Catalytic, enantioselective hetero-Diels-Alder reaction with novel, chiral bis-titanium(IV) catalyst

Article abstract of DOI:10.1055/s-2002-31927

Our recently designed chiral bis-titanium(IV) catalyst can be successfully utilized for the catalytic enantioselective hetero-Diels-Alder reaction of aldehyde and Danishefsky's diene. The high asymmetric induction is achievable in the case of sterically l

Full text of DOI:10.1055/s-2002-31927

LETTER
931
Catalytic, Enantioselective Hetero-Diels–Alder Reaction with Novel, Chiral
Bis-Titanium(IV) Catalyst
Catalytic
E
nan
a
tioselective
t
H
eter
o
s
r
R
eactio
h
n
i Kii, Takuya Hashimoto, Keiji Maruoka*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
Fax +81(75)7534041; E-mail: maruoka@kuchem.kyoto-u.ac.jp
Received 16 March 2002
furnish, after acidic hydrolysis, 2-(2-phenylethynyl)-2,3-
dihydro-4H-pyran-4-one 4 (R = C CPh) in 78% yield
with 98% ee.3 It should be noted that the enantioselectiv-
ity of the hetero-Diels–Alder reaction is lowered (e.g.,
83% ee for phenylpropargyl aldehyde 3 (R = C CPh)) un-
der similar reaction condition with a chiral mono-Ti(IV)
complex 2 derived from Ti(i-PrO)4, (S)-binaphthol, and 4-
chloro-2-(tritylamino)benzophenone as monodentate
ligand (each 10 mol%).4
Abstract: Our recently designed chiral bis-titanium(IV) catalyst
can be successfully utilized for the catalytic enantioselective hetero-
Diels–Alder reaction of aldehyde and Danishefsky’s diene. The
high asymmetric induction is achievable in the case of sterically less
hindered aldehydes.
Key words: hetero-Diels–Alder, asymmetric synthesis, catalyst, ti-
tanium(IV) complex
Our recent publication on the practical, catalytic enanti-
oselective allylation of aldehydes with allyltributyltin in
the presence of bis-titanium(IV) catalyst 1 prompted us to
examine the possibility of its application to other catalytic
enantioselective reactions.1 Among several asymmetric
reactions, our attention has been focused on a catalytic
asymmetric cycloaddition. Herein, we wish to disclose the
catalytic enantioselective hetero-Diels–Alder reaction of
aldehyde and Danishefsky’s diene by the aid of our re-
cently designed chiral bis-titanium(IV) catalyst 1 as
shown in Scheme 1.2
Other selected examples are listed in Table. Several char-
acteristic features of the present hetero-Diels–Alder reac-
tion are as follows: (1) In general, sterically less hindered
aldehydes give rise to higher enantioselectivity compared
to benzaldehyde and valeraldehyde (entries 5 and 6). (2)
Both the reactivity and enantioselectivity of the hetero-
Diels–Alder reaction are lowered under similar reaction
condition with a chiral mono-Ti(IV) complex 2 [e.g., 29%
and 60% ee for benzaldehyde 3 (R = Ph)]. (3) The steric
hindrance of diene parts is not influential to the asymmet-
ric induction. For example, switching of methoxy group
of Danishefsky’s diene to isopropoxy and t-butoxy groups
gives similar enantioselectivity in the asymmetric hetero-
Diels–Alder reaction of benzaldehyde: 43%, 76% ee;
50%, 71% ee, respectively.
O
OSiMe3
catalyst 1 (10 mol%)
H3O
+
R-CHO
OMe
CH2Cl2, 0 °C
R
O
3
4
The chiral bis-titanium(IV) catalyst 1 is also applicable to
the asymmetric aldol reaction of aldehydes with ketene
silyl thioacetal with fairly high enantioselectivity
(Scheme 2).5,6
(PriO)2
(OPri)2
(OPri)2
O
Ti
O
O
Ti
H
Ti
O
O
O
H
H
Tr N
O
N Tr
Tr
N
O
H3O
Ph
SBut
catalyst 1 (10 mol%)
SBut
+
PhCHO
CH2Cl2,
-10 °C, 24 h
OH O
Cl
Cl
5
OSiMe3
1
Cl
2
96% (86% ee)
Scheme 1
Scheme 2
The chiral bis-titanium(IV) catalyst 1 is prepared as de-
scribed previously by simply mixing of 2,2 -bis(tritylami-
no)-4,4 -dichlorobenzophenone with Ti(i-PrO)4 (2 equiv)
in CH2Cl2 and subsequent treatment with (S)-binaphthol
(2 equiv).1a Reaction of phenylpropargyl aldehyde 3 (R =
C CPh) with Danishefsky’s diene (1.2 equiv) under the
influence of in situ generated chiral bis-Ti(IV) catalyst 1
(10 mol%) in CH2Cl2 proceeds smoothly at 0 °C for 5 h to
Typical experimental procedure for the preparation of chiral
bis-Ti(IV) catalyst 1 and the hetero-Diels–Alder reaction of al-
dehyde and Danishefsky’s diene with chiral bis-Ti(IV) catalyst
1 is as follows:
A
solution of 2,2 -bis(tritylamino)-4,4 -dichlorobenzophenone
(76.6 mg, 0.1 mmol) in CD2Cl2 (2 mL) was carefully degassed and
then treated with Ti(i-PrO)4 (59 L, 0.2 mmol) at room temperature
under argon. After 1 h, (S)-binaphthol (57.3 mg, 0.2 mmol) was
added at r.t., and the mixture was stirred there for 15 h. The solution
was transferred by cannula to a 5-mm NMR tube, and the NMR
spectra were taken at room temperature. This catalyst 1 contains in
situ generated i-PrOH. 1H NMR (CD2Cl2) 9.09 (2 H, s, NH), 7.96
Synlett 2002, No. 6, 04 06 2002. Article Identifier:
1437-2096,E;2002,0,06,0931,0932,ftx,en;Y03602ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

