Enantioselective Prevost and Woodward reactions using chiral hypervalent iodine(iii): Switchover of stereochemical course of an optically active 1,3-dioxolan-2-yl cation

Article abstract of DOI:10.1039/c1cc10129c

Optically active 1,3-dioxolan-2-yl cation intermediates were generated during enantioselective dioxyacetylation of alkene with chiral hypervalent iodine(III). Regioselective attack of a nucleophile toward the intermediate resulted in reversal of enantioselectivity of the dioxyacetylation. The Royal Society of Chemistry.

Full text of DOI:10.1039/c1cc10129c

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COMMUNICATION
´
Enantioselective Prevost and Woodward reactions using chiral
hypervalent iodine(III): switchover of stereochemical course of an
optically active 1,3-dioxolan-2-yl cationw
Morifumi Fujita,* Mikimasa Wakita and Takashi Sugimura
Received 7th January 2011, Accepted 25th January 2011
DOI: 10.1039/c1cc10129c
Optically active 1,3-dioxolan-2-yl cation intermediates were
generated during enantioselective dioxyacetylation of alkene
with chiral hypervalent iodine(III). Regioselective attack of a
nucleophile toward the intermediate resulted in reversal of
enantioselectivity of the dioxyacetylation.
Reactions involving neighboring group participation have
great advantages for powerful stereocontrol and unique
Scheme 1 Enantioselective Prevost and Woodward reactions.
´
stereoselectivity due to a bridged form of the cationic inter-
mediate. The Pre
vost reaction1 and the Woodward reaction2
´
proceed via a 1,3-dioxolan-2-yl cation intermediate3 in the
course of oxidation of alkene with I2 in the presence of silver
carboxylate.4–6 Regioselective attack of a nucleophile toward
the intermediate results in diastereoselective formation of the
oxidation products: addition of water at the 2-position of the
1,3-dioxolan-2-yl cation results in retention of configuration of
the cation intermediate (Woodward reaction),2 while SN2
displacement with carboxylate at the 4- or 5-position results
Scheme 2 Optically active hypervalent iodine(III).
favorable for success in enantioselective formation of a
dioxolanyl cation. Switchover of stereochemical course of
the optically active dioxolanyl cation leads to reversal of
enantioselectivity, as well as that of diastereoselectivity.
As optically active hypervalent iodine reagents, we
employed the lactate-derived aryl-l3-iodane 3–6, which gave high
enantioselectivity in oxylactonization of o-alk-1-enylbenzoate.11a
The structures are given in Scheme 2. Reaction of 1 with the
iodine reagents 3–6 was started by injection of boron trifluoride
diethyl etherate into a dichloromethane solution containing
acetic acid at ꢀ80 1C. When the reaction was terminated at ꢀ40 1C
by addition of water (conditions A), a regioisomeric mixture of
the monoacetoxy products 20 and 200 was obtained (Table 1).
Acetylation of the regioisomeric mixture gave a diacetoxy
product syn-2 as a single diastereomer. The enantiomeric purity
of the syn product was 88–96% ee of (1S,2S) configuration.
Higher enantioselectivity was obtained when the isopropyl
substituted reagent 4 was used (entries 2 and 8 in Table 1).
When the reaction was similarly started at ꢀ80 1C and the
reaction mixture was allowed to warm up to room temperature
(conditions B), anti-2 with (1R,2S) configuration was preferentially
obtained as summarized in Table 2. The reaction was carried
out in the presence of both acetic acid and trimethylsilyl
acetate because the conditions were suitable for selective
formation of the anti product as examined with an achiral
iodane reagent (Table S2 in ESIw). Exclusive formation of the
in inversion of configuration (Pre
´
vost reaction).1 To the best
of our knowledge asymmetric variants of the Pre
´
vost and
Woodward reactions have not yet been reported,6 although
optically active 1,3-dioxolan-2-yl cation intermediates play an
important role in stereocontrolled transformation of polyoxy-
functionalized compounds.7 Most of the optically active
dioxolanyl cation intermediates have been generated from
optically active substrates via diastereoselective transformation.
