Umpolung of vinyloxiranes: Regio- and stereoselectivity of the In/Pd-mediated allylation of carbonyl compounds

Full text of DOI:10.1021/jo016017x

J . Org. Chem. 2001, 66, 7919-7921
7919
Ta ble 1. Rea ction of 2-Vin yloxir a n e w ith Ald eh yd esa
Um p olu n g of Vin yloxir a n es: Regio- a n d
Ster eoselectivity of th e In /P d -Med ia ted
Allyla tion of Ca r bon yl Com p ou n d s
Shuki Araki,* Keiko Kameda, J iro Tanaka,
Tsunehisa Hirashita, Hatsuo Yamamura, and
Masao Kawai
%
yield
Department of Applied Chemistry,
Nagoya Institute of Technology, Gokiso-cho,
Showa-ku, Nagoya 466-8555, J apan
1
,3-diol 1,5-diol
b
c
entry
R
conditions
(syn:anti)
(E:Z)
1
2
3
4
5
6
7
Ph
DMI, room temp, 5 h
62 (22:78) 33 (29:71)
n-C5H11 DMI, room temp, 20 h 59 (37:63) 31 (28:72)
araki@ach.nitech.ac.jp
Received August 9, 2001
Ph
Ph
Ph
Ph
Ph
THF, -20 °C, 24 h
THF, room temp, 15 h 54 (24:76) 36 (32:68)
THF, 50 °C, 15 h 23 (36:64) 38 (43:57)
H2O, room temp, 15 h 79 (23:77) trace
53 (19:81) 11 (36:64)
1:1 THF/H2O,
room temp, 15 h
86 (18:82) trace
The use of vinyloxiranes as nucleophilic allylating
reagents is a synthetically important method. However,
this umpolung has hitherto been realized with a limited
a
Reactions were carried out with 2:2:1 InI/oxirane/RCHO and
Pd(PPh3)4 (5 mol %). Determined by 1H NMR. c Determined by
b
1
2
number of low-valent metals such as chromium, tin, and
1
3
C NMR.
3
samarium. Recently, we demonstrated that a variety of
allylic substrates, including 2-phenyl-3-vinyloxirane, can
be converted to allylic indium(III) reagents via a reduc-
tive transmetalation of a π-allylpalladium(II) complex
Sch em e 1
4
with indium(I) salts. Here we disclose the full scope of
the reactions of allylic indium reagents derived from
vinyloxiranes with carbonyl compounds, which exert
marked differences in the regio- and stereoselectivity
depending on the reaction temperature, solvents, carbo-
nyl compounds, and substitution pattern of vinyloxiranes.
The In/Pd-mediated reaction of 2-vinyloxirane with
aldehydes was first examined under various reaction
conditions. The results are summarized in Table 1. In
polar organic solvents such as 1,3-dimethyl-2-imidazoli-
dinone (DMI) and THF, both the 1,3- and 1,5-diols were
formed in modest selectivities from the aromatic and
aliphatic aldehydes. By lowering the reaction tempera-
ture, we observed a slight preference for the anti-1,3-diol.
The regioselectivity of this coupling also depends on
the electrophiles; ketones show a strong preference for
,5-diols (Table 3). 2-Vinyloxirane gave the exclusive
1
formation of the 1,5-diols in good to moderate yields,
except for the reaction with cyclohexanone, which gave
a small amount (7% yield) of the 1,3-diol together with
the major 1,5-diol (41% yield) (entry 4). The reactions of
the methyl-substituted vinyloxiranes with acetophenone
were sluggish (entries 5-8), and only 2-(1-methylvinyl)-
oxirane yielded the corresponding 1,5-diol in a moderate
yield with complete Z-selectivity.
2 2
In less polar organic solvents such as CH Cl and hexane,
no coupling products were obtained. Interestingly, the
same reaction in aqueous media showed high selectivity
for the 1,3-diol, and negligible amounts of the 1,5-diol
were formed in these solvents (entries 6 and 7).