932
S. Kii et al.
LETTER
98% ee by capillary GLC analysis [GL SCIENCE CP-CHIRASIL-
DEX CB, 80 kPa, column temp = 150 °C, tR = 52.54 min, tR = 54.63
min] in comparison with the racemic sample.
Table Asymmetric Hetero-Diels–Alder Reaction of Aldehydes and
Danishefsky’s Diene Catalyzed by Chiral Bis-Ti(IV) Complex 1a
Entry Aldehyde (R-CHO)
Condition %Yieldb %eec
(°C, h)
(Config.)
Acknowledgement
1
2
3
4
5
6
7
8
PhCH2CH2CHO
CH3(CH2)4CHO
CH3(CH2)6CHO
PhC CCHO
0, 3
77
57
79
78d
45d
64
60
58
97
This work was supported by a Grant-in-Aid for Scientific Research
on Priority Areas (No. 706: Dynamic Control of Stereochemistry)
and Scientific Research (No. 13853003) from the Ministry of Edu-
cation, Science, Sports and Culture, Japan.
0, 5
95 (S)e
92
0, 5
0, 3
98
References
CH3(CH2)3C CCHO
Ph-CHO
0, 7
95
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(4) The hetero-Diels–Alder reaction of phenylpropargyl
aldehyde 3 (R = C CPh) proceeded smoothly with a chiral
mono-Ti(IV) complex 2 (10 mol%) to give adduct 4 (R = C
CPh) in 47% yield. In contrast, however, the reactivity of the
hetero-Diels–Alder reaction of benzaldehyde 3 (R = Ph) are
lowered (e.g., 29% yield) under similar reaction condition
with a chiral mono-Ti(IV) 2 (10 mol%).
(5) The absolute configuration of the aldol 5 was determined to
be S by correlation to the authentic sample according to the
literature: Kobayashi, S.; Uchiro, H.; Fujishita, Y.; Shiina, I.;
Mukaiyama, T. J. Am. Chem. Soc. 1991, 113, 4247.
(6) Reviews: (a) Carreira, E. M. In Comprehensive Asymmetric
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Eds.; Springer: Heidelberg, 1999, 998. (b) Mahrwald, R.
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0, 3
71 (S)e
64
(CH3)2CHCHO
0, 5
CH3(CH2)3CH=CHCHO 0, 5
69
a The hetero-Diels–Alder reaction of aldehyde and Danishefsky’s
diene (2 equiv) was carried out in the presence of chiral bis-Ti(IV)
catalyst 1 (10 mol%) in CH2Cl2 under the given reaction conditions.
b Isolated yield.
c Determined by capillary GLC analysis using GL SCIENCE
CP-CHIRASIL-DEX CB.
d Use of 1.2 equiv of Danishefsky’s diene.
e See ref.7
(4 H, d, J = 8.1 Hz, binaphthyl-H), 7.60 (4 H, d, J = 8.7 Hz, binaph-
