Diastereoselectivity during 2-pyridone photo-[4+4] cycloaddition. The tribenzylsilyl protecting group

Article abstract of DOI:10.1016/S0040-4039(01)00953-4

The use of a silyloxy group as a stereocontrol element on the most distant carbon of a pyrindinone during intermolecular [4+4] photocycloaddition was tested using silyl groups varying in size (tert-butyldimethylsilyl

Full text of DOI:10.1016/S0040-4039(01)00953-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5155–5157
Diastereoselectivity during 2-pyridone photo-[4+4] cycloaddition.
The tribenzylsilyl protecting group
Scott McN. Sieburth,* Christina B. Madsen-Duggan and Fangning Zhang
Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA
Received 7 May 2001; revised 3 June 2001; accepted 4 June 2001
Abstract—The use of a silyloxy group as a stereocontrol element on the most distant carbon of a pyrindinone during
intermolecular [4+4] photocycloaddition was tested using silyl groups varying in size (tert-butyldimethylsilyl<triisopropylsilyl<
tribenzylsilyl). The ratio of the diastereomeric products was proportional to the size of the silyl group, with the largest,
tribenzylsilyl, giving the best ratio of 10:1. The expected stereochemistry was confirmed by X-ray crystallography. © 2001 Elsevier
Science Ltd. All rights reserved.
Cycloaddition reactions are highly valued as synthetic
methods, in part because of their generally high selec-
tivities. The [4+4] photodimerization of 2-pyridones is a
higher-order cycloaddition that occurs with a very high
regioselectivity (exclusively head-to-head) and good rela-
tive stereoselectivity (trans-2 dominating over cis-3).1 In
addition, we have found that stereoselectivity engen-
dered by a chiral center near a pyridone can be substan-
tial. For intramolecular photocycloaddition of tethered
pyridones 1, the stereogenic center on the tether con-
trols formation of the nearest chiral center, yielding
only the anti relationship of the silyloxy group and the
adjacent carbonyl in 2 and 3.2 In this paper we describe
the use of a silyloxy group to control the face selectivity
for the intermolecular photocycloaddition of 4, with a
stereogenic center remote from the newly forming chiral
carbons (Fig. 1).
In comparison to 1, the silyloxy group in 4 is remote
from the centers of reactivity and the developing stereo-
genic centers, and is located on the flexible flap of a
cyclopentene ring with the potential to adopt a confor-
mation that would minimize its steric impact and
thereby lower its stereochemical influence. Silyl groups
are also known for their attenuated steric bulk.3 The
‘A’ value for a trimethylsilyl group is significantly
Figure 1. A tether substituent in 1 exerts a strong stereochemical influence. The remote stereocenter in 4 has the potential to act
similarly.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00953-4

5156
S. McN. Sieburth et al. / Tetrahedron Letters 42 (2001) 5155–5157
smaller than a tert-butyl group even though it has a
substantially larger volume.4 Nevertheless, Eliel and
Satici found that for silyl ethers of cyclohexanols,
increased sterics led to a greater preference for an axial
conformation.5 Should this prove to be the case for 9,
such a conformation would enhance the desired steric
effect.
byproduct 10 could be minimized by very slow addition
of the diyne to the irradiated catalyst and isocyanate in
refluxing xylene (Fig. 2).
Cross [4+4] photocycloaddition of 9 with 4-methoxy-2-
pyridone 5 was carried out using the standard condi-
tions devised earlier: a 1:7 molar ratio of 9:5 in
methanol with a total (pyrindinone+pyridone) concen-
tration of 0.5 M.7,8 This reaction relies on the photosta-
bility of 4-alkoxy-2-pyridones toward dimerization,9,10
and the discovery that they can, nonetheless, undergo
[4+4] photocycloaddition with other pyridones.7,11
The starting pyrindinone 9 was prepared using Voll-
hardt’s cobalt-catalyzed cycloaddition of isocyanates
with 1,6-diynes. The requisite diynes 8 were synthesized
in two steps from propargyl bromide and ethyl formate,
employing the aluminum-mediated method of
Sondheimer6 to minimize allene formation, followed by
O-silylation with the necessary chlorosilane or silyl
triflate. The cross cyclization of the diyne 8 and
phenethylisocyanate to give 9 initially gave a mixture
with 10, a product formed by trimerization of 8, pre-
sumably as a mixture of diastereomers. Formation of
In each case, two major photoproducts were formed
that differed only in the stereochemistry of the silyloxy
group, with one of the two isomers dominating. In
contrast to the high stereoselectivity found for 1 (Fig. 1)
for which only anti-products were observed,2 the tert-
butyldimethylsilyl (TBS) group of 9a had little influ-
27%
20%
Figure 2. Synthesis of pyrindinone 9.
Figure 3. Photocycloaddition of pyrindinones 9a–c with 5 yields primarily 6. Crystal structure of tribenzylsilylether product 6c.

