Copper(I)-catalyzed intramolecular asymmetric [2 + 2] photocycloaddition. Synthesis of both enantiomers of cyclobutane derivatives

Article abstract of DOI:10.1021/ol049696h

Equation presented. A simple approach for asymmetric induction in Cu(I)-catalyzed [2 + 2] photocycloaddition, where asymmetric catalysts or chiral auxiliaries were inefficient, has been developed using the concept of chirality transfer from the readily av

Full text of DOI:10.1021/ol049696h

ORGANIC
LETTERS
2004
Vol. 6, No. 12
1903-1905
Copper(I)-Catalyzed Intramolecular
Asymmetric [2 + 2] Photocycloaddition.
Synthesis of Both Enantiomers of
Cyclobutane Derivatives
Niladri Sarkar, Abhijit Nayek, and Subrata Ghosh*
Department of Organic Chemistry, Indian Association for the CultiVation of Science,
JadaVpur, Kolkata 700032, India
ocsg@mahendra.iacs.res.in
Received February 20, 2004
ABSTRACT
A simple approach for asymmetric induction in Cu(I)-catalyzed [2 + 2] photocycloaddition, where asymmetric catalysts or chiral auxiliaries
were inefficient, has been developed using the concept of chirality transfer from the readily available 2, 3-di-O-cyclohexylidine-(R)-(+)-
glyceraldehyde. An anion-induced cleavage of the tetrahydrofuran ring of the resulting oxa-bicyclo[3.2.0]heptanes led to a convenient access
to the synthetically useful cis-1,2-disubstituted cyclobutanes in enantiomerically pure form.
The [2 + 2] photocycloaddition reaction, giving rise to
cyclobutanes, is an extremely useful synthetic tool1,2 in
organic synthesis. Its asymmetric version using a removable
chiral auxiliary works efficiently in the case of photocy-
cloaddition3 between an alkene and an enone. However,
copper(I) catalysis2 required for photocycloaddition between
two nonconjugated alkenes proceeds with low des with a
variety of chiral auxiliaries.4 More strikingly, asymmetric
catalysis, which is highly successful in inducing high
enantioselectivity in a variety of reactions,5 including many
cycloaddition processes, fails to induce significant asymmetry
in copper(I)-catalyzed photocycloaddition.4 The multifaceted
application of copper(I)-catalyzed [2 + 2] photocycloaddition
in organic synthesis6 thus necessitates the development of
its asymmetric version. We herein report a simple general
solution to the problem of asymmetric induction in intramo-
lecular copper(I)-catalyzed [2 + 2] photocycloaddition
reaction.
(1) Reviews: (a) Crimmins, M. T. Chem. ReV. 1988, 88, 1453. (b)
DeKeukeleire, D.; He, S. H. Chem. ReV. 1993, 93, 359. (c) Winkler, J. D.;
Mazur-Bowen, C.; Liotta, F. Chem. ReV. 1995, 95, 2003. (d) Namyslo, J.
C.; Kaufmann, D. E. Chem. ReV. 2003, 103, 1485. Selected recent works:
(e) Mehta, G.; Srinivas, K. Tetrahedron Lett. 1999, 40, 4877; Tetrahedron
Lett. 2001, 42, 2855; Chem. Commun. 2001, 1892; Tetrahedron Lett. 2002,
43, 3319. (f) Kemmler, M.; Bach, T. Angew. Chem. Int. Ed. 2003, 42, 4824.
(g) Bach, T.; Kemmler, M.; Herdtweck, E. J. Org. Chem. 2003, 68, 1994.
(2) (a) Salomon, R. G. Tetrahedron 1983, 39, 485. (b) Ghosh, S. In CRC
Handbook of Organic Photochemistry and Photobiology; Horspool, W.,
Lenci, F., Eds.; CRC Press: Boca Raton, FL, 2003; Chapter 18, pp 1-24.
(3) (a) Demuth, M.; Mikhail, G. Synthesis 1989, 145. (b) Ionue, Y. Chem.
ReV. 1992, 741. (c) Bach, T. Synthesis 1998, 683. (d) Faure, S.; Piva-Le
Blanc, S.; Bertrand, C.; Pete, J. P.; Faure, R.; Piva, O. J. Org. Chem. 2002,
67, 1061. (e) Pedrosa, R.; Andre´s, C.; Nieto, J.; del Pozo, S. J. Org. Chem.
2003, 68, 4923.
(4) (a) Langer, K.; Mattey, J. J. Org. Chem. 1995, 60, 7256. (b) Lee-
Ruff, E.; Mladenova, G. Chem. ReV. 2003, 103, 1449.
(5) Noyori, R. Asymmetric Catalysis in Organic Synthesis; John Wiley
and Sons: New York, 1994.
(6) For some selected works, see: (a) McMurry, J. E.; Choy, W.
Tetrahedron Lett. 1980, 21, 2477. (b) Rosini, G.; Marotta, E.; Petrini, M.;
Ballini, R. Tetrahedron 1985, 41, 4633. (c) Lal, K.; Zarate, E. A.; Youngs,
W. J.; Salomon, R. G. J. Am. Chem. Soc. 1986, 108, 1311. (d) Hertel, R.;
Mattey, J.; Runsink, J. J. Am. Chem. Soc. 1991, 113, 657. (e) Ghosh, S.;
Patra, D.; Saha, G. Chem. Commun. 1993, 783. (f) Patra, D. Ghosh, S. J.
Org. Chem. 1995, 60, 2526. (g) Haque, A.; Ghatak, A.; Ghosh, S.; Ghoshal,
N. J. Org. Chem. 1997, 62, 5211. (h) Samajdar, S.; Patra, D.; Ghosh, S.
Tetrahedron Lett. 1998, 54, 1789. (i) Samajdar, S.; Patra, D.; Ghosh, S.
Tetrahedron Lett. 1999, 40, 4401. (j) Holt, D. J.; Jenkins, P. R.; Ghosh, S.
Synlett 1999, 1003. (k) Bach, T. Spiegel, A. Synlett 2002, 1305. (l) Banerjee,
S.; Ghosh, S. J. Org. Chem. 2003, 68, 3981. Also see ref 2.
10.1021/ol049696h CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/15/2004

