Enantioselective catalysis of hetero Diels-Alder reaction and diethylzinc addition using a single catalyst

Article abstract of DOI:10.1021/ol034143c

(Matrix presented) Integration of two asymmetric reactions in one pot with the promotion of a single catalyst has been achieved in high efficiency and excellent stereoselectivity for hetero Diels-Alder reaction of Danishefsky's diene and diethylzinc addit

Full text of DOI:10.1021/ol034143c

ORGANIC
LETTERS
2
003
Vol. 5, No. 7
091-1093
Enantioselective Catalysis of Hetero
Diels−Alder Reaction and Diethylzinc
Addition Using a Single Catalyst
1
Haifeng Du and Kuiling Ding*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road,
Shanghai 200032, The People’s Republic of China
kding@pub.sioc.ac.cn
Received January 26, 2003
ABSTRACT
Integration of two asymmetric reactions in one pot with the promotion of a single catalyst has been achieved in high efficiency and excellent
stereoselectivity for hetero Diels−Alder reaction of Danishefsky’s diene and diethylzinc addition to aldehydes. The strategy described in the
present work demonstrated the ability of a single catalyst to promote two distinct enantioselective reactions in one pot.
The development of organometallic catalysts that are capable
of catalyzing multiple, mechanistically distinct reactions
directly or by simple modification has been an increasing
the integration of two reactions in one pot with the promotion
of a single catalyst is a great challenge for chemists. As an
example of such a system, we demonstrate the ability of a
single catalyst to promote two different reactions in one pot
through a tandem method.
1
demand for expedient and efficient synthetic processes.
Asymmetric catalysis of organic reactions has provided a
powerful strategy for multiamplification of chirality to obtain
2
optically active compounds. However, there were very few
reports on the tandem catalysis of two distinct enantiose-
3
lective reactions using a single chiral catalyst. Therefore,
(1) For leading examples of tandem catalysis, see: (a) Louie, J.;
Bielawski, C. W.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 11312. (b)
Bielawski, C. W.; Louie, J. R.; Grubbs, H. J. Am. Chem. Soc. 2000, 122,
1
2872. (c) Drouin, S. D.; Zamanian, F.; Fogg, D. E. Organometallics 2001,
0, 5495. (d) Orita, A.; Nagano, Y.; Nakazawa, K.; Otera, J. AdV. Synth.
2
Catal. 2002, 344, 548. (e) Chen, J.; Otera, J. Angew. Chem., Int. Ed. 1998,
3
7, 91.
2) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley-
Zinc complexes of 1,1′-bi-2-naphthol (BINOL-Zn, 1) have
been reported to promote enantioselective cyclization of
unsaturated aldehydes and Diels-Alder reaction of N-
alkoxyacrylamides with cyclopentadiene in a stoichiometric
manner. Very recently, we found that 3,3′-dibromo-1,1′-bi-
2
2-naphthol (3,3′-Br BINOL-Zn, 2) was an efficient catalyst
(
Interscience: New York, 1994. (b) Catalysis Asymmetric Synthesis, 2nd
ed.; Ojima, I., Ed.; Wiley-VCH: New York, 2000. (c) Kagan, H. B.
ComprehensiVe Organic Chemistry; Pergamon: Oxford, 1992; Vol. 8. (d)
ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yama-
moto, H., Eds.; Springer: Berlin, 1999; Vols. I-III. (e) Lewis Acids in
Organic Synthesis; Yamamoto, H., Ed.; Wiley-VCH: New York, 2001.
4
1
0.1021/ol034143c CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/01/2003