S. McN. Sieburth et al. / Tetrahedron Letters 42 (2001) 5155–5157
5157
ence, giving only a 1.5:1 ratio of products. Use of the
larger triisopropylsilyl (TIPS, 9b) group gave little
improvement, yielding products in a ratio of 2:1.
References
1. Sieburth, S. McN. In Advances in Cycloaddition; Har-
mata, M., Ed. The Inter- and Intramolecular [4+4] Pho-
tocycloaddition of 2-Pyridones and Its Application to
Natural Product Synthesis.; JAI: Greenwich, CT, 1999;
Vol. 5, pp. 85–118.
2. Sieburth, S. McN.; Hiel, G.; Lin, C.-H.; Kuan, D. P. J.
Org. Chem. 1994, 59, 80–87.
3. Hwu, J. R.; Wang, N. Chem. Rev. 1989, 89, 1599–1615.
4. Kitching, W.; Olszowy, H. A.; Drew, G. M.; Adcock, W.
J. Org. Chem. 1982, 47, 5153–5156.
In considering other protecting groups that would
present a greater steric advantage, we found that tri-
benzylchlorosilane was one of the few commercially
available reagents with b-branching, often a prime factor
in relevant steric bulk.12 Use of this silyl ether (TBnS, 9c)
gave a substantial improvement in the stereochemical
outcome, with a product ratio of 10:1.
The expected diastereomeric result of this photoreaction
was confirmed by X-ray crystallography of the major
TBnS product 6c (Fig. 3).13 While this does not necessar-
ily represent the minimum energy conformation of the
tribenzylsilyloxy group, the structure is consistent with
Eliel’s finding that bulky silyl ethers prefer an axial
conformation.5 The large size of this unit and its potential
as a blocking reagent approach is readily apparent.
5. Eliel, E. L.; Satici, H. J. Org. Chem. 1994, 59, 688–689.
6. Sondheimer, F.; Amirl, Y.; Gaoni, Y. J. Am. Chem. Soc.
1962, 84, 2270–2274.
7. Sieburth, S. McN.; Lin, C.-H. Tetrahedron Lett. 1996, 37,
1141–1144.
8. Sieburth, S. McN.; Lin, C.-H.; Rucando, D. J. Org.
Chem. 1999, 64, 950–953.
9. De Selms, R. C.; Schleigh, W. R. Tetrahedron Lett. 1972,
3563–3566.
10. Fujii, H.; Shiba, K.; Kaneko, C. J. Chem. Soc., Chem.
Commun. 1980, 537–538.
11. Sieburth, S. McN.; Chen, J.; Ravindran, K.; Chen, J.-l. J.
Am. Chem. Soc. 1996, 118, 10803–10810.
12. Isaacs, N. S. Physical Organic Chemistry, 2nd ed.; Wiley:
New York, 1995.
13. Compound 6c crystallizes in the monoclinic space group
Although the tribenzylsilyl group has been known for
nearly a century,14 we are aware of only two prior uses
to control stereochemistry. Both examples are part of the
pioneering studies of E. J. Corey in the design and use
of silicon-protecting groups.15,16 The stereoselectivities
reported here reinforce and complement these earlier
findings. In particular, the tribenzylsilyl group is useful
where steric influence is important and the more typically
used TIPS group is insufficiently bulky.
,
P21/c with a=11.6918(1), b=30.906(4), c=10.248(1) A,
3
,
i=101.248 (3)°, V=3631.8 (5) A , and Z=4. Final
least-squares refinement using 1315 unique reflections
with I>3|(I) gave R (Rw)=0.063 (0.059).
14. Martin, G.; Kipping, F. S. J. Chem. Soc. 1909, 95,
302–314.
Acknowledgements
15. Corey, E. J.; Ensley, H. E. J. Org. Chem. 1973, 38,
3187–3189.
16. Corey, E. J.; Nicolaou, K. C.; Toru, T. J. Am. Chem.
Soc. 1975, 97, 2287–2288.
This work was supported by grants from the National
Institutes of Health. The authors would like to thank Jun
Xiao, Jianfeng Jiang and Professor Joseph Lauher for
assistance with the X-ray crystallography.
.