Highly Stereoselective approach to Alk-2-yne-1,4-diols by oxazaborolidine-mediated reduction of Alk-2-yne-1,4-diones

Article abstract of DOI:10.1021/jo0495687

We performed the borane-mediated reduction of a series of symmetrical alk-2-yne-1,4-diones (5) in the presence of the oxazaborolidine (R)-6 to afford (R,R)-alk-2-yne-1,4-diols ((R,R)-1) in good yields and high stereoselectivities (up to 99.9% ee). In some cases, the stereochemical purity of 1 was improved by a two-step process: (i) temporary transformation of 1 into its vic-dibromo derivatives 9, which allowed us to remove the minor meso isomer by chromatography, and (ii) regeneration of the enantioenriched diols 1 with SmI₂. Reduction of the hexacarbonyldicobalt complexes 8 derived from 5 was also successful.

Full text of DOI:10.1021/jo0495687

High ly Ster eoselective Ap p r oa ch to Alk -2-yn e-1,4-d iols by
Oxa za bor olid in e-Med ia ted Red u ction of Alk -2-yn e-1,4-d ion es†
Xavier Ariza, J ordi Bach,‡ Ramon Berenguer,§ J aume Farra`s,* Montserrat Fontes,
J ordi Garcia,* Marta Lo´pez,| and J ordi Ortiz
Departament de Qu´ımica Orga`nica, Universitat de Barcelona, C/ Mart´ı i Franque`s 1-11,
E-08028 Barcelona, Catalonia, Spain
jordigarciagomez@ub.edu
Received March 16, 2004
We performed the borane-mediated reduction of a series of symmetrical alk-2-yne-1,4-diones (5) in
the presence of the oxazaborolidine (R)-6 to afford (R,R)-alk-2-yne-1,4-diols ((R,R)-1) in good yields
and high stereoselectivities (up to 99.9% ee). In some cases, the stereochemical purity of 1 was
improved by a two-step process: (i) temporary transformation of 1 into its vic-dibromo derivatives
9, which allowed us to remove the minor meso isomer by chromatography, and (ii) regeneration of
the enantioenriched diols 1 with SmI2. Reduction of the hexacarbonyldicobalt complexes 8 derived
from 5 was also successful.
In tr od u ction
lective, modular way to prepare chiral diols 1 (Scheme
1).9 However, this approach is less satisfactory when
R-unbranched aldehydes (RCHO, R ) n-alkyl) are in-
volved, resulting in lower yields and/or selectivities.10
On the other hand, the stereoselective reduction of alk-
2-yne-1,4-diones (5) is an alternative, obvious approach
to compounds 1. On the basis of our success in the
reduction of simpler acetylenic ketones with borane
catalyzed by (R)- and (S)-B-methyl-4,5,5-triphenyl-1,3,2-
oxazaborolidines, (R)- and (S)-6,11 we concluded that
In the course of studies directed toward the synthesis
of paraconic acids and related metabolites,1 we needed
an efficient and stereoselective access to alk-2-yne-1,4-
diols (1) as precursors of chiral (E)- or (Z)-alk-2-ene-1,4-
diols (2 or 3).2 The preparation of these unsaturated 1,4-
diols (1-3) is a challenge not only because they are often
present in natural products3 but also because they are
amenable to conversion into other functionalities in a
stereoselective way.4 In addition, the related C2-sym-
metrical saturated 1,4-diols (4), easily derived from 1-3
by hydrogenation,5 have been used in the preparation
inter alia of trans-2,5-disubstituted pyrrolidines,6 thi-
olanes,7 and phosphine ligands of interest for asymmetric
hydrogenation.8
(5) Current preparations of enantiopure saturated 1,4-diols in-
clude: Enzymatic resolutions of mixtures of meso and racemic iso-
mers: (a) Mattson, A.; O¨ hrner, N.; Hult, K.; Norin, T. Tetrahedron:
Asymmetry 1993, 4, 925-930. (b) Kim, M.-J .; Lee, I. S. Synlett 1993,
767-768. (c) Nagai, H.; Morimoto, T.; Achiwa, K. Synlett 1994, 289-
290. (d) Caron, G.; Kazlauskas, R. J . Tetrahedron: Asymmetry 1994,
5, 657-664. Dynamic kinetic resolution: (e) Persson, B. A.; Huerta,
F. F.; Ba¨ckvall, J .-E. J . Org. Chem. 1999, 64, 5237-5240 and references
therein. Electrochemical Kolbe-type coupling of chiral â-hydroxy
acids: (f) Ross, S. D.; Finkelstein, M.; Rudd, E. J . Anodic Oxidation;
Academic Press: New York, 1975. (g) Burk, M. J .; Feaster, J . E.;
Harlow, R. L. Tetrahedron: Asymmetry 1991, 2, 569-592. Microbial
reduction of diketones using baker’s yeast: (h) Lieser, J . K. Synth.
Commun. 1983, 13, 765-767. Reduction of diketones using chiral
reagents or auxiliaries: (i) Kuwano R.; Sawamura M.; Shirai J .;
Takahashi M.; Ito Y. Tetrahedron Lett. 1995, 36, 5239-5242. (j)
Quallich G. J .; Keavey K. N.; Woodall T. M.; Tetrahedron Lett. 1995,
36, 4729-4732.
(6) For a review on the synthesis of 2,5-disubstituted pyrrolidines,
see: (a) Pichon, M.; Figade`re, B. Tetrahedron: Asymmetry 1996, 7,
927-964. (b) Whitesell, J . K. Chem. Rev. 1989, 89, 1581-1590. (c)
Chong, J . M.; Clarke, I. S.; Koch, I.; Olbach, P. C.; Taylor, N. J .
Tetrahedron: Asymmetry 1995, 6, 409-418. See also ref 5b.
(7) (a) Otten, S.; Fro¨lich, R.; Haufe, G. Tetrahedron: Asymmetry
1998, 9, 189-191. (b) J ulienne, K.; Metzner, P.; Henryon, V.; Greiner,
A. J . Org. Chem. 1998, 63, 4532-4534.
In this context, we recently reported that the addition
of chiral 1-alkyn-3-ols (or their protected derivatives) to
R- or â-branched aldehydes mediated by zinc triflate,
Et3N, and (+)- or (-)-N-methylephedrine is a stereose-
* To whom correspondence should be addressed. Tel: +34-934034819.
Fax: +34-933397878.
† In memory of Professor Satoru Masamune.
