Rhodium-catalyzed asymmetric arylation of N-tosyl ketimines

Article abstract of DOI:10.1021/ja106114q

A rhodium-catalyzed addition of sodium tetraarylborates to N-tosyl ketimines is described. Highly efficient asymmetric catalysis has been achieved by employing a chiral diene ligand, constructing chiral amine derivatives possessing α-tetrasubstituted carbon stereocenters with high enantioselectivity.

Full text of DOI:10.1021/ja106114q

Published on Web 09/01/2010
Rhodium-Catalyzed Asymmetric Arylation of N-Tosyl Ketimines
Ryo Shintani,* Momotaro Takeda, Takaoki Tsuji, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity, Sakyo, Kyoto 606-8502, Japan
Received July 10, 2010; E-mail: shintani@kuchem.kyoto-u.ac.jp; thayashi@kuchem.kyoto-u.ac.jp
yield (entry 6). In comparison, [RhCl(binap)]2,12 a rhodium/
bisphosphine complex, did not catalyze the addition of sodium
tetraphenylborate to 1a (entry 7).
Abstract: A rhodium-catalyzed addition of sodium tetraarylbo-
rates to N-tosyl ketimines is described. Highly efficient asymmetric
catalysis has been achieved by employing a chiral diene ligand,
constructing chiral amine derivatives possessing R-tetrasubsti-
On the basis of the results in Table 1, we examined chiral diene
ligands13-15 for the development of its asymmetric variant and
tuted carbon stereocenters with high enantioselectivity.
found that the reaction of 1a with sodium tetraphenylborate
smoothly proceeded in the presence of ester-attached C1-symmetric
dienes (R,R,R)-L111d,16 and (R,R,R)-L216 to give 2a with 82% and
Catalytic asymmetric addition of carbon-based nucleophiles to
ketimines provides straightforward access to enantioenriched chiral
amines possessing an R-tetrasubstituted carbon stereocenter.1 Streck-
er-2 and Mannich-type3 reactions are most widely used in the
literature, but the use of organometallic reagents as the nucleophile
has been much less studied. In fact, to the best of our knowledge,
only an allylboronate4 and dialkylzincs5 have been employed under
copper catalysis to effect allylation and methylation/ethylation,
respectively. In this context, herein we describe the development
of a rhodium-catalyzed arylation of N-tosyl ketimines by using air-
stable sodium tetraarylborates as effective nucleophiles to give R,R-
disubstituted arylmethylamine derivatives, including its highly
enantioselective variant by the use of a chiral diene ligand.6,7
Initially, we chose N-tosyl imine of 4′-chloroacetophenone (1a) as
a model substrate8 and attempted an addition of phenylboronic acid
(2.0 equiv) under the catalysis of [Rh(OH)(cod)]2 (5 mol % Rh) in
aqueous dioxane at 80 °C (Table 1, entry 1).9 Although phenylboronic
acid was completely consumed under these conditions, addition product
2a was obtained only in 16% yield, and no significant improvement
was observed by the use of phenylboroxine or phenylboronic acid
neopentylglycol ester as the nucleophile in anhydrous dioxane (22-24%
yield, entries 2 and 3). In contrast, somewhat higher yield of 2a
was realized by using triphenylborane in methanolic dioxane (42%
yield, entry 4). Similar reactivity was also observed with potassium
phenyltrifluoroborate10 in the presence of [RhCl(cod)]2 (5 mol %
Rh) (45% yield, entry 5), and the use of sodium tetraphenylborate11
as the nucleophile led to the formation of 2a in as high as 91%
78% ee, respectively (Table 2, entries 1 and 2). The use of C2-
symmetric diene (R,R)-L317 with benzyl groups on the olefins
turned out to be somewhat more effective (87% ee, entry 3), and
changing its substitutents to phenyl groups ((R,R)-L4)17 led to the
formation of 2a with 90% ee (entry 4). Although electron-rich
4-methoxyphenyl-substituted diene (R,R)-L5 did not show further
improvement on the enantioselectivity (90% ee, entry 5), modifica-
tion of the ligand substituents to electron-deficient 4-trifluorom-
ethylphenyl groups ((R,R)-L6)17b enhanced the enantioselectivity
to 95% ee (entry 6). The best yield and ee were achieved by
lowering the reaction temperature to 60 °C (83% yield, 97% ee,
entry 7), and the absolute configuration of the product was
determined to be S by X-ray crystallographic analysis.18
Table 2. Rhodium-Catalyzed Asymmetric Addition of Sodium
Tetraphenylborate to 1a: Effect of Ligand
entry
diene
yield (%)a
ee (%)b
1
2
3
4
5
6
7c
(R,R,R)-L1
(R,R,R)-L2
(R,R)-L3
(R,R)-L4
(R,R)-L5
(R,R)-L6
(R,R)-L6
77
70
83
68
76
73
83
82 (S)
78 (S)
87 (S)
90 (S)
90 (S)
95 (S)
97 (S)
Table 1. Rhodium-Catalyzed Addition of Phenylboron Reagents to
1a: Effect of Catalyst and Nucleophile
a Isolated yield. b Determined by chiral HPLC on a Chiralcel OD-H
entry
Rh catalyst
Ph-B
additive
yield (%)a
column with hexane/2-propanol ) 95/5. c The reaction was run at 60 °C.
1
2
3
4
5
6
7
[Rh(OH)(cod)]2
[Rh(OH)(cod)]2
[Rh(OH)(cod)]2
[Rh(OH)(cod)]2
[RhCl(cod)]2
PhB(OH)2
(PhBO)3
PhB(OR)2
Ph3B
PhBF3K
Ph4BNa
Ph4BNa
H2O
none
none
MeOH
MeOH
MeOH
MeOH
16
22
24
42
45
91c
0
b
Under the conditions using [RhCl((R,R)-L6)]2 as the catalyst, several
aryl methyl ketone-derived imines 1a-d effectively undergo pheny-
lation to give the corresponding 1,1-diarylethylsulfonamides (2a-d)
in high yield with excellent enantioselectivity (94-97% ee; Table 3,
entries 1-4).19 In addition, indanone- and tetralone-derived imines
(1e,f) as well as a dialkyl ketimine (1g) can be employed as suitable
substrates for the present catalysis (g98% ee, entries 5-7). With regard
[RhCl(cod)]2
[RhCl(binap)]2
a Determined by 1H NMR analysis against an internal standard.
b (OR)2 ) OCH2CMe2CH2O. c Isolated yield.
9
13168 J. AM. CHEM. SOC. 2010, 132, 13168–13169
10.1021/ja106114q  2010 American Chemical Society

