Cationic-oxazaborolidine-catalyzed enantioselective diels-alder reaction of a,b-unsaturated acetylenic ketones

Article abstract of DOI:10.1002/anie.200904339

Yne also a good dienophile: The cationic oxazaborolidine 1 promoted the formation of Diels-Alder adducts between acetylenic ketones and both cyclic and acyclic dienes in excellent yield with 99% ee (see scheme; Tf= trifluoromethanesulfonyl, TMS=trimethyls

Full text of DOI:10.1002/anie.200904339

Communications
DOI: 10.1002/anie.200904339
Asymmetric Catalysis
Cationic-Oxazaborolidine-Catalyzed Enantioselective Diels–Alder
Reaction of a,b-Unsaturated Acetylenic Ketones**
Joshua N. Payette and Hisashi Yamamoto*
The catalytic, enantioselective Diels–
Alder reaction is one the most exten-
sively studied transformations in the
field of asymmetric catalysis.[1] This
attention is justified, especially in view
of the myriad of natural product syn-
theses that make use of this reaction.[2]
The current state of asymmetric Diels–
Alder catalysis is certainly impressive.
The Lewis and Brønsted acid activation
of a,b-unsaturated aldehydes, ketones,
esters, and amides, as well as simple
carbonyl and imino compounds, and
Scheme 1. Regioselective Diels–Alder reaction catalyzed by 1 to provide adducts derived from
treatment with various dienes has pro-
2-substituted cyclopentadienes. Tf=trifluoromethanesulfonyl.
vided cycloadducts in excellent yields
with excellent enantioselectivities.[1,3]
Despite these advances, dienophiles
are still mostly limited to compounds containing sp2-hybri-
dized reactive centers. In 1997, Corey and Lee and our
research group independently disclosed the first asymmetric
Diels–Alder reactions of cyclic dienes and a,b-unsaturated
acetylenic aldehydes with boron-based catalysts.[4a,b] Recently,
Ishihara and Fushimi reported a copper-catalyzed asymmetric
Diels–Alder reaction of cyclic dienes and propiolamides.[4f]
Besides these studies, the development of asymmetric [4+2]
cycloaddition reactions of acetylenes has remained nearly
nonexistent, thus leaving a tremendous gap in an otherwise
robust field of chemistry.[4] We herein describe a highly regio-
and enantioselective Diels–Alder reaction of both cyclic and
acyclic dienes with a,b-acetylenic ketones under the catalysis
of the chiral cationic oxazaborolidine Lewis acid 1.
We previously reported regio- and enantioselective Diels–
Alder reactions of mixtures of 1- and 2-substituted cyclo-
pentadienes with the l-valine-derived cationic oxazaboroli-
dine catalyst 1 (Scheme 1). Notably, this catalyst system was
able to discriminate between two similar regioisomeric
nucleophiles.[5] We recognized that the use of a chiral catalyst
to not only differentiate the enantiofaces of an electrophile
but also to direct the attack of an incoming nucleophile might
serve as a useful strategy in the development of new
asymmetric methodologies. To demonstrate the feasibility of
this approach, we sought to apply 1 to the Diels–Alder
reaction of acetylenes. Unlike cycloaddition reactions of sp2-
hybridized dienophiles, exo and endo transition states of
acetylenic dienophiles give opposite enantiomers. Thus,
discrimination between these two modes of diene approach
is vital for high levels of enantioselectivity to be attained.
We investigated the [4+2] cycloaddition reaction of
acyclic dienes with varying substitution patterns and trime-
thylsilylacetylenes 2 and 3 in the presence of 1 (5 or 10 mol%;
Table 1).[6] In all cases, the adducts were isolated in good to
excellent yield as a single regioisomer with 99% ee. Use of
Dane’s diene (4; X = OMe) or the equivalent compound
without the methoxy substituent as well as related 3-vinyl-
indene (5) with 2 and 3 gave the corresponding cycloadducts
as single isomers through electrophilic attack at the terminal
methylene carbon atom.[7]
Open-chain dienes and non-aromatic inner–outer dienes
with one endo- and one exocyclic double bond could also be
applied in this reaction. X-ray crystallographic analysis
indicated that the absolute configuration of brominated
derivatives of 7a and 7b were identical. Finally, the reaction
of less bulky 1-phenyl-2-propyn-1-one and diene 8 under the
standard reaction conditions provided the corresponding
cycloadduct in 90% yield with 99% ee (Scheme 2). Thus,
the large terminal TMS group is not essential for high levels of
reactivity or asymmetric induction.
[*] J. N. Payette, Prof. Dr. H. Yamamoto
Department of Chemistry, The University of Chicago
5735 South Ellis Avenue, Chicago, IL 60637 (USA)
Fax: (+1)773-702-0805
E-mail: yamamoto@uchicago.edu
Cyclopentadiene was also investigated as a substrate for
this reaction. The use of 1 (5 mol%) with 2 or 3 and
cyclopentadiene at À788C in CH2Cl2 provided the corre-
sponding cycloadducts 9a and 9b in 88% yield with 74% ee
and in 90% yield with 71% ee, respectively. When the TMS
[**] Support of this research was provided by the National Institutes of
Health (2R01M068433-05). We also thank Dr. Ian M. Steele for X-ray
crystal-structure determination.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200904339.