‡ Current address: Laboratoris Almirall Prodesfarma, C/Cardener
68-74, 08024, Barcelona.
§ Current address: Esteve Qu´ımica, C/Caracas 17, 08030, Barcelona.
| Current address: Institut Catala` d’Investigacio´, Pg. Lluis Com-
panys 23, 08010, Barcelona.
(1) (a) Ariza, X.; Garcia, J .; Lo´pez, M.; Montserrat, L. Synlett 2001,
120-122. (b) Ariza, X.; Ferna´ndez, N.; Garcia, J .; Lo´pez, M.; Mont-
serrat, L.; Ortiz, J . Synthesis 2004, 128-134.
(2) Allylic diols 2 and 3 are easily obtainable from 1 by LiAlH4
reduction and partial hydrogenation, respectively (see ref 1).
(3) See, for example: (a) Grabley, S.; Granzer, E.; Huetter, K.;
Ludwig, D.; Mayer, M.; Thiericke, R.; Till, G.; Phillipps, S.; Wink, J .;
Zeeck, A. J . Antibiot. 1992, 45, 56-65. (b) Nagle, D. G.; Gerwick, W.
H. J . Org. Chem. 1994, 59, 7227-7237. (c) Arnone, A.; Nasini, G.; de
Pava, O. V. Phytochemistry 2000, 53, 1087-1090. (d) Bode, H. B.;
Walker, M.; Zeeck, A. Eur. J . Org. Chem. 2000, 1451-1456.
(4) For a review on substrate-directable chemical reactions, see:
Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993, 93, 1307-
1370.
(8) (a) Burk, M. J . J . Am. Chem. Soc. 1991, 113, 8518-8519. (b)
Fiaud, J .-C.; Legros, J .-Y. Tetrahedron Lett. 1991, 32, 5089-5092. (c)
Burk, M. J .; Harper, T. G. P.; Kalberg, C. S. J . Am. Chem. Soc. 1995,
117, 4423-4424 and references therein. See also ref 5g.
(9) (a) Amador, M.; Ariza, X.; Garcia, J .; Ortiz, J . Tetrahedron Lett.
2002, 43, 2691-2694. See also: (b) Diez, R. S.; Adger, B.; Carreira, E.
M. Tetrahedron 2002, 58, 8341-8344.
(10) In many cases, the aldehyde is partially consumed in the
formation of self-condensation aldol products.
10.1021/jo0495687 CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/03/2004
J . Org. Chem. 2004, 69, 5307-5313
5307

Ariza et al.
SCHEME 1
F IGURE 1.
SCHEME 2 a
compounds 5 could be suitable substrates for such
reductions.12 This was based on two facts: (i) our previous
experience in simpler ketones indicated that the presence
of the triple bond could cause a sufficient difference in
steric requirements on both sides of the carbonyl group
since the acetylenic moiety behaves as an even “smaller”
group than a linear saturated chain in oxazaborolidine-
mediated reductions; (ii) from a statistical point of view,
one might expect much higher enantioselectivities in the
reduction of diketones 5 than those noted for related
monoketones, since most of the minor enantiomer formed
in the reduction of the first carbonyl group would become
a meso compound after the second reduction. Thus, the
enantiopurity of the final diols would be enhanced at the
expense of the formation of potentially removable meso
byproducts.13
The present work details the performance of ox-
azaborolidines 6 in the reduction of diketones 5 with BH3/
SMe2 (Figure 1). The extension of this asymmetric
process to the hexacarbonyldicobalt complexes 8 (acting
as synthetic equivalents of 5) was also investigated.14 We
also report that the temporary transformation of 1
(arising from reduction of 5 or 8) into their vic-dibromo
derivatives 9 facilitated removal of the minor meso-1
isomer by chromatography. The process provides an
attractive and general route to highly enantioenriched
diols 1.
a
Reagents and conditions: (a) (i) n-C4H9CtCH, BuLi, THF,
-78 °C, (ii) n-C3H7CHO, THF, -78 °C; (b) (i) t-BuOOH, SeO2,
CH2Cl2, rt, 24 h, (ii) NaBH4, MeOH, 0 °C; (c) ref 16; (d) CrO3, aq
H2SO4, 0 °C; (e) Co2(CO)8, pentane/CH2Cl2, rt.
creasing steric demand in going from 5a (R ) Me) to 5e
(R ) t-Bu), was synthesized by J ones oxidation of the
corresponding alk-2-yne-1,4-diols 1 (mixture of stereoi-
somers) as shown in Scheme 2. Among the diols required,
only hex-3-yne-2,5-diol, 1a , was commercially available.
Compound 1b was obtained by allylic oxidation (SeO2/
t-BuOOH) of commercial oct-4-yne according to a Sharp-
less procedure.15 Similarly, the adaptation of this protocol
to dec-5-yn-4-ol, 10, allowed the synthesis of propargylic
diol 1c. However, compounds 1d -f were better obtained
by one-pot double addition of dilithium acetylide to
aldehydes.16 Further transformation of diketones 5 into
the corresponding hexacarbonyldicobalt complexes 8 was
achieved by treatment with Co2(CO)8 in pentane/CH2Cl2.
Red u ction of Dik eton es. Having in hand diketones
5 and 8, we undertook their oxazaborolidine-mediated
reduction. First, we performed the slow addition of a
solution of diketone 5a (1.0 mmol) to an ice-cooled THF
solution of BH3/SMe2 (2.2 mmol) and (R)-6 (2.0 mmol) in
THF to afford cleanly the propargylic diol (R,R)-1a in
good yield (85%) but in moderate stereoselectivity
Resu lts a n d Discu ssion
P r ep a r a tion of Sym m etr ica l 1,4-Dik eton es. A rep-
resentative set of alk-2-yne-1,4-diones, 5a -f, with in-
(11) (a) Bach, J .; Berenguer, R.; Garcia, J .; Loscertales, T.; Vilarrasa,
J . Org. Chem. 1996, 61, 9021-9025. For related reductions, see: (b)
Corey, E. J ., Helal, C. J . Tetrahedron Lett. 1995, 36, 9153-9156. (c)
Parker, K. A.; Ledeboer, M. W. J . Org. Chem. 1996, 61, 3214-3127.