Scheme 1. Tandem Asymmetric Catalysis of Hetero Diels-Alder Reaction and Diethylzinc Addition Using a Single Catalyst
for the hetero Diels-Alder (HDA) reaction of aldehydes with
-20 °C. Under the optimized conditions, adduct 6 could be
obtained in quantitative yield with up to 98.7% ee.
5
Danishefsky’s diene. The asymmetric activation of 3,3′-Ph
2
-
BINOL-Zn complex (3) with diimine has been found to be
a useful strategy for achieving high efficiency and enantio-
selectivity in catalytic asymmetric diethylzinc addition to
aldehydes.6 As an effort to explore the application of
activated Zn catalyst for two distinct asymmetric reactions,
we first investigated its possibility for the promotion of HDA
reaction of Danishefsky’s diene (4) with benzaldehyde (5)
7
(eq 1).
The investigation using 1 in combination with diimine
prepared by condensation of (S,S)-1,2-diaminocyclohexane
with benzaldehyde as the catalyst for HDA reaction between
4
and 5 (eq 1) showed that the reaction proceeded smoothly
With these leading results in hand, we switched our
attention to the screening of highly efficient and enantiose-
lective catalysts for diethylzinc addition to benzaldehyde (eq
at 0 °C to give (S)-2-phenyl-2,3-dihydro-4H-pyran-4-one 6
with moderate enantioselectivity (63.6% ee). This result
prompted us to further improve the enantioselectivity of the
reaction by tuning the steric and electronic modifications in
the diol ligands and diimine activators through a combina-
2
) by combining 2 with a variety of diimine activators. The
literature results showed that in the catalysis of diethylzinc
addition to aldehydes, the steric hindrance of diimine
activators was critical for getting maximum activation of
8
torial approach. Accordingly, a library of chiral diol ligands
(with 12 members), including commercially available or
6
BINOL-Zn catalyst. Accordingly, a library of diimines with
easily prepared BINOL and biphenol derivatives, and a
library of diimines (with 20 members) derived from enan-
tiopure 1,2-diaminocyclohexane were created. High through-
put screening of the chiral Zn catalyst library (240 members)
generated by assembling the members of diol ligand and
diimine activator libraries with Zn showed that all of the
catalysts could promote the HDA reaction of 4 with 5 at 0
eight members (see Supporting Information) was created by
condensation of enantiopure 1,2-diphenylethylenediamine or
1
2
,2-diaminocyclohexane with 2 equiv of 2,6-dichloro- and
,4,6-trimethylbenzaldehydes. A rapid screening of the chiral
catalyst library composed of 2 and the chiral activators for
diethylzinc addition to benzaldehyde at 0 °C disclosed that
2
/A8 was the best combination, affording (S)-1-phenylpro-
°
C to give the desired product 6. The details of the results
panol ((S)-7) with 72% ee. The enantioselectivity of the
reaction could be improved to 94.5% at a lower reaction
temperature (-20 °C). Reexamination of the 2/A8 catalyst
system for HDA reaction at -20 °C resulted in the formation
of (R)-6 with 97.4% ee and quantitative yield.
So far, we have discovered such a catalyst (2/A8) that is
highly efficient and enantioselective for both HDA reaction
and diethyl zinc addition of benzaldehyde. This catalyst
system provided an excellent opportunity to conduct two
asymmetric reactions in one pot using a single catalyst. Then
terephthalaldehyde 8 was taken as a substrate for tandem
asymmetric HDA reaction and diethylzinc addition to gener-
ate dihydropyranone and secondary alcohol moieties in one
substrate (Scheme 1). The HDA reaction was first carried
out in the presence of 10 mol % 2/A8 for 30 h at -20 °C in
toluene, and then 3 equiv of diethyl zinc was introduced to
were presented in Supporting Information. It was found that
the absolute configuration of product was mainly controlled
by the chirality of diol ligands and that the level of
enantioselectivity of the reaction might be affected by the
chirality and steric environment of diimine activators. We
were pleased to find that complex 2 in the presence of various
diimines was particularly efficient for the reaction, affording
adduct 6 in up to quantitative yield and 94.2% ee. The
reaction catalyzed by the lead catalysts discovered above was
further optimized by decreasing the reaction temperature to
(3) For leading references on tandem asymmetric catalysis, see: (a) Yu,
H.-B.; Hu, Q.-S.; Pu, L. J. Am. Chem. Soc. 2000, 122, 6500. (b) Tian, J.;
Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. Angew. Chem., Int. Ed. 2002,
4
1, 3636.
(4) (a) Sakane, S.; Maruoka, K.; Yamamoto, H. Tetrahedron Lett. 1985,
2
6, 5535. (b) Corminboeuf, O.; Renaud, P. Org. Lett. 2002, 4, 1735.
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Org. Lett., Vol. 5, No. 7, 2003