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Chemie
Table 1: Diels–Alder reaction of ethyl and phenyl acetylenic ketones with
various dienes.[a,b]
Diene
Product of the reaction with
Scheme 3. Effect of the silyl group in Diels–Alder reactions with
cyclopentadiene.
opposite enantiomers, we postulate that an increase in the
bulk of the dienophile leads to greater selectivity between the
two sterically similar transition states formed from cyclo-
pentadiene and the catalyst–dienophile complex. In the case
of acyclic dienes, the size of the dienophile is less important,
as the steric requirements of the exo and endo modes of
approach are significantly different. In accord with our
previous study on Diels–Alder reactions of 1- and 2-substi-
tuted cyclopentadienes, these results further demonstrate the
important role that interactions between the nucleophile and
catalyst–substrate complex may have in determining which of
several possible transition states is favored.
4
5
4a
73% yield
99% ee
4b[d]
96% yield
99% ee
5a[e]
96% yield
99% ee
5b
85% yield
99% ee
Our previous studies with 1, as well as studies by Corey
and co-workers with their proline-derived oxazaborolidine
system, indicated that the presence on the electrophile of an
acidic formyl, vinylic, or a hydrogen atom capable of hydro-
gen bonding with the oxygen atom of the catalyst was
necessary for a highly ordered transition state to be main-
tained.[3b,5,8] The uniformity of the enantioselectivities
observed for 2 and 3 in Table 1 and the agreement in the
absolute configuration of 7a and 7b suggest that both
acetylenes may coordinate in a related fashion, and that the
presence of an a hydrogen atom is unnecessary. As in the case
of 3, it is conceivable that the binding of 1 with 2 also lacks the
typical hydrogen-bonding interactions postulated for other
oxazaborolidinium-mediated reactions. At the onset of our
investigation, we believed this interaction was essential to fix
the Lewis acid in an anti coordination geometry relative to the
alkyne. However, if catalyst/dienophile complexation does
not involve hydrogen bonding, syn or anti coordination modes
of the dienophile are both plausible.[9,10]
6
7
6a
7a
94% yield
99% ee
6b
7b
93% yield
99% ee
96% yield
99% ee
96% yield
99% ee
8
8a
94% yield
99% ee
8b
88% yield
99% ee
[a] See the Supporting Information for details. [b] Yields of the isolated
product are given. [c] In the reactions to form 8a,b, 5 mol% of the
catalyst was used; for all other reactions, 10 mol% of the catalyst was
used. [d] The use of 4 with X=OMe resulted in decomposition. [e] The
ee value could not be determined by HPLC. The ee value of the adduct
derived from 6-bromo-3-vinyl-1H-indene is given. TMS=trimethylsilyl.
The X-ray crystal structure of an oxazaborole complex
related to catalyst 1 (Figure 1)[11] suggests that the dienophile
À
should coordinate trans to the isopropyl group and N H
atom. In this case, the absolute configuration of the products
can be rationalized on the basis of an endo or exo transition
state of the anti- or syn-coordinated catalyst–dienophile
complex, respectively.
In summary, the cationic oxazaborolidine 1 has been
shown to catalyze Diels–Alder reactions of acetylenic ketones
with various cyclic and acyclic dienes with excellent levels of
asymmetric induction.[12] These findings will hopefully stim-
ulate more studies of Lewis acid mediated reactions with this
oft-neglected class of electrophiles. Furthermore, our results
demonstrate that the exploitation of interactions between the
nucleophile and the catalyst–substrate complex may serve as
Scheme 2. Diels–Alder reaction of an acetylenic ketone without a
terminal silyl group.
group was replaced with the larger tert-butyldimethylsilyl
(TBS) group, the enantioselectivity was increased to up to
95% ee (Scheme 3). Since exo or endo transition states give
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Communications
[1] D. A. Evans, J. S. Johnson in Comprehensive Asymmetric
Catalysis, Vol. 3 (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto),
Springer, Berlin, 1999, chap. 33.1.
[2] K. C. Nicolaou, S. A. Snyder, T. Montagnon, G. Vassilikogian-
nakis, Angew. Chem. 2002, 114, 1742 – 1773; Angew. Chem. Int.
Ed. 2002, 41, 1668 – 1698.
[3] a) E. J. Corey, T. Shibata, T. W. Lee, J. Am. Chem. Soc. 2002, 124,
3808 – 3809; b) E. J. Corey, Angew. Chem. 2009, 121, 2134 – 2151;
Angew. Chem. Int. Ed. 2009, 48, 2100 – 2117; c) K. Futatsugi, H.
Yamamoto, Angew. Chem. 2005, 117, 1508 – 1511; Angew. Chem.
Int. Ed. 2005, 44, 1484 – 1487; d) A. G. Doyle, E. N. Jacobsen,
Chem. Rev. 2007, 107, 5713 – 5743; e) Acid Catalysis in Modern
Organic Synthesis, Vol. 1 (Eds.: H. Yamamoto, K. Ishihara),
Wiley-VCH, Weinheim, 2008.
