Vinylogous Mannich-type reaction catalyzed by an iodine-substituted chiral phosphoric acid

Article abstract of DOI:10.1002/adsc.200700521

2-Trimethylsiloxyfuran underwent a vinylogous Mannich-type reaction with aldimines under the action of a new chiral phosphoric acid, bearing iodine on the 6,6′-positions of the binaphthyl group, as a chiral Bronsted acid to give γ-butenolide derivatives bearing an amino functionality with high diastereo- and enantioselectivity.

Full text of DOI:10.1002/adsc.200700521

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DOI: 10.1002/adsc.200700521
Vinylogous Mannich-Type Reaction Catalyzed by an Iodine-Sub-
stituted Chiral Phosphoric Acid
Takahiko Akiyama,a,* Yasuhiro Honma,a Junji Itoh,a and Kohei Fuchibea,b
a
Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588 Japan
Fax : (+81)-3-5992-1029; e-mail: takahiko.akiyama@gakushuin.ac.jp
Present address: Department of Chemistry, Graduate Schoolof Pure and Appiled Sciences, University of Tsukuba, 1-1-1
b
Tenodai, Tsukuba, Ibaraki 305-8571, Japan
Received: November 1, 2007; Revised: January 8, 2008; Published online: February 5, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: 2-Trimethylsiloxyfuran underwent a vinyl-
ogous Mannich-type reaction with aldimines under
the action of a new chiralphosphoric acid, bearing
iodine on the 6,6’-positions of the binaphthylgroup,
as a chiralBrønsted acid to give g-butenolide deriv-
atives bearing an amino functionality with high dia-
stereo- and enantioselectivity.
Chiral Brønsted acid catalysts have recently
emerged as a new class of environmentally benign
[7]
chiralcataylsts.
We have reported that chiralphos-
phoric acid 1 (Figure 1) is a usefulchiralBrønsted
acid catalyst for the electrophilic activation of aldi-
mines.[8] The phosphoric acid has recently been recog-
nized to be an efficient chiralcatayl st for a number of
enantioselective reactions.[9,10] We focused our atten-
tion on the application of chiral Brønsted acid cata-
lysts to the vinylogous Mannich-type reaction. We
report herein the use of the novelphosphoric acid 2b
(Figure 1), bearing iodine groups on the 6,6’-positions
in the vinylogous Mannich-type reaction, producing g-
butenolides with high enantioselectivities.[11] Aliphatic
aldimines as well as aromatic aldimines proved to be
Keywords: addition to imines; amines; asymmetric
À
catalysis; asymmetric synthesis; C C bond forma-
tion; organic catalysis
The g-butenolide skeleton is one of the most ubiqui- good substrates.
tous structures found in naturalproducts. Thus, the
At the outset, we examined the catalytic activity of
development of novel methods for the stereoselective chiralphosphoric acids 1a–c. Aldimine 3a underwent
synthesis of butenolide derivatives has continuously a vinylogous Mannich-type reaction with trimethylsi-
attracted the attention of synthetic organic chemists.[1,2] loxyfuran 4 in the presence of 5 mol% of 1a to afford
The vinylogous Mannich-type reaction of trimethyl- g-butenolide derivative 5a in 98% yield in favor of
siloxyfuran with aldimine is a useful means to prepare the anti isomer (anti/syn 79/21). ChiralHPLC anayl sis
g-butenolide derivatives bearing an amine functionali- revealed that the anti isomer was obtained preferen-
ty. A wide range of Lewis acids has been developed tially in 48% ee (Table 1, entry 1). The introduction of
as catalysts for the reaction.[3,4]
a bulky aryl group to 3,3’-positions improved the
In contrast, the enantioselective, catalyzed-version enantioselectivity, while use of 2,4,6-(i-Pr)3C6H2-sub-
of the vinylogous Mannich-type reaction has been stituted phosphoric acid 1c gave 5a in 74% ee
little explored. Martin and co-workers reported the (entry 3). Interestingly, the introduction of halogen
enantioselective synthesis of g-butenolide derivatives atoms onto the 6,6’-positions of the binaphthylrings
(O-i-Pr)4/(S)-BINOL system,[3f] but
catalyzed by the TiACHTREUNG
the enantioselectivities and the chemical yields were
moderate. In this regard, the development of an effi-
cient catalyst for the synthesis of g-butenolide deriva-
tives in terms of both yields and optical purity is still
desired. Recently, Hoveyda and co-workers reported
a highly enantioselective vinylogous Mannich-type re-
action catalyzed by a silver salt, in which only aromat-
ic aldimines were employed.[5] Organocatalyzed vinyl-
ogous Mannich-type reactions have been also report-
ed lately.[6]
Figure 1.
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399