centers in product 10 are tentatively assigned to be R and S
as shown in Scheme 1 on the basis of the results obtained
using benzaldehyde as a substrate mentioned above. The
conversion and chemical selectivity for the first HDA step
was very high (monoadduct:diadduct > 96:4). The high
chemical selectivity of the first step is probably due to the
fact that the formyl group is strongly electron withdrawing,
which facilitates the first HDA reaction. After HDA reaction,
the substrate is much less reactive than the starting dialdehyde
because of electron-donating property of R-dihydropyranyl
moiety in the monoadduct. We have also carried out tandem
asymmetric HDA reaction and diethylzinc addition of
isophthalaldehyde 9 using the catalyst system of 2/A8 and
observed excellent stereoselectivity for the formation of
product 13 (entry 2 in Table 1).
Table 1. Tandem Asymmetric Reaction of Dialdehydes
Catalyzed by 2/A8a
entry substrate Et2Zn (%) yield (%)d ee (%)b,e de (%)c,e
b
c
c
1
8
14 + 300
10 (92)
10 (97.4) 10 (95.0)
11 (>99) 11 (96.9)
1
1
1 (<3)
2 (<3)
12 (nd)
12 (nd)
b
2
9
14 + 300
13 (82)
13 (95.9) 13 (94.9)
14 (>99) 14 (96.6)
1
1
4 (6.5)
5 (10)
15 (nd)
15 (nd)
a
All of the reactions were carried out at -20 °C in toluene with a molar
ratio of dialdehyde:Danishefsky’s diene:3,3′-Br2-BINOL:A8 ) 1:1.3:0.1:
0
.1. For the first step HDA reaction. For diethylzinc addition. d Isolated
b
c
e
yields. Determined by HPLC on Chiralcel OD or AD column. The de is
the diastereoselectivity of the second alkylation step.
In summary, a new type of chiral zinc catalyst has been
found to show excellent stereoselectivity in asymmetric
catalysis of both HDA reaction of Danishefsky’s diene and
diethylzinc addition to aldehydes. The strategy described in
the present work demonstrated the ability of a single catalyst
to promote two distinct enantioselective reactions in one pot,
which might provide a new direction to the design of chiral
catalysts for asymmetric synthesis. Research on the extension
of the scope of substrates for this reaction and use of achiral
diimine activators in the catalyst system is underway in our
laboratory.
continue the second step, asymmetric addition, under the
same experimental conditions without workup of the first
HDA step product. As shown in Table 1, two asymmetric
reactions proceeded efficiently and selectively to give product
10. It was found that the ee for the HDA reaction was 97.4%,
and the de for the diethylzinc addition step was 95.0%, which
were essentially the same as those obtained using benzal-
dehyde as a substrate. The configurations of two chiral
(
5) Du, H.; Hu, J.; Li, X.; Ding, K. Org. Lett. 2002, 4, 4349.
(6) For asymmetric activation of BINOL-Zn catalysts, see: (a) Ding,
K.; Ishii, A.; Mikami, K. Angew. Chem., Int. Ed. 1999, 38, 497. (b) Mikami,
K.; Angelaud, R.; Ding, K.; Ishii, A.; Tanaka, A.; Sawada, N.; Kudo, K.;
Senda, M. Chem. Eur. J. 2001, 7, 730. (c) Costa, A. M.; Jimeno, C.;
Gavenonis, J.; Carroll, P. J.; Walsh, P. J. J. Am. Chem. Soc. 2002, 124,
Acknowledgment. Financial support from the NSFC,
CAS, and the Major Basic Research Development Program
of China (Grant G2000077506) is gratefully acknowledged.
6
929.
7) For comprehensive reviews on HDA reactions, see: (a) Danishefsky,
(
S. J.; Deninno, M. P. Angew. Chem., Int. Ed. Engl. 1987, 26, 15. (b)
Jorgensen, K. A. Angew. Chem., Int. Ed. 2000, 39, 3558. (c) Maruoka, K.
In Catalysis Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH:
New York, 2000; Chapter 8A.
Supporting Information Available: Experimental details
and spectral data for products, chiral HPLC analysis of the
products, and data of the screening of the chiral catalyst
library. This material is available free of charge via the
Internet at http://pubs.acs.org.
(8) For reviews on combinatorial asymmetric catalysis, see: (a) Jandeleit,
B.; Schaefer, D. J.; Powers, T. S., Turner, H. W.; Weinberg, W. H. Angew.
Chem., Int. Ed. 1999, 38, 2494. (b) Shimizu, K. D.; Snapper, M. L.;
Hoveyda, A. H. Chem. Eur. J. 1998, 4, 1885. (c) Francis, M. B.; Jamison,
T. F.; Jacobsen, E. N. Curr. Opin. Chem. Biol. 1998, 2, 422. (d) Reetz, M.
T. Angew. Chem., Int. Ed. 2001, 40, 284. (e) Reetz, M. T.; Jaeger, K.-E.
Chem. Eur. J. 2000, 6, 407. (f) Tsukamoto, M.; Kagan, H. B. AdV. Synth.
Catal. 2002, 344, 453.
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