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Catalytic Enantioselective Crossed AldehydeЦKetone Benzoin Cyclization.

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Zuschriften
Asymmetric Synthesis
DOI: 10.1002/ange.200600268
Catalytic Enantioselective Crossed Aldehyde–
Ketone Benzoin Cyclization**
Hiroshi Takikawa, Yoshifumi Hachisu, Jeffrey W. Bode,
and Keisuke Suzuki*
Despite the exceptionally long history of the benzoin reaction
in the toolbox of organic methodology,[1] it has found only
limited use in the synthesis of complex molecules. Two major
limitations have stymied advances in synthetic applications.
First, catalytic reaction conditions are usually limited to the
synthesis of homobenzoins. Second, the resulting products are
often labile, even when the desired reactivity can be
obtained.[2] It is thus not surprising that recent innovations
in this area have focused on new methods for the selective
generation of acyl anions,[3, 4] novel applications of the
catalyst-bound Breslow intermediate,[5, 6] and expansion of
the scope of the electrophilic reaction partners[7] to include
electron-deficient olefins,[8] imines,[9] disulfides,[10] and aryl
fluorides.[11]
In the context of our studies on the selective synthesis of
natural products with a-keto tertiary alcohols, such as
eucomol (1),[12] we recently reported the viability of benzoin
cyclizations of ketoaldehydes with thiazolium catalysts, thus
affording the desired structure under mild conditions.[13] With
the hope of opening an enantioselective access to these and
other natural products, we were attracted to chiral, nonracemic azolium salts as precatalysts for this synthetically
valuable process.[14] Enders et al. reported chiral triazolium
salts for intramolecular Stetter reactions[15] and, in an
impressive advance, the utility of chiral triazolium salt 6 as
a precatalyst for enantioselective intermolecular benzoin
homodimerizations.[16] Contemporaneously, Rovis and coworkers developed a class of triazolium salts derived from
[*] H. Takikawa, Y. Hachisu, Dr. J. W. Bode,[+] Prof. Dr. K. Suzuki
Department of Chemistry
Tokyo Institute of Technology
SORST-JST Agency
2-12-1 O-okayama, Meguro-ku, Tokyo 152-8551 (Japan)
Fax: (+ 81) 3-5734-2788
E-mail: ksuzuki@chem.titech.ac.jp
amino alcohols and documented their remarkable application
to highly diastereo- and enantioselective intramolecular
Stetter reactions[17] and to catalytic, enantioselective redox
esterifications of a,a-dichloroaldehydes.[18]
Although it was initially believed that the intramolecular
aldehyde–ketone benzoin[19] reaction was limited to preorganized substrates as a result of competing homobenzoin and
intramolecular aldol processes, we[20a] and Enders and Niemeier[20b] recently showed that the thiazolium-catalyzed
benzoin cyclization is a general process for the formation of
five- and six-membered a-hydroxyketones. Just recently,
Enders et al. disclosed a chiral g-lactam-derived triazolium
salt that effects catalytic, enantioselective aldehyde–ketone
benzoin cyclizations of three substrate classes in 67–
98 % ee.[21] Prompted by this report, we report herein the
use of Rovis; aminoindanol-derived chiral triazolium salts as
exceptional catalysts for a highly enantioselective aldehyde–
ketone benzoin cyclization of a wide variety of substrates in
up to 99 % ee (Scheme 1).[22]
Scheme 1. Catalytic, enantioselective ketoaldehyde benzoin cyclizations.
