Angewandte
Communications
Chemie
Cyclization
Metal-Free Enantioselective Oxidative Arylation of Alkenes:
À
Hypervalent-Iodine-Promoted Oxidative C C Bond Formation
Mio Shimogaki, Morifumi Fujita,* and Takashi Sugimura
Table 1: Optimization of the reaction conditions of oxyarylation.[a]
Abstract: The enantioselective oxyarylation of (E)-6-aryl-1-
silyloxylhex-3-ene was achieved using a lactate-based chiral
hypervalent iodine(III) reagent in the presence of boron
trifluoride diethyl etherate. The silyl ether promotes the
oxidative cyclization, and enhances the enantioselectivity. In
addition, the corresponding aminoarylation was achieved.
T
he 1,2-difunctionalization of alkenes offers an attractive
strategy for constructing diverse molecular complexity. The
reaction can simultaneously introduce two vicinal bifunc-
tional groups onto a hydrocarbon chain in a stereoselective
manner. Traditionally, transition-metal-catalyzed transforma-
tions have dominated the field, particularly those conducted
in an enantioselective fashion.[1] Recently, hypervalent
iodine(III) reagents[2,3] have attracted considerable attention
as powerful metal-free alternatives for oxidative 1,2-difunc-
tionalization of alkenes, thus leading to the introduction of
a wide range of functional groups, such as oxygen,[4,5] nitro-
gen,[6] halogen,[7,8] and sulfur nucleophiles.[9] Compared to the
most often reported carbon–heteroatom bond-forming pro-
cesses, the scope of oxidative carbon–carbon bond formation
is still limited.[10] There are several reports on hypervalent-
Entry
R
Acid
Yield [%]
ee [%]
1
2
3
4
H
TBS
H
TBS
H
H
Tf2NH
Tf2NH
69
63
76
77
82
80
86
73
63
55
78
78
78
75
88
88
TMSOTf
TMSOTf
TBSOTf
BF3·OEt2
BF3·OEt2
BF3·2AcOH
5
6[b]
7
TBS
TBS
8
[a] 1a (0.20 mmol), 3c (0.24 mol), and acid (0.80 mmol) in CH2Cl2
(8 mL) at À808C for 1–2 h, unless otherwise noted. [b] For 4 h.
Tf =trifluoromethanesulfonyl, TMS=trimethylsilyl.
À
iodine-mediated oxidative C C bond formation of alkenes
achieved in the presence of transition-metal catalysts.[11]
Herein, we report the enantioselective addition of a carbon
nucleophile during the oxidation of an alkene with a chiral
hypervalent iodine(III) reagent under metal-free condi-
tions.[12,13]
During our exploration of intramolecular oxyarylation of
alkenes with hypervalent iodine(III) reagents,[14] we found
that (E)-6-phenylhex-3-en-1-ol (1aa) and its silyl ether 1ab
effectively afforded 1,2,3a,4,5,9b-hexahydronaphtho[2,1-
b]furan (2a) as the desired carbocyclization product
(Table 1). The presence of NOE crosspeaks between 3a-H/
9b-H, 3a-H/2-H, and 9b-H/2-H confirmed the cis-fused
oxolane ring of 2a. For enantiocontrol, lactate-based chiral
hypervalent iodine reagents (3; Figure 1) were used in the
presence of Lewis and Brønsted acids. At the beginning,
several Lewis and Brønsted acids were examined in the
reaction of 1a with 3c (Table 1). Despite the fact that the silyl
ether has been widely employed as a protecting group, it is
noteworthy that the tert-butyldimethylsilyl (TBS) ether 1ab
Figure 1. Structures of chiral hypervalent iodine(III) reagents.
also affords the desired product 2a. The reaction of 1ab in the
presence of BF3·OEt2 (entry 7) was found to be the optimal
set of reaction conditions for enantiocontrol.
Thus, further screening of the effect of the silyl group was
conducted in the presence of BF3·OEt2 (Table 2). The
reaction of the hydroxy substrate 1aa required more time
and led to a lower ee value (entry 1) compared with that of the
silyloxy substrates 1ab–ae. The triethylsilyl (TES) derivative
1ac led to a lower enantioselectivity compared with those of
the TBS, triisopropylsilyl (TIPS), and tert-butyldiphenylsilyl
(TBDPS) derivatives (entries 5 and 10). While the bulky
TBDPS group of 1ae slightly enhances the enantioselectivity
(entries 3, 7, and 8), compared with that of the TBS group, the
TBS substrate 1ab led to consistently satisfactory results in all
the reactions examined in Table 2. In particular, in the
[*] M. Shimogaki, Prof. Dr. M. Fujita, Prof. Dr. T. Sugimura
Graduate School of Material Science
University of Hyogo
3-2-1 Kohto, Kamigori, Hyogo (Japan)
E-mail: fuji@sci.u-hyogo.ac.jp
Supporting information for this article can be found under:
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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