First Pauson-Khand reaction on sugar acetylenes

Article abstract of DOI:10.1016/S0022-328X(99)00320-4

Pauson-Khand reaction was achieved on the sugar acetylenes having an allylic ether substituent at the two-position of the tetrahydropyran ring to provide tri-cyclic products with high stereospecificity. This is the first example of Pauson-Khand reactions with compounds on carbohydrate or tetrahydropyranose ring, and the scope is described.

Full text of DOI:10.1016/S0022-328X(99)00320-4

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Journal of Organometallic Chemistry 589 (1999) 122–125
Communication
First Pauson–Khand reaction on sugar acetylenes
Minoru Isobe *, Shigeyuki Takai
Laboratory of Organic Chemistry, School of Bioagricultural Sciences, Nagoya Uni6ersity, Chikusa, Nagoya 464-8601, Japan
Received 11 March 1999
Abstract
Pauson–Khand reaction was achieved on the sugar acetylenes having an allylic ether substituent at the two-position of the
tetrahydropyran ring to provide tri-cyclic products with high stereospecificity. This is the first example of Pauson–Khand
reactions with compounds on carbohydrate or tetrahydropyranose ring, and the scope is described. © 1999 Elsevier Science S.A.
All rights reserved.
Keywords: Pauson–Khand reaction; Sugar acetylene; biscobaltoctacarbonyl
The general precursor sugar acetylenes (1) are readily
available by C-glycosidation of glycals with silylacetyle-
nes in acidic media [1,3]. When 2-acetoxy-glucal 3, for
example, is treated with bis(trimethylsilyl)acetylene in
Among synthetic reactions involving organometals as
catalysts, the Pauson–Khand reaction has occupied a
leading position for synthesis of cyclopentanone or
cyclopentenone derivatives. Most of those examples are
the presence of tin tetrachloride, and then with sodium
found in the precursor compounds having no stereo-
borohydride in the presence of cerium(III) chloride, the
genic centers. We became interested in performing Pau-
son–Khand reaction, a [2+2+1]cyclization with an
acetylene and an olefin attached to a pyranose ring at
the adjacent position, in order to obtain optically active
products that are potentially useful for natural product
synthesis. We have recently established a new method
to synthesize the sugar acetylenes for use as reagents
[1]. The current study of the Pauson–Khand [2] reac-
tion on the sugar acetylene 1 should give the tricyclic
products 2 as shown in Eq. (1). These products would
also provide some additional aspects for the sugar
acetylenes as synthetic intermediates.
alkynylated product 4 is obtained [4]. This acetylene
alcohol (4) was then converted into the corresponding
allyl ether (6) in two steps via the corresponding car-
bonate (5) in the presence of palladium as catalyst [5].
In this case about 23% of the allylic alcohol (4) was
recovered. The product 6 was obtained with retention
of configuration, which suggested the p-allyl complex of
palladium and the carbonate 5 took place at the non-
cyclic allyl ether group rather than the cyclic one. The
1,2-cis-en-yne compound (6) was first converted to the
corresponding biscobalthexacarbonyl complex (7), and
was then subjected to one of several Pauson–Khand
conditions. Treatment of 7 with six equivalents of N-
methylmorphorine N-oxide (NMO) at room tempera-
ture under nitrogen [6] yielded the tri-cyclic product 8
as crystals (m.p. 86.3°, [a]D= +195°) in 98% yield. To
the best of our knowledge this is the first example of
successful Pauson–Khand reaction related to a sugar-
based acetylene [7] (Scheme 1).
(1)
Such a successful Pauson–Khand reaction with the
1,2-cis-en-yne precursor 7 prompted us to examine a
1,2-trans-ene-yne precursor 9, which was obtainable
* Corresponding author.
E-mail address: isobem@agr.nagoya-u.ac.jp (M. Isobe)
0022-328X/99/$ - see front matter © 1999 Elsevier Science S.A. All rights reserved.
PII: S0022-328X(99)00320-4