C O M M U N I C A T I O N S
to the nucleophilic component, several other aryl groups can be
effectively added to the N-tosyl imine of acetophenone (1h) with high
enantiomeric excesses (95-98% ee, entries 8-12). Highly enantiose-
lective preparation of 1,1-diarylethylsulfonamides having substituents
on both of the aryl groups is also possible, as exemplified in entry 13.
The tosyl group on the nitrogen atom of (S)-2b can be easily removed
to give 1,1-diarylethylamine (S)-3 in 86% yield, retaining its enantio-
meric purity (eq 1).
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Table 3. Rhodium-Catalyzed Asymmetric Addition of Sodium
Tetraarylborates to 1: Scope
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entry
1
Ar
product
yield (%)a
ee (%)b
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M. J. Am. Chem. Soc. 2006, 128, 7687.
1
2
3
4
1a
1b
1c
1d
1e
1f
1g
1h
1h
1h
1h
1h
1a
Ph
Ph
Ph
Ph
Ph
Ph
Ph
(S)-2a
(S)-2b
(S)-2c
(S)-2d
(S)-2e
(S)-2f
(R)-2g
(R)-2a
(R)-2b
(R)-2h
(R)-2i
(R)-2c
(S)-2j
83
78
82
82
97
53
64
86
92
91
63
95
75
97
97
94
94
>99.5
98
98
98
98
98
95
98
96
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a Isolated yield. b Determined by chiral HPLC. c The reaction was run
for 48 h with 10 mol % of catalyst. d The reaction was run at 80 °C.
e The reaction was run in THF. f The reaction was run at 90 °C.
In addition to N-tosyl ketimines, the present catalysis has also
been applied to the reaction with N-nosyl ketimines. For example,
a reaction of the N-nosyl imine of 4′-chloroacetophenone (4) with
sodium tetraphenylborate gave addition product 5 in 59% yield with
95% ee (eq 2).
In summary, we have disclosed that rhodium/diene complexes
can effectively catalyze the addition of sodium tetraarylborates to
N-tosyl ketimines. A highly efficient asymmetric variant has also
been described to provide chiral amine derivatives possessing an
R-tetrasubstituted carbon stereocenter by employing chiral diene
(R,R)-L6 as the ligand.
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(18) See Supporting Information for details.
Acknowledgment. Support has been provided by a Grant-in-
Aid for Scientific Research (S) (19105002), the MEXT, Japan.
(19) N-Tosyl imines of 2′-methylacetophenone and 4′-chloropropiophenone do
Supporting Information Available: Experimental procedures and
compound characterization data (PDF) and X-ray data (CIF). This
material is available free of charge via the Internet at http://pubs.acs.org.
not undergo phenylation effectively under the present conditions.
JA106114Q
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