Cyclopropylation of arylamines at the 2-position with cyclopropylmagnesium carbenoids

Article abstract of DOI:10.1016/j.tet.2009.09.096

Direct cyclopropylation of arylamines at the 2-position with 1-chlorocyclopropyl phenyl sulfoxides was achieved. The reaction of N-lithio arylamines with cyclopropylmagnesium carbenoids, which are generated from 1-chlorocyclopropyl phenyl sulfoxides with

Full text of DOI:10.1016/j.tet.2009.09.096

Tetrahedron 65 (2009) 10025–10035
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Cyclopropylation of arylamines at the 2-position
with cyclopropylmagnesium carbenoids
*
Yukie Yamada, Mirai Mizuno, Shinobu Nagamoto, Tsuyoshi Satoh
Graduate School of Chemical Sciences and Technology, Tokyo University of Science; Ichigaya-funagawara-machi 12, Shinjuku-ku, Tokyo 162-0826, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Direct cyclopropylation of arylamines at the 2-position with 1-chlorocyclopropyl phenyl sulfoxides was
achieved. The reaction of N-lithio arylamines with cyclopropylmagnesium carbenoids, which are gen-
erated from 1-chlorocyclopropyl phenyl sulfoxides with i-PrMgCl via the sulfoxide–magnesium exchange
reaction, is the key of this procedure. This method offers an unprecedented way for the synthesis of
arylamines having a cyclopropane ring at the 2-position directly from arylamines.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 27 August 2009
Received in revised form
24 September 2009
Accepted 24 September 2009
Available online 26 September 2009
Keywords:
Magnesium carbenoid
Cyclopropylmagnesium carbenoid
Cyclopropylation
Cyclopropylation of arylamine
2-Cyclopropylated arylamine
1. Introduction
methods have appeared.7 In 2006, we reported that the reaction of
cyclopropylmagnesium carbenoid, generated from 1-chloro-
Arylamines are obviously one of the most important and fun-
damental compounds in organic, synthetic organic, and medicinal
chemistry. Arylamines have long been widely used as the materials
for dyes, medicine, and other chemical products. In view of the
importance of arylamines, innumerable studies have been carried
out concerning their chemistry and synthesis.1
Concerning the alkylation of the aromatic ring of arylamines un-
der the Friedel–Crafts-type reaction, as the treatment of an arylamine
with Lewis acid results in the formation of inactive complex, direct
alkylation of arylamine is known to be difficult.2 An even more dif-
ficult process is the direct cyclopropylation of the aromatic ring under
the Friedel–Crafts-type conditions. As the cyclopropyl carbocations
that were generated under the Friedel–Crafts-type conditions were
known to be rearranged spontaneously to their corresponding allylic
cations,3 direct cyclopropylation of aromatic ring of the arylamines
has not been reported yet. On the other hand, some direct N-cyclo-
propylation of arylamines was reported by the reaction of arylamines
with 1-bromoethoxycyclopropane,4 [(1-ethoxycyclopropyl)oxy]tri-
methylsilane,5 and cyclopropylbismuth reagent.6
cyclopropyl phenyl sulfoxide with i-PrMgCl, with N-lithio aryl-
amines gave
-amino-substituted cyclopropylmagnesiums.8
Protonation of the -amino-substituted cyclopropylmagnesium
a
a
intermediates gave N-cyclopropylated arylamines in good yields.8
In continuation of our study for the reaction of the cyclo-
propylmagnesium carbenoids with arylamines, we found that the
reaction of N-lithio arylamines with cyclopropylmagnesium carbe-
noids having at least one methyl group on the cyclopropane ring
gave 2-cyclopropylated arylamines. As no report has been published
concerning direct cyclopropylation of arylamines on the aromatic
ring, we were highly interested in this reaction and investigated it in
detail. In this paper, we report, in detail, the reaction of N-lithio
arylamines with cyclopropylmagnesium carbenoids having various
substituents 2, derived from 1-chlorocyclopropyl phenyl sulfoxides
1 with i-PrMgCl, to give 2-cyclopropylated arylamines 3 and/or
N-cyclopropylated arylamines 4 (Scheme 1).9
2. Results and discussion
Recently, we are investigating the chemistry and synthetic uses
of cyclopropylmagnesium carbenoids and some new synthetic
2.1. Synthesis of 1-chlorocyclopropyl phenyl sulfoxides 1
At first, various 1-chlorocyclopropyl phenyl sulfoxides 1a–f were
synthesized as shown in Scheme 2. 1-Chlorocyclopropyl phenyl
sulfoxide 1a was synthesized from commercially available cyclo-
propyl phenyl sulfide as reported previously in almost quantitative
* Corresponding author. Tel.: þ81 3 5228 8272; fax: þ81 3 5261 4631.
E-mail address: tsatoh@rs.kagu.tus.ac.jp (T. Satoh).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.096

