The copper(I) catalysed [2+2] intramolecular photoannulation of carbohydrate derivatives

Article abstract of DOI:10.1055/s-1999-3120

Carbohydrate derivatives 1a, lb, 3a and 3b have been subjected to copper(I) catalysed photoannulation to produce tetracyclic products 2a, 2b, 4a and 4b respectively as single enantiomers. The same reaction carded out on substrates 5a and 5b leads stereose

Full text of DOI:10.1055/s-1999-3120

LETTER
1003
The Copper(I) Catalysed [2+2] Intramolecular Photoannulation of
Carbohydrate Derivatives
David J. Holt,a William D. Barker,a Paul R. Jenkins,a* Subrata Ghosh,b* David R. Russella and John Fawcetta
a Department of Chemistry, Leicester University, Leicester, LE1 7RH, UK
Fax +44(116)2523789; E-mail: for PRJ: kin@le.ac.uk
b Indian Association for the Cultivation of Science, Department of Organic Chemistry, Calcutta 700032, India
Received 15 March 1999
This paper is dedicated to Professor A. Eschenmoser
control of these reactions, could be applied in carbohy-
drate examples to produce single enantiomerically pure
diastereoisomers.
Abstract: Carbohydrate derivatives 1a, 1b, 3a and 3b have been
subjected to copper(I) catalysed photoannulation to produce tetra-
cyclic products 2a, 2b, 4a and 4b respectively as single enanti-
omers. The same reaction carried out on substrates 5a and 5b leads
stereoselectively to the spiro products 6a and 6b respectively. Pho-
toannulation of substrate 7 gave an approximate 1:1 mixture of
spiro products 8 and 9. A mechanistic rationalisation of these results
is proposed.
Key words: annulation, carbohydrates, copper, cycloadditions,
photochemistry
Synthetic chemists have used carbohydrates as polyhy-
droxylated chiral starting materials for many years.1
When the chosen target molecule in these ventures is cy-
clic, methods for the annulation of the carbohydrate start-
ing material are required, and there are many varied
strategies to achieve this objective.2 One potentially use-
ful method for carbohydrate annulation involves a [2+2]
photoannulation. To the best of our knowledge there are
three applications of intramolecular enone-olefin [2+2]
photoannulation in a carbohydrate example,3 in which ste-
reoselectivity was not always observed. There are also
two examples of intermolecular enone-olefin [2+2] pho-
toannulation on sugar derivatives, one of which occurs in
low yield with poor stereoselectivity.4 We now report the
stereoselective formation of several cyclobutane carbohy-
drate derivatives, in good yield, via the copper(I) cataly-
sed [2+2] photoannulation of the corresponding
unactivated 1,6-dienes.
The formation of coordination complexes between cop-
per(I) and olefins is well known.5, 6 Applications of these
complexes in catalysed photoannulation reactions has
been studied by Salomon for many years.7 In particular
copper(I) catalysed [2+2] cycloaddition has been espe-
cially successful. Coordination of the copper(I) to both
olefins produces a complex which absorbs the light and
cyclizes. The product does not coordinate, and so is re-
leased from the copper, which then coordinates another
molecule of diene to complete the cycle.
Continuing our interest in new methods for carbohydrate
annulation8 we have investigated the application of the
copper(I) triflate catalysed [2+2] photoannulation to this
problem. We were particularly interested to see if the
promising results of Salomon and Ghosh,9 on the stereo-
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1004
D. J. Holt et al.
LETTER
The 1,6-dienes10 1a-b, 3a-b, 5a-b and 7 were selected and hydroxyl group are on the b-face of the molecule. In the
the results of the photoannulation reactions are sum- same way the chelated structures 11a and 11b lead to the
marised in Table 1. The first photoannulation substrate products 4a and 4b in which the cyclobutane and the hy-
was the trans glucose derivative 1a, which was irradiated droxyl group are on the a-face of the molecule.
at 254 nm in benzene, using a Rayonet photochemical re-
actor, with a catalytic amount copper(I) triflate benzene
complex.11 Two diastereoisomeric products are possible
in this reaction, arising from the facial selectivity of the
[2+2] cycloaddition. The 13C NMR spectrum of the crude
product showed that only one diastereoisomer was
formed, and only a single peak was observed by HPLC.