[4] a) K. Ishihara, S. Kondo, H. Kurihara, H. Yamamoto, S. Ohashi,
S. Inagaki, J. Org. Chem. 1997, 62, 3026 – 3027; b) E. J. Corey,
T. W. Lee, Tetrahedron Lett. 1997, 38, 5755 – 5758; c) A. Rahm,
A. L. Rheingold, W. D. Wulff, Tetrahedron 2000, 56, 4951 – 4965;
d) K. Maruoka, A. B. Concepcion, H. Yamamoto, Bull. Chem.
Soc. Jpn. 1992, 65, 3501 – 3503; e) D. A. Evans, S. J. Miller, T.
Lectka, P. von Matt, J. Am. Chem. Soc. 1999, 121, 7559 – 7573;
f) K. Ishihara, M. Fushimi, J. Am. Chem. Soc. 2008, 130, 7532 –
7533.
[5] J. N. Payette, H. Yamamoto, J. Am. Chem. Soc. 2007, 129, 9536 –
9537. In contrast, the catalyst EtAlCl2 (20 mol%) gives the
adducts of ethyl acrylate and 1- and 2-methylcyclopentadiene in
a 7:3 ratio; it thus favors the formation of the product derived
from 2-methylcyclopentadiene.
Figure 1. ORTEP view (50% probability level) of an oxazaborole com-
plex related to 1.
a useful approach in the development of new asymmetric
methodologies. Current investigations in our laboratory are
focused on the geometry and energetics of the Lewis acid
coordination of acetylenic electrophiles.
Experimental Section
[6] For a discussion of the a-silicon effect, see: J. B. Lambert,
Tetrahedron 1990, 46, 2677 – 2689.
[7] a) M. Yu, S. J. Danishefsky, J. Am. Chem. Soc. 2008, 130, 2783 –
2785; b) Q.-Y. Hu, G. Zhou, E. J. Corey, J. Am. Chem. Soc. 2004,
126, 13708 – 13713.
[8] For oxazaborolidinium activation of methyl aryl ketones, see:
a) D. H. Ryu, E. J. Corey, J. Am. Chem. Soc. 2005, 127, 5384 –
5387; for a discussion of the role of hydrogen bonding in
enantioselective Lewis acid catalysis, see: b) E. J. Corey, T. W.
Lee, Chem. Commun. 2001, 1321 – 1329.
[9] a) DFT studies on oxazaborolidinium catalysis suggest that
hydrogen bonding between the catalyst and the substrate may
not always occur: M. N. Paddon-Row, L. C. H. Kwan, A. C.
Willis, M. S. Sherburn, Angew. Chem. 2008, 120, 7121 – 7125;
Angew. Chem. Int. Ed. 2008, 47, 7013 – 7017; for experimental
support for these findings, see: b) E. P. Balskus, E. N. Jacobsen,
Science 2007, 317, 1736 – 1740.
General Procedure: CH2Cl2 (1.4 or 1.95 mL) and a solution of the
oxazaborolidine in CH2Cl2 (0.1m; 600 mL, 0.06 mmol or 300 mL,
0.03 mmol) were placed in a dried Schlenk flask under an inert
atmosphere. This solution was cooled to À788C, and a solution of
1-(bis(trifluoromethanesulfonyl)methyl)-2,3,4,5,6-pentafluoroben-
zene in CH2Cl2 (0.1m; 500 mL, 0.05 mmol or 250 mL, 0.025 mmol) was
added dropwise. The resulting slightly cloudy mixture was stirred for
15 min at this temperature, and then a solution of the acetylenic
ketone (0.5 mmol) in a minimal amount of CH2Cl2 was added
dropwise. The mixture was stirred for a further 1–2 min, and then a
solution of the diene (0.65 mmol, 1.3 equiv) in a minimal amount of
CH2Cl2 was added dropwise. The resulting mixture was allowed to
warm to À208C. It was stirred for a total of 12 h, and then the reaction
was quenched with aqueous saturated NaHCO3 (5 mL) at À208C.
The reaction mixture was allowed to warm to room temperature and
was then extracted three times with Et2O. The combined extracts
were dried over Na2SO4, filtered, and concentrated in vacuo. The
crude product was purified by flash column chromatography with
hexanes/ethyl acetate (20:1)
[10] For a discussion of the Corey–Bakshi–Shibata (CBS) reduction
of alkynyl ketones, see: E. J. Corey, C. J. Helal, Angew. Chem.
1998, 110, 2092 – 2118; Angew. Chem. Int. Ed. 1998, 37, 1986 –
2012.
[11] The X-ray crystal structure does not indicate the presence of a
Received: August 3, 2009
Published online: September 22, 2009
À
hydrogen bond between O2 H and O3.
[12] Acetylenic esters were screened as dienophiles with various
cyclic and acyclic dienes. However, presumably as a result of
their lower reactivity, no product was detected.
Keywords: acetylenes · asymmetric catalysis · boron · Diels–
.
Alder reaction · oxazaborolidines
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