Thus, direct enantioselective formation of an optically active
dioxolanyl cation from an achiral alkene substrate during the
asymmetric Pre
dimensions to the reaction controlled by a dioxolanyl cation.
Herein we report an asymmetric variant of Prevost and
´
vost and Woodward reactions adds new
´
Woodward reactions with use of an optically active hypervalent
iodine reagent as shown in Scheme 1. Recent development of
chiral hypervalent iodine reagents for asymmetric oxidation8–11 is
Graduate School of Material Science, University of Hyogo,
3-2-1 Kohto, Kamigori, Hyogo 678-1297, Japan.
E-mail: fuji@sci.u-hyogo.ac.jp; Fax: +81 791-58-0115;
Tel: +81 791-58-0170
w Electronic supplementary information (ESI) available: Experimental
procedures, characterization data for all new compounds, and
additional results of the reaction. CCDC 798662. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/
c1cc10129c
c
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Chem. Commun., 2011, 47, 3983–3985 3983

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Table
1
Enantioselective formation of the syn product under
Table 3 Switchover of enantioselectivity in the reaction of styrene
derivativesa
conditions Aa
Entry
1
Ar*I(OAc)2 20 : 200 Yieldb (%) syn : anti eec (%)
Conditions Aa
Conditions Bb
1
2
3
4
5
6
7
8
1a
1a
1a
1b
1c
1d
1e
1e
3
4
6
3
3
3
3
4
6 : 4
7 : 3
6 : 4
6 : 4
6 : 4
6 : 4
6 : 4
7 : 3
55
49
51
48
44
40
56
63
>98 : 2
>98 : 2
>98 : 2
>98 : 2
>98 : 2
98 : 2
88
95
94
92
89
88
90
96
Yield (%) ee (%) Yield (%) ee (%)
Entry
1
Ar*I(OAc)2
1
2
3
4
5
6
7
8
1f
1f
1f
1g
1h
1i
1i
1i
1j
1j
1j
3
4
5
3
3
3
4
5
3
4
5
69
59
68
54
35
54
59
49
74
76
53
64(S)
74(S)
89(S)
34(S)
11(S)
30(S)
40(S)
60(S)
88(S)
92(S)
92(S)
71
82
76
68
50
64
72(R)
70(R)
70(R)
16(R)
1(R)
>98 : 2
>98 : 2
32(R)
a
1 = 0.4 mmol, Ar*I(OAc)2 = 0.5 mmol, BF3ꢁOEt2 = 0.8 mmol in
CH2Cl2 (4 mL) and acetic acid (0.2 mL). Reaction was started at ꢀ80 1C
and terminated at ꢀ40 1C. The crude products obtained were treated
9
10
11
60c,d
66c
83(R)c,d
85(R)c
87(R)c
b
c
with acetic anhydride and pyridine. Yield of 2. ee of syn-2.
81c
a
Reaction was started at ꢀ80 1C in the presence of AcOH and
terminated at ꢀ40 1C. The crude products obtained were treated with
Table 2 Enantioselective formation of the anti product under
conditions Ba
b
acetic anhydride and pyridine. Reaction was started at ꢀ80 1C in the
presence of TMSOAc and terminated at rt, otherwise noted. Results of
the reaction in the presence of both AcOH and TMSOAc are given in
c
d
Table S3 (ESIw). In the presence of AcOH and TMSOAc. The
reaction in the presence of only TMSOAc gave 2j in 64% yield with
84% ee of R-2j.
The reversal of syn/anti selectivity (Tables 1 and 2) can be
ee (%)
explained by a mechanism involving the 1,3-dioxolan-2-yl
Yield (%)
2
anti
syn
cation similar to that proposed for the Prevost and Woodward
´
Entry
1
Ar*I(OAc)2
syn : anti
reactions. That is, addition of water at the 2-position of the
1,3-dioxolan-2-yl cation results in formation of the syn product
with retention of configuration (Scheme 1). In contrast, the
anti product must form via SN2 displacement with acetic acid
(or acetate). Enantioface-differentiating attack of the iodine
reagent may preferentially give the (4S,5S)-1,3-dioxolan-2-yl
cation. The preference of (1R,2S) configuration of the anti
product indicates that SN2 displacement of the cation with
acetic acid takes place regioselectively at the benzylic position
(the 4-position), where positive charge is localized. If SN2 at
the 5-position was involved in the reaction pathways, ee of the
anti product should decrease. The SN2 at the 5-position can be
excluded, judging from the comparison of ee values of the
syn and anti products. The SN1 pathway must give a mixture
of the syn and anti products, and may be involved in the
reaction of the p-methyl substrate 1d (entry 5 in Table 2): an
electron donating aryl group in 1d must stabilize the benzylic
cation intermediate and facilitate the SN1 pathway.