Our studies began with a survey of the chiral heterocyclic
salts for the catalytic cyclization of a model ketoaldehyde 3,
which is readily obtained by the cyclocondensation of an aryl
nitrile oxide and 1,3-diketone[23] [Eq. (1)]. Although trials
with the enantiomerically pure thiazolium salt 5[24] were
disappointing, significant asymmetric induction was observed
with chiral triazolium salts 6,[16] 7,[25] 2 a, and 2 b[17c] (Table 1,
entries 1–5). Further studies revealed optimal conditions in
terms of base (1,8-diazabicyclo[5.4.0]undec-7-ene (DBU),
Table 1: Optimization of the selective benzoin cyclization of 3.[a]
+
[ ] Present address:
Department of Chemistry and Biochemistry
University of California
Santa Barbara, CA 93106-9510 (USA)
[**] We thank Prof. Dr. Dieter Enders for the generous donation of
catalyst 6; Banyu Pharmaceutical Co., Ltd. for the gift of (1S,2R)-1amino-2-indanol; and Dr. Hidehiro Uekusa and Sachiyo Kubo for
the X-ray analysis. This study was partially supported by the 21st
Century COE program (Tokyo Institute of Technology), Grants-inAid for Scientific Research (JSPS), and Research Fellowships for
Young Scientists (from JSPS to H.T.).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
3572
Entry
[b]
1
2
3
4
5
6
7
Cat. (mol %)
Base (mol %)
t [h]
Yield [%]
ee [%]
5 (10)
6 (40)
7 (10)
2 a (10)
2 b (10)
2 b (10)
2 b (10)
DBU (10)
KOtBu (40)
KOtBu (10)
KOtBu (10)
KOtBu (10)
NEt3 (10)
DBU (10)
4
44
6.5
8
8
24
14.5
24
13
86
28
44
8
87
58 (S)
98 (R)
87 (R)
99 (R)
99 (R)
99 (R)
99 (R)
[a] Unless otherwise indicated, all reactions were performed on a 1.0mmol scale at a concentration of 0.3 m in THF at room temperature; the
enantiomeric excess was determined by HPLC analysis on chiralpak
AD-H. [b] The reaction was performed in tBuOH at 40 8C.
2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. 2006, 118, 3572 –3574
Angewandte
Chemie
entries 5–7), which led to product
formation in high yield and with
99 % ee in favor of the R enantiomer.[26]
A substrate screen revealed the
broad substrate scope of the reaction.
Various ketoaldehydes underwent
highly enantioselective cyclization
under the catalytic conditions
(Table 2).[26] Entry 1 shows the reaction of an aliphatic ketoaldehyde 8,
which cyclized with excellent selectivity. Alkyl aryl ketoaldehydes 9 and 10
are also viable substrates. The selectivity was excellent for six-membered
ring formation (entry 2), whereas the
selectivity was substantially lower for
five-membered
ring
formation
(entry 3).
Biaryl ketoaldehydes (entries 4–6)
proved to be good substrates for the
enantioselective cyclizations, but
careful studies on the absolute configuration of the products revealed that
the facial selectivity was opposite to
that observed for all other substrate
classes. The origin of this unexpected
reversal is under investigation, but
may be due to changes in the enol
geometry of the Breslow intermediate. The enantiomeric excess varied
according to the size of the substituent
at the ketone moiety, thus giving
39 % ee (S) for the methyl ketone,
90 % ee (S) for the ethyl ketone, and
85 % ee (S) for the isopropyl ketone
(entries 4–6, respectively).
In anticipation of the application
of the Rovis catalysts to the synthesis
of complex anthraquinoid and naphthoquinoid structures, we were
pleased to find that isoxazole substrates 14 and 15 cyclized in good yield
and with high enantioselectivity
Table 2: Enantioselective cyclization of ketoaldehydes.[a]
Entry
Keto aldehyde
Products
t [h]
Yield [%]
ee [%]
1[b]
8
16
24
44
96
2
9
17
7
70
96
3[c]
10
18
0.5
69
60
4[d]
11
19
15
73[e]
39
5
12
20
18
47[e]
90
6
13
21
19
74[e]
85
7[d]
14
22
6
91
98
8[f ]
15
23
19
73
99
[a] Unless otherwise indicated, all reactions were performed with 20 mol % 2 b and 20 mol % DBU in
THF at room temperature; the enantiomeric excess was determined by HPLC analysis on chiralpak ADH or chiralcel OD-H; the absolute configuration was confirmed by X-ray analysis of the corresponding
(S)-camphanyl esters.[26] [b] The corresponding homobenzoin product was obtained (28 %); the
enantiomeric excess of 16 was determined by GC analysis on a chrompak chirasil-dex CB. [c] The
reaction was performed with 25 mol % 2 b and 20 mol % KOtBu. [d] The reaction was performed with
10 mol % 2 b and 20 mol % DBU. [e] The corresponding intramolecular aldol products were also
obtained (entry 4: 18 %, entry 5: 37 %, entry 6: 8 %). [f ] The reaction was performed with 40 mol % 2 b
and 40 mol % DBU; the crude product was acetylated prior to analysis.