10026
Y. Yamada et al. / Tetrahedron 65 (2009) 10025–10035
NR5Li
R3
R2
R1
R4
R6
R1
R4
R1
R1
R4
NHR5
R6
R2
R3
R2
R3
R2
R3
i-PrMgCl
Cl
SPh
Cl
MgCl
NR5
+
R4
R6
O
3
1
2
4
Scheme 1.
1a R1=R2=R3=R4=H
R1
R4
R2
R3
1b R1=CH3, R2=R3=R4=H
1c R1=R2=CH3, R3=R4=H
1d R1=R2=CH2CH3, R3=R4=H
1e R1=R2=R3=CH3, R4=H
1f R1=R2=R3=R4=CH3
Cl
SPh
O
OH
1) CH3SO2Cl, TEA, CH2Cl2, 80%
2) LDA, THF, 78%
OH 1) PhSSPh, Bu3P, THF, 69%
H3C
H3C
H3C
2) m-CPBA, CH2Cl2,
S(O)Ph
OH
S(O)Ph
0 °C, 83%
6
5
NCS
H3C
Cl
CCl4, 93%
S(O)Ph
1b
CH2OSO2CH3
Cl
EtOOC
H3C
H3C
COOEt
PhS(O)CHCl2
1) NaBH4, THF-MeOH, 99%
H3C
Cl
2) CH3SO2Cl, TEA, CH2Cl2, 84%
NaHMDS, THF, 84%
S(O)Ph
S(O)Ph
7
8
H3C
H3C
NaBH4
Cl
DMI, 76%
S(O)Ph
1c
CH3
Cl
C2H5
C2H5
C2H5
OH
H3C
H3C
H3C
H3C
COOEt
Cl
C2H5
OH
S(O)Ph
S(O)Ph
1d
1e
9
10
CH3
H3C
H3C
CH3
CH3
Lit. 7a
H3C
H3C
Cl
S(O)Ph
CH3
1f
Scheme 2. Synthesis of 1-chlorocyclopropyl phenyl sulfoxides 1a–f.
11
yield.8 1-Chloro-2-methylcyclopropyl phenyl sulfoxide 1b was syn-
thesized from commercially available 2-methyl-1,3-propanediol as
follows. Thus, one hydroxyl group of the diol was converted to sulfide
group under the conventional reaction to give hydroxyl-sulfide,
which was oxidized with m-chloroperbenzoic acid (m-CPBA) to give
sulfoxide 5. The hydroxyl group of 5 was treated with meth-
anesulfonyl chloride and the resultant mesylate was treated with
2.5 equiv of LDA to give cyclopropyl phenyl sulfoxide 6 as 1:1 mixture
of two diastereomers. Finally, sulfoxide 6 was chlorinated with NCSto
afford the desired product 1b as 1:1 mixture of two diastereomers.
1-Chloro-2,2-dimethylcyclopropyl phenyl sulfoxide 1c was
synthesized from ethyl 2-methylacrylate. Thus, the reaction of ethyl
2-methylacrylate with dichloromethyl phenyl sulfoxide in the
presence of NaHMDS afforded cyclopropane 7 as a single di-
astereomer.10 The ester group of 7 was reduced with NaBH4 in THF
with methanol11 and the resultant hydroxyl group was mesylated
to give 8 in good yield. Finally, the mesyloxy group of 8 was reduced
with NaBH4 in 1,3-dimethyl-2-imidazolidinone (DMI) at 70 ꢀC to
give the desired product 1c in 76%.
1-Chloro-2,2-diethylcyclporopyl phenyl sulfoxide 1d was syn-
thesized from 2,2-diethyl-1,3-propanediol 9 in the same way de-
scribed for the synthesis of 1b. 1-Chloro-2,2,3-trimethylcyclopropyl
phenyl sulfoxide 1e was synthesized from ethyl 2-methylbut-2-
enoate 10 in the same way described for the synthesis of 1c.
1-Chloro-2,2,3,3-tetramethylcyclopropyl phenyl sulfoxide 1f was
synthesized from 2,3-dimethyl-2-butene 11.7a
2.2. Reaction of cyclopropylmagnesium carbenoids 2 with
N-lithio non-substituted arylamines and N-lithio
para-substituted arylamines
As reported previously,8 to a solution of i-PrMgCl (2.5 equiv) in
THF at –78 ꢀC was added a solution of 1a in THF and the reaction
mixture was stirred at the temperature for 10 min to generate
cyclopropylmagnesium carbenoid 2a (Scheme 3). To this was added
a solution of N-lithio N-methyl p-anisidine (2 equiv), generated
from N-methyl p-anisidine with n-BuLi, through a cannula and the
reaction mixture was slowly allowed to warm to ꢁ40 ꢀC for over 1 h