Takahiko Akiyama et al.
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Table 1. Effect of the 6,6’-substituents of the chiralBrønsted
Table 2. Enantioselective synthesis of g-butenolide deriva-
acid.[a]
tives catalyzed by chiral Brønsted acid.[a]
Entry Catalyst Time [h] Yield [%][b] anti/syn ee [%][c]
Entry
R
Time Yield anti/
[h]
ee
[%][b] syn
[%][c]
1
2
3
4
5
1a
1b
1c
2a
2b
7
98
79/21
77/23
93/7
84/16
91/9
48
38
74
79
82
15
13
19
19
100
100
69
1
Ph (3a)
p-FC6H4 (3b)
p-BrC6H4 (3c)
19
24
31
100
100
82
91/9
95/5
92/8
82
87
55
2
3[d]
100
A
(>99)[e]
4[d]
5
p-NO2C6H4 (3d) 22
m-NO2C6H4 (3e) 15
o-NO2C6H4 (3f) 24
p-CF3C6H4 (3g)
p-NCC6H4 (3h)
4-pyridyl( 3i)
2-furyl( 3j)
85
86
100
95
89
30
77
77
84
97/3
68/32
98/2
69/31
83/17
94/6
68/32
88/12
88/12
96
96
92
99
90
98
89
90
92
[a]
[b]
[c]
3.0 equiv. of trimethylsiloxyfuran were employed.
Isolated yield.
The ee of the anti isomer.
6[d]
7
20
28
23
15
15
18
8
9
10
11[f]
12[f]
had a beneficialeffect on the enantiosecltivity
(entry 4) and use of 2b bearing iodine groups on the
6,6’-positions resulted in the formation of 5a in 82%
ee (entry 5).
c-C6H11 (3k)
i-Pr (3l)
[a]
3.0 equiv. of trimethylsiloxyfuran were employed.
Isolated yield.
The ee of the anti isomer.
1c was used instead of 2b.
After two recrystallization from benzene.
Aldimine was generated in situ in the presence of
Na2SO4 and treated with siloxyfuran and 2b.
These conditions were applicable to the synthesis of
g-butenolide derivatives using various aldimines as
substrates (Table 2). The use of aldimines derived
from aromatic aldehydes gave addition products in
high yields, good to high diastereoselectivities, and ex-
cellent ee (up to 99% ee) (entries 2–8). Furthermore,
we found that 2b is effective for the reaction with al-
dimine 3i bearing a basic pyridine moiety (entry 9).
An aldimine derived from a heteroaromatic aldehyde
also gave an adduct with high enantioselectivity
(entry 10). It is noted that aliphatic aldimines 3k–l
gave g-butenolide derivatives with high enantioselec-
tivities (entries 11 and 12). The absolute stereochem-
istry of 5c (R=p-BrC6H4; entry 3) was determined by
X-ray crystallographic analysis, while those of the
other g-butenolide derivatives were assigned by anal-
ogy.[12]
[b]
[c]
[d]
[e]
[f]
g-Butenolide 5a was readily transformed into d- Scheme 1. Transformation of the adduct.
lactam 6 via three successive reactions: reduction of
the olefinic double bond, protection of the phenolic
hydroxy group, and treatment with a base. A good erted by the iodine substituents on the phosphoric
yield was obtained without sacrificing the enantiomer- acid moiety might played a role rather than a steric
ic purity (Scheme 1).
effect.
In summary, we have developed a method for the
We surmise that the present vinylogous Mannich-
type reaction proceeded via a 9-membered transition enantioselective synthesis of g-butenolide derivatives,
state (Figure 2) similar to the Mannich-type reaction which involves the vinylogous Mannich-type reaction
previously proposed by us based on theoretical calcu- catalyzed by a novel chiral phosphoric acid bearing
lations.[8a,g] In order to gain an insight into the effect iodine groups at the 6,6’-positions. Aliphatic as well
of the iodine substituents of 2b, the dihedralangel s of
as aromatic aldimines turned out to be good sub-
1c and 2b were calculated with Spartan (HF 3- strates and g-butenolide derivatives were obtained in
21G*)[13] to be 52.98 and 52.88, respectively. Based on high yields, with good to high diastereo-and enantio-
these results, we suppose that an electronic effect ex- selectivities.
400
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Vinylogous Mannich-Type Reaction
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Typical Procedure for the Enantioselective Synthesis
of Butenolide Derivatives (Entry 7, Table 2)
To a solution of aldimine 3g (45.2 mg, 0.170 mmol) and (R)-
6,6’-diiodo-3,3’-bis(2,4,6-triisopropylphenyl)-1,1’-binaphthyl
phosphate 2b (8.9 mg, 0.00886 mmol) in toluene (1 mL) was
added trimethylsiloxyfuran 4 (88 mL, 0.507 mmol) at 08C.
Aftereing stirred at the temperature for 20 h and confirming
the disappearance of the aldimine by TLC, the mixture was
quenched by addition of saturated aqueous NaHCO3 solu-
tion, saturated KF solution, THF and MeOH. The solution
was extracted with ethylacetate. The combined organic
layers were successively washed with brine, dried over anhy-
drous Na2SO4, and concentrated to dryness. The crude prod-
uct was purified by silica gel column chromatography
(hexane/EtOAc=1/1) to give the product 5g; yield: 56.1 mg
0.163 mmol, 95%) and with 99% ee, which was determined
by chiral HPLC analysis on a Daicel Chiralcel OD-H
column.
Acknowledgements
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This work was partially supported by a Grant-in-Aid for Sci-
entific Research on Priority Areas “Advanced Molecular
Transformation of Carbon Resources” from the Ministry of
Education, Science, Sports, Culture, and Technology, Japan.
J. I. thanks the JSPS Research Fellowships for Young Scien-
tists.
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