The six stereogenic centres in the enantiomerically pure
starting material 1a would not reasonably be expected to
change on irradiation, and so we conclude that product 2a,
obtained in 86% isolated yield, is enantiomerically pure.
Scheme 2
The absolute configurations of the two new centres in 2a
were confirmed in the X-ray crystal structure12 by com-
parison with the unchanged stereogenic centres.
We propose transition states 12a and 12b in Scheme 2 to
explain the stereochemistry of the products 6a and 6b. Co-
Similar treatment of the more hindered trans diene 1b ordination of one of the olefins and the sugar ring oxygen
gave a modest 18% yield of product 2b, whereas the cis to the copper(I) leads only to the observed products 6a and
glucose derivatives 3a and 3b led to single diastereoiso- 6b on irradiation.
mers 4a and 4b in 86% and 89% yield respectively.
In contrast to the stereospecific photoannulation of 5a and
To extend the range of this work we prepared two sub- 5b, substrate 7 gave an approximate 1:1 mixture of the
strates 5a and 5b for spiro photoannulation. Irradiation two possible products 8 and 9. Clearly in compound 7 the
under our usual conditions produced the products 6a and anomeric oxygen is too far away to coordinate to the cop-
6b as single enantiomers in moderate yield, whose struc- per(I)-diene chelate. This is in agreement with the lack of
tures were confirmed by X-ray crystallography.13 Diene 7 selectivity observed by Mackor and Evers in the photobi-
gave an approximate 1:1 mixture of the two possible prod- cyclisation of 4-hydroxy 1,6-heptadiene.14
ucts 8 and 9 in a 63% yield.
In conclusion we have demonstrated the remarkable
stereocontrol of copper(I) triflate in the photoannulation
of six unactivated 1,6-diene carbohydrate derivatives.
Acknowledgement
This work was supported by the Engineering and Physical Sciences
Research Council, Pharmachemie BV, Haarlem, Holland and the
Indian National Science Academy - Royal Society study visit grant
to Prof. S. Ghosh.
References and Notes
(1) S. Hanessian, Total Synthesis of Natural Products; The
Chiron Approach, Pergamon: Oxford, 1993.
(2) R. J. Ferrier, S. Middleton, Chem. Rev. 1993, 93, 2779; J. C.
Lopez, B. Fraser-Reid, Chem. Commun. 1997, 2251.
(3) R. J. Ferrier, P. Prasit, G. J. Gainsford, Y. Le Page, J. Chem.
Soc., Perkin Trans. 1 1983, 1635; A. Tenaglia, D. Barillé,
Synlett 1995, 776; A. M. Gómez, S. Mantecón, S. Velazquez,
Scheme 1
S. Valverde, P. Herczegh, J. C. López, Synlett 1998, 1402.
(4) D. R. Hicks, J. L. Primeau, B. Fraser-Reid, Carbohydr. Res.
1982, 108, 41; M. Fetizon, D. D. Khac, N. D. Tho,
Tetrahedron Lett. 1986, 26, 1777.
(5) D. J. Trecker, J. P. Henry, J. E. McKeon, J. Am. Chem. Soc.
1965, 87, 3261.
In order to explain the stereochemistry of these reactions
we returned to the work of Salomon and Ghosh,9 in which
there is a preference for the formation of the endo product
in the photobicyclisation of 1,6-heptadiene-3-ols. Apply-
ing these arguments to the photoannulation of our diene
glucose derivatives we arrive at the hypotheses illustrated
in Scheme 1. Coordination of the two olefins and the hy-
droxyl oxygen as shown in structures 10a and 10b means
that in the products 2a and 2b the cyclobutane ring and the
(6) D. P. Schwendiman, C. Kutal, Inorg. Chem. 1977, 16, 719.
(7) R. G. Salomon, Tetrahedron 1983, 39, 485.
(8) R. V. Bonnert, P. R. Jenkins, J. Chem. Soc., Chem. Commun.
