Diastereodivergent [3 + 2] Annulation of Aromatic Aldimines with Alkenes via C-H Activation by Half-Sandwich Rare-Earth Catalysts

Article abstract of DOI:10.1021/jacs.0c01171

Stereodivergent catalysis is of great importance, as it can allow efficient access to all possible stereoisomers of a given product with multiple stereocenters from the same set of starting materials. We report herein the first diastereodivergent [3 + 2]

Full text of DOI:10.1021/jacs.0c01171

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Communication
Diastereodivergent [3+2] Annulation of Aromatic Aldimines with
Alkenes via C-H Activation by Half-Sandwich Rare-Earth Catalysts
Xuefeng Cong, Gu Zhan, Zhenbo Mo, Masayoshi Nishiura, and Zhaomin Hou
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.0c01171 • Publication Date (Web): 08 Mar 2020
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Diastereodivergent [3+2] Annulation of Aromatic Aldimines with
Alkenes via C−H Activation by Half-Sandwich Rare-Earth Catalysts
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, ,
Xuefeng Cong,† Gu Zhan,‡ Zhenbo Mo,‡ Masayoshi Nishiura,† ‡ Zhaomin Hou* † ‡
†Advanced Catalysis Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-
0198, Japan
‡
Organometallic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama 351-0198,
Japan
Supporting Information Placeholder
our interest in exploring the annulation of aldimines with alkenes
by rare-earth catalysts. We report here for the first time the
diastereodivergent [3+2] annulation of aromatic aldimines with
alkenes by half-sandwich rare-earth catalysts with different sterics
ABSTRACT: Stereodivergent catalysis is of great importance, as
it can allow efficient access to all possible stereoisomers of a given
product with multiple stereocenters from the same set of starting
materials. We report herein the first diastereodivergent [3+2]
annulation of aromatic aldimines with alkenes via C−H activation
by half-sandwich rare-earth catalysts. This protocol provides an
efficient and general route for the selective synthesis of both trans
and cis diastereoisomers of multi-substituted 1-aminoindanes from
the same set of aldimines and alkenes, featuring 100% atom
efficiency, excellent diastereoselectivity, broad substrate scope,
and good functional group compatibility. The diastereodivergence
is achieved by fine-tuning the sterics or ligand/metal combination
of the half-sandwich rare-earth metal complexes.
(
C
1
Scheme 1). A scandium catalyst bearing the sterically demanding
Me SiMe ligand selectively gave a trans-diastereoisomer of the
-aminoindane, whereas the analogous yttrium complex bearing a
smaller C Me H ligand afforded the cis-diastereoisomer. This
5
4
3
5
4
protocol offers an unprecedented efficient route for the selective
synthesis of both trans and cis diastereoisomers of 1-aminoindane
derivatives from the same set of aldimine and alkene starting
materials.
Scheme 1. Diastereodivergent [3+2] Annulation of
Aldimines with Alkenes via C−H Activation by Rare-Earth
Catalysts
Aminoindanes are valuable compounds in biochemical and
pharmacological research. In particular, multi-substituted 1-
NHR1
[
Sc]
1
with large ligand
R
aminoindanes containing contiguous stereogenic centers are
important components in a large number of biologically active
molecules and pharmaceuticals, in which the absolute and relative
configurations are often crucial for the expression of biological
trans-selective
H
trans-3
NR1
+
R
H
NHR1
R
2
[Y]
activities. Therefore, the development of efficient and selective
1
2
with small ligand
methods that can provide a full set of all possible diastereoisomers
of a given 1-aminoindane compound is of much interest and
importance. The catalytic tandem [3+2] annulation of aromatic
imines with alkenes, which involves the insertion of an alkene unit
into an ortho-C−H bond of the aromatic substituent in the imine
substrate followed by the intramolecular addition (cyclization) to
the imine group, is among the most atom-efficient routes for the
cis-selective
cis-3
At first, we examined the reaction of N-tert-butyl benzaldimine
(
1a) with styrene (2a) by using a series of half-sandwich scandium
11
complexes bearing different Cp ligands. In the presence of
3,4
3 6 5 4 5 4 3
[Ph C][B(C F ) ] as a cocatalyst, the C Me SiMe -ligated
scandium complex Sc-1 showed high activity and high
synthesis of multi-substituted 1-aminoindanes. Obviously, the
diastereodivergent catalysis of this transformation would be an
ideal route for the efficient synthesis of different diastereomers of
the 1-aminoindane products from the same set of imine and alkene
stereoselectivity at 120 C, quantitatively affording the [3+2]
annulation
diastereoselectivity (d.r. > 19:1) (Table 1, entry 1). When a less
sterically demanding C Me -ligated scandium complex Sc-2 was
product
trans-3aa
with
excellent
trans-
5
,6
starting materials.
However, such catalyst-controlled
diastereodivergent synthesis of 1-aminoindane compounds has not
been reported previously despite great interest and extensive
5
5
used, the diastereoselectivity was significantly deteriorated,
yielding a 3.5:1 mixture of trans-3aa and cis-3aa (Table 1, entry
2). Intriguingly, the use of a further smaller C Me H-ligated
5 4
complex Sc-3 reversed the diastereoselectivity, giving a cis-rich
diastereoisomer mixture although the selectivity was low (trans-
3-6
studies in this area.
We have recently found that half-sandwich rare-earth alkyl
complexes can serve as efficient catalysts for various chemical
7
8
transformations,
including C−H addition to alkenes,
9
5 5
3aa/cis-3aa = 1:1.5) (Table 1, entry 3). When the smallest C H -
ligated complex Sc-4 was employed, the cis-selectivity was greatly
copolymerization of polar and non-polar olefins, and
diastereodivergent asymmetric carboamination/annulation of
cyclopropenes with aminoalkenes. These findings have invoked
1
0
increased to trans-3aa/cis-3aa = 1:19, albeit in relatively low yields
12
(
37-45%) (Table 1, entries 4 and 5).
