Highly enantioselective [2+2]-cycloaddition reactions catalyzed by a chiral aluminum bromide complex

Article abstract of DOI:10.1021/ja0765262

Enantioselective [2+2]-cycloaddition pathways to chiral cyclobutanes are rare and not generally utilized for synthesis. A new cycloaddition reaction of vinyl ethers with trifluoroethyl acrylate in the presence of a catalytic amount of chiral oxazaborolidi

Full text of DOI:10.1021/ja0765262

Published on Web 09/27/2007
Highly Enantioselective [2+2]-Cycloaddition Reactions Catalyzed by a Chiral
Aluminum Bromide Complex
Eda Canales and E. J. Corey*
Department of Chemistry and Chemical Biology, HarVard UniVersity, Cambridge, Massachusetts 02138
Received August 29, 2007; E-mail: corey@chemistry.harvard.edu
Table 1. Enantioselective [2+2]-Cycloaddition of Trifluoroethyl
Acrylate to Enol Ethers with 10 mol % of Catalyst 1 in CH2Cl2 at
-78 °C
There are just a few reported examples of catalytic enantiose-
lective [2+2]-cycloaddition reactions of achiral components. Narasa-
ka et al. described the application of chiral TADDOL-TiCl2 catalyst
to the cycloaddition of allenyl thioethers and N-fumaryl-1,3-
oxazolidinone.1 Later, Engler et al. used the same catalyst for the
cycloaddition of methoxy-1,4-benzoquinones to a few styrenes.2
The products of these specialized reactants were not utilized for
synthetic objectives. Here we describe the positive results of a
project aimed at developing a new and useful methodology for the
synthesis of chiral cyclobutanes starting from the known Lewis acid-
catalyzed reaction of vinyloxysilanes and R,â-unsaturated esters
to form racemic [2+2]-adducts.3 The present approach was
stimulated by our recent finding that the oxazaborolidine-aluminum
bromide complex 1 is exceedingly effective as a chiral catalyst for
many Diels-Alder reactions of achiral components.4
Catalyst 1 is conveniently generated in situ by the addition of a
commercially available solution of aluminum bromide in CH2Br2
(Aldrich) to a cold (<-20 °C) CH2Cl2 solution of the known
oxazaborolidine component5,6 (ratio of AlBr3 to oxazaborolidine,
0.8:1). In a typical example, the slow addition of 1 equiv of 2,3-
dihydrofuran to a solution of 0.1 equiv of catalyst 1 and 5 equiv of
trifluoroethyl acrylate in CH2Cl2 at -78 °C and further reaction at
-78 °C for 3 h produced after isolation the exo-[2+2]-cycloadduct
2 in 87% yield and with 99% ee.7,8 This process represents a very
direct and practical route to this previously unknown chiral
cyclobutane.9
We next tested the catalytic [2+2]-cycloaddition process with
enol silyl derivatives of various ketones since, if operable, this
operation might be broadly useful. The reaction of the tert-
butyldimethylsilyl (TBS) and triisopropylsilyl (TIPS) enol ethers
of cyclohexanone with trifluoroethyl acrylate (the most reactive
acrylate ester6k) and 0.1 equiv of catalyst 1 in CH2Cl2 at -78 °C
proceeded smoothly to give [2+2]-cycloaddition products. The
results for these two reactions are summarized in Table 1. Although
the endo ester predominated in each case, the selectivity (97:3) was
greater for the TIPS-enol ether (4) than for the TBS-enol ether (3)
(82:18) (entries 2 and 3 in Table 1). A 96:4 enantioselectivity was
determined for the predominating endo ester, the absolute config-
uration of which was ascertained by reduction of CO2CH2CF3 to
CH2OH in 3 and comparison of optical rotation with the known
bicyclic primary alcohol.10
a See ref 7 for determination of enantioselectivity. b Enantioselectivity
was determined by reduction of COOCH2CF3 to CH2OH, conversion to
the Mosher ester, and 1H NMR analysis. c Enantioselectivity was determined
by GC analysis of enone 12.