1
2
3
4
5
6
7
1a
1a
1a
1c
1d
1e
1e
3
4
6
3
3
3
4
70
56
54
53
58
47
55
o2 : 98b
o2 : 98
o2 : 98
o2 : 98
18 : 82
88
96
93
84
88
90
92
88
88
o2 : 98
o2 : 98
a
1 = 0.4 mmol, Ar*I(OAc)2 = 0.5 mmol, BF3ꢁOEt2 = 0.8 mmol in
CH2Cl2 (4 mL), acetic acid (0.2 mL), and trimethylsilyl acetate (0.2 mL).
b
Reaction was started at ꢀ80 1C and terminated at rt. The syn isomer
1
was not detected by H NMR (600 MHz), but GC analysis showed a
small amount of the syn isomer (syn-2a : anti-2a = 1 : 99).
anti product was observed with the exception of the p-methyl
substrate 1d (entry 5 in Table 2). The decrease in diastereo-
selectivity for 1d may be due to partial contribution from the
SN1 mechanism as discussed below.
Results of the reaction of styrene derivatives are summarized
in Table 3. The reaction quenched at low temperature
(conditions A) gave the S product, while the reaction mixture
allowed to warm up to room temperature (conditions B)
contained the R product. Thus, reversal of enantioselectivity
was achieved. The enantioselectivity depends on the aromatic
substituent of the styrene substrates. Among the styrene
derivatives employed, 2-chlorostyrene (1j) gave the highest
enantioselectivity (entries 9–11 in Table 3).
The reaction of styrene substrates 1f–j also can be explained
within the framework of the reaction mechanism represented
above. The S-product is obtained with retention of configuration
of the S-dioxolanyl cation, and the R-product forms via
inversion of the configuration (SN2 at the benzyl position).
Enantiomeric purity of the R-product could decrease if the
SN1 at the benzyl (the 4-) position and SN2 at the 5-position
c
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Notes and references
z Dioxyacetylation of indene similarly proceeds, and the results are
given in ESI.w
1 C. Prevost, C. R. Hebd. Seances Acad. Sci., 1933, 196, 1129.
´
2 R. B. Woodward and F. V. Brutcher, Jr, J. Am. Chem. Soc., 1958,
80, 209.
Scheme 3 Trapping with ketene silyl acetal.
3 For a review for dioxolanyl cation, see: C. U. Pittman, Jr,
S. P. McManus and J. W. Larsen, Chem. Rev., 1972, 72, 357.
4 C. V. Wilson, Org. React., 1957, 9, 332; R. C. Cambie and
P. S. Rutledge, Org. Synth., 1979, 59, 169; J. Rodriguez and
J. P. Dulcere, Synthesis, 1993, 1177; A. R. Vaino and
W. A. Szarek, Adv. Carbohydr. Chem. Biochem., 2001, 56, 9.
5 Hypervalent iodine has been used in Prevost and Woodward reactions,
´
see: (a) V. V. Zhdankin, R. Tykwinski, B. Berglund, M. Mullikin,
R. Caple, N. S. Zefirov and A. S. Koz’min, J. Org. Chem., 1989, 54,
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Song and V. M. Dong, J. Am. Chem. Soc., 2008, 130, 2962; (e) J.
Seayad, A. M. Seayad and C. L. L. Chai, Org. Lett., 2010, 12, 1412.
Scheme 4 Trapping with trimethylsilyl bromide.
took place. These may be major reasons for the decrease in the ee
value under conditions B rather than that under conditions A.