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Table 1. Catalyst Screening for [3+2] Annulation of
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Benzaldimine 1a with Styrene
H
t
t
Table 2. Trans-Diastereoselective [3+2] Annulation of
Aldimine 1a with Various Alkenes by Sc-1
NH Bu
NH Bu
[Ln] (7.5 mol%)
[Ph3C][B(C6F5)4] (7.5 mol%)
a
t
N Bu
+
Ph
Ph +
Ph
Toluene, 120 oC, 24 h
H
H
t
t
NH Bu
NH Bu
Sc-1
[Ph C][B(C F ) ]
1a
2a
cis-3aa
trans-3aa
t
N Bu
3
6 5 4
+
R
R
or
Toluene, 120 oC, 24 h
H
SiMe3
R
trans-3
(R = aryl)
trans-3
Ln
Ln
Ln
Ln
N
N
N
N
1a
2
(
R = alkyl)
N
N
N
N
Ln-1
Ln-2
Ln-3
Ln-4
X = H, trans-3aa, 94%, d.r. > 19:1
X = Me, trans-3ab, 89%, d.r. > 19:1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
t
NH Bu
Entry
[Ln]
Yield (%)b
d.r. (trans : cis)c
> 19 : 1
3.5 : 1
X = Bu, trans-3ac, 98%, d.r. > 19:1
t
X
X = Ph, trans-3ad, 89%, d.r. > 19:1
1
2
3
Sc-1
Sc-2
Sc-3
Sc-4
Sc-4
Y-1
99
99
99
37
45
90
97
95
50
X = Cl, trans-3ae, 67%, d.r. > 19:1b
X = Br, trans-3af, 67%, d.r. > 19:1b
t
t
t
NH Bu
NH Bu
NH Bu
1 : 1.5
4
1 : 19
5d
Me
Me
1 : 19
trans-3ag, 88%, d.r. > 19:1
trans-3ah, 46%, d.r. > 19:1
trans-3ai, 91%, d.r. > 19:1
6d,e
7d,e
8d,e
9d,e
1 : 4
t
t
t
NH Bu
NH Bu
NH Bu
Y-2
1 : 8
Cl
Y-3
< 1 : 19
< 1 : 19
4
3
Y-4
Cl
trans-3aj, 62%, d.r. 5:1c
trans-3ak, 65%, d.r. 5:1c
trans-3al, 85%, d.r. 7:1c
a
Reaction conditions: 1a (0.2 mmol), 2a (0.8 mmol), [Ln] (7.5 mol
t
t
NH Bu
NH Bu
o
%
), [Ph
3 6 5 4
C][B(C F ) ] (7.5 mol %), toluene (2 mL), 120 C, 24 h,
b
unless otherwise noted.
Combined NMR yield of both
diastereomers. Determined by NMR analysis. [Ln] (10 mol %),
Ph
N
c
d
OTBDPS
Et
3
e
[
Ph
In sharp contrast with the exclusive formation of trans-3aa by
Sc-1, the C Me SiMe -ligated yttrium analog Y-1 afforded the cis-
3aa as a major product (1:4 d.r.) (Table 1, entry 6).
the trend observed above, the less hindered C Me
complex Y-2 showed a higher cis-diastereoselectivity (1:8 d.r.)
Table 1, entry 7). Remarkably, the even smaller C Me H-ligated
complex Y-3 exclusively afforded cis-3aa (< 1:19 d.r.) in 95%
yield (Table 1, entry 8). The C -ligated yttrium complex Y-4 also
3
C][B(C
6
F
5
)
4
] (10 mol %). 2a (0.6 mmol).
trans-3am, 50%, d.r. 8:1c
trans-3an, 50%, d.r. 7:1c
a
Reaction conditions: 1a (0.2 mmol), 2 (0.8 mmol), Sc-1 (7.5
mol%), [Ph C][B(C F ) ] (7.5 mol%), toluene (2 mL), 120 C, 24
3 6 5 4
h, isolated yields of trans-isomers, d.r. determined by NMR
o
5
4
3
1
3–15
In line with
-ligated yttrium
b
5
5
analysis of the crude product, unless otherwise noted. Sc-1 (12
c
mol%), [Ph C][B(C F ) ] (12 mol%).
3
6 5 4
Sc-1 (10 mol%),
(
5
4
3 6 5 4
[Ph C][B(C F ) ] (10 mol%).
The reactions of various N-tert-butyl aromatic aldimines with
styrene catalyzed by Sc-1 are shown in Table 3. Alkyl (3ba, 3ca,
ia, 3ua)- and aryl (3da, 3ja, 3oa3ta)-substituted benzaldimines
were all suitable for the trans-selective annulation with styrene,
affording the corresponding trans-diastereoselective products in
895% yields with excellent d.r. (> 19:1). Functional groups such
5
H
5
gave cis-3aa with high diastereoselectivity, but in a lower yield
similar to what was observed in the case of the analogous Sc-4
(Table 1, entry 9).
3
Having established the catalyst-controlled diastereodivergent
[3+2] annulation of 1a with 2a as shown above, we then examined
the substrate scope of this transformation by using Sc-1 and Y-3.
Table 2 summarizes the trans-selective annulation of 1a with
various alkenes catalyzed by Sc-1. Para-substituted styrenes with
either alkyl or aryl substituents worked well with 1a, exclusively
affording the corresponding 1-amino-2-aryl-trans-substituted
indane derivatives trans-3ab‒3ad with high yields (89‒98%) and
excellent diastereoselectivity (d.r. > 19:1). Chloro and bromo
substituents were compatible (trans-3ae and trans-3af). Meta- and
ortho-methyl-substituted styrenes also reacted with 1a in a trans-
diastereoselective fashion to give trans-3ag and trans-3ah with d.r.
5
as halides (F, Cl, Br, I) (3ea3ha, 3va3xa), SiMe (3ma), NMe
3
2
(3la, 3qa), SMe (3ka, 3oa), OMe (3pa), vinyl (3na), and aromatic
heterocycles (3ra3ta) were compatible, thus offering more
opportunities for further elaboration of the aminoindane products.