(12) In this connection, it should be noted that the oxazaborolidine-
mediated reduction of the related (E)-alk-2-ene-1,4-diones affords 1,4-
diols 2 in good yields and enantioselectivities but, in general, suffers
from low diastereoselectivities (dl/meso ratio from 5.6:1 to ∼1:1). In
contrast, (Z)-alk-2-ene-1,4-diones give low yields of the desired (Z)-
1,4-diol 3 under the same conditions. See: Bach, J .; Berenguer, R.;
Garcia, J .; Lo´pez, M.; Manzanal, J .; Vilarrasa, J . Tetrahedron 1998,
54, 14947-14962.
(15) Chabaud, B.; Sharpless, K. B. J . Org. Chem. 1979, 44, 4202-
4204.
(13) For
a discussion of this statistical effect applied to two-
directional chain syntheses, see: Poss C. S.; Schreiber S. L. Acc. Chem.
Res. 1994, 27, 9-17. See also: Magnuson, S. R. Tetrahedron 1995,
51, 2167-2213.
(14) A part of this work appeared as a preliminary communication:
Bach, J .; Berenguer, R.; Garcia, J .; Loscertales, T.; Manzanal, J .;
Vilarrasa, J . Tetrahedron Lett. 1997, 38, 1091-1094.
(16) Sudweeks, W. B.; Broadbent, H. S. J . Org. Chem. 1975, 40,
1131-1136. These authors described the preparation of 1d and 1e in
32% and 31% using the magnesium acetylide. We obtained better
results (76% and 98% yield, respectively) by using the dilithium
acetylide. However, when R-unbranched aldehydes as propanal were
used, much lower yields were recorded.
5308 J . Org. Chem., Vol. 69, No. 16, 2004

Highly Stereoselective Approach to Alk-2-yne-1,4-diols
TABLE 1. Red u ction of Dik eton es 5 a n d 8 w ith BH3/SMe2 in th e P r esen ce of Oxa za bor olid in es (R)-6 a n d (4R,5S)-7a
entry
diketone
catalyst
product
yieldb (%)
dl/meso ratiob,c
eeb,c (%)
1
5a , R ) Me
(R)-6
(R)-6
(R)-6
(R)-6
(R)-6
(R)-6
(4R,5S)-7
(4R,5S)-7
(4R,5S)-7
(4R,5S)-7
(R,R)-1a
(R,R)-1b
(R,R)-1c
(R,R)-1d
(R,R)-1e
(R,R)-1f
(S,S)-1a
(S,S)-1b
(S,S)-1c
(S,S)-1d
85 (65)
85 (81)
86 (77)
90 (90)
98 (95)
75 (23)
72
96
95
71
72:28 (62:38)
87:13 (72:18)
90:10 (75:25)
88:12 (84:16)
99.9:0.1 (97:3)
91:9 (86:14)
90:10
98.6:1.4
92:8
95:5
85 (80)
98 (96)
99 (98)
97 (96)
99.9 (99)
98 (98)
98
98
98
96
2
5b, R ) Et
3d
4
5c, R ) Pr
5d , R ) cyclohexyl
5e, R ) t-Bu
5f, R ) Ph
5
6
7
8a , R ) Me
8
8b, R ) Et
9e
10
8c, R ) Pr
8d , R ) cyclohexyl
a
Reactions were carried out by slow addition of diketone (1 mmol) to a mixture of BH3/SMe2 (2.2 mmol) and oxazaborolidine (2 mmol)
in ice-cooled THF. Yields and stereochemical results for diketones 8 are referred to diols 1 (after treatment of the diols arising from the
b
carbonyl reduction with CAN in acetone). Within parentheses, values using 0.2 mmol of catalyst. c Determined by HPLC and/or 19F
d
NMR analysis of the corresponding Mosher diesters. Better results were obtained than those reported in our preliminary communication
(ref 14). e Excesses of BH3/SMe2 (3 mmol) and (4R,5S)-7 (4 mmol) were needed to complete the reduction.
(72:28 dl/meso ratio, 85% ee). Despite this disappointing
result, we reduced the remaining diketones. To our
satisfaction, better results (>96% ee) were observed in
the reduction of 5b-f where the R group was bigger than
Me (entries 2-5 in Table 1). However, a small amount
of the concomitant, inseparable meso isomer was always
produced in such reductions, especially if only 0.2 mmol
of catalyst was used.17 As shown in Table 1, the best
result was obtained for 5e (R ) t-Bu, 99.9:0.1 dl/meso
ratio, 99.9% ee).
The configuration of alcohols 118 and the fact that
higher selectivities were noted in diketones with steri-
cally demanding R groups may be explained according
to the mechanism proposed by Corey et al.19 for similar
F IGURE 2.
processes. Thus, the R configuration in diols 1 could arise
from an arrangement like 11a , in which the R group,
which is larger than the acetylenic moiety, is located far
from the Me group on the boron atom (see Figure 2). The
alternative arrangement, 11b, which would lead to the
S isomer, is clearly less attainable. An increase of the
steric requirements in the R group may increase the
energetic difference between 11a and 11b and raise the
stereoselectivities. Obviously, synthesis of diols (S,S)-1
F IGURE 3.
using oxazaborolidine (S)-6 is also feasible.
Looking for a better diastereoselectivity (especially for
diketones with R ) Me or n-alkyl), we turned our
attention to the reduction of the hexacarbonyldicobalt
expected, the temporary transformation of the acetylenic
moiety in a much bulkier group not only enhanced but
also reversed the selectivity, leading to propargylic
complexes 8, derived from 5. Since our previous experi-
alcohols (S,S)-1a -d , in good yields and selectivities after
regeneration of the triple bond with the aid of a mild
oxidant like Ce(IV). However, an excess of BH3/SMe2
(3 mmol) and catalyst (4 mmol) were needed to complete
the reduction of 8d . The origin of the configuration of
the new stereocenters can be explained by a complex like
12 in which the huge cobalt complex is placed far from
the Me group on the boron atom (see Figure 3). It should
be noted that in contrast to reduction of diketones 5, at
least 2 mmol of (4R,5S)-7 is needed to complete the
reduction. This fact suggests that the oxazaborolidine is
not easily liberated after reduction and it does not enter
ence11a,20 indicated that oxazaborolidines 6 were inef-
ficient for the reduction of very crowded ketones, we
treated 8a -d with BH3/SMe2 in the presence of the less
sterically demanding oxazaborolidine (4R,5S)-7.21 As
(17) Reduction of diketone 5f using 0.2 mmol of catalyst led to a
complex mixture from which diol (R,R)-1f was isolated in low yield.
This disappointing result was not completely unexpected in the light
of our previous experience in the reduction of the related 1,4-
diphenylbut-2-ene-1,4-dione (see ref 12).