Table 2 summarizes the reactions of a series of vinyl-
oxiranes with a methyl group in different positions. It is
evident that the regioselectivity of the coupling is highly
dependent on the position of the methyl group; i.e.,
The present allylation reaction has been considered
to proceed via a reductive transmetalation of an interme-
4
diate π-allylpalladium(II) to allylindium(III) reagents.
2
-methyl-2-vinyloxirane (entries 3 and 4) gave the 1,3-
diol exclusively, whereas 2-(1-propenyl)oxirane (entries
and 8) gave only the corresponding 1,5-diol. The latter
The allylic indium compounds derived from vinyloxiranes
can be considered to exist as two forms: four- and six-
membered cyclic alkoxyindiums (Scheme 1). As the
coupling of allylic indium reagents with carbonyl com-
7
oxirane gave no 1,3-diol even in an aqueous solvent. No
significant effect of the methyl substituent was observed
in the cases of 2-methyl-3-vinyloxirane (entries 1 and 2)
and 2-(1-methylvinyl)oxirane (entries 5 and 6).
5
pounds generally takes place at the γ-carbon, it is
reasonable to postulate that the 1,5- and 1,3-diols are
formed from the four- and six-membered cyclic alkoxy-
indiums, respectively. The high 1,3-diol selectivity of
2-methyl-2-vinyloxirane (Table 2, entries 3 and 4) can
be ascribed to the destabilization of the four-membered
ring intermediate, where the methyl group on the in-
dium-bearing R-carbon makes the intermediate unfavor-
able both sterically and electronically. In turn, the methyl
*
To whom correspondence should be addressed. Phone and Fax:
81-52-735-5206.
1) Fujiwara, O.; Takai, K.; Utimoto, K. J . Org. Chem. 1990, 55,
705-1706.
2) Masuyama, Y.; Nakata, J .; Kurusu, Y. J . Chem. Soc., Perkin
Trans. 1 1991, 2598-2599.
3) Aurrecoechea, J . M.; Iztueta, E. Tetrahedron Lett. 1995, 36,
129-7132.
4) Araki, S.; Kamei, T.; Hirashita, T.; Yamamura, H.; Kawai, M.
Org. Lett. 2000, 2, 847-849.
+
(
1
(
(
7
(
(5) Li, C. J .; Chan, T. H. Tetrahedron 1999, 55, 11149-11176.
1
0.1021/jo016017x CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/24/2001

7
920 J . Org. Chem., Vol. 66, No. 23, 2001
Ta ble 2. Rea ction of Su bstitu ted Vin yloxir a n es w ith Ben za ld eh yd ea
Notes
a
b
All reactions were carried out in a Barbier-type manner with 2:2:1 InI/oxirane/PhCHO and Pd(PPh3)4 (5 mol %). A: DMI, 5-7 h. B:
c
1
d
13
1
:1 THF/H2O, 15 h. Determined by H NMR. Determined by C NMR. e E:Z ratio. f Ratio of syn:anti. g Determined by GC.
Ta ble 3. Rea ction of Vin yloxir a n es w ith Keton esa
Sch em e 2
vinyloxirane
R4 R5
ketone
R1
%
yield
entry
R3
R6
R2
(E:Z)b
1
2
3
4
5
H
H
H
H
H
H
H
Ph
Et
Me
Me
Me
78 (33:67)
39 (21:79)
52 (42:58)
41 (37:63)
10
H
H
H
H
H
H
H
H
H
H
H
H
n-C6H13
(CH2)5
Ph
c
Me
Me
(
cis:trans ) 55:45)
6
7
8
H
H
H
Me
H
H
H
Me
H
H
H
Me
Ph
Ph
Ph
Me
Me
Me
0
Sch em e 3
54 (0:100)
0
(
E:Z ) 96:4)
a
Reactions were carried out with 2:2:1 InI/oxirane/ketone and
Pd(PPh3)4 (5 mol %) in DMI at room temperature for 5-24 h.
b
13
c
Determined by C NMR. A small amount (7% yield) of the 1,3-
diol was also formed.