In the case of meta-substituted benzaldimines (3ia3ta), the
reaction selectively occurred at the CH bond para to the
substituent probably due to steric influence. 2-Naphthyl aldimine
was also suitable for this reaction, affording trans-3ya in 63% yield
with excellent trans-diastereoselectivity (> 19:1 d.r.). The reaction
of thiofluorenyl aldimine with styrene gave trans-3za (>19:1 d.r.)
in 31% yield together a considerable amount of an unpurified
amino-free indene product probably formed by the deamination of
>
19:1, although a lower yield was observed in the case of ortho-
methylstyrene probably due steric influence. 2-Vinylnaphthalene
was also suitable for this reaction, giving the desired product trans-
3ai in high yield and high diastereoselectivity (d.r. > 19:1). The
3+2] annulation of aliphatic alkenes with 1a afforded the
corresponding 1-amino-3-alkyl-trans-substituted indane
derivatives trans-3aj‒3an with d.r. in a range of 5:1 to 8:1.
Notably, the OTBDPS and NPhEt functional groups were
compatible. No reaction between 1a and vinyltrimethylsilane was
observed, probably due to steric hindrance.
4
b,17
trans-3za.
Remarkably, the reaction of a (+)-δ-tocopherol-
derived aldimine with styrene also efficiently afforded the targeted
trans-annulation product trans-3aaa in 68% yield with excellent
diastereoselectivity at the indane ring (> 19:1 d.r.), demonstrating
the useful potential of this protocol in the synthesis of aminoindane
derivatives bearing naturally occurring structures. The
configuration of trans-3ha was unequivocally determined by the
X-ray crystallographic analysis.
[
1
6
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Table 4. Cis-Diastereoselective [3+2] Annulation of
Aldimine 1a with Various Styrenes by Y-3
a
Table 3. Trans-Diastereoselective [3+2] Annulation of
Various Aldimines with Styrene by Sc-1a
H
t
NH Bu
Y-3
H
NtBu
t
[Ph3C][B(C6F5)4]
Sc-1 (7.5 mol%)
NH Bu
R
+
R
t
Toluene, 120 oC, 24 h
N Bu
[Ph C][B(C F ) ] (7.5 mol%)
3
6
5
4
H
+
Ph
2a
Ph
Toluene, 120 oC, 24 h
cis-3
1a
2
H
R
R
1
trans-3, d.r. > 19:1
X = H, cis-3aa, 90%, d.r. > 19:1
X = Me, cis-3ab, 90%, d.r. > 19:1
t
NH Bu
trans-3ba, R = Me, 68%
t
t
t
X = Bu, cis-3ac, 65%, d.r. 3:1
NH Bu
trans-3ca, R = Bu, 58%
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
X
X = Ph, cis-
3ad
, 87%, d.r. 15:1
trans-3da, R = Ph, 64%
trans-3ea, R = F, 93%
trans-3fa, R = Cl, 87%
trans-3ga, R = Br, 93%
trans-3ha, R = I, 91%
Ph
X = Cl, cis-3ae, 70%, d.r. 14:1
X = Br, cis-3af, 55%, d.r. 2:1
R
t
t
t
NH Bu
NH Bu
NH Bu
X-ray structure of trans-3ha
trans-3ia, R = Me, 90%b
t
NH Bu
t
NH Bu
trans-3ja, R = Ph, 95%b
R
Me
cis-3ag, 73%, d.r. > 19:1
Me
trans-3ka, R = SMe, 90%b
trans-3la, R = NMe2, 70%b,c
Ph
Ph
cis-3ah, 92%, d.r. > 19:1
cis-3ai, 75%, d.r. 4.5:1
a
trans-3na, 80%c
Reaction conditions: 1a (0.2 mmol), 2 (0.6 mmol), Y-3 (10 mol%),
trans-3ma, R = SiMe3, 88%
o
3 6 5 4
[Ph C][B(C F ) ] (10 mol%), toluene (2 mL), 120 C, 24 h, isolated
R
t
t
X
t
yields of cis-isomers, d.r. determined by NMR analysis of the crude
product.
NH Bu
NH Bu
NH Bu
Me2N
Ph
Ph
Ph
Table 5. Cis-Diastereoselective [3+2] Annulation of Various
trans-3oa, R = SMe, 89%b
trans-3pa, R = OMe, 70%b,d
trans-3ra, X = O, 82%
trans-3sa, R = S, 84%
trans-3qa, 93%b
a
Aldimines with Styrene by Y-3
Cl
t
H
t
Me
NH Bu
t
NH Bu
NHtBu
Ph
NH Bu
Y-3 (10 mol %)
t
N Bu
[Ph C][B(C F ) ] (10 mol %)
N
3
6 5 4
Ph
Me
Ph
Ph
+
Ph
2a
Toluene, 120 oC, 24 h
Cl
H
R
R
trans-3ua, 60%b
trans-3va, 55%
trans-3ta, 88%
1
cis-3, d.r. > 19:1
cis-3ba, R = Me, 90%
t
t
t
NH Bu
NH Bu
NH Bu
t
t
NH Bu
cis-3ca, R = Bu, 88%
F
cis-3da, R = Ph, 91%
cis-3ea, R = F, 94%
Ph
Ph
Ph
Ph
F
R
R
F
trans-3wa, 60%
F
cis-
3fa, R = Cl, 90%
trans-3xa, 92%
trans-3ya, 63%
cis-3ga, R = Br, 91%
cis-3ha, R = I, 91%
X-ray structure of cis-3ha
tBuHN
NHtBu
Ph
6
cis-3ia, R = Me, 86%
cis-3ja, R = Ph, 91%
cis-3la, R = NMe2, 60%
cis-3ma, R = TMS, 62%
cis-3na, R = Vinyl, 46%
t
t
NH Bu
NH Bu
Ph
2
Ph
Ph
SMe
S
O
cis-3ka, 90%, (C2:C6 = 4:1)
trans-3za, 31%
trans-3aaa, 68%b,d,e
R
6
t
t
t
NH Bu
NH Bu
NH Bu
a
Reaction conditions: 1 (0.2 mmol), 2a (0.8 mmol), Sc-1 (7.5
Me2N
2
o
mol%), [Ph
3
C][B(C
F
6 5
)
4
] (7.5 mol%), toluene (2 mL), 120 C, 24
Ph
Ph
Ph
O
h, isolated yields of trans-isomers, d.r. > 19:1 in all cases as shown
cis-3oa, R = SMe, 90%
cis-3pa, R = OMe, 89%
cis-3ra, 85%
(C2:C6 = 4:1)
b
by NMR analysis of the crude product, unless otherwise noted.
