurry was filtered trough
a SiO2 path (2 cm, φ ) 4.2 cm). The solid residue was washed
with CH2Cl2, and the residue after evaporation of the solvent
was purified by flash chromatography as indicated in the
Supporting Information for the individual cases. Method B:
In a typical experiment, to a solution of Ph3P (1.50 g, 5.74
mmol) in CH2Cl2 (4 mL) at room temperature was added
dropwise a solution of CBr4 (0.95 g, 2.87 mmol) in CH2Cl2 (3
mL). The resulting orange slurry was stirred 40 min at the
same temperature, and then Et3N (0.92 mL, 6.60 mmol) was
added. After cooling the resulting purple slurry to 0 °C, the
appropriate aldehyde 2 (1.43 mmol) in CH2Cl2 (3 mL) was
added dropwise. The mixture was allowed to reach rt and was
stirred at that temperature for 2 h. The solvents were partially
evaporated until 3-5 mL remained, and the resulting residue
was filtered through a SiO2 path (2 cm, φ ) 4.5 cm, saturated
with Et3N). The solid residue was washed with the minimum
volume of CH2Cl2 and then with 25% EtOAc/hexanes. The
resulting slurry was filtered, and the solvents were evaporated
at reduced pressure. The crude product was purified by flash
chromatography as indicated in the Supporting Information
for the individual cases.
Gen er a l P r oced u r es for Deh yd r obr om in a tion of Di-
br om oolefin s. P r ep a r a tion of Alk yn es 5. Method A: In a
typical experiment, n-BuLi (1.6 M in hexanes, 11.68 mmol)
was added dropwise to a solution of the appropriate dibro-
moolefin (5.17 mmol) in THF (9 mL) at -100 °C. The mixture
was kept at -80 °C for 10 min, it was then allowed to reach 0
°C, and H2O (10 mL) was added. The layers were separated,
the aqueous layer was extracted with Et2O, and the combined
organic extracts were dried (Na2SO4). The crude product was
purified by flash chromatography as indicated in the Support-
ing Information for the individual cases. Method B: In a typical
experiment, a solution of LDA (0.43 M in THF, 17.6 mmol)
was added dropwise to a solution of the appropriate dibro-
moolefin (8.0 mmol) in THF (35 mL) at -78 °C. Aditional
portions of LDA (0.43 M, 2 × 4.3 mmol) were added until
disappearance of the dibromoolefin as judged by TLC. After
addition of H2O (90 mL), the mixture was allowed to reach rt.
The layers were separated, the aqueous layer was extracted
with EtOAc, and the combined organic extracts were washed
with brine and then dried (Na2SO4). The residue obtained after
evaporation of the solvents was purified by flash chromatog-
raphy as indicated in the Supporting Information for the
individual cases.
Exp er im en ta l Section
Gen er a l. All reactions involving air- and moisture-sensitive
materials were performed using standard benchtop tech-
niques.53 Tetrahydrofuran (THF) was freshly distilled from
sodium/benzophenone and, for reactions with SmI2, it was
deoxygenated prior to use. Acetic anhydride, CH2Cl2, DMSO,
DMF, pyridine, triethylamine, and diisopropylamine were
distilled from CaH2. EtOH and MeOH were dried by treatment
with Mg-I2 and distillation. Carbon tetrabromide was purified
by sublimation. Triphenylphosphane was purified by recrys-
tallization from hexanes. n-Tributylphosphane (Fluka, 95%)
was used from a Sure-Seal bottle. Flash column chromatog-
raphy54 was performed on silica gel (230-400 mesh). HPLC
purifications were carried out with a LiChrosorb Si60 column
(7 µm, 25 × 2.5 cm) using a refraction index detector. Routine
1H and 13C NMR spectra were obtained at 250 and 62.9 MHz,
respectively, using CDCl3 as solvent and internal reference (δ
7.26 for 1H and δ 77.0 for 13C). IR data include only charac-
teristic absorptions. Mass spectra were obtained at 70 eV.
Gen er a l P r oced u r es for Oxid a tion of Alcoh ols 1 a n d
Wittig Meth ylen a tion . P r ep a r a tion of En op yr a n osid es
3. In a typical experiment, to a solution of oxalyl chloride (760
µL, 8.7 mmol) in CH2Cl2 (35 mL) at -40 °C under argon was
added dimethyl sulfoxide (710 µL, 10.0 mmol). After 10 min a
solution of 1 (6.7 mmol) in CH2Cl2 (12 mL) was added, and
the resulting mixture was stirred for 1 h at -40 °C. Triethy-
lamine (2.8 mL, 20.1 mmol) was then added, and the mixture
was allowed to reach rt over a period of 30 min. The solution
was successively extracted with saturated NaHCO3 and water
and dried (Na2SO4). Removal of the solvent in vacuo afforded
a residue that was dissolved in benzene and evaporated (three
times) to yield the intermediate aldehyde 2. Without further
manipulation, this crude aldehyde was used in the next step
as follows. n-BuLi (1.4 M in hexanes, 5.5 mL, 7.7 mmol) was
added to a suspension of methyltriphenylphosphonium bro-
mide (2.80 g, 7.84 mmol) in THF (28 mL) at 0 °C. After 30
o
min the mixture was cooled at -78 C, and a solution of the
foregoing aldehyde in THF (9 mL) was added. After 15 min,
the reaction mixture was allowed to warm to room tempera-
(49) Chiara, J . L.; Martinez, S.; Bernabe, M. J . Org. Chem. 1996,
61, 6488-6489. Intramolecular radical addition of samarium ketyls
to a CdC bond would be expected to afford trans products.50 One
possibility to enter a radical cyclization pathway would be the Pd(0)-
mediated isomerization of allylic substrates51 3 to generate ring-opened
intermediates iv capable of ketyl radical cyclization. However, attempts
to effect the isomerization of 3a or 3c to iv with Pd(Ph3P)4 under
refluxing conditions were unsuccessful, even in the presence of Lewis
acids.52
Gen er a l P r oced u r e for Acetolysis of Meth yl P yr a n o-
sid es 3 a n d 5. P r ep a r a tion of Aceta tes 4 a n d 6. In a typical
experiment, to a solution of 3 or 5 (0.54 mmol) in Ac2O (2.87
mL, 30.4 mmol) at 0 °C was added concd H2SO4 (26 µL, 0.49
mmol). After 8 min, the solution was poured over H2O (15 mL),
and solid NaHCO3 was added until neutral pH. The phases
were separated, and the aqueous layer was extracted with
CH2Cl2. The combined organic layers were washed with brine
and dried (Na2SO4). The residue after evaporation was purified
by flash chromatography as specified in the Supporting
Information for the individual cases.