indium reagents. Hence, the anti-diastereomers are
formed dominantly. No anti-selectivity is observed in the
reaction with 2-(1-methylvinyl)oxirane (Table 2, entries
substituent destabilizes the corresponding six-membered
ring intermediate from 2-(1-propenyl)oxirane, and hence
no 1,3-diol is formed from this oxirane (Table 2, entry
6
5
and 6), where the methyl substituent diminishes the
7
). The preference for the 1,5-diols in the reactions of the
energy difference between the two transition states. The
observed high Z-selectivity in the 1,5-diol products from
ketones can be rationalized by a steric reason: the
ketones tend to couple with the less-hindered γ-carbon
of the four-membered ring allylindium rather than that
of the six-membered ring intermediate. The enhanced
2
3
-(1-methylvinyl)oxirane (Table 2, entries 5 and 6; Table
, entry 7) is worth noting, probably occurring via the
7
bicyclic transition state depicted in Scheme 3.
1
,3-selectivity in aqueous media indicates that the rate
In summary, an efficient and convenient method for
umpolung of vinyloxiranes has been demonstrated by
converting them to nucleophilic allylic indium reagents.
The regio- and stereoselectivities of the coupling with
carbonyl compounds have been found to depend on the
reaction temperature, solvents, carbonyl compounds, and
substitution pattern of vinyloxiranes.
of addition to the six-membered ring intermediate is
enhanced compared to that to the four-membered one in
the presence of water; however, the reason is unknown.
The stereoselection of the present carbonyl allylation
with vinyloxiranes is generally not very high; neverthe-
less, good anti-selectivity and Z-preference are observed
in some cases for the 1,3- and 1,5-diol products, respec-
tively. The anti-selectivity in the reactions of benzalde-
hyde with 2-vinyloxirane (Table 1) and 2-methyl-2-
vinyloxirane (Table 2, entries 3 and 4) can be explained
by the transition state in Scheme 2: in the transition
state leading to the syn isomers, there should be steric
crowding between the phenyl group of benzaldehyde and
the pseudoaxial hydrogen of the six-membered ring allylic
(6) The anti-diastereoselectivity of the chromium-induced coupling
reaction of vinyloxiranes and carbonyl compounds is explained by a
1
similar boat-formed transition state.
(7) A transition state akin to the present bicyclic one is postulated
in the reaction of intramolecularly chelated 1-benzyloxymethyl-2-
methyl-2-propenylindium with aldehydes, which also shows
high Z-selectivity: Behnke, D.; Hennig, L.; Findeisen, M.; Welzel, P.;
Muller, D.; Thormann, M.; Hofmann, H. J . Tetrahedron 2000, 56,
1081-1095.

Notes
J . Org. Chem., Vol. 66, No. 23, 2001 7921
Exp er im en ta l Section
syn:anti ) 22:78) and 5-phenyl-2-pentene-1,5-diol (30 mg, 33%,
E:Z ) 29:71).
Typ ica l Exp er im en ta l P r oced u r e. To a mixture of in-
dium(I) iodide (0.24 g, 1.0 mmol) and Pd(PPh (29 mg, 0.025
mmol) in dry DMI (2 mL) were added 2-ethenyloxirane (80 µL,
.0 mmol) and benzaldehyde (51 µL, 0.50 mmol). The reaction
mixture was stirred under argon for 5 h at room temperature.
Diluted hydrochloric acid (1 M) was added, and the products
were extracted with ether. The extracts were washed with
saturated aqueous sodium hydrogencarbonate and brine and
dried over anhydrous sodium sulfate. The solvent was removed,
and the residue was chromatographed on silica gel (2:1 hexane/
AcOEt) to give 2-ethenyl-1-phenyl-1,3-propanediol (56 mg, 62%,
3
)
4
Ack n ow led gm en t. We thank Professor K. Takai of
Okayama University, Professor E. J . Thomas of Uni-
versity of Manchester, and Professor P. Welzel of Leipzig
University for their generosity in sending NMR data.
1
Su p p or tin g In for m a tion Ava ila ble: Spectral and ana-
lytical data for all products. This material is available free of
charge via the Internet at http://pubs.acs.org.
J O016017X