(18) Absolute configurations were established by comparison of the
sign of specific rotation of saturated diols arising from hydrogenation
(H2, Pt/C) of 1 with that given in the literature (see refs 12 and 14
and references therein).
(19) For a review, see: Corey, E. J .; Helal, Angew. Chem., Int. Ed.
Engl. 1998, 37, 1986-2012.
(20) Alemany, C.; Bach, J .; Garcia, J .; Lo´pez, M.; Rodriguez, A. B.
Tetrahedron 2000, 56, 9305-9312.
(21) (a) Quallich, G. J .; Woodall, T. M. Tetrahedron Lett. 1993, 34,
4145-4148. (b) Quallich, G. J .; Blake, J . F.; Woodall, T. M. J . Am.
Chem. Soc. 1994, 116, 8516-8525.
J . Org. Chem, Vol. 69, No. 16, 2004 5309

Ariza et al.
into a true catalytic cycle.11a Finally, when we attempted
to extend this strategy to the more crowded ketones 8e
and 8f, they remained unchanged under similar condi-
tions. In conclusion, the reduction of the Co complexes
of acetylenic diketones could gave excellent stereoselec-
tivities but this process is unsuitable for substrates with
high steric requirements.
SCHEME 3 a
a
Reagents and conditions:(a) pyridinium tribromide, CH2Cl2,
Tem p or a r y Tr a n sfor m a tion of Diols 1 in to vic-
Dibr om oa lk en es 9. The main drawback of the above-
mentioned approach to enantioenriched alk-2-yne-1,4-
diols lies in the difficulty in removing the undesired
meso-1 diols from their chiral isomers (R,R)- or (S,S)-1
either by fractional crystallization (for solid diols 1d and
1e) or by column chromatography. In contrast, our
previous experience indicates that the dl and meso
isomers of allylic diols 2 arising from 1 can be, in general,
readily separated by chromatography. Looking for a
temporary transformation of 1 into a kind of compound
that allows us the separation of diastereomers, our
interest was drawn to vic-dibromides 9. The treatment
of samples of (R,R)-1 contaminated with meso isomer
with pyridinium tribromide in CH2Cl2, smoothly fur-
nished 9 in >90% overall yield.22 However, the sterically
more demanding 1e remained unchanged under similar
conditions and a more vigorous brominating agent (Br2
in CH2Cl2) was needed to attain 9e but in low yield (31%).
To our satisfaction, chromatographic behaviors of meso-
and (R,R)-9 were quite dissimilar, even more than those
noted for the parent allylic diols 2.23 Thus, we were able
to remove easily by flash chromatography on silica gel
the minor meso-9 isomers, these being eluted first in all
the cases studied. Having in hand highly stereoenriched
diols 9, the study of their transformation back to chiral
diols 1 (free of meso isomer) was next addressed. A
variety of methods has been devised to accomplish the
reductive dehalogenation of vic-dibromides to alkynes,
including metallic samarium,24 Zn powder,22c,d Ni cata-
lysts,25 sodium sulfide in dimethylformamide,26 and di-
organotellurides.27 Although in our hands (R,R)-9a was
efficiently transformed in (R,R)-1a either with Zn/
AcOH22c or Sm(0), for the rest of compounds 9 even better
and more reproducible results were obtained by using
freshly prepared SmI2 in THF,28 to yield enantioenriched
(R,R)-1 in high yield (Scheme 3).
rt; (b) SmI2, THF, rt.
SCHEME 4 a
a
Reagents and conditions: (a) ref 15; (b) CrO3, aq H2SO4,
acetone, 0 °C; (c) Ac2O (1 equiv), 4-(dimethylamino)pyridine cat.,
pyridine, CH2Cl2, 0 °C; (d) (i) Ph3P, PhCO2H, diethyl azodicar-
boxylate, THF, 0 °C, (ii) NH3, MeOH, rt; (e) pyridinium tribromide,
CH2Cl2, rt.
2-yne-1,4-diol, 1g, was chosen as a representative model
since its preparation by allylic oxidation of cyclodode-
cyne29 with SeO2/t-BuOOH had been described by Cha-
baud and Sharpless.15 Thus, we carried out the reported
protocol assuming that the obtained diol 1g was a
mixture of diastereomers. However, when we trans-
formed an analytical sample of the diol into its Mosher’s
diester, we obtained only two singlets of equal intensity
in its 19F NMR spectrum (instead of four expected
signals: two singlets for the meso isomer and one more
for each enantiomer) and we could not separate either
of the assumed diastereomers by HPLC. In addition, the
treatment of 1g with pyridinium tribromide in CH2Cl2
led to a single dibromoderivative. These unexpected
results suggest that we had obtained a single diastere-
omer. To confirm this we transformed the diol into its
monoacetate 14 and then inverted the configuration of
the remaining hydroxyl group using Mitsunobu’s protocol
with benzoate as nucleophile.30After removal of the
benzoate group the other diastereomer of 1g was isolated
(see Scheme 4).
A Sp ecia l Ca se: Cyclod od ec-2-yn e-1,4-d iol. We
then examined the cyclic propargylic 1,4-diols. Cyclododec-
(22) Transformation of 1a into 9a by treatment with bromine in
chloroform was described almost a century ago: (a) Dupont, M. G. C.
R. Acad. Sci. 1909, 149, 1381-1383. See also: (b) Hermann, H.; Luttke,
W. Chem. Ber. 1971, 104, 479-491. (c) Schoepfer, J .; Eichenberger,
E.; Neier, R. J . Chem. Soc., Chem. Commun. 1993, 246-248. The use
of bromine in the presence of Hu¨nig’s base has been also reported: (d)
Adje´, N.; Breuilles, P.; Uguen, D. Tetrahedron Lett. 1993, 34, 4631-
4634.
(23) Ab initio calculations at 6-311G level of theory using Gaussian-
04 series of programs indicate that the minimum energy conformations
of meso-2a and meso-9a are apolar (µ ) 0 D, Ci symmetry). In contrast,
the dipole moment for the minimum energy conformations of dl-2a
and dl-9a are 0.01 and 2.46 D, respectively.
Oxidation of 1g with J ones reagent gave diketone 5g,
which in turn was subjected to the borane-mediated
reduction in the presence of oxazaborolidine (R)-6.31
Unfortunately, reduction of 5g was less efficient than
that noted for acyclic alkynediones 5a -f, leading to (R,R)-
1g in acceptable enantioselectivity (90% ee) but unpuri-
fied by a considerable amount of meso diol (2.1:1 dl/meso
(24) Yanada, R.; Negoro, N.; Yanada, K.; Fujita, T. Tetrahedron Lett.