1987, 6; R. V. Bonnert, J. Howarth, P. R. Jenkins, N. J.
Lawrence, J. Chem. Soc., Perkin Trans. 1 1991, 1225; A. J.
Wood, P. R. Jenkins, J. Fawcett, D. R. Russell, J. Chem. Soc.,
Chem. Commun. 1995, 1567; R. V. Bonnert, M. J. Davies, J.
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LETTER
Howarth, P. R. Jenkins, J. Chem. Soc., Chem. Commun. 1987,
148; R. V. Bonnert, M. J. Davies, J. Howarth, P. R. Jenkins,
N. J. Lawrence, J. Chem. Soc., Perkin Trans. 1 1992, 27; A. J.
Wood, P. R. Jenkins,Tetrahedron Lett. 1997, 38, 1853; A. N.
Boa, J. Clark, P. R. Jenkins, N. J. Lawrence, J. Chem. Soc.,
Chem. Commun. 1993, 151; A. J. Wood, D. J. Holt, M.-C.
Dominguez, P. R. Jenkins, J. Org. Chem. 1998, 63, 8522.
(9) R. G. Salomon, D. J. Coughlin, S. Ghosh, M. G. Zagorski, J.
Am. Chem. Soc. 1982, 104, 998.
[2+2] Intramolecular Photoannulation of Carbohydrates
1005
6a - M.p. 141.5-143oC; [a]D12 = + 36.6 (c = 3.3 in CHCl3); Rf
= 0.26, petroleum ether (40-60oC)/diethyl ether (1/1);
1H NMR (250 MHz; CDCl3) d = 7.55-7.30 (m, 5 H, Ph), 5.50
(s, 1 H, 12-H), 4.67 (s, 1 H, 1-H), 4.24 (dd, J = 4.4, 10.1 Hz, 1
H, 6eq-H), 3.98-3.80 (3 H, CHH, 11-H and 5-H), 3.70 (t, J =
10.1 Hz, 1 H, 6ax-H), 3.49 (s, 3 H, OMe), 3.49 (m, 1 H, over-
lapping, 4-H), 3.16-2.93 (2 H, 7-H and 10-H), 2.22 (m, 1 H,
CHH, 9-H), 2.01 (m, 2 H, CHH, 8-H), 1.87 (m, 2 H, CHH, 3-
H), 1.67 (m, 1 H, CHH, 9-H); 13C NMR(62.9 MHz, CDCl3) d
= 137.8 (C, Ph), 129.5 (CH, Ph), 128.7 (CH, Ph), 126.6 (CH,
Ph), 102.3 (CH, C12), 99.6 (CH, C1), 83.8 (C, C2), 77.4 (CH,
C4), 73.1 (CH2, C11), 69.9 (CH2, C6), 64.1 (CH, C5), 55.4
(CH3, OMe), 45.6 (CH, C7), 39.1 (CH, C10), 32.7 (CH2, C3),
24.1 (CH2, C9), 19.6 (CH2, C8); HRMS (FAB): m/z(%): 333
(56) [MH+]. Anal. Found: C, 68.53; H, 7.27. C19H24O5 requires
C, 68.66; H, 7.28%.
(10) D. J. Holt, W. D. Barker, P. R. Jenkins, D. L. Davies, S.
Garratt, J. Fawcett, D. R. Russell and S. Ghosh, Angew.
Chem., Int. Ed. Engl. 1998, 37, 3298.
(11) Typical Synthetic Procedure for the [2+2]
photoannulation: All operations were performed under
nitrogen. Solvents were dried by using standard methods.
Yields reported refer to products purified by column
chromatography.