cis-3qa, 82%
c
d
e
3 6 5 4
Sc-1 (10 mol%), [Ph C][B(C F ) ] (10 mol%). 36 h. 40 h. 1:1
R
t
S
t
t
NH Bu
NH Bu
NH Bu
d.r. based on original chiral centers of the substrate.
N
Ph
The cis-selective annulations of 1a with various styrenes
catalyzed by Y-3 are shown in Table 4. Para-methyl-, phenyl-, and
chloro-substituted styrenes all showed high cis-selectivity to give
the corresponding cis-annulation products cis-3ab, cis-3ad, and
Ph
Me
Ph
1
R
R = Me, R1 = H, cis-3ua, 85%
R = Cl, R1 = Cl, cis-3va, 85%
cis-3sa, 88%
cis-3ta, 82%
t
t
NH Bu
NH Bu
t
NH Bu
t
cis-3ae in 70-90% yields with high d.r. (14:1 to >19:1). Bu- and
F
Ph
Ph
Br-substituted styrenes were less selective possibly due to steric
Ph
F
1
8
influence. Meta- and ortho-methyl-substituted styrenes also
worked well with 1a, affording the cis-selective products cis-3ag
and cis-3ah, respectively with excellent diastereoselectivity (>
F
F
cis-
cis-3wa, 70%
3xa, 80%
cis-3ya, 84%
tBuHN
Ph
19:1).
2-Vinylnaphthalene
showed
relatively
lower
t
NH Bu
diastereoselectivity, giving cis-3ai in 75% yield with 4.5:1 d.r. The
annulation reaction of aliphatic alkenes with 1a by Y-3 did not take
place under the similar conditions, in agreement with the metal
Ph
S
O
19
influences observed previously in olefin polymerization.
cis-3za, 88%b
cis-3aaa, 83%c
a
Reaction Conditions: 1 (0.2 mmol), 2a (0.6 mmol), Y-3 (10 mol%),
C][B(C F ) ] (10 mol%), toluene (2 mL), 120 C, 24 h, isolated
3 6 5 4
o
[Ph
yields of cis-isomers, d.r. > 19:1 in all cases as shown by NMR
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b
analysis of the crude product, unless otherwise noted.. 16:1 d.r.
Scheme 2 shows two examples of gram-scale reactions catalyzed
by Sc-1 and Y-3, respectively, which gave the corresponding
diastereoselective annulation products in excellent yields and
excellent d.r., demonstrating again the synthetic usefulness of this
c
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(cis/trans). 1:1 d.r. based on original chiral centers of the substrate.
The aldimine substrate scope for the cis-diastereoselective [3+2]
annulation with styrene by Y-3 is shown in Table 5. It is generally
similar to that for the trans-diastereoselective reactions catalyzed
by Sc-1. Alkyl, aryl, vinyl, silyl, halogen, and heteroatom
substituents were all compatible, affording the corresponding cis-
diastereoselective annulation products in good yields with high d.r.
2
0,21
protocol.
A possible mechanism for the diastereodivergent annulations of
aldimine 1a with styrene 2a by Sc-1 and Y-3 is shown in Scheme
3. The coordination of the nitrogen atom of 1a to the metal atom of
the cationic alkyl species, which was generated by the reaction of
(
16:1 to > 19:1 d.r.). The configuration of cis-3ha was
11
unequivocally determined by the X-ray crystallographic analysis.
In the case of 3-thiomethyl- and 3-furyl-substituted benzaldimines,
the C‒H activation occurred at both the C2 and C6 positions to give
the regioisomers with a ratio of C2/C6 = 4:1 in high cis-
diastereoselectivity (see cis-3ka and cis-3ra). The preference of
C−H activation at the C2 position was probably due to an
interaction of the thiomethyl/furyl groups in the aldimines with the
yttrium atom in Y-3. Such C2‒H activation was not observed in the
case of Sc-1 (see trans-3ka and trans-3ra, Table 3) probably
Sc-1 or Y-3 with [Ph
activation (deprotonation) of the phenyl group in 1a with the metal
alkyl species would give five-membered metallacycle
3 6 5 4
C][B(C F ) ], followed by ortho-C−H
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
intermediate like A. In the case of Sc-1, the 2,1-insertion of styrene
into the Sc−aryl bond in A via a transition state like B should afford
C, in which an interaction between the Sc atom and the phenyl
group in the styrene unit might be difficult because of steric
t
repulsion with the
C
5
Me
4
SiMe
3
and N Bu groups. The
intramolecular nucleophilic addition of the resulting Sc−C bond to
the C=N unit in C would give the cyclization product D with a
sterically favored trans configuration. The C−H activation
because of the steric hindrance of the C
5
Me
4
SiMe
3
ligand.
Scheme 2. Gram Scale Reactions
(
deprotonation) of 1a by the Sc−N bond in D should release trans-
2
2
t
3aa and regenerate the catalyst species A. In the case of Y-3, the
interaction between the Y atom and both the C=C double bond and
the phenyl group in styrene could be possible to give a transition
state like E, because the metal size of Y is larger than that of Sc and
N Bu
t
NH Bu
Sc-1 (7.5 mol %),
Ph3C][B(C6F5)4] (7.5 mol %)
Toluene, 120 oC, 24 h
H
[
+
Ph
Br
Br
trans-3ga, 90% (1.24 g), d.r. > 19:1
5 4 5 4 3
the C Me H ligand in E is much smaller than the C Me SiMe
1g, (4 mmol)
2a
1
4,23
ligand in B.