(50) Curran, D. P.; Porter, N. A.; Giese, B. Stereochemistry of Radical
Reactions; VCH: New York,1996.
(51) Amatore, C.; J utand, A.; Meyer, G.; Mottier, L. Chem. Eur. J .
1999, 5, 466-473.
(52) Pe´rez, E., Aurrecoechea, J . M. Unpublished results.
(53) Brown, H. C.; Kramer, G. W.; Levy, A. B.; Midland, M. M.
Organic Synthesis Via Boranes; Wiley & Sons: New York, 1975.
(54) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923-
2925.
Rea ction s w ith Sm I2/P d (0). Preparation of Pd(0) catalyst
solutions: Pd(Ph3P)4 (catalyst A) was prepared using the
literature procedure55 and directly dissolved in admixture with
the substrate. A THF solution of Pd(OAc)2‚4Bu3P (catalyst B)

Synthesis of Vinyl- and Alkynylcyclopentanetetraols
J . Org. Chem., Vol. 65, No. 20, 2000 6501
was prepared by adding n-Bu3P (80 µL, 0.30 mmol) to a
solution of Pd(OAc)2 (15 mg, 0.07 mmol) in THF (4 mL). An
immediate color change from orange to yellow was observed.
A portion of this solution was immediately added to a solution
of the carbohydrate substrate in THF to obtain a final molar
ratio of substrate to catalyst of about 19:1. A THF solution of
Pd(OAc)2‚Bu3P (catalyst C) was similarly prepared using
n-Bu3P (37 µL, 0.14 mmol) and Pd(OAc)2 (31 mg, 0.14 mmol)
in THF (5 mL) and proceeding as indicated above for catalyst
B. Gen er a l Rin g-Con tr a ction P r oced u r e w ith Sm I2/-
P d (0). A SmI2 (ca. 0.1 M in THF) was prepared as reported11b
from Sm metal and diiodomethane. In a typical experiment,
to a solution of SmI2 (1.88 mmol) in THF (19 mL) was added
a mixture of the starting carbohydrate 3-6 or 11 or 13 (0.63
mmol) and the Pd(0) catalyst (0.03 mmol) in THF (4 mL). The
resulting solution was stirred at the temperature indicated
in Tables 1, 2 and Scheme 5 until consumption of the starting
material as judged by TLC (0.5-60 h). After cooling, saturated
K2CO3 (15 mL) was added. The layers were separated, the
aqueous layer was extracted with Et2O, and the combined
organic extracts were washed with brine and dried (Na2SO4).
The residue after evaporation was purified as specified in the
Supporting Information for the individual cases to afford 9,
10, 12, 14. Yields and specific reaction conditions are given in
Tables 1, 2 and Scheme 5. Characterization data is included
in the Supporting Information.
Ack n ow led gm en t. Financial support by the Direc-
cio´n General de Investigacio´n Cient´ıfica y Te´cnica
(DGICYT PB95-0344) and by the Universidad del Pa´ıs
Vasco (UPV 170.310-EC216/97 and UPV 170.310-EB001/
99) is gratefully acknowledged. We also thank the
Ministerio de Educacio´n y Cultura and the Departa-
mento de Educacio´n, Universidades e Investigacio´n
(Gobierno Vasco, Spain) for Fellowships to M.A. and
B.L.
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for all new compounds and experimental procedures for
1
1d , 13; copies of H NMR spectra for 4b, 5d , 6a , (1S,5R)-9a ,
(1R,5R)-9b, (1R,5S)-9c, (1R,5R)-9c, (1S,5R)-9d , (1R,5R)-9d ,
(1R,5S)-10a , 10a ′, 18, (1S,5S)-10b, (1S,5R)-10b, (1S,5S)-10c,
(1R,5R)-10c, (1S,5R)-10c, (1R,5R)-10d , 12, 14, and chart with
a summary of NOE data. This material is available free of
charge via the Internet at http://pubs.acs.org.
(55) Coulson, D. R. Inorg. Synth. 1972, 13, 121-124.
J O0005619