1996, 37, 9313-9316.
(25) Malanga, C.; Mannucci, S.; Lardicci, L. Tetrahedron 1998, 54,
1021-1028.
(26) Fukunaga, K.; Yamaguchi, H. Synthesis 1981, 879-880.
(27) Butcher, T. S.; Zhou, F.; Detty, M. R. J . Org. Chem. 1998, 63,
169-176.
(29) (a) Lalezari, I.; Shafiee, A.; Yalpani, M. J . Heterocycl. Chem.
1972, 1411-1412. (b) Lalezari, I.; Shafiee, A.; Yalpani, M. J . Org.
Chem. 1971, 36, 2836-2838.
(28) Girard, P.; Namy, J . L.; Kagan, H. B. J . Am. Chem. Soc. 1980,
102, 2693-2698. It is worth noting that diol 1f was sensitive to
epimerization when a large amount of SmI2 was used.
(30) Mitsunobu, O. Synthesis 1981, 1-28.
(31) It is worth noting that NaBH4 reduction of diketone 5g gave a
∼1:1 mixture of dl-1g and meso-1g.
5310 J . Org. Chem., Vol. 69, No. 16, 2004

Highly Stereoselective Approach to Alk-2-yne-1,4-diols
SCHEME 5 a
pressure) and BH3/SMe2 (222 µL, 2.2 mmol) in THF (3 mL) at
0 °C under Ar. Upon completion of the addition, TLC revealed
the disappearance of the starting diketone. The reaction was
cautiously quenched by slow addition of MeOH (1 mL) at 0
°C. The solution was stirred for 15 min at rt and then
concentrated under reduced pressure. The residue was purified
by flash chromatography (CH2Cl2/MeOH 95:5) to yield 97 mg
(85%) of enantioenriched (R,R)-hex-3-yne-2,5-diol, (R,R)-1a . An
analytical sample of the crude was treated with an excess of
(S)-Mosher acid chloride (derived from (R)-acid)33 to give a
mixture of Mosher diesters. The analysis by HPLC (Tracer
Spherisorb S3W column, 0.9 mL/min, hexane/THF 98:2, tR
(R,R) ) 13.4 min, tR (R,S) ) 16.6 min, tR (S,S) ) 19.6 min)
revealed a 72:28 dl/meso ratio and 85% ee. A similar reduction
using a molar ratio (R)-6/diketone ) 0.2 led to (R,R)-1a in 65%
yield, with a dl/meso ratio of 62:38 and 80% ee.
a
Reagents and conditions: (a) BH3:SMe2 (2.2 mmol), (R)-6
(2 mmol), THF, 0 °C; (b) pyridinium tribromide, CH2Cl2, rt; (c)
SmI2, THF, rt.
ratio, see Scheme 5). Fortunately, the meso isomer could
be removed easily by transformation of the mixture of
diols 1g into their dibromo derivatives 9g followed by
reductive debromination of the isolated (R,R)-9g (Scheme
5). As far as the amount of catalyst is concerned, a
decrease in the ratio of oxazaborolidine/diketone to 0.2
reduced the yield and the stereoselectivity (32%, ∼1:1 dl/
meso ratio, 65% ee). Apparently, the lack of conforma-
tional flexibility in the cyclic diketone makes the stere-
oselective reduction slower since an arrangement such
as 11a (Figure 2), assumed in the noncyclic diketones
1a -f, is now less favorable. Accordingly, we can expect
an increasing significance of the uncatalyzed reduction
by borane as the relative amount of oxazaborolidine
decreases.
(S,S)-Hex-3-yn e-2,5-d iol [(S,S)-1a ]. Alternatively, to a
solution of Co2(CO)8 (376 mg, 1.1 mmol) in anhyd pentane (5
mL) under Ar at rt was added a solution of diketone 5a (110
mg, 1.0 mmol) in anhyd pentane (3 mL) and CH2Cl2 (0.5 mL)
via cannula. The dark red solution was stirred at rt. After 1
h, TLC revealed the disappearance of the starting ketone. The
solution was filtered through silica gel (CH2Cl2). The solvent
was removed under reduced pressure to afford 8a (335 mg,
85%) as a brown oil which was stored under Ar and used in
the reduction step without further purification: Rf 0.38
(CH2Cl2); 1H NMR (CDCl3, 200 MHz) δ 2.51 (s, 6H); 13C NMR
δ 30.8 (CH3), 86.2 (CtC), 197.1 (CO), 199.4 (CO); IR (film)
2980, 2050, 1680, 1550, 1210, 1150. A solution of diketone 8a
(316 mg, 0.80 mmol) in THF (1 mL) was added dropwise over
∼50 min to a solution of BH3/SMe2 (176 µL, 1.76 mmol) and
(4R,5S)-7 (1.6 mmol, from a toluene solution after removing
the solvent under reduced pressure) in THF (1 mL), at 0 °C
under Ar. Upon completion of the addition, TLC revealed the
disappearance of the starting diketone. The reaction was then
cautiously quenched by adding 1 mL of MeOH, stirred for an
additional 10 min, and allowed to warm to rt. The mixture
was evaporated under reduced pressure. The crude propargylic
diol complex was dissolved in dry acetone (4 mL), and solid
CAN was cautiously added at 0 °C until the vigorous gas
release had finished. After 5 min (TLC monitoring), the
volatiles were removed and the residue was partitioned with
CH2Cl2 (20 mL) and saturated aqueous NaHCO3 (5 mL). The
aqueous layer was extracted with CH2Cl2 (4 × 20 mL). The
combined organic phases were dried over MgSO4. Evaporation
of the solvent and purification by flash chromatography
(hexane/EtOAc 6:4) yielded 66 mg (0.58 mmol, 72%) of (S,S)-
1a . An analytical sample of (S,S)-1a was transformed into the
corresponding Mosher ester derived from Mosher’s (R)-acid.