each instance for the adducts 4-8. The absolute configurations of
the products 6 and 7 in entries 5 and 6 were established by the
chemical correlations described below.14 The absolute configuration
of adduct 5 was ascertained by reduction of the carboxylic ester
function to the corresponding primary alcohol, conversion to the
4-bromophenylurethane with 4-bromophenylisocyanate-trieth-
ylamine, desilylation with Bu4NF, crystallization, and X-ray dif-
fraction analysis.14 The absolute configuration of 8 was determined
by conversion to the bicyclic ketone 12 as described below and
X-ray diffraction analysis.14
Entries 4-7 in Table 1 summarize the results for four other
substrates. Excellent yields and enantioselectivities were found in
9
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J. AM. CHEM. SOC. 2007, 129, 12686-12687
10.1021/ja0765262 CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
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The protonated oxazaborolidinium cation 9, X ) CF3SO3 or
The predominating diastereomer for the cyclic vinyl ethers in entries
2-7 of Table 1 depends on the bulk of the silyloxy group, on further
substitution at the vinyl group (H vs CH3), and on ring size. This
variability is probably the result of differing steric interactions for
the series of vinyl ether substrates.
(CF3SO2)2N-,6 was decidedly inferior to the AlBr3 complex 1 in
catalyzing the [2+2]-cycloadditions shown in Table 1, apparently
due to side reactions involving the enol ether component.
In our judgment, a reasonable working hypothesis is that the
[2+2]-cycloaddition occurs by an asynchronous process involving
the same type of R-CH hydrogen-bonded complex of catalyst 9
with trifluoroethyl acrylate that has previously been proposed6b for
Diels-Alder reactions of this dienophile, i.e., 13. The reaction of
this complex with 2,3-dihydrofuran, for example, would then
proceed via the pretransition-state assembly 14 in which the bonding
is principally between the â-carbon of trifluoroethyl acrylate and
C(3) of 2,3-dihydrofuran, as described earlier for [2+3]-cycload-
dition reactions of 2,3-dihydrofuran and benzoquinones.6j
The silyl enol ethers in entries 511 and 612 of Table 1 were
prepared by the procedures described previously for these com-
pounds. The silyl enol ether in entry 713 of Table 1 was made by
the conversion of 2-methylcycloheptanone to the potassium enolate
by stirring with KH in THF at ambient temperature (23 °C) for 5.5
h and reacting subsequently with TBSCl at 23 °C for 8 h.
The bicyclic [2+2]-adducts shown in Table 1 are very useful
chiral intermediates for further synthetic elaboration. For instance,
the adduct 6 from 2-methylcyclopentanone enol silyl ether and
trifluoroethyl acrylate can be transformed efficiently into the bicyclic
R,â-enone 10 as shown in Scheme 1. Reaction of 6 with the
Scheme 1. Conversion of [2+2]-Cycloadduct 6 to
(R)-1,2,3,6,7,7a-Hexahydro-7a-methyl-5H-indene-5-one
Acknowledgment. E.C. is the recipient of a Pfizer postdoctoral
fellowship.
Supporting Information Available: Experimental procedures and
characterization data; X-ray crystallographic data. This material is
available free of charge via the Internet at http://pubs.acs.org.
References
(1) Hayashi, Y.; Nihata, S.; Narasaka, K. Chem. Lett. 1990, 2091-2094.
(2) Engler, T. A.; Letavic, M. A.; Iyengar, R.; LaTessa, K. O.; Reddy, J. P.
J. Org. Chem. 1999, 64, 2391-2405.
(3) (a) Clark, R. D.; Untch, K. G. J. Org. Chem. 1979, 44, 253-255. (b)
Takasu, K.; Ueno, M.; Inanaga, K.; Ihara, M. J. Org. Chem. 2004, 69,
517-521. (c) Inanaga, K.; Takasu, K.; Ihara, M. J. Am. Chem. Soc. 2005,
127, 3668-3669.
(4) Liu, D.; Canales, E.; Corey, E. J. J. Am. Chem. Soc. 2007, 129, 1498-
1499.
(5) (a) Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc. 1987, 109,
5551-5553. (b) Corey, E. J.; Bakshi, R. K.; Shibata, S.; Chen, C.-P.;
Singh, V. K. J. Am. Chem. Soc. 1987, 109, 7925-7926. (c) Corey, E. J.;
Helal, C. J. Angew. Chem., Int. Ed. 1998, 37, 1986-2012.
(6) (a) Corey, E. J.; Shibata, T.; Lee, T. W. J. Am. Chem. Soc. 2002, 124,
3808-3809. (b) Ryu, D. H.; Lee, T. W.; Corey, E. J. J. Am. Chem. Soc.
2002, 124, 9992-9993. (c) Ryu, D. H.; Corey, E. J. J. Am. Chem. Soc.
2003, 125, 6388-6390. (d) Ryu, D. H.; Zhou, G.; Corey, E. J. J. Am.
Chem. Soc. 2004, 126, 4800-4802. (e) Hu, Q.-Y.; Zhou, G.; Corey, E. J.
J. Am. Chem. Soc. 2004, 126, 13708-13713. (f) Zhou, G.; Hu, Q.-Y.;
Corey, E. J. Org. Lett. 2003, 5, 3979-3982. (g) Snyder, S. A.; Corey, E.
J. J. Am. Chem. Soc. 2006, 128, 740-742. (h) Hong, S.; Corey, E. J. J.
Am. Chem. Soc. 2006, 128, 1346-1352. (i) Yeung, Y.-Y.; Hong, S.; Corey,
E. J. J. Am. Chem. Soc. 2006, 128, 6310-6311. (j) Zhou, G.; Corey, E.
J. J. Am. Chem. Soc. 2005, 127, 11958-11959. (k) Ryu, D. H.; Zhou,
G.; Corey, E. J. Org. Lett. 2005, 7, 1633-1636.
magnesium amide from O,N-dimethylhydroxylimine in THF at
-30 °C produced in 1 h the Weinreb amide which was treated in
the same flask with methylmagnesium bromide at -30 to 0 °C for
5 h to give, after column chromatography on silica gel, the corres-
ponding methyl ketone (80% overall). Desilation of this intermediate
followed by treatment with 5% methanolic NaOH gave the known
(R)-bicyclo[3,2,1]nonenone 10 in 80% yield; [R]24 -94 (c 1,
D
EtOH).15 The [2+2]-cycloadducts 7 and 8 were transformed in the
same way into the known R,â-enones 11 and 12, respectively.16
(7) Enantiomeric purity was determined by gas chromatographic analysis using
a J&W Scientific Cyclosil-B column.
(8) The absolute configuration of 2 was determined by conversion to the
crystalline 4-bromoanilide followed by single-crystal X-ray diffraction
analysis (see SI).
(9) For a recent review on chiral cyclobutanes, see Lee-Ruff, E.; Mladenova,
G. Chem. ReV. 2003, 103, 1449-1483.
(10) Takasu, K.; Nagao, S.; Ueno, M.; Ihara, M. Tetrahedron 2004, 60, 2071-
2078. This paper describes diastereoselective cycloaddition reactions of
vinyl ethers with 8-phenylmenthyl acrylate in the presence of EtAlCl2.
(11) Saraber, F. C. E.; Baronovsky, A.; Jansen, B. J. M.; Posthumus, M. A.;
de Groot, A. Tetrahedron 2006, 62, 1726-1742.
The absolute configuration of 12 was established unambiguously
by conversion to the crystalline thiosemicarbazone and X-ray
diffraction analysis,14 thereby confirming the absolute configura-
tional assignment for 8 that is shown in Table 1.
Since the absolute configurations of all of the [2+2]-cycloadducts
(2-8) listed in Table 1 have been established, we are in position
to discuss the mechanistic pathways for their formation. It is clear
that in every case attack by the vinyl ether occurs at the same face
of the acrylate ester (si face), exactly as predicted from our
mechanistic model for the S-proline-derived catalyst 1.6a-c The face
selectivity for the silyl enol ether partner is not invariable, however.
(12) Takasu, K.; Ishii, T.; Inanaga, K.; Ihara, M. Org. Synth. 2006, 83, 193.
(13) Ikura, K.; Ryu, I.; Ogawa, A.; Kambe, N.; Sonoda, N. Tetrahedron Lett.
1989, 30, 6887-6890.
(14) See Supporting Information for details.
(15) Pfau, M.; Revial, G.; Guigant, A.; Angelo, J. J. Am. Chem. Soc. 1985,
107, 273-274.
(16) (a) Doering, W. E.; Birladeanu, L.; Sarma, K.; Shao, L. S. J. Am. Chem.
Soc. 1996, 118, 6660-6665. (b) Goubaud, V.; Azerad, R. Synth. Commun.
1996, 26, 915-922.
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