À
À
Table 2: Functional-group tolerance of the C H Bond amination using
We first examined the intramolecular C H bond amina-
complex 4 as the catalyst.[a]
tion of 2,5-diethylbenzenesulfonyl azide (8a) with the com-
plexes 1–7 as the catalysts at room temperature in toluene
(Table 1).[16] All the aminations occurred only at the benzylic
À
Table 1: Survey of iridium–salen catalysts for intramolecular C H bond
amination with 2,5-diethylbenzenesulfonyl azide (8a).[a]
Entry
x (mol%)
R
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
8b
8c
8d
8e
8 f
8g
8h
8i
3
3
5
5
5
5
5
5
–
77
96
92
88
4,6-(Et)2
5-MeO
5-Me2N
5-Br
4-Br
5-MeO2C
5-NO2
71 (69)
88 (83)
63 (89)
63 (93)[d]
75 (85)
49 (99)
93 (93)
86 (84)
85 (88)
92 (92)[d]
84 (87)
79 (88)
Entry
Cat.
Yield [%][b]
ee [%][c]
1
2
3
1
2
3
4
5
6
7
78
88
86
85
90
72
71
42
84
75
91
88
50
48
[a] Reaction was run on a 0.3 mmol scale in toluene (0.75 mL) under N2.
[b] Yield of isolated product. The values in the parentheses are for
reactions run in AcOEt (0.75 mL). [c] Determined by HPLC analysis. The
values in parenteses are for reactions run in AcOEt (0.75 mL). [d] Run on
a 0.1 mmol scale.
4[d]
5
6
7
[a] Reaction was run on a 0.1 mmol scale in toluene (0.25 mL) under N2,
unless otherwise mentioned. [b] Yield of isolated product. [c] Deter-
mined by HPLC analysis. [d] Run on a 0.3 mmol scale in toluene
(0.75 mL).
true for substrates having electron-donating groups. Thus, we
optimized the reaction of 8i with regard to solvent and found
that the reaction proceeded in ethyl acetate with a higher
yield and enantioselectivity (99% yield, 89% ee; entry 8).[18]
The reactions of 8 f, 8g, and 8h also gave better or equal
results (88, 92, and 87% ee, respectively) in ethyl acetate,
whereas the reactions of 8d and 8e, which have an electron-
donating group, gave slightly inferior or equal results
(entries 3 and 4).
We additionally examined the cyclization of several 2-
alkyl-substituted derivatives other than 2-ethyl-substituted
ones (Table 3). To our surprise, the reaction of 2,5-dicyclo-
hexylbenezenesulfonyl azide (8j) primarily occurred not at
the expected benzylic (a) position but at the homobenzylic
(b) position to give the six-membered sultam 10j with high
enantioselectivity (entry 1).[19,20] To estimate the effect of the
position with modest to good enantioselectivity to give the
five-membered sultam 9a, and no amination was observed at
the CH3 of the ethyl group.[17] This regioselectivity is identical
with that of the cobalt-catalyzed cyclization.[5a] The enantio-
selectivity increased, as the substituent (R2) at C2’ of the
binaphthyl moieties of the ligand became bulkier. Complex 4,
which possesses a concave shape that results from the
structural nature of the 4-TBDPSC6H4 group at C2’,[14b]
showed the best enantioselectivity at 91% ee (entry 4).
Although the structure of the ethylenediamine moiety did
not significantly affect the enantioselectivity, the cyclohex-
anediamine unit is a better structural element than the
diphenylethylenediamine unit (e.g., entries 4 and 5). The
diastereometric complexes 6 and 7 were less efficient
(entries 6 and 7).
Subsequently, we examined 2-ethylbenzenesulfonyl azide
and its C4-, C5-, or C6-substitued derivatives with 4 in toluene
(Table 2). The cyclization of an ortho-disubstituted substrate
proceeded with high enantioselectivity (entry 2). The sub-
strates bearing an electron-donating or a halo group were also
aminated at the benzylic position with high enantioselectivity
ranging from 85 to 93% ee (entries 3–6). Notably, the reaction
proceeded even in the presence of a basic amino group with
high enantioselectivity (entry 4). The substrate bearing an
ester group also underwent the amination with 84% ee
(entry 7). However, the presence of a more electron-with-
drawing nitro group diminished the enantioselectivity to 79%
ee (entry 8). We wondered if the best solvent for the reactions
of the substrates bearing an electron-withdrawing groups held
À
steric crowding around the C H bond on the regioselectivity,
we examined the reaction of 2,5-di-n-propylbenzenesulfonyl
azide (8k). The reaction with 4 occurred less selectively at the
b position (a/b = 1:2),[5a] albeit with high enantioselectivity of
97% ee (b cyclization). However, the reaction with 2 was
found to proceed with high b selectivity (a/b = 1: > 20) and
enantioselectivity (entry 2). The reaction of 8l bearing a 2-
phenylethyl group with 4 also showed modest b selectivity (a/
b = 1:2), despite the fact that the b-carbon atom is a benzylic
carbon atom, and high enentioselectivity (entry 3). These
results suggested that some factor other than steric crowding
and bond energy affects the regioselectivity. We further
examined the cyclization of 8m bearing a pent-3-yl group, an
acyclic sec-alkyl group. The reaction with 4 showed modest
a selectivity, and the minor b cyclization was moderately
trans-selective with the enantiomeric excess of the trans
product being 97% ee (entry 4). In contrast, the reaction with
Angew. Chem. Int. Ed. 2011, 50, 9884 –9887
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
9885