M. Isobe, S. Takai / Journal of Organometallic Chemistry 589 (1999) 122–125
123
from 7 via acidic epimerization. Treatment with trifl-
uoromethanesulfonic acid (0.1 M solution of TfOH) at
room temperature afforded 9 (containing a small
amount of 7 as a mixture in a ratio of 30:1). This
product was subjected to NMO in dichloromethane
under the same conditions as above to provide 10 (m.p.
119°, [a]D= +222.1°) (Scheme 2).
Similar examples were achieved with 1,2-cis- and
1,2-trans-en-yne precursors of acetylene bis-cobalthexa-
carbonyl complex having tert-butyldiphenylsilyl protec-
tion at the six-position as 13 and 15, which were prepared
from the acetate 6, respectively as shown in Scheme 3.
In this case the a–b isomerization took place in 40:1
ratio under the same acidic conditions as the above
Scheme 1.
Scheme 2.
Scheme 3.

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M. Isobe, S. Takai / Journal of Organometallic Chemistry 589 (1999) 122–125
Scheme 4.
Scheme 5.
10, in fact, showed an NOE with 2-H, but the 7-H
overlapped with other proton signals.) The stereochem-
ical process might be determined by approach of the
initial coordination of p-electrons on the side chain to
exchange the carbon monoxide ligands to one of the
cobalt atoms. Scheme 5 shows one possible process of
the P–K reaction [8]; thus, the side chain olefin and one
of the cobalt atoms in the starting material A approach
each other, intramolecular ligand exchanges A to B. In
this case, the terminal olefin is predestined to approach
to the cobalt complex such that the subsequent [2+2]
cycloaddition takes place through a minimum-energy
surface. Fig. 1 illustrates the intermediates from 1,2-
trans materials explaining the stereochemical course, so
that 2-H directed to the a orientation, where only one
of the two apical carbonyl groups can exchange with
olefin. Fig. 2 illustrates the 1,2-cis cases, where the
tetrahydropyran ring takes an inverted conformation,
but the approach between the two reaction cite should
case. The P–K reaction to both 13 and 15 again
proceeded with NMO to produce the corresponding
tricyclic compounds 14 (colorless oil, [h]D= +78.8°)
and 16 (m.p. 134.4°, [a]D= +115.7°) in high yields,
respectively. Among these P–K tricyclic products the
last compound (16) from trans-ene-yne precursor (15)
clearly indicated an NOE between 2-H and 7-H so that
the stereochemistry of the 2-H should be a. Conse-
quently the stereochemistry of 14, which showed no
NOE, should be assigned as 2-H being a as well.
The third examples are the cases of terminal
acetylene (without trimethylsilyl group). Two 1,2-cis-
precursors (19 and 21) were prepared from 6 by hydrol-
ysis of the trimethylsilyl and acetyl groups with
dipotassium carbonate (Scheme 4). In this case the a–b
epimerization did not take place due to insufficient
steric congestion without the trimethylsilyl group, so
the P–K reaction was examined only with the 1,2-cis-
en-yne precursors. Both the TBDPS derivative 19 and
the free alcohol 21 afforded the tricyclic P–K products
20 (as oil, [a]D= 82.4°) and 22 (m.p. 168.3°, [a]D=
281.1°) in 96 and 90% yield, respectively.
The stereochemistry of the products was assigned
from NMR; thus, all of the P–K products from 1,2-cis-
precursors showed no NOE between 2-H and 7-H.
Only compound 16 indicated a clear NOE. (Compound
Fig. 1.

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125
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happen in a similar manner to the trans case. This
explanation would lead to the high stereoselective
product having 2-H in alpha orientation (Scheme 5).
Additional examples of this reaction including more
detailed data will be described in full elsewhere.
Acknowledgements
This research was supported by a grant from JSPS-
RFTF.
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