(entries 7 and 8). Further studies on the application of this
process to the synthesis of natural products are ongoing.
Scheme 2 shows the application of this approach to the
asymmetric synthesis of 4-chromanones, a key structural
Scheme 2. Enantioselective synthesis of the eucomol core.
Angew. Chem. 2006, 118, 3572 –3574
2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.de
3573
Zuschriften
motif in natural products, including ( )-eucomol (1). In
addition to providing a concise entry to this interesting class
of natural products, the successful enantioselective cyclization
of readily enolizable ketone 24 demonstrated the uniquely
mild reaction conditions for enantioselective carbon–carbon
bond formation.
Received: August 17, 2004
Revised: January 21, 2006
Published online: April 25, 2006
.
Keywords: asymmetric synthesis · C C coupling · cyclization ·
N-heterocyclic carbenes · tertiary alcohols
[1] M. Pohl, B. Lingen, M. MCller, Chem. Eur. J. 2002, 8, 5289 – 5295.
[2] “The benzoin and related acyl anion equivalent reactions”: A.
Hassner, K. M. L. Rai in Comprehensive Organic Synthesis,
Vol. 1 (Eds.: B. M. Trost, I. Fleming), Pergamon, Oxford, 1991,
pp. 541 – 577.
[3] For the development of crossed benzoin-type reactions of acyl
silanes and aldehydes, see: a) X. Linghu, J. S. Johnson, Angew.
Chem. 2003, 115, 2638 – 2640; Angew. Chem. Int. Ed. 2003, 42,
2534 – 2536; b) X. Linghu, J. R. Potnick, J. S. Johnson, J. Am.
Chem. Soc. 2004, 126, 3070 – 3071; c) X. Linghu, C. C. Bausch,
J. S. Johnson, J. Am. Chem. Soc. 2005, 127, 1833 – 1840.
[4] The exquisite specificity of enzymes has enabled the development of a highly enantioselective crossed-benzoin reaction that
employs 2-substituted benzaldehydes as activated aldehyde
precursors: P. DCnkelmann, D. Kolter, A. Nitsche, A. S.
Demir, P. Siegert, B. Lingen, M. Puhl, M. MCller, J. Am.
Chem. Soc. 2002, 124, 12 084 – 12 085.
[5] For the seminal work of Breslow on the mechanism of
thiazolium-catalyzed benzoin reactions, see: R. Breslow, J. Am.
Chem. Soc. 1958, 80, 3719 – 3725.
[6] K. Zeitler, Angew. Chem. 2005, 117, 7674 – 7678; Angew. Chem.
Int. Ed. 2005, 44, 7506 – 7510.
[7] For recent highlights and reviews, see: a) J. S. Johnson, Angew.
Chem. 2004, 116, 1348 – 1350; Angew. Chem. Int. Ed. 2004, 43,
1326 – 1328; b) D. Enders, T. Balensiefer, Acc. Chem. Res. 2004,
37, 534 – 541; c) M. Christmann, Angew. Chem. 2005, 117, 2688 –
2690; Angew. Chem. Int. Ed. 2005, 44, 2632 – 2634.
[8] H. Stetter, H. Kuhlmann, Org. React. 1991, 40, 407 – 496.
[9] a) J. A. Murry, D. E. Frantz, A. Soheili, R. Tillyer, E. J. J.
Grabowski, P. J. Reider, J. Am. Chem. Soc. 2001, 123, 9696 –
9697; b) for an enantioselective variant, see: S. M. Mennen, J. D.
Gipson, Y. R. Kim, S. J. Miller, J. Am. Chem. Soc. 2005, 127,
1654 – 1655.
[10] W. H. Rastetter, J. Adams, J. W. Frost, L. J. Nummy, J. E.
Frommer, K. B. Roberts, J. Am. Chem. Soc. 1979, 101, 2752 –
2753.