An Y---phenyl interaction could remain in the
t
N Bu
t
NH Bu
styrene insertion product F, which upon cyclization should yield
the cis product G because of the amino---phenyl chelation to the Y
atom. Finally, the acid-base reaction between G and 1a releases cis-
Y-3 (10 mol %),
[Ph3C][B(C6F5)4] (10 mol %)
H
+
Ph
Toluene, 120 oC, 24 h
I
3
aa and regenerates the catalyst species A.
I
h, (4 mmol)
1
2a
cis-3ha, 91% (1.42 g), d.r. > 19:1
Scheme 3. Proposed Reaction Mechanism of Diastereodivergent [3+2] Annulation of Aldimine1a with Styrene 2a
R
R
[Ph3C][B(C6F5)4]
+
N
Ln
N
Ln
N
t
H
N Bu
H
NMe2
1a
tBu
tBu
H
N
H
N
+
Sc
+
Y
SiMe3
R = H
R = SiMe3
Ln = Sc
Ln = Y
E
B
Ph
Ph
R
t
Bu
tBu
tBu
N
H
+
+
+
H
N
Y
Ln
H
N
Sc
SiMe3
t
t
NH Bu
NH Bu
H
H
A
C
F
Ph
Ph
cis-3aa
trans-3aa
tBu
tBu
H
N
+
H
N
+
Y
Sc
H
1a
H
SiMe3
1a
G
D
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Journal of the American Chemical Society
In summary, we have achieved for the first time the
diastereodivergent [3+2] annulation of aromatic aldimines with
alkenes via C−H activation by fine-tuning the metal/ligand
combination or steric environment of a series of half-sandwich
rare-earth metal catalysts. The combination of a sterically
Bioorg. Med. Chem. 2012, 20, 5986−5991. (c) Yu, H.; Kim, I. J.; Folk, J.
E.; Tian, X.; Rothman, R. B.; Baumann, M. H.; Dersch, C. M.; Flippen-
Anderson, J. L.; Parrish, D.; Jacobson, A. E.; Rice, K. C. Synthesis and
Pharmacological Evaluation of 3-(3,4-Dichlorophenyl)-1-indanamine
Derivatives as Nonselective Ligands for Biogenic Amine Transporters. J.
Med. Chem. 2004, 47, 2624–2634. (d) Di Stefano, A.; Sozio, P.; Cacciatore,
I.; Cocco, A.; Giorgioni, G.; Costa, B.; Montali, M.; Lucacchini, A.; Martini,
C.; Spoto, G.; Di Pietrantonio, F.; Di Matteo, E.; Pinnen, F. Preparation and
Pharmacological Characterization of trans-2-Amino-5(6)-fluoro-6(5)-
hydroxy-1-phenyl-2,3-dihydro-1H-indenes as D2-like Dopamine Receptor
Agonists. J. Med. Chem. 2005, 48, 2646–2654.
1
2
3
4
5
6
7
8
9
5 4 3
demanding ligand such as C Me SiMe with scandium (Sc-1),
which is the smallest metal in the rare-earth series, preferably
affords the annulation products in a trans-selective fashion. In
contrast, the analogous catalyst with a smaller ligand such as
5 4
C Me H and a larger metal ion such as Y (Y-3) enables the
(3) Hummel, J. R.; Boerth, J. A; Ellman, J. A. Transition-Metal-
selective formation of the cis-diastereoisomers. This protocol
features broad substrate scope, high regio- and diastereoselectivity,
and good functional group compatibility, offering an efficient route
for the selective synthesis of both cis and trans diastereomers of a
new family of multi-substituted 1-aminoindance derivatives from
the same set of aldimine and alkene starting materials.
Catalyzed C–H Bond Addition to Carbonyls, Imines, and Related Polarized
π Bonds. Chem. Rev. 2017, 117, 9163−9227.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(4) For examples of transition-metal-catalyzed tandem [3+2] annulation
of aromatic imines with C=C π bonds, see: (a) Kuninobu, Y.; Nishina, Y.;
Okaguchi, K.; Shouho, M.; Takai, K. Reactions and Mechanistic Studies of
Rhenium-Catalyzed Insertion of Alpha,Beta-Unsaturated Carbonyl
Compounds into a C−H Bond. Bull. Chem. Soc. Jpn. 2008, 81, 1393−1401.
(
b) Tran, D. N.; Cramer, N. Syn-Selective Rhodium(I)-Catalyzed
ASSOCIATED CONTENT
Supporting Information
Allylations of Ketimines Proceeding through Directed C−H
a
Activation/Allene Addition Sequence. Angew. Chem., Int. Ed. 2010, 49,
8181−8184. (c) Kuninobu, Y.; Yu, P.; Takai, K. Rhenium-Catalyzed
Diastereoselective Synthesis of Aminoindanes via the Insertion of Allenes
into a C−H Bond. Org. Lett. 2010, 12, 4274−4276. (d) Nishimura, T.; Ebe,
Y.; Hayashi, T. Iridium-Catalyzed [3+2] Annulation of Cyclic N-Sulfonyl
Ketimines with 1,3-Dienes via C−H Activation. J. Am. Chem. Soc. 2013,
The Supporting Information is available free of charge on the ACS
Publications website.
Synthetic procedures, characterization data for all new compounds
(PDF).
1
35, 2092−2095. (e) Nishimura, T.; Nagamoto, M.; Ebe, Y.; Hayashi, T.
Enantioselective [3+2] Annulation via C–H Activation Between Cyclic N-
acyl ketimines and 1,3-Dienes Catalyzed by Iridium/Chiral Diene
Complexes. Chem. Sci. 2013, 4, 4499–4504. (f) Liu, W. P.; Zell, D.; John,
M.; Ackermann, L. Manganese Catalyzed Synthesis of Cis-Beta-Amino
Acid Esters Through Organometallic C−H Activation of Ketimines. Angew.
