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configuration of 7b, k and o was determined by comparison
of the optical rotation with known compounds (see the Sup-
porting Information). Using the identical enantiopure reagent
2b, the same direction of asymmetric induction is assumed in
the other products 7. Sterically hindered iso-propyl substituted
styrene 6c rearranged with only moderate enantioselectivity,
which was not improved by the use of a less sterically encum-
bered reagent 3,[29] which gave 7c in 88% yield, and only 39%
ee was obtained. It is noteworthy that access to ketone 7c is
not possible by the intermolecular catalytic Negishi coupling
protocol reported by Lou and Fu.[7c] 1,2-Substituted styrenes
6j–r (used as a mixture of E and Z isomers) gave the expected
rearranged ketones in good yields. It should be noted that in
the case of 7k–p, products resulting from alkyl-group migra-
tion were not observed. In the reaction of 7j, traces of an iso-
Scheme 3. Chemoselectivity of the oxidative rearrangement. [a] Minor
enantiomer was not detected.
1
propyl migration product were observed in the H NMR spec-
trum of the crude mixture, but not in sufficient quantities to
allow characterization.
When alkene 6n containing cyclopentyl ring was subjected
to the rearrangement reaction conditions, rearranged ketone
7n was obtained in good yield and high selectivity (87% ee).
Unfortunately, 1-cyclopropyl-2-methylstyrene bearing a cyclo-
propyl ring as substituent, gave a complex reaction mixture.
Furthermore, oxidation of (E/Z)-1-(but-2-en-2-yl)naphthalene
(6p) with reagent 2b gave a mixture of 3-(naphthalene-1-yl)-
butan-2-one (7p; 89% ee) and 3-(naphthalene-2-yl)butan-2-
one with 85% ee.
Heterocyclic substituted alkenes were also used in the oxida-
tive rearrangement. An E/Z mixture of the alkene 6q bearing
a thiophene moiety gave rearranged product 7q through
thienyl migration in good yields. Compound 6r gave the
phenyl migrated product 7r in 18% yield with 55% ee
together with various side products. Alkenes with pyridyl
substituent, (E)-2-(1-phenylprop-1-en-1-yl)pyridine and (Z)-2-(1-
phenylprop-1-en-1-yl)pyridine, afforded only trace amounts of
the rearranged products.
Scheme 4. Plausible reaction pathway to explain the observed regio- and
stereochemical outcome.
with the Koser reagent. The reaction of (Z)-6t at À788C gave
a ratio of 7t’/t (5:1), which diminished to 7t’/t (1:1) when the
reaction was performed at room temperature.
Stereoselective rearrangements were also attempted with
tetra-substituted alkenes to construct quaternary carbon
stereogenic centres. 1,1-Diphenyl-2-methylbut-1-ene (6s), pre-
pared by a one-pot cross-Pinacol coupling/rearrangement reac-
tion,[30] was also exposed to the rearrangement reaction. The
use of (diacetoxyiodo)benzene as iodine(III) reagent gave the
rearranged product in 12% isolated yield after nine hours;
however, the rearranged ketone by using reagent 2b was not
obtained in sufficient quantities to allow full characterization.
When excess of alkene 6m (E/Z: 1:2.5; 2 equiv) was subject-
ed to the standard reaction conditions, unreacted 6m was
recovered with an enriched E/Z ratio of 3:1, suggesting that
(Z)-aryl substituent migration is faster at À788C. In addition,
(E)-6t and (Z)-6t were independently synthesized and rear-
ranged efficiently to ketones 7t and t’, respectively, with high
stereoselectivities (Scheme 3). Under the standard reaction
conditions (À788C), the (Z)-aryl substituent migrates selectively
with 2b; however, when the reaction is conducted at higher
temperature (À208C), (E)-aryl substituent migration became
Taking this evidence into account, a plausible mechanistic
pathway is proposed in Scheme 4. Electrophilic addition of
iodine 2c to the alkene followed by ring opening with metha-
nol would result in l3-iodane B. Following bond rotation to C,
reductive elimination of the aryliodonio moiety gave a 1,2-aryl
migration with stereochemical inversion at this centre to give
the observed product. However, it is not entirely clear why
only conformer C is reactive at lower temperature. It is likely
that relief of steric interactions between the Ar and R groups
in C contribute to an increased propensity for this conformer
to rearrange, providing the (Z)-aryl migration product.
Key intermediate in the proposed mechanism is the cyclic
iodonium ion A, because its restricted conformational space
allows a regio- and stereoselective nucleophilic attack, as was
demonstrated by using methanol (Scheme 4). At the same
time, it may serve as the starting point for the formation of
a non-classical carbenium ion that could lead also to the major
product observed (Scheme 5).
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competitive ((Z)-6t!7t’/t (8:1)), as was determined by H NMR
DFT calculations were employed to analyse the bonding sit-
uation and the stability of A1 in comparison to the “open”
spectroscopy. A similar trend in chemoselectivity was obtained
Chem. Eur. J. 2016, 22, 4030 – 4035
4032 ꢀ 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim