Highly diastereoselective radical cyclization of a glucose-derived enol ether radical cation/phosphate anion pair

Article abstract of DOI:10.1016/S0957-4166(03)00538-X

Diastereomeric 3-O-allyl-4,6-O-benzylidene-2-O-(diphenylphosphatoxy) β-D-gluco- and β-D-manno-pyranosyl phenylselenides were prepared and subjected to treatment with tributyltin hydride and AIBN. The gluco-compound undergoes smooth radical cyclization to

Full text of DOI:10.1016/S0957-4166(03)00538-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 2861–2864
Highly diastereoselective radical cyclization of a glucose-derived
enol ether radical cation/phosphate anion pair
David Crich,* Dae-Hwan Suk and Sanxing Sun
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607-7061, USA
Received 2 May 2003; accepted 14 May 2003
Abstract—Diastereomeric 3-O-allyl-4,6-O-benzylidene-2-O-(diphenylphosphatoxy) b-
D
-gluco- and b-D-manno-pyranosyl
phenylselenides were prepared and subjected to treatment with tributyltin hydride and AIBN. The gluco-compound undergoes
smooth radical cyclization to a single diastereomeric product in high yield whereas the manno-isomer reacts only reluctantly to
give a complex mixture. This difference in behavior is interpreted as arising from the formation of two different contact radical
ion pairs in which the phosphate group shields opposite faces of the enol ether (glycal) radical cation.
© 2003 Elsevier Ltd. All rights reserved.
The advent of the fragmentative approach to the gener-
ation of alkene radical cations1,2 has opened up whole
new vistas3 in the chemistry of these long-revered reac-
tive intermediates.4 Among the more exciting of the
new avenues is the possibility of exploiting a stereo-
chemical memory effect in the contact ion pair arising
from fragmentation of a stereochemically defined b-
(phosphatoxy)alkyl radical or related precursor. Previ-
ously, we have demonstrated how such an effect can be
exploited in the nucleophilic trapping of formally pla-
nar alkene radical cations.5 We now show that the
ion-pair geometry has a profound influence on radical
type cyclizations of fragmentatively generated alkene
radical cations, as manifested by the dramatically dif-
ferent results obtained with a formally diastereomeric
pair of contact radical ionic pairs.
By means of time-resolved laser flash photolyses and
the probe 1, Newcomb et al. have determined6 that enol
ether radical cations, of which 2 is an example, undergo
5-exo-radical cyclization within the initial contact ion
pair, i.e. before equilibration with any solvent-separated
ion pairs and/or free ions, even in polar solvents such
as acetonitrile and acetonitrile/trifluoroethanol mixtures
(Scheme 1). Moreover, the rate constant for cyclization
of enol ether alkene radical cation 2, as reported by the
kinetically transparent opening of the cyclopropyl-
carbinyl radical 3, was estimated to be 1–2×109 s−1 at
ambient temperature, i.e. approximately four orders of
Scheme 1. Estimated rate constants for fragmentation and
cyclization in acetonitrile at ambient temperature.
* Corresponding author. Tel.: 312 996 5189; fax: 312 996 2183;
e-mail: dcrich@uic.edu
Scheme 2. Glycal radical cation generation.
0957-4166/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00538-X