[11] Y. Suzuki, T. Toyota, F. Imada, M. Sato, A. Miyashita, Chem.
Commun. 2003, 1314 – 1315.
[12] a) C. Tamm, Fortschr. Chem. Org. Naturst. 1981, 40, 105 – 152;
b) F. A. Davis, M. C. Weismiller, J. Org. Chem. 1990, 55, 3715 –
3717; c) S.-S. Jew, H.-A. Kim, J.-H. Kim, H.-G. Park, Heterocycles 1997, 46, 65 – 70.
[13] Y. Hachisu, J. W. Bode, K. Suzuki, J. Am. Chem. Soc. 2003, 125,
8432 – 8433.
[14] For pioneering studies on catalytic, asymmetric benzoin reactions with chiral thiazolilum salts, see: J. C. Sheehan, D. H.
Hunneman, J. Am. Chem. Soc. 1966, 88, 3666 – 3667.
[15] D. Enders, K. Breuer, J. Runsink, J. H. Teles, Helv. Chim. Acta.
1996, 79, 1899 – 1902.
[16] D. Enders, U. Kallfass, Angew. Chem. 2002, 114, 1822 – 1824;
Angew. Chem. Int. Ed. 2002, 41, 1743 – 1745.
3574
www.angewandte.de
[17] a) M. S. Kerr, J. Read de Alaniz, T. Rovis, J. Am. Chem. Soc.
2002, 124, 10 298 – 10 299; b) M. S. Kerr, T. Rovis, Synlett 2003,
12, 1934 – 1936; c) M. S. Kerr, T. Rovis, J. Am. Chem. Soc. 2004,
126, 8876 – 8877; d) J. Read de Alaniz, T. Rovis, J. Am. Chem.
Soc. 2005, 127, 6284 – 6289; e) M. S. Kerr, J. Read de Alaniz, T.
Rovis, J. Org. Chem. 2005, 70, 5725 – 5728.
[18] N. T. Reynolds, T. Rovis, J. Am. Chem. Soc. 2005, 127, 16 406 –
16 407.
[19] Although the resulting products are more appropriately labeled
acyloins rather than benzoins, we have adopted the term benzoin
reaction as a general rubric for the nucleophilic addition of
aldehydes to carbonyl compounds by the transient intermediacy
of an acyl anion equivalent. Although imperfect, this nomenclature avoids confusion with the acyloin reaction, a fundamentally different process that affords otherwise identical products.
[20] a) Y. Hachisu, J. W. Bode, K. Suzuki, Adv. Synth. Catal. 2004,
346, 1097 – 1100; b) D. Enders, O. Niemeier, Synlett 2004, 2111 –
2114.
[21] D. Enders, O. Niemeier, T. Balensiefer, Angew. Chem. 2006, 118,
1491 – 1495; Angew. Chem. Int. Ed. 2006, 45, 1463 – 1467.
[22] This work was presented in full at the Pacifichem Conference
2005 in Honolulu, Hawaii, USA, December 20, 2005 and the
85th CSJ Spring Meeting in Kanagawa University, Japan, March
26, 2005.
[23] For the preparation of the ketoaldehyde substrates, see: a) J. W.
Bode, Y. Hachisu, T. Matsuura, K. Suzuki, Tetrahedron Lett.
2003, 44, 3555 – 3558; b) J. W. Bode, K. Suzuki, Tetrahedron Lett.
2003, 44, 3559 – 3563; c) T. Matsuura, J. W. Bode, Y. Hachisu, K.
Suzuki, Synlett 2003, 11, 1746 – 1748.
[24] R. L. Knight, F. J. Leeper, Tetrahedron Lett. 1997, 38, 3611 –
3614.
[25] R. L. Knight, F. J. Leeper, J. Chem. Soc. Perkin Trans. 1 1998,
1891 – 1893.
[26] The absolute configurations of the tertiary alcohols were
confirmed by X-ray analysis of the derived (S)-camphanyl
esters following studies to confirm the chiral integrity of benzoin
products under the esterification conditions (see the Supporting
Information for details).
2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. 2006, 118, 3572 –3574
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