The analysis by HPLC revealed a 90:10 dl/meso ratio and 98%
ee. (S,S)-Hex-3-yne-2,5-diol: mp 53-4 °C (lit.34 mp 58-60 °C);
Rf 0.40 (EtOAc); [R]D20 -50.6 (c ) 2.1, CHCl3) [lit.34 [R]D25 -57.3
Con clu sion
This paper describes a preparative approach to enan-
tioenriched alk-2-yne-1,4-diols based on the borane-
mediated reduction of the parent alk-2-yne-1,4-diones (or
their Co2(CO)6 complexes) in the presence of a chiral
oxazaborolidine. The temporary transformation of such
diols into their vic-dibromo derivatives allowed us to
remove the meso isomer to afford highly enantioenriched
propargylic diols. This methodology seems especially
valuable for linear diols in which the alternative ap-
proach by direct addition of an alkynol to the aldehyde
is less suitable. However, this reduction gave lower
stereoselectivity when it was applied to a cyclic diketone
as cyclodec-2-yne-1,4-dione.
Exp er im en ta l Section
Gen er a l P r oced u r e for P r ep a r a tion of Dik eton es 5:
Oct-4-yn e-3,6-d ion e (5b). To a stirred solution of oct-4-yne-
3,6-diol (1b) (0.524 g, 3.68 mmol) in acetone (20 mL) in an ice
bath was added dropwise a solution of J ones reagent (8.0 g of
CrO3/7.6 mL of concd H2SO4/20 mL H2O) until an orange color
persisted. The reaction mixture was partitioned by adding H2O
(20 mL) and CH2Cl2 (50 mL). The phases were separated, and
the aqueous layer was extracted with CH2Cl2. The combined
organic phases were washed with brine, dried (Na2SO4), and
concentrated under reduced pressure. The residue was purified
by flash chromatography (CH2Cl2) to give 400 mg (79%) of oct-
4-yne-3,6-dione, 5b, as a yellow oil: Rf 0.58 (CH2Cl2); 1H NMR
(CDCl3, 200 MHz) δ 1.20 (t, 6H, J ) 7.4 Hz), 2.68 (q, 4H, J )
7.4 Hz); 13C NMR δ 7.1, 38.6, 84.1 (CtC), 186.8 (CO); IR (neat)
2980, 2200, 1710, 1680, 1450. Anal. Calcd for C8H10O2: C,
69.55; H, 7.29. Found: C, 69.38; H, 7.51.
1
(c ) 1.53, CHCl3)]; H NMR (CDCl3, 200 MHz) δ 1.45 (d, 6H,
J ) 6.4 Hz), 2.40 (bs, 2H, OH), 4.57 (q, 2H, J ) 6.4 Hz); 13C
NMR δ 24.0 (CH3), 57.8 (CHOH), 85.9 (CtC); IR (neat) 3400,
2960, 2920, 1020.
Typ ica l P r oced u r e for th e P r ep a r a tion of vic-Dibr om o
Diols 9: (E)-2,3-Dibr om o-1,4-d icycloh exylbu t-2-en e-1,4-
d iol (9d ). Pyridinium tribromide (600 mg, 1.88 mmol) was
slowly added to a solution of 470 mg (1.88 mmol) of (S,S)-
dicyclohexylbut-2-yne-1,4-diol, (S,S)-1d (95:5 dl/meso ratio and
96% ee) in 20 mL of CH2Cl2 cooled in an ice bath. The solution
was stirred at rt overnight. Then, TLC revealed the disap-
pearance of the starting propargylic diol. Reaction was cau-
tiously quenched by addition of satd aq NaHSO3 (10 mL), and
(32) (a) Acheson, R. M.; Bite, M. G.; Cooper, M. W. J . Chem. Soc.,
Perkin Trans. 1 1976, 1908-1911. See also: (b) Dunn, P. J .; Rees, C.
W. J . Chem. Soc., Perkin Trans. 1 1987, 1579-1584.
(33) Dale, J . A.; Dull, D. L.; Mosher, H. S. J . Org. Chem. 1969, 34,
2543-2549.
(34) Kim, M.-J .; Lee, I. S.; J eong, N.; Choi, Y. K. J . Org. Chem. 1993,
58, 6483-6485.
Gen er a l P r oced u r e for Oxa za bor olid in e-Med ia ted Re-
d u ction of Dik eton es 5 a n d 8: P r ep a r a tion of (R,R)-Hex-
3-yn e-2,5-d iol [(R,R)-1a ]. A solution of hex-3-yne-2,5-dione
5a 32 (110 mg, 1.0 mmol) in THF (3 mL) was added slowly (∼1
h) to a solution of oxazaborolidine (R)-6 (2 mmol, from a
toluene solution after removing the solvent under reduced
J . Org. Chem, Vol. 69, No. 16, 2004 5311

Ariza et al.
the aqueous layer was extracted with more CH2Cl2. The
combined organic layers were dried (MgSO4), and the solvent
was eliminated under reduced pressure. The residue was
purified by flash chromatography (CH2Cl2 and then CH2Cl2/
MeOH 99:1) to give (S,S)-9d (693 mg, 1.69 mmol) along with
meso-9d (35 mg, 0.09 mmol) (94% overall yield). (1S,2E,4S)-
2,3-Dibromo-1,4-dicyclohexylbut-2-ene-1,4-diol [(S,S)-9d ]: mp
Diethyl azadicarboxylate (DEAD, 0.66 mmol) in THF (1 mL)
was slowly added to a solution of 14 (106 mg, 0.44 mmol), Ph3
P
(173 mg, 0.66 mmol), and benzoic acid (81 mg, 0.66 mmol) in
THF (2 mL) at 0 °C under Ar. After 30 min, the reaction was
quenched by addition of EtOH (1 mL). The reaction mixture
was filtered, and the volatiles were removed under reduced
pressure. The residue was purified by flash chromatography
through a short pad of silica gel (hexane/CH2Cl2 1:1) to afford
a crude benzoate derivative (Rf 0.11, hexane/CH2Cl2 1:1), which
was treated with 5 M NH3 in MeOH (1 mL, 5 mmol) without
further purification. After 3 days at rt, the solvent was
removed and the residue was purified by flash chromatography
to afford dl-1g (59 mg, 0.30 mmol, 68% overall yield).
118-120 °C; Rf 0.10 (CH2Cl2/MeOH 95:5); [R]20 -15.1 (c )
D
1.0, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 0.90-1.21 (m, 12H,
CH2), 1.44-1.76 (m, 10H, CH2 and CH), 2.06 (bs, 2H, OH),
4.56 (d, 2H, J ) 9.0 Hz, CHOH); 13C NMR δ 25.6, 25.8, 26.2,
28.1 and 29.1 (CH2), 42.5 (CH), 78.3 (CHOH), 127.4 (CBr));
IR (KBr) 3855, 2923, 2830, 1440, 680. MS (NH3/CI) m/z (rel
int) 428 (100, 79Br81Br, [M + NH4+]); HRMS (EI) calcd for
C16H26O279Br81Br (M+) 410.0279, found 410.0285. Anal. Calcd
for C16H26O2Br2: C, 46.85; H, 6.39; Br, 38.96. Found: C, 46.85;
H, 6.42; Br, 38.88.