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D. Crich et al. / Tetrahedron: Asymmetry 14 (2003) 2861–2864
and then to the 3-O-allyl derivative 12 by standard
means and, finally, phosphorylated with diphenyl
chlorophosphate to give the gluco radical precursor 49
(Scheme 3).
The manno-isomer 510,11 was similarly obtained
(Scheme 4).
Photolysis of 4 with tributyltin hydride and AIBN in
benzene resulted in the formation of a single major
compound, identified as the glycal 17,12 in 95% yield
and whose stereochemistry was confirmed by single-
crystal X-ray diffraction. We envisage formation of this
compound as proceeding via radical cyclization on the
initial contact ion pair 8 leading to the formation of 16,
followed finally by chain transfer and deprotonation
(Scheme 5, path a). In ring closures of 2-(3-
butenyl)cyclohexyl radicals and their substituted and
heterocyclic variants, cyclization typically affords the
cis-fused bicyclic system, hence our assignment of the
manno-stereo chemistry to intermediate radical 16. The
endo-position of the methyl radical in 16 can be seen as
arising from a Beckwith–Houk13 chair-like transition
state for cyclization in which both substituents (C1 and
C4 of the pyranose ring) are pseudo-equatorial. Alter-
native possibilities that cannot be entirely ruled out
include the transient formation of a fused cyclobutane
radical cation 1814 followed by opening to 16 (Scheme
5, path b) and the collapse of the initial contact ion pair
to the anomeric phosphate 1915 followed by cyclization
and eventual elimination of phosphoric acid (Scheme 5,
path c).
Scheme 3. Preparation of gluco-radical precursor 4.
Scheme 4. Preparation of manno-radical precursor 5.
magnitude faster than that of an analogous uncharged
alkyl radical.7
In the light of the above we reasoned that radical
precursors 4 and 5 would lead, via the anomeric radi-
cals 6 and 7, to diastereomeric contact ion pairs 8 and
9 (Scheme 2) and that these latter would exhibit funda-
mentally distinct behavior owing to the differential
shielding of the alkene radical cation by the phosphate
counter ion.
A dramatically different result was observed with the
manno-precursor 5. First, prolonged heating of 5 over a
period of more than a day with tributyltin hydride with
repeated additions of AIBN was required in order to
drive the reaction to completion. Such behavior is
usually indicative of the breakdown of the chain reac-
Se-Phenyl 2,3,4,6-tetra-O-acetyl-b-D
-selenoglucoside8
was converted to the tetraol 10 by Zemplen deacetyla-
tion. This was elaborated to the benzylidene acetal 11,
Scheme 5. Cyclization of the gluco-precursor 4.