Chem., Int. Ed. 2015, 54, 4092−4096. (g) Ebe, Y.; Hatano, M.; Nishimura,
T. Iridium-Catalyzed Annulation of Aromatic Imines with 1,3-Dienes via
Direct Functionalization of an Aromatic C−H Bond. Adv. Synth. Catal.
2015, 357, 1425−1436. (h) Liu, B.; Hu, P.; Zhang, Y.; Li, Y.; Bai, D.; Li,
X. Rh(III)-Catalyzed Diastereodivergent Spiroannulation of Cyclic Imines
with Activated Alkenes. Org. Lett. 2017, 19, 5402−5405. (i) Liang, Y.-F.;
Müller, V.; Liu, W.; Münch, A.; Stalke, D.; Ackermann, L.
AUTHOR INFORMATION
Corresponding Author
*
houz@riken.jp.
ORCID
Xuefeng Cong: 0000-0002-0530-1721
Zhenbo Mo: 0000-0002-5021-9540
Masayoshi Nishiura: 0000-0003-2748-9814
Zhaomin Hou: 0000-0003-2841-5120
Methylenecyclopropane
Stereoselective C−H/C−C Activation. Angew. Chem., Int. Ed. 2017, 56,
415−9419. (j) Chaudhary, B.; Auti, P.; Shinde, S. D.; Yakkala, P. A.; Giri,
Annulation
by
Manganese(I)-Catalyzed
9
Notes
D.; Sharma, S. Rh(III)-Catalyzed [3+2] Annulation via C–H Activation:
Direct Access to Trifluoromethyl-Substituted Indenamines and
Aminoindanes. Org. Lett. 2019, 21, 2763−2767.
The authors declare no competing financial interests.
(
5) Selected reviews on stereodivergent catalysis: (a) Miller, L. C.;
ACKNOWLEDGMENT
Sarpong, R. Divergent Reactions on Racemic Mixtures. Chem. Soc. Rev.
2011, 40, 4550−4562. (b) Mahatthananchai, J.; Dumas, A. M.; Bode, J. W.
Catalytic Selective Synthesis. Angew. Chem., Int. Ed. 2012, 51,
This work was supported in part by JSPS KAKENHI Grants (Nos.
JP19H00897, JP17H06451, JP17K05824). We thank Mrs. Akiko
Karube for high resolution mass spectrometry (HRMS) analyses.
1
0954−10990. (c) Schindler, C. S.; Jacobsen, E. N. A New Twist on
Cooperative Catalysis. Science 2013, 340, 1052−1053. (d) Bihani, M.; Zhao,
J. C.-G. Advances in Asymmetric Diastereodivergent Catalysis. Adv.
Synth.Catal. 2017, 359, 534−556. (e) Zhan, G.; Du, W.; Chen, Y.-C.
Switchable Divergent Asymmetric Synthesis via Organocatalysis. Chem.
Soc. Rev. 2017, 46, 1675−1692. (f) Lin, L.; Feng, X. Catalytic Strategies
for Diastereodivergent Synthesis. Chem. - Eur. J. 2017, 23, 6464−6482. (g)
Krautwald, S.; Carreira, E. M. Stereodivergence in Asymmetric Catalysis.
J. Am. Chem. Soc. 2017, 139, 5627−5639.
REFERENCES
(1) (a) Bar-Am, Orit.; Weinreb, Orly.; Amit, T.; Youdim, M. B. H. The
neuroprotective mechanism of 1-(R)-aminoindan, the major metabolite of
the anti-parkinsonian drug rasagiline. J. Neurochem. 2010, 112, 1131–1137.
(b) Chazalette, C.; Masereel, B.; Rolin, S.; Supuran, C. T. Carbonic
anhydrase inhibitors. Design of anticonvulsant sulfonamides incorporating
indane moieties. Bioorg. Med. Chem. Lett. 2004, 14, 5781−5786. (c) Thiry,
A.; Ledecq, M.; Masereel, B. Indanesulfonamides as Carbonic Anhydrase
Inhibitors. Toward Structure-Based Design of Selective Inhibitors of the
Tumor-Associated Isozyme CA IX. J. Med. Chem. 2006, 49, 2743−2749.
(6) Selected examples of catalyst-controlled stereodivergent chemical
transformations: (a) Tian, X.; Cassani, C.; Liu, Y.; Moran, A.; Urakawa, A.;
Galzerano, P.; Arceo, E.; Melchiorre, P. Diastereodivergent Asymmetric
Sulfa-Michael Additions of α-Branched Enones using a Single Chiral
Organic Catalyst. J. Am. Chem. Soc. 2011, 133, 17934–17941. (b)
Krautwald, S.; Sarlah, D.; Schafroth, M. A.; Carreira, E. M. Enantio- and
Diastereodivergent Dual Catalysis: α-Allylation of Branched Aldehydes.
Science 2013, 340, 1065−1068. (c) Kan,S. B. J.; Maruyama, H.; Akakura,
M.; Kano, T.; Maruoka, K. Catalyst-Controlled, Enantioselective, and
Diastereodivergent Conjugate Addition of Aldehydes to Electron-Deficient
Olefins. Angew .Chem. Int. Ed. 2017, 56, 9487–9491. (d) Piou, T.;
Romanov-Michailidis, F.; Ashley, M. A.; Romanova-Michaelides, M.;
Rovis, T. Stereodivergent Rhodium(III)-Catalyzed cis-Cyclopropanation
Enabled by Multivariate Optimization. J. Am. Chem. Soc. 2018, 140,
9587−9593.
(d) Graham, J. M.; Coughenour, L. L.; Barr, B. M.; Rock, D. L.; Nikam, S.
S. 1-Aminoindanes as novel motif with potential atypical antipsychotic
properties. Bioorg. Med. Chem. Lett. 2008, 18, 489–493.
(2) (a) Casimiro-Garcia, A.; Trujillo, J. I.; Vajdos, F.; Juba, B.; Banker,
M. E.; Aulabaugh, A.; Balbo, P.; Bauman, J.; Chrencik, J.; Coe, J. W.;
Czerwinski, R.; Dowty, M.; Knafels, J. D.; Kwon, S.; Leung, L.; Liang, S.;
Robinson, R. P.; Telliez, J.-B.; Unwalla, R.; Yang, X.; Thorarensen, A.
Identification of Cyanamide-Based Janus Kinase 3 (JAK3) Covalent
Inhibitors. J. Med. Chem. 2018, 61, 10665−10699. (b) Ugliarolo, E. A.;
Cavallaro, L. V.; Moglioni, A. G. Synthesis and biological evaluation of
novel homochiral carbocyclic nucleosides from 1-amino-2-indanols.
ACS Paragon Plus Environment

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Page 6 of 7
(
7) A recent review: Nishiura, M.; Guo, F.; Hou, Z. Half-Sandwich Rare-
Earth-Catalyzed Olefin Polymerization, Carbometalation, and
Hydroarylation. Acc. Chem. Res. 2015, 48, 2209−2220.
8) Selected examples: (a) Guan, B.-T.; Hou, Z. Rare-Earth-Catalyzed
2017, 36, 1557−1565. (b) Luo, G.; Liu, F.; Luo, Y.; Zhou, G.; Kang, X.;
Hou, Z; Luo, L. Computational Investigation of Scandium-Based Catalysts
for Olefin Hydroaminoalkylation and C−H Addition. Organometallics
2019, 38, 1887−1896.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
C−H Bond Addition of Pyridine to Olefins. J. Am. Chem. Soc. 2011, 133,
18086−18089. (b) Oyamada, J.; Hou, Z. Regioselective C-H Alkylation of
Anisoles with Olefins Catalyzed by Cationic Half Sandwich Rare Earth
Alkyl Complexes. Angew. Chem., Int. Ed. 2012, 51, 12828−12832. (c)
Guan, B.-T.; Wang, B.; Nishiura, M.; Hou, Z. Yttrium-Catalyzed Addition
of Benzylic C−H Bonds of Alkyl Pyridines to Olefins. Angew. Chem., Int.
Ed. 2013, 52, 4418−4421. (d) Song, G.; O, W. W. N.; Hou, Z.
Enantioselective C−H Bond Addition of Pyridines to Alkenes Catalyzed by
Chiral Half-Sandwich Rare-Earth Complexes. J. Am. Chem. Soc. 2014, 136,
12209−12212. (e) Song, G.; Wang, B.; Nishiura, M.; Hou, Z. Catalytic C−H
Bond Addition of Pyridines to Allenes by a Rare-Earth Catalyst. Chem. -
Eur. J. 2015, 21, 8394−8398. (f) Song, G.; Luo, G.; Oyamada, J.; Luo, Y.;
Hou, Z. Ortho-Selective C−H Addition of N,N-Dimethyl Anilines to
Alkenes by a Yttrium Catalyst. Chem. Sci. 2016, 7, 5265−5270. (g) Nako,
A. E.; Oyamada, J.; Nishiura, M.; Hou, Z. Scandium-Catalysed
Intermolecular Hydroaminoalkylation of Olefins with Aliphatic Tertiary
Amines. Chem. Sci. 2016, 7, 6429−6434. (h) Shi, X.; Nishiura, M.; Hou, Z.
C−H Polyaddition of Dimethoxyarenes to Unconjugated Dienes by Rare
Earth Catalysts. J. Am. Chem. Soc. 2016, 138, 6147−6150. (i) Shi, X.;
Nishiura, M.; Hou, Z. Simultaneous Chain-Growth and Step-Growth
Polymerization of Methoxystyrenes by Rare-Earth Catalysts. Angew.
Chem., Int. Ed. 2016, 55, 14812−14817. (j) Luo, Y.; Teng, H.; Nishiura,
(17) Kuninobu, Y.; Nishina, Y.; Shouho, M.; Takai, K. Rhenium- and
Aniline-Catalyzed One-Pot Annulation of Aromatic Ketones and α,β-
Unsaturated Esters Initiated by C−H Bond Activation. Angew. Chem., Int.
Ed. 2006, 45, 2766−2768.
(18) A possible interaction between the phenyl ring in a styrene substrate
and the Y atom in the catalyst is highly important to achieve the cis-
selectivity (see Scheme 4). A large substituent like tert-butyl and Br even
at the para-position of the styrene phenyl unit (such as in the case of 3ac
and 3af, Table 4) could show significant repulsion with the tert-butyl group
in 1a, thus lowering the cis-selectivity.
(19) Luo, Y.; Baldamus, J.; Hou, Z. Scandium Half-Metallocene-
Catalyzed Syndiospecific Styrene Polymerization and Styrene-Ethylene
Copolymerization: Unprecedented Incorporation of Syndiotactic Styrene-
Styrene Sequences in Styrene-Ethylene Copolymers. J. Am. Chem. Soc.
2004, 126, 13910−13911.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(20) For the reaction of other N-substituted benzaldimines, see
Supporting Information (Table S6).
(21) The reactions of N-cumyl-substituted benzaldimine 1ae with
styrene 2a catalyzed by Sc-1 and Y-3, followed by decumylation of the
annulated products could afford the corresponding trans and cis
unsubstituted primary 1-aminoindanes, respectively. See the Supporting
Information (Scheme S1) for details.
(22) For the formation of 1-amino-3-alkyl-trans-substituted indane
derivatives in the case of aliphatic alkenes through a 1,2-insertion
mechanism (Table 2, trans-3aj‒3an), see Supporting Information (Figure
S3).
(23) For examples of metal-phenyl interaction in rare-earth-catalyzed
transformations of styrene, see: (a) Fu, P.-F.; Brard, L.; Li, Y.; Marks, T. J.
Regioselection and Enantioselection in Organolanthanide-Catalyzed Olefin
Hydrosilylation. A Kinetic and Mechanistic Study. J. Am Chem. Soc. 1995,
117, 7157–7168. (b) Molander, G. A.; Schmitt, M. H. Organoyttrium-
Catalyzed Sequential Cyclization/Silylation Reactions of Nitrogen-
Heteroaromatic Dienes Demonstrating “Aryl-Directed” Regioselectivity. J.
Org. Chem. 2000, 65, 3767–3770. (c) Hultzsch, K. C.; Voth, P.; Beckerle,
K.; Spaniol, T. P.; Okuda, J. Single-Component Polymerization Catalysts
for Ethylene and Styrene: Synthesis, Characterization, and Reactivity of
3
M.; Hou, Z. Asymmetric Yttrium-Catalyzed C(sp )−H Addition of 2-
Methyl Azaarenes to Cyclopropenes. Angew. Chem., Int. Ed. 2017, 56,
9
207−9210. (k) Luo, Y.; Ma, Y.; Hou, Z. α-C−H Alkylation of Methyl
Sulfides with Alkenes by a Scandium Catalyst. J. Am. Chem. Soc. 2018,
140, 114−117. (l) Lou, S.; Mo, Z.; Nishiura, M.; Hou, Z. Construction of
All-Carbon
Quaternary
Stereocenters
by
Scandium-Catalyzed
Intramolecular C-H Alkylation of Imidazoles with 1,1-Disubstituted
Alkenes. J. Am. Chem. Soc. 2020, 142, 1200−1205.
(9) (a) Wang, C.; Luo, G.; Nishiura, M.; Song, G.; Yamamoto, A.; Luo,
Y.; Hou, Z. Heteroatom-Assisted Olefin Polymerization by Rare-Earth
Metal Catalysts. Sci. Adv. 2017, 3, No. e1701011. (b) Wang, H.; Yang, Y.;
Nishiura, M.; Higaki, Y.; Takahara, A.; Hou, Z. Synthesis of Self-Healing
Polymers by Scandium-Catalyzed Copolymerization of Ethylene and
Anisylpropylenes. J. Am. Chem. Soc. 2019, 141, 3249−3257. (c) Wang, H.;
Zhao, Y.; Nishiura, M.; Yang, Y.; Luo, G.; Luo. Y.; Hou, Z. Scandium-
Catalyzed Regio- and Stereoselective Cyclopolymerization of
Functionalized α,ω-Dienes and Copolymerization with Ethylene. J. Am.
Chem. Soc. 2019, 141, 12624−12633.
Alkyl and Hydrido Yttrium Complexes Containing
a
Linked
Amido−Cyclopentadienyl Ligand. Organometallics 2000, 19, 228–243. (d)
Ryu, J.-S.; Li, G. Y.; Marks, T. J. Organolathanide-Catalyzed
Regioselective Intermolecular Hydroamination of Alkenes, Alkynes,
Vinylarenes, Di- and Trivinylarenes, and Methylenecyclopropanes. Scope
and Mechanistic Comparison to Intramolecular Cyclohydroaminations. J.
Am. Chem. Soc. 2003, 125, 12584–12605. (e) Kang, X.; Yamamoto, A.;
Nishiura, M.; Luo, Y.; Hou, Z. Computational Analyses of the Effect of
Lewis Bases on Styrene Polymerization Catalyzed by Cationic Scandium
Half-Sandwich Complexes. Organometallics 2015, 34, 5540–5548.
(10) Teng, H.-L.; Luo, Y.; Nishiura, M.; Hou, Z. Diastereodivergent
Asymmetric Carboamination/Annulation of Cyclopropenes with
Aminoalkenes by Chiral Lanthanum Catalysts. J. Am. Chem. Soc. 2017, 139,
16506−16509.
(11) Li, X.; Nishiura, M.; Mori, K.; Mashiko, T.; Hou, Z. Cationic
scandium aminobenzyl complexes. Synthesis, structure and unprecedented
catalysis of copolymerization of 1-hexene and dicyclopentadiene. Chem.
Commun. 2007, 4137−4139.
(12) The reaction with a higher catalyst loading did not significantly
improve the product yield, probably due to the instability (or ligand
redistribution) of the cationic active species generated from Sc-4. See: Hou,
Z.; Luo, Y.; Li, X. Cationic Rare Earth Metal Alkyls as Novel Catalysts for
Olefin Polymerization and Copolymerization. J. Organomet. Chem. 2006,
6
91, 3114−3121. See also ref. 7.
13) Shima, T.; Nishiura, M.; Hou, Z. Tetra-, Penta-, and Hexanuclear
Yttrium Hydride Clusters from Half-Sandwich Bis(aminobenzyl)
(
Complexes
Containing
Various
Cyclopentadienyl
Ligands.
Organometallics 2011, 30, 2513−2524.
3
+
3+
(14) Ionic radius with coordination number of six, Sc : 0.745 Å, Y :
0
.900 Å. See: Shannon, R. D. Revised Effective Ionic Radii and Systematic
Studies of Interatomie Distances in Halides and Chaleogenides. Acta
Crystallogr., Sect.A: Cryst. Phys., Diffr., Theor. Gen. Crystallogr. 1976, 32,
7
51−767.
15) For reactions using other rare-earth metal catalysts, see Supporting
(
Information.
(16) α-Olefins usually undergo 1,2-insertion with rare-earth alkyl
catalysts. For examples, see refs. 8a-d. For computational studies, see: (a)
Liu, F.; Luo, G.; Hou, Z.; Luo, Y. Mechanistic Insights into Scandium-
Catalyzed Hydroaminoalkylation of Olefins with Amines: Origin of
Regioselectivity and Charge-Based Prediction Model. Organometallics
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[
Sc]
NHR1
R
with lagre ligand
H
trans-selective
R2
up to 98% yield
NR1
R
>
19:1 d.r.
H
R2
[Y]
NHR1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
with small ligand
R
cis-selective
2
R
up to 94% yield
> 19:1 d.r.
ACS Paragon Plus Environment