Tetrahedron Letters
Catalytic enantioselective C(sp3)AH functionalization:
intramolecular benzylic [1,5]-hydride shift
b
b
b,
Jie Yu a, , Nan Li , Dian-Feng Chen , Shi-Wei Luo
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a Department of Applied Chemistry, Anhui Agricultural University, Hefei 230036, China
b Department of Chemistry, University of Science and Technology of China, Hefei 230026, China
a r t i c l e i n f o
a b s t r a c t
The catalytic asymmetric [1,5]-hydride transfer/cyclization sequence involving benzylic C(sp3)AH bond
was established, providing tetrahydronaphthalene derivatives in moderate to high yield with up to
69% ee, by employing the copper complex of side-armed bisoxazoline as chiral catalyst.
Ó 2014 Elsevier Ltd. All rights reserved.
Article history:
Received 20 January 2014
Revised 11 March 2014
Accepted 19 March 2014
Available online 27 March 2014
Keywords:
Asymmetric catalysis
[1,5]-Hydride transfer
Benzylic C(sp3)AH bond
Side-armed bisoxazoline
Introduction
Results and discussion
Much effort has long been exerted to develop novel C(sp3)AH
bond functionalization owing to its atomic and step economy.1 In
recent years, the C(sp3)AH functionalization via the [1,5]-hydride
shift/cyclization sequence toward rapid buildup of molecular com-
plexity, called the ‘internal redox process’, has received increasing
attention.2 Generally accepted mechanism of the [1,5]-hydride
shift/cyclization demonstrates that the hydride from an appropriate
sp3-C position occurs to migrate with the electronic assistance of
the adjacent heteroatom for the stabilization of the generated car-
bocation, followed by a subsequent 6-endo cyclization to the cation
species, providing structurally diverse nitrogen or oxygen-con-
tained heterocycles 2 (Scheme 1, Eq. 1). The direct enantioselective
processes have also been continuously reported3 since the pioneer-
ing work by Seidel described the first enantioselective catalytic
[1,5]-hydride shift/cyclization reaction.3a More significantly, the
benzylic hydrogen could also participate in the hydride shift with-
out the assistance of an adjacent heteroatom.4 For example, Akiy-
ama and co-workers4e–g have recently established a successful
hydride shift from an aliphatic tertiary position to trigger cycliza-
tion reactions. However, a catalytic enantioselective variant of the
corresponding carbon analogue (3, Scheme 1) remains elusive.
Herein, we report the first asymmetric benzylic [1,5]-hydride
shift/cyclization reaction for the construction of a carbobicyclic
skeleton with two chiral stereogenic centers.
Our initial investigation commenced with the evaluation of
chiral Lewis acid catalysts for the reaction of 2-oxo-2-phenylace-
tate derived benzylidene malonate 3a.5 However, either scandium
triflate or zinc hexafluoroantimonate complex with chiral bisoxaz-
oline ligand 5a6 led to disappointing results (Table 1, entries 1 and
2). Gratifyingly, a chiral complex generated from copper hexafluo-
roantimonate7 and (S,S)-tBu-BOX 5a was able to give 4a in moder-
ate yield with 30% ee (entry 3). However, the stereoselectivity of
this reaction could not be improved by using either (S,S)-Ph-BOX
5b or (S,S)-Bn-BOX 5c (entries 4 and 5). Therefore we tested other
chiral bisoxazoline ligands.8
Compared with the parental molecules, the bisoxazolines with a
side arm have already been widely applied to transition metal-cat-
alyzed asymmetric reactions,9 and generally exhibited somewhat
higher reactivity and better enantiofacial discrimination.10 We
were pleased to find that the transformation of 3a proceeded
smoothly to afford 4a in good yield with 47% ee by employing
the side-arm bisoxazoline 6a (entry 6). The enantioselectivity
could be enhanced to 51% ee when a phenyl ester group was intro-
duced at the C1 position (3b, entry 7). These results encouraged us
to evaluate various side-armed bisoxazoline ligands 6 to improve
the enantioselectivity. Further studies showed that the pendant
groups of side-armed ligands 6 played an extremely important role
in the stereocontrol of product 4b (entries 8–14),5 the use of 4-(t-
butyl)phenyl substituted ligand 6b delivered the best outcomes
comprised of 64% isolated yield and 63% ee (entry 8). However,
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Corresponding authors. Tel.: +86 055165786906 (J.Y.).
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.