Scheme 1
Scheme 2
The present approach relies on the transfer of the chirality
at C-2 of 2,3-di-O-cyclohexylidine-(R)-(+)-glyceraldehyde
17 to cis-1,2-disubstituted cyclobutanes through a “relay”
process as new chiral centers are generated sequentially. Of
the two chirality transfer steps, the first one is illustrated by
the synthesis of both enantiomers of the oxa-bicyclo[3.2.0]-
heptane derivative 4a (Scheme 1). Reaction of the aldehyde
1 with vinylmagnesium bromide followed by allylation of
the resulting carbinols afforded an inseparable mixture of
the diene 2a8 and its C-3 epimer in a ca. 3:2 ratio in overall
excellent yield. Smooth cycloaddition took place when an
ether solution of this diene mixture was irradiated with a
Hanovia 450W mercury vapor lamp through a quartz
immersion well in the presence of copper(I)trifluoromethane
sulfonate (CuOTf) (20-25 mol %) to lead to the photoadduct
3a and its C-2 epimer. The exo stereochemical assignment
of the substituents at C-1, C-2, and C-5 is based on analogy9
to the formation of the exo adducts from photocycloaddition
of 3-alkyl-1,6-dienes. The chiral center present in the chiral
auxiliary of the adduct 3a was then destroyed by a three-
step sequence involving acid-induced deketalization (80%
aqueous acetic acid)-oxidative cleavage of the resulting diol
(RuCl3-NaIO4-CH3CN-CCl4-H2O) and esterification
(CH2N2) to afford the ester 4a, [R]25D + 16.9 (c 1.38, CHCl3).
Similarly, the C-2 epimer of the adduct 3a gave the other
enantiomer of 4a, [R]25D -17.6 (c 1.39, CHCl3). In a similar
fashion, the dienes 2b and 2c and their C-3 epimeric
diastereoisomers afforded in each case a pair of the cyclobu-
tanes 4b and 4c.
required 1,6-diene unit can be crafted conveniently on the
glyceraldehyde derivative 1 (Scheme 2). Wittig-Horner
reaction of the aldehyde 1 with triethyl phosphonoacetate
(TEPA) followed by LiAlH4 reduction of the resulting
unsaturated ester afforded the allyl alcohol 5. Ortho ester
Claisen rearrangement of the allyl alcohol 5 on heating with
triethyl orthoacetate afforded a 1:1 chromatographically
separable mixture of the unsaturated esters 6 (Rt ) 2.67 min)
and 7 (Rt ) 2.87 min). The pure ester 7 was then converted
to the aldehyde 8 by LiAlH4 reduction followed by Swern
oxidation of the resulting alcohol. Addition of vinylmagne-
sium bromide to the aldehyde 8 resulted in a diastereoiso-
meric mixture of the dienols 9. Irradiation of this diene
mixture in the presence of CuOTf followed by Swern
oxidation of the photoadducts gave the ketone 10. The
stereochemical assignment of the adduct 10 was based on
analogy to earlier works9 on photocycloaddition of 3-alkyl-
substituted dienes. As before, the chirality in the chiral
pendant was removed to provide the cyclobutane derivative
11, [R]25D +248.1 (c 0.8, CHCl3). Similarly, the unsaturated
ester 6 gave the other enantiomer of the cyclobutane
derivative 11, [R]25D -250.2 (c 2.4, CHCl3). The CD spectra
of each pair of the cyclobutane derivatives of the structures
4c and 11 confirmed their enantiomeric relationship. The
synthesis of both enantiomers of cyclobutane derivatives
from 2,3-di-O-cyclohexylidine-(R)-(+)-glyceraldehyde 1 is
noteworthy, as the enantiomer (S)-(-)-1 is not readily
available. This concept of asymmetric induction has not been
employed earlier4 in intramolecular Cu(I)-catalyzed [2 + 2]
photocycloaddition reactions.
This sequence can also be extended for the synthesis of
both enantiomers of the bicyclo[3.2.0]heptane 11. The
(7) (a) Chattopadhyay, A.; Dhotare, B.; Hassarajani, S. J. Org. Chem.
1999, 64, 6874. (b) For a review on application of optically pure
glyceraldehyde derivatives in organic synthesis, see: Jurczak, J.; Pikul, S.;
Bauer, T. Tetrahedron 1986, 42, 447.
(8) Stereochemical assignment of the dienes 2 and 9 will be described
in a full account of this work.
(9) (a) Raychaudhuri, S. R.; Ghosh, S.; Salomon, R. G. J. Am. Chem.
Soc. 1982, 104, 6841. (b) Ghosh, S.; Raychaudhuri, S. R.; Salomon, R. G.
J. Org. Chem. 1987, 52, 83.
The synthetic potential of this protocol could be enhanced
if fragmentation of the relatively inert tetrahydrofuran ring
in the oxa-bicyclo[3.2.0]heptanes could be achieved. We
anticipated that generation of a radical 12 or an anion 13
1904
Org. Lett., Vol. 6, No. 12, 2004

aldehydes 17 and 23 prepared from the esters 4c and 4b gave
the disubstituted cyclobutanes 20 and 24 in 51 and 58%
yields, respectively. The product 20 appears to arise from
isomerization of the initially formed olefin 19. To the best
of our knowledge, the present protocol for the fragmenta-
tion10 of tetrahydrofuran rings is unprecedented. Cis-1,2-
disubstituted cyclobutanes obtained in this way are of
considerable synthetic use. For example, the cyclobutane
dervative 18, when treated with Dowex-50, smoothly rear-
ranged to the known cyclopentanone 216f [R]25D -63 (c 0.8,
CHCl3), an intermediate in our synthesis6i of the monoterpene
might trigger fragmentation of the tetrahydrofuran ring.
Toward this end, the lithium enolate generated from the ester
4c was methylated to produce exclusively the exo methylated
product 14 (Scheme 3).
â-necrodol 22. The cyclobutane derivative 24 [R]25 -4.1
D
Scheme 3
(c 0.9, CHCl3) has already been transformed to (-)-grandisol
2511a by one-carbon homologation.
In conclusion, we developed a simple approach for
asymmetric induction in intramolecular Cu(I)-catalyzed [2
+ 2] photocycloaddition where asymmetric catalysts or chiral
auxiliaries were inefficient. This, in combination with the
new protocol developed for the cleavage of tetrahydrofuran
rings present in oxa-bicyclo[3.2.0]heptanes, resulted in the
synthesis of useful cis-1,2-disubstituted cyclobutanes in
enantiomerically pure form.
Acknowledgment. This work was supported by Depart-
ment of Science and Technology, Government of India. N.S.
and A.N. wish to thank CSIR, New Delhi, for research
Fellowships.
1
Supporting Information Available: Copies of H and
13C NMR spectra of compounds 2-4, 9, and 10 along with
their diastereoisomers, 11, 14, 16-18, 20, and 23, 1H NMR
spectrum of the compound 24, CD spectra of compounds
4c and 11, and a representative experimental procedure. This
material is available free of charge via the Internet at
http://pubs.acs.org.
The ester 14 was then reduced to the alcohol 15.
Transformation of the alcohol 15 to the corresponding
bromide or xanthate, probable precursors for the radical 12,
could not be achieved. Wolff-Kishner reduction of aldehyde
group to methyl is known to proceed through a carbanionic
intermediate. Thus, we anticipated that the aldehyde 16 could
be a precursor for the anion equivalent to 13. Swern oxidation
of the alcohol 15 afforded the aldehyde 16. The aldehyde
16, when subjected to Wolff-Kishner condition, underwent
smooth fragmentation to deliver the disubstituted cyclobutane
18 in 54% yield. The fragmentation process is general. The
OL049696H
(10) For reviews on ring-opening reactions of cyclic ethers, see: (a)
Maercker, A. Angew. Chem., Int. Ed. Engl. 1987, 26, 972. (b) Ranu, B. C.;
Bhar, S. Org. Prep. Proc. Int. 1996, 28, 371. (c) Larock, R. C.
ComprehensiVe Organic Transformations; Wiley-VCH: Weinheim, Ger-
many, 1999; p 1013.
(11) (a) Meyers, A. I.; Fleming, S. A. J. Am. Chem. Soc. 1986, 108,
306. For recent enantioselective synthesis, see: (b) Hamon, D. P. G.; Tuck,
K. L. Tetrahedron Lett. 1999, 40, 7569. (c) de March, P.; Figueredo, M.;
Font, J.; Raya, J. Org. Lett. 2000, 2, 163.
Org. Lett., Vol. 6, No. 12, 2004
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