P r ep a r a tion of (R,R)-Cyclod od ec-2-yn e-1,4-d iol [(R,R)-
1g]. Oxidation of meso-1g,15 according to the above-described
general procedure, gave diketone 5g in 70% yield as a
yellowish oil. Cyclododec-2-yne-1,4-dione (5g): Rf 0.84 (CH2Cl2/
MeOH 95:5); 1H NMR (CDCl3, 300 MHz) δ 1.56 (m, 8H, CH2),
1.87 (m, 4H, CH2), 2.60-2.65 (m, 4H, COCH2); 13C NMR δ 23.8,
25.3 and 25.8 (CH2), 43.4 (COCH2), 85.2 (CtC), 188.2 (CO);
IR (neat) 3334, 2361, 1682; MS (NH3/CI) m/z (rel int) 210 (8,
[M + NH4+]). Anal. Calcd for C12H16O2: C, 74.97; H, 8.39.
Found: C, 74.81; H, 8.12. Reduction of diketone 5g (192 mg,
1 mmol) was performed with oxazaborolidine (R)-6 (2 mmol)
and BH3/SMe2 (222 µL, 2.2 mmol) according to the procedure
employed for 5a to yield enantioenriched (R,R)-1g in 71% yield.
An analytical sample of the crude was treated with an excess
of (S)-Mosher acid chloride (derived from (R)-acid) to give a
mixture of Mosher diesters. A careful analysis by 19F NMR
revealed a 2.1:1 dl/meso ratio and 90% ee. When the same
reaction was carried out using a molar ratio of (R)-6/diketone
) 0.2 the compound (R,R)-1g was obtained in only 32% yield,
with a dl/meso ratio ∼1:1 and 65% ee.
(1R,2E,4S)-2,3-Dibr om o-1,4-d icycloh exylbu t-2-en e-1,4-
d iol (m eso-9d ): mp 185-187 °C; Rf 0.65 (CH2Cl2/MeOH 95:
5); 1H NMR (CDCl3, 300 MHz) δ 0.90-1.21 (m, 12H, CH2),
1.44-1.75 (m, 10H, CH2 and CH), 2.12 (bs, 2H, OH), 4.56 (d,
2H, J ) 9.0 Hz, CHOH); 13C NMR δ 25.7, 25.8, 26.2, 28.3 and
29.1 (CH2), 42.5 (CH), 78.3 (CHOH), 127.2 (CBr)); IR (KBr)
3855, 2920, 2830, 1440, 685. MS (NH3/CI) m/z (rel int)
428 (100, 79Br81Br, [M + NH4+]); HRMS (EI) calcd for
C
16H26O279Br81Br (M+) 410.0279, found 410.0283. Anal. Calcd
for C16H26O2Br2: C, 46.85; H, 6.39; Br, 38.96. Found: C, 46.73;
H, 6.45; Br, 38.83.
Rep r esen ta tive P r oced u r e of Tr a n sfor m a tion of vic-
Dibr om o Com p ou n d s 9 in to P r op a r gylic Diols 1: P r ep a -
r a tion of (S,S)-1d . To a freshly prepared 0.1 M THF solution
of SmI227 (13 mL, 1.3 mmol) was added a solution of (1S,2E,4S)-
2,3-dibromo-1,4-dicyclohexylbut-2-ene-1,4-diol, (S,S)-9d , (135
mg, 0.33 mmol) in dry THF (3 mL) under Ar at rt. The progress
of the reaction was monitored by TLC. After 20 min, the
mixture was filtered, the solvent was removed under reduced
pressure, and the crude was purified by flash chromatography
(CH2Cl2/MeOH 97:3) to yield (S,S)-1d (82 mg, 96%). (S,S)-
Dicyclohexylbut-2-yne-1,4-diol, (S,S)-1d : mp 105-106 °C [lit.16
Pyridinium tribromide (283 mg, 0.88 mmol) was slowly
added to a solution of 144 mg (0.73 mmol) of (R,R)-1g (2.1:1
dl/meso ratio and 90% ee) in 10 mL of CH2Cl2 according to
the procedure described for 1d . The mixture of dibromo
derivatives was purified by flash chromatography to afford
(R,R)-9g (167 mg, 0.47 mmol, 64%) along with meso-9g (78
mg, 0.22 mmol, 30%). (1R,2E,4R)-2,3-Dibromocyclododec-2-
ene-1,4-diol, (R,R)-9g: mp 139-141 °C; Rf 0.21 (CH2Cl2/MeOH
95:5); [R]20D +18.2 (c ) 0.8, CHCl3); 1H NMR (CDCl3, 300 MHz)
δ 1.21 (m, 10H, CH2), 1.60 (m, 2H, CH2), 1.77 (m, 2H), 1.89
(m, 2H), 2.10 (bs, 2H, OH), 5.02 (dd, 2H, J ) 10.2, 4.5 Hz,
CHOH); 13C NMR δ 22.7, 23.0, 23.2, 25.2, 26.0, 26.3, 33.1 and
34.6 (CH2), 74.0 (CHOH), 128.7 (CBrd); IR (KBr) 3346, 2925,
2854, 1465, 1038, 693. MS (NH3/CI) m/z (rel int) 374 (20,
79Br81Br, [M + NH4+]); HRMS (EI) calcd for C12H20O279Br81Br
(M+) 355.9810, found 355.9815. Anal. Calcd for C12H20O2Br2:
C, 40.48; H, 5.66; Br, 44.88. Found: C, 40.41; H, 5.51; Br,
45.10.
mp 102-106 °C for a mixture of stereoisomers]; Rf 0.18
1
(CH2Cl2/MeOH 95:5); [R]20 -63.0 (c ) 4.0, CHCl3); H NMR
D
(CDCl3, 200 MHz) δ 0.60-1.30 (m, 10H, CH2), 1.35-1.95 (m,
12H, CH2 and CH), 4.11 (d, 2H, J ) 8.8 Hz, CHOH); 13C NMR
δ 23.4, 25.9, 26.4, 28.1 and 28.6 (CH2), 44.0 (CH), 67.1 (CHOH),
73.6 (CtC); IR (KBr) 3400, 2910, 2830, 1450. MS (NH3/CI)
m/z (rel int) 268 (100, [M + NH4+]); HRMS (EI) calcd for
C
C
16H26O2 (M+) 250.1933, found 250.1936. Anal. Calcd for
16H26O2: C, 76.75; H, 10.47. Found: C, 76.45; H, 10.47.