thyl-H), 6.89 (4 H, br s, binaphthyl-H), 6.51 (2 H, dd, J = 2.1, 8.4
Hz, benzophenone 5,5 -CH), 6.29 (2 H, d, J = 2.1 Hz, benzophenone
3,3 -CH), 4.51 [4 H, br s, TiOCH(CH3)2], 4.07 [4 H, br s,
HOCH(CH3)2], 1.88 (4 H, s, i-PrOH), 1.19 [36 H, br d, J = 6.0 Hz,
TiOCHCH3 and HOCH(CH3)2], 1.17 (12 H, br d, J = 6.0 Hz,
TiOCHCH3); 13C NMR (CD2Cl2) 199.46 (C=O), 158.79 (binaph-
thoxy C-O), 149.26 (benzophenone 2,2 -CN), 144.49, 138.00,
134.36, 132.90, 129.89, 128.70, 128.00, 126.94, 126.40, 125.29,
123.18, 121.02, 120.20, 118.18, 116.39, 114.92, 80.70 [Ti-
OCH(CH3)2], 71.30 (CPh3), 64.20 [HOCH(CH3)2], 24.86
[CH(CH3)2], 24.78 [CH(CH3)2]; IR (CH2Cl2) 3609, 3356, 2972,
1614, 1591, 1560, 1504, 1464, 1427, 1366, 1237, 1225, 1163, 1130,
1022, 1001, 951, 887, 818, 772 cm–1.
A
solution of 2,2 -bis(tritylamino)-4,4 -dichlorobenzophenone
(38.3 mg, 0.05 mmol) in CH2Cl2 (1 mL) was carefully degassed and
then treated with Ti(i-PrO)4 (30 L, 0.1 mmol) at room temperature
under argon. After 1 h, (S)-binaphthol (28.6 mg, 0.1 mmol) was
added at room temperature, and the mixture was stirred there for 15
h. The solution was cooled to –15 °C, and treated sequentially with
phenylpropargyl aldehyde (61 L, 0.5 mmol) and Danishefsky’s di-
ene (117 L, 0.6 mmol) at –15 °C. The whole mixture was allowed
to warm to 0 °C and stirred there for 5 h. The reaction mixture was
quenched by saturated NaHCO3, extracted with CH2Cl2, and the or-
ganic extracts were dried over Na2SO4. After evaporation of sol-
vents, the residual oil was diluted with THF (5 mL) and treated with
aqueous 1 N HCl (1 mL) at 0 °C for 30 min. With usual work-up,
the crude products were extracted with ether and the organic ex-
tracts were dried over Na2SO4. Evaporation of solvents and purifi-
cation of the residue by column chromatography on silica gel
(diethyl ether–hexane = 1:2) gave 2-(2-phenylethynyl)-2,3-dihy-
dro-4H-pyran-4-one 4 (R = C CPh) as a colorless oil (77 mg, 78%
yield). The enantiomeric purity of the product was determined to be
(7) Schaus, E. S.; Brånalt, J.; Jacobsen, E. N. J. Org. Chem.
1998, 63, 403.
Synlett 2002, No. 6, 931–932 ISSN 0936-5214 © Thieme Stuttgart · New York