D. Crich et al. / Tetrahedron: Asymmetry 14 (2003) 2861–2864
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P.; Sibi, M., Eds.; Wiley-VCH: Weinheim, 2001; Vol. 2,
pp. 188–206.
2. (a) Newcomb, M.; Horner, J. H.; Whitted, P. O.; Crich,
D.; Huang, X.; Yao, Q.; Zipse, H. J. Am. Chem. Soc.
1999, 121, 10685–10694; (b) Crich, D.; Huang, X.; New-
comb, M. J. Org. Chem. 2000, 65, 523–529; (c) New-
comb, M.; Miranda, N.; Huang, X.; Crich, D. J. Am.
Chem. Soc. 2000, 122, 6128–6129; (d) Bales, B. C.;
Horner, J. H.; Huang, X.; Newcomb, M.; Crich, D.;
Greenberg, M. M. J. Am. Chem. Soc. 2001, 123, 3623–
3629; (e) Crich, D.; Huang, W. J. Am. Chem. Soc. 2001,
123, 9239–9245.
3. (a) Crich, D.; Ranganathan, K.; Huang, X. Org. Lett.
2001, 3, 1917–1919; (b) Crich, D.; Neelamkavil, S. Org.
Lett. 2002, 4, 2573–2575.
Scheme 6. Retarded cyclization and decomposition in the
manno-series.
4. For reviews on the oxidative approach to alkene radical
cations, see: (a) Hintz, S.; Heidbreder, A.; Mattay, J. In
Topics in Current Chemistry; Mattay, J., Ed.; Springer:
Berlin, 1996; Vol. 177, pp. 77–124; (b) Bauld, N. L.;
Bellville, D. J.; Harirchian, B.; Lorenz, K. T.; Pabon, R.
A.; Reynolds, D. W.; Wirth, D. D.; Chiou, H.-S.; Marsh,
B. K. Acc. Chem. Res. 1987, 20, 371–378; (c) Schmittel,
M.; Burghart, A. Angew. Chem., Int. Ed. Engl. 1997, 36,
2550–2589.
tion due to the failure of one or more of the propaga-
tion steps. A complex reaction mixture was obtained
from which only minor amounts (<10%) of 17 could be
isolated. Instead, a number of unidentified products
were formed, all in minor amounts strongly suggesting
that decomposition of one or more intermediates had
taken place.
5. (a) Crich, D.; Ranganathan, K. J. Am. Chem. Soc. 2002,
124, 12422–12423; (b) Crich, D.; Gastaldi, S. Tetrahedron
Lett. 1998, 39, 9377–9380.
We suggest that the difference in reactivity between
precursors 4 and 5 is due to the different placement of
the phosphate counter ion in the respective contact ion
pairs 8 and 9. In effect, in 8 (Scheme 5) the phosphate
is located on the opposite face of the radical cation to
that from which the alkene must approach resulting in
a clean cyclization, smooth propagation and a high
yield of product. In the case of 9, on the other hand, if
the cyclization is to lead to a cis-fused product the
alkene of essence has to approach the same face of the
radical cation as is shielded by the counter ion. This
obvious steric impedance to such a trajectory retards
cyclization and permits competing decomposition of the
alkene radical cation, one possibility for which is shown
in Scheme 6.
6. Horner, J. H.; Taxil, E.; Newcomb, M. J. Am. Chem.
Soc. 2002, 124, 5402–5410.
7. In the particular example illustrated the slow step, with a
lower limit of >2×108 s−1, was the fragmentation.6
8. Yu, B.; Xie, J.; Deng, S.; Hui, Y. J. Am. Chem. Soc.
1999, 121, 12196–12197.
1
9. 4: mp=95–97°C; [h]D20=−26.7 (c, 3.0, CHCl3); H NMR
(CDCl3), l: 3.45–3.54 (m, 1H), 3.62 (t, J=9.8 Hz, 1H),
3.70–3.85 (m, 2H), 4.12–4.20 (m, 1H), 4.28–4.41 (m, 2H),
4.49–4.60 (m, 1H), 4.98 (d, J=9.8 Hz, 1H), 5.00–5.18 (m,
2H), 5.53 (s, 1H), 5.71–5.85 (m, 1H), 7.15–7.60 (m, 20 H);
13C NMR (CDCl3), l: 68.6, 71.7, 73.7, 78.8 (d), 80.0,
81.1, 81.9 (d), 101.1, 117.5, 120.1 120.2, 120.3, 120.4,
125.1, 125.8, 126.6, 128.2, 128.4, 128.9, 129.0, 129.0,
129.5, 129.6, 134.4, 135.5, 136.9, 150.7 (q); 31P NMR
(CDCl3), l: −12.8. Anal. calcd for C34H33O8PSe: C,
60.09; H, 4.89; Found: C, 60.56; H, 5.56.
These observations closely parallel the results of our
study on intramolecular nucleophilic attack by amines
on alkene radical cations derived by a related fragmen-
tation approach wherein attack on the opposite face of
the radical cation to the one shielded by the departing
phosphate is strongly favored.5a
10. Acetobromomannose was prepared according to the liter-
ature method: Talley, E. A.; Reynolds, D. D.; Evans, W.
L. J. Am. Chem. Soc. 1943, 65, 575–582.
11. 5: mp=154–155°C; [h]2D4=−29.6 (c, 1.0, CHCl3); 1H
NMR (CDCl3), l: 3.36–3.46 (m, 1H), 3.65–3.69 (m, 1H),
3.75–3.84 (m, 2H), 4.11–4.18 (m, 1H), 4.24–4.33 (m, 2H),
5.09 (d, J=3.9 Hz, 1H), 5.15 (d, J=10.8 Hz, 1H),
5.32–5.39 (m, 2H), 5.43 (s, 1H), 5.81–5.93 (m, 1H),
7.16–7.59 (m, 20H); 13C NMR (CDCl3), l: 68.8, 71.9,
73.3, 77.0, 77.7, 80.3 (d), 83.4 (d), 102.0, 118.0, 120.5,
120.98, 121.02, 121.11, 121.14, 125.5, 125.7, 126.4, 128.6,
129.4, 129.6, 129.7, 129.9, 130.1, 134.3, 134.8, 137.7,
151.3 (q); 31P NMR (CDCl3), l: −11.6. Anal. calcd for
C34H33O8PSe: C, 60.09; H, 4.89; Found: C, 60.28; H,
5.01.
Acknowledgements
We thank the NSF (CHE 9986200) for support of this
work and our colleagues Bhushan Surve and Professor
D. A. Wink for the X-ray structure determination.
References
1
12. 17: mp=73–75°C; [h]2D0=+0.6 (c, 1.1, CHCl3); H NMR
1. For reviews, see: (a) Beckwith, A. L. J.; Crich, D.;
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3.37 (t, J=8.0 Hz, 1H), 3.74–3.91 (m, 3H), 4.12 (t, J=8.0
Hz, 1H), 4.40–4.46 (m, 1H), 4.51–4.56 (m, 1H), 5.61 (s,

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D. Crich et al. / Tetrahedron: Asymmetry 14 (2003) 2861–2864
1H), 6.15 (t, J=1.9 Hz, 1H), 7.30–7.40 (m, 3H), 7.49–
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137.0. Anal. calcd for C16H18O4: C, 70.06; H, 6.61;
Found: C, 69.71; H, 6.62.
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