P r ep a r a tion of (RS,SR)-Cyclod od ec-2-yn e-1,4-d iol (d l-
1g). Acetic anhydride (100 µL, 1.06 mmol) was added to a
stirred solution of 200 mg (1.02 mmol) of meso-1g,15 pyridine
(100 µL, 1.25 mmol), and a catalytic amount of 4-(N,N-
dimethylamino)pyridine (DMAP) in dry CH2Cl2 (2 mL) at 0
°C. The progress of the reaction was monitored by TLC. When
TLC revealed the disappearance of the starting diol (3 h), more
CH2Cl2 (20 mL) was added and the solution was washed with
0.5 M aq HCl, satd aq NaHCO3, and brine. The organic phase
was dried (Na2SO4) and concentrated under reduced pressure.
The residue was purified by flash chromatography (CH2Cl2/
MeOH 98:2) to give 52 mg (0.18 mmol, 18%) of the diacetate
of meso-1g and 114 mg (0.48 mmol, 47%) of the desired
4-hydroxycyclododec-2-ynyl acetate, 14:35 colorless oil; Rf 0.23
(1R,2E,4S)-2,3-Dibr om ocyclod od ec-2-en e-1,4-d iol (m e-
so-9 g): mp 149-150 °C; Rf 0.30 (CH2Cl2/MeOH 95:5); 1H NMR
(CDCl3, 300 MHz) δ 1.34 (m, 10H, CH2), 1.62 (m, 2H, CH2),
1.81 (m, 2H), 1.95 (m, 1H), 2.42 (m, 1H), 5.00 (m, 2H, CHOH);
13C NMR δ 21.7, 23.0, 23.2, 25.7, 26.0, 26.3, 33.1 and 34.0
(CH2), 74.4 and 82.5 (CHOH), 122.5 and 126.1 (CBrd); IR
(KBr) 3210, 2925, 2856, 1463, 1057, 708; MS (NH3/CI) m/z (rel
int) 374 (15, 79Br81Br, [M + NH4+]); HRMS (EI) calcd for
C
12H20O279Br81Br (M+) 355.9810, found 355.9818.
A sample of (R,R)-9g (arising from 1g of 90% ee, free of
1
(CH2Cl2/MeOH 98:2); H NMR (CDCl3, 300 MHz) δ 1.38-1.85
meso-9g) was treated with SmI2 according to the procedure
described for 9d to give (R,R)-1g in 93% yield. An analytical
sample of the crude was treated with an excess of (S)-Mosher
acid chloride to give a mixture of Mosher diesters. A careful
analysis by 19F NMR revealed 94:6 R,R/S,S ratio in the sample.
(R,R)-Cyclododec-2-yne-1,4-diol [(R,R)-1g]: mp 103-4 °C; Rf
(m, 16H, CH2), 2.17 (s, 3H, CH3), 4.51 (m, 1H, CHOH), 5.46
(td, 1H, J ) 8.7, 1.8 Hz, CHOAc); 13C NMR δ 21.0 (CH3), 21.7,
21.8, 24.0, 24.1, 25.3, 25.5, 31.2 and 34.6 (CH2), 62.7 and 64.6
(CHO-), 82.6 and 87.1 (CtC), 169.1 (CO); IR (film) 3435, 1735,
1234; Anal. Calcd for C14H22O3: C, 70.56; H, 9.30. Found: C,
70.92; H, 9.12.
0.10 (CH2Cl2/MeOH 95:5); [R]20 +32.6 (c ) 2.3, CHCl3); 1H
D
NMR (CDCl3, 300 MHz) δ 1.37-1.85 (m, 16H, CH2), 4.35 (m,
2H, CHOH); 13C NMR δ 21.5, 24.0, 26.0 and 35.2 (CH2), 62.9
(CHOH), 86.7 (CtC); IR (KBr) 3345, 2932, 2850, 1465, 1038;
(35) Saimoto, H.; Shinoda, M.; Matsubara, S.; Oshima, K.; Hiyama,
T.; Nozaki, H. Bull. Chem. Soc. J pn. 1983, 56, 3088-3092.
5312 J . Org. Chem., Vol. 69, No. 16, 2004

Highly Stereoselective Approach to Alk-2-yne-1,4-diols
MS (NH3/CI) m/z (rel int) 214 (100, [M + NH4+]); HRMS (EI)
calcd for C12H20O2 (M+) 196.1463, found 196.1467.
de Catalunya (2000SGR00021). We also thank the
Generalitat de Catalunya for a doctorate studentship
to J .O. and the Universitat de Barcelona for a doctorate
studentship to M.L. We are also grateful to Mrs. A.
Molero for her help in the preparation of compounds
9f and to Prof. J . Vilarrasa for helpful discussions.
In a similar way, reduction of meso-9g afforded propargylic
diol meso-1g in 95% yield. meso-Cyclododec-2-yne-1,4-diol
(meso-1g): mp 123-4 °C (lit.15 mp 122-123 °C); Rf 0.10 (CH2-
1
Cl2/MeOH 95:5); H NMR (CDCl3, 300 MHz) δ 1.37-1.84 (m,
16H, CH2), 4.52 (td, 2H, J ) 4.5, 3.9 Hz, CHOH); 13C NMR δ
21.6, 21.7, 24.0, 24.1, 25.6, 25.9 and 35.0 (CH2), 62.7 (CHOH),
86.2 (CtC); IR (KBr) 3276, 2925, 2853, 1447, 1050. MS (NH3/
CI) m/z (rel int) 214 (100, [M + NH4+]).
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails for preparation of compounds 1b-e (mixture of stereoi-
somers), enantioenriched diols 1b-f, and characterization data
for compounds 5c-e and 9a -c,e,f. This material is available
free of charge via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. This work has been supported
by the Ministerio de Educacio´n y Cultura (PB98-1272,
DGESIC) and Direccio´ General de Recerca, Generalitat
J O0495687
J . Org. Chem, Vol. 69, No. 16, 2004 5313