The intermediate formation of the dioxolanyl cation was
confirmed by trapping reaction with ketene silyl acetal (KSA)
as shown in Scheme 3.z The reaction was started in the absence
of KSA, and the nucleophile was added into the reaction
mixture at ꢀ40 1C. The trapping product 7 was obtained as a
single diastereomer. The structure was determined by nOe
observed in 1H NMR spectroscopy, and the diastereo-
selectivity must be attributed to the steric fence due to the
indane moiety during the addition of KSA toward the 1,3-
dioxolan-2-yl cation. The 1,3-dioxolanyl framework remains
in the trapping product 7 without its ring-opening. This is
most convincing evidence for intermediate formation of the
1,3-dioxolan-2-yl cation.
6 Diastereoselective Prevost and Woodward reactions of chiral alkene
´
substrates have been reported, see: (a) J. H. Kim, M. J. C. Long,
J. Y. Kim and K. H. Park, Org. Lett., 2004, 6, 2273; (b) J. H. Kim,
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7 For recent examples, see: J.-L. Giner, W. V. Ferris, Jr and
J. J. Mullins, J. Org. Chem., 2002, 67, 4856; T. Zheng,
R. S. Narayan, J. M. Schomaker and B. Borhan, J. Am. Chem.
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8 For a recent review, see: M. Ngatimin and D. W. Lupton, Aust. J.
Chem., 2010, 63, 653.
9 For enantioselective oxidation of styrene with chiral hypervalent
iodine(III), see: U. H. Hirt, B. Spingler and T. Wirth, J. Org. Chem.,
1998, 63, 7674; U. H. Hirt, M. F. H. Schuster, A. N. French,
O. G. Wiest and T. Wirth, Eur. J. Org. Chem., 2001, 1569.
10 For recent examples, see: (a) U. Ladziata, J. Carlson and V. V.
Zhdankin, Tetrahedron Lett., 2006, 47, 6301; (b) R. D. Richardson,
T. K. Page, S. Altermann, S. M. Paradine, A. N. French and T.
Wirth, Synlett, 2007, 538; (c) T. Dohi, A. Maruyama, N. Takenaga,
K. Senami, Y. Minamitsuji, H. Fujioka, S. B. Caemmerer and Y.
Kita, Angew. Chem., Int. Ed., 2008, 47, 3787; (d) S. M. Altermann,
R. D. Richardson, T. K. Page, R. K. Schmidt, E. Holland,
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5315; (e) S. Quideau, G. Lyvinec, M. Marguerit, K. Bathany,
Trimethylsilyl bromide was also employed as a nucleophile
for trapping the dioxolanyl cation (Scheme 4). The bromide
was introduced at the benzyl position of the trapping product
8, which has (1R,2S) configuration. The regio and diastereo-
selectivities are consistent with the anti selectivity observed in
the reaction giving the diacetate product 2 (Table 2). The ee
value of the bromide 8 is similar to that of the acetate anti-2a
(entries 1 and 2 in Table 2). These results agree well with the
reaction pathway involving the optically active dioxolanyl
cation, which was trapped by a nucleophile at the benzylic
position through the SN2 mechanism.
Nucleophilic attack of acetate and bromide takes place at the
4-position of the dioxolanyl cation, and addition of water and
KSA takes place at the 2-position. Regioselectivity of the nucleo-
philic attack may be thermodynamically controlled. Nucleophilic
addition at the 2-position of the dioxolanyl cation may be
kinetically favorable, but addition of acetate and bromide at the
2-position may be reversible. In contrast, addition of H2O and
ketene silyl acetal at the 2-position must be irreversible.
In summary, we demonstrate convenient preparation of an
optically active 1,3-dioxolan-2-yl cation, which serves for
regio- and stereoselective trapping of several kinds of nucleo-
phile. The selectivity depends on the nature of nucleophile,
and contributes to the switchover of stereochemical course of
the reaction.
A. Ozanne-Beaudenon, T. Buffeteau, D. Cavagnat and A. Chenede,
´ ´
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We are very grateful to Dr H. Akutsu and Prof. S. Nakatsuji
(Hyogo) for X-ray crystallographic analyses and to Prof.
T. Okuyama (Hyogo) for reading this manuscript.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 3983–3985 3985