(12) Crystal data for 2a: crystal dimensions 0.54 x 0.24 x 0.12
mm, triclinic, space group P1, a = 8.467(2), b = 10.304(3), c =
10.464(5)Å, α = 90.40(3), β = 109.34(3), γ = 101.30(2)°, V =
842.2(5) Å3, Z = 2, ρcalcd =1.311 g cm-3, 2θmax = 48°, Mo-Kα
radiation (λ = 0.7107 Å), ω scan, 190K, 2512 reflections, 2368
independent reflections used for refinement. The data were
corrected for Lorentz and polarisation effects but not for
absorption (µ = 0.094 mm-1, min/max transmission = 0.963/
0.991). The structure was solved by direct methods and
refined F² (SHELXTL/PC ver 5.0), 2 unique molecules in the
asymmetric unit with different orientation of the phenyl group
at C12, hydroxyl H atoms were located from difference
Fourier maps, all other H atoms were included in calculated
positions (C-H = 0.96Å) using a riding model. R1 = 0.063
[I>2σ(I)], wR2 = 0.169 for all data, for 313 parameters,
maximum ∆ρ = +0.26, -0.31 e Å-3.
(CF3SO3Cu)2.C6H6 (10 mg, 0.02 mmol) was added to a
solution of diene 1a (140 mg, 0.42 mmol) in benzene (10 mL),
in a quartz photolysis tube, water-cooled by a cold finger
extending into the solution. Irradiation was carried out at 254
nm, using a Rayonet photochemical reactor, for 6 hours. The
reaction mixture was diluted with diethyl ether (40 mL) and
washed with aqueous ammonia solution (35%, 2x20 mL). The
organic layer was washed with water (20 mL), dried (MgSO4)
and concentrated under reduced pressure. The crude product
was purified by column chromatography (silica gel, petroleum
ether (40-60oC)/diethyl ether, 3/1) to yield 2a as a white solid
(121 mg, 86%).
Sample spectroscopic data for two photoannulated products:
2a - M.p. 101-103oC; [a]D20 = + 34.2 (c = 4.1 in CHCl3); Rf =
0.36, petroleum ether (40-60oC)/diethyl ether (1/1); 1H NMR
(400 MHz; CDCl3) d = 7.55-7.33 (m, 5 H, Ph), 5.59 (s, 1 H,
12-H), 4.60 (s, 1 H, 1-H), 4.31 (dd, J = 4.7, 10.2 Hz, 1 H, 6eq-
H), 3.88 (dd, J = 9.2, 11.0 Hz, 1 H, 4-H), 3.87 (t, J = 10.2 Hz,
1 H, overlapping, 6ax-H), 3.70 (ddd, J = 4.7, 9.2, 10.2 Hz, 1
H, 5-H), 3.42 (s, 3 H, OMe), 2.84-2.73 (2 H, 7-H and 10-H),
2.29-2.15 (2 H, CHH, 9-H and CHH, 11-H), 2.15 (br s, 1 H,
overlapping, OH), 2.08-1.97 (3 H, CHH, 8-H and 3-H), 1.81
(m, 1 H, CHH, 9-H), 1.58 (dt, J = 5.7, 12.3 Hz, 1 H, CHH, 11-
H); 13C NMR (100.6 MHz, CDCl3) d = 138.2 (C, Ph), 129.3
(CH, Ph), 128.7 (CH, Ph), 126.6 (CH, Ph), 102.9 (CH, C1),
102.3 (CH, C12), 81.9 (C, C2), 81.4 (CH, C4), 69.6 (CH2, C6),
65.1 (CH, C5), 55.6 (CH3, OMe), 48.0 (CH, C3), 42.7 (CH,
C7), 37.1 (CH, C10), 33.6 (CH2, C11), 29.4 (CH2, C9), 17.2
(CH2, C8); HRMS (FAB): m/z(%): 333 (15) [MH+]; calcd for
C19H25O5 [MH+]: 333.1702, found: 333.1703. Anal. Found: C,
68.75; H, 7.32. C19H24O5 requires C, 68.66; H, 7.28%.
(13) Crystallographic data for compounds 2a, 6a and 6b in this
paper have been deposited with the Cambridge
Crystallographic Data Centre as deposition numbers CCDC-
110883, 110884 and 110885 respectively. Copies of the data
can be obtained free of charge on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK (Fax: +44(1223)-336-
033; E-mail: deposit@ccdc.cam.ac.uk).
(14) J. Th. M. Evers and A. Mackor, Tetrahedron Lett. 1978, 821.
Article Identifier:
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Synlett 1999, S1, 1003–1005 ISSN 0936-5214 © Thieme Stuttgart · New York