Y. Yamada et al. / Tetrahedron 65 (2009) 10025–10035
10027
R2 R1
N(Li)CH3
H
(2 eq)
R1
i-PrMgCl
(2.5 eq)
NCH3
R1
NHCH3
R2
R1
R2
R2
H
OCH3
Cl
S(O)Ph
Cl
MgCl
+
THF
1
2a R1=R2=H
OCH3
OCH3
13
2b R1=CH3, R2=H
2c R1=R2=CH3
12
Entry
Conditions
13 / Yield%
12 / Yield%
2
0a)
2a
12a 82
12b 25
1
2
3
4
-78 ~ -40 °C
-78 ~ 0 °C
-78 ~ 0 °C
-78 ~ 0 °C
13b 16a)
2b
2c
2c
13c 59a)
13c 60b)
0
0
a) Method A: A solution of N-lithio arylamine was added to a
solution of the cyclopropylmagnesium carbenoid through a
cannular.
b) Method B: The cyclopropylmagnesium carbenoid was
generated in the presence of N-lithio arylamine.
Scheme 3. Reaction of cyclopropylmagnesium carbenoids 2a–c, derived from 1a–c with i-PrMgCl, with N-lithio N-methyl p-anisidine giving N-cyclopropylated and C-cyclo-
propylated N-methyl p-anisidine 12 and 13, respectively.
(Method A). This reaction gave N-cyclopropyl N-methyl p-anisidine
12a in 82% yield (see entry 1 in Scheme 3).8
a similar yield (60%; entry 4 in Scheme 3). Despite the yield was
similar, the operation became easier by using Method B. In some
cases, we used both the Methods A and B, and the better yield will be
reported.
As described above, although the real reason is still not clear, the
reaction with cyclopropylmagnesium carbenoid having one methyl
group on the cyclopropane ring 2b gave both N-cyclopropylated
arylamine 12b and C-cyclopropylated arylamine 13b. In addition,
very interestingly, the reaction with cyclopropylmagnesium carbe-
noid having geminal methyl groups 2c gave only C-cyclopropylated
arylamine 13c. These results were reproduced in the reaction of 2b
and 2c with N-lithio 1-naphthylamine (Scheme 4).
To investigate the generality of this reaction, we carried out this
reaction with cyclopropylmagnesium carbenoid having a methyl
group on the cyclopropane ring 2b, generated from 1b with
i-PrMgCl, with N-lithio N-methyl p-anisidine. This reaction gave the
expected N-cyclopropylated compound 12b (25%) and, somewhat
surprisingly, 2-cyclopropylated N-methyl p-anisidine 13b in 16%
yield (entry 2 in Scheme 3). Interestingly, 12b and 13b were
obtained as single diastereomers and the structure was determined
to be as shown in Scheme 3 by NOESY experiment. Further, the
reaction was carried out with cyclopropylmagnesium carbenoid
R1
R2
NHLi
R1
NH2
NH
R2
R1
(2 eq)
R2
Cl
MgCl
+
THF, -78 ~ 0 °C
2b R1=CH3, R2=H (Method A)
2c R1=R2=CH3 (Method B)
14b (47%)
14c (0%)
15b (22%)
15c (69%)
Scheme 4. Reaction of cyclopropylmagnesium carbenoids 2b and 2c with N-lithio 1-naphthylamine giving N-cyclopropylated and C-cyclopropylated naphthylamines, 14 and 15,
respectively.
having geminal dimethyl groups on the cyclopropane ring 2c. Quite
surprisingly, this reaction only gave 2-cyclopropylated N-methyl
p-anisidine 13c in 59% yield (entry 3 in Scheme 3).
Thus, the reaction of cyclopropylmagnesium carbenoid 2b with
N-lithio 1-naphthylamine gave a mixture of both the N-cyclo-
propylated 1-naphthylamine 14b (47%) and C-cyclopropylated
1-naphthylamine 15b (22%). The reaction of 2c with N-lithio
1-naphthylamine again gave only C-cyclopropylated 1-naphthyl-
amine 15c (69%) as a single product. As mentioned above, no report
was published concerning direct cyclopropylation of arylamines on
the aromatic ring. The results described above are the first exam-
ples of direct cyclopropylation of arylamines on the aromatic ring at
the 2-position.
As transfer of a solution of N-lithio N-methyl p-anisidine in THF
to the solution of cyclopropylmagnesium carbenoid through a can-
nula was a bother, we tried to generate the cyclopropylmagnesium
carbenoid in the presence of N-lithio N-methyl p-anisidine. Thus,
a solution of 1-chloro-2,2-dimethylcyclopropyl phenyl sulfoxide 1c
in THF was added to a solution of N-lithio N-methyl p-anisidine at
ꢁ78 ꢀC. After 10 min, i-PrMgCl (2.5 equiv) was added to the reaction
mixture to generate the cyclopropylmagnesium carbenoid 2c and
the temperature of the reaction mixture was slowly allowed to
warm to 0 ꢀC (Method B). From this treatment, 13c was obtained in
As we were highly interested in the direct cyclopropylation of
arylamines at the 2-position, generality of this reaction was in-
vestigated by using cyclopropylmagnesium carbenoid 2c with

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Y. Yamada et al. / Tetrahedron 65 (2009) 10025–10035
Table 2
various N-lithio non-substituted and para-substituted arylamines.
The results are summarized in Table 1. N-Methylaniline and
N-phenylaniline (diphenylamine) gave moderate yields of the
desired 2-cyclopropylated products 16a and 16b (entries 1 and 2).
The Method B was effective in the case of the reaction with
N-phenylaniline (compare entries 2 and 3). p-Anisidine and its
derivatives gave variable yields (entries 4–6).
Reaction of cyclopropylmagnesium carbenoids 2d–f with N-lithio arylamines under
Method B giving 2-cyclopropylated arylamines 17
N(Li)H
NH2
Method B
Cl
MgCl
R1
R1
+
X
X
THF
-78 ~ 0 °C
(2 eq)
2
17
Table 1
Reaction of cyclopropylmagnesium carbenoid 2c with N-lithio arylamines giving
2-cyclopropylated arylamines 16
Entry
2
Arylamine
17/Yield/%
17a/35
NH2
N(Li)R
C2H5
C2H5
Cl
MgCl
CH3
NHR
CH3
1
2
(2 eq)
X
H3C
H3C
Cl
NMe2
2d
X
MgCl
THF
4-(dimethylamino)aniline
2c
-78 ~ 0 °C
16
NH2
Entry
Arylamine
NHR
16/Yield/%
2d
17b/55
1
2
3
R¼CH3
R¼Ph
R¼Ph
16a/40a
16b/50a
16b/69b
1-naphthylamine
NH2
NHR
3
4
2d
17c/38
17d/44
4
5
6
R¼H
16c/26a
13c/59a
16d/22a
R¼CH3
R¼Bn
1-aminoanthracene
CH3
H3C
H3C
OCH3
Cl
MgCl
4-(Dimethylamino)aniline
NHCH3
2e
2e
2e
7
16e/9a
5
6
1-Naphthylamine
1-Aminoanthracene
17e/47
17f/65
CH3
Cl
H3C
H3C
Cl
MgCl
NHR
7
4-(Dimethylamino)aniline
17g/15
8
9
R¼H
16f/58b
16g/64a
CH3
R¼CH3
2f
8
9
2f
2f
1-Naphthylamine
1-Aminoanthracene
17h/43
17i/56
N(CH3)2
NHCH3
10
16h/22a
16i/70a
2.3. Reaction of cyclopropylmagnesium carbenoid 2c with
meta-substituted arylamines, ortho-substituted arylamines,
and nitrogen-containing heterocyclic compounds
NH2
11
We next investigated the reaction of cyclopropylmagnesium
carbenoid 2c with N-lithio meta-substituted arylamines. The re-
action must be interesting because two regioisomers would be
expected to be formed. We studied the reactivity and regiose-
lectivity of the reaction of cyclopropylmagnesium carbenoid 2c
with eight N-lithio meta-substituted arylamines under Method B
and the results are summarized in Table 3.
The reaction with N-lithio m-anisidine gave, as expected, two
C-cyclopropylated arylamines 18a and 19a and the main product
was proved to be 2-cyclopropylated m-anisidine 18a (entry 1). The
reaction with N-lithio N-methyl m-anisidine again gave 2-cyclo-
propylated N-methyl m-anisidine 18b as the main product (entry
2). The yield was found to be higher when the nitrogen of N-lithio
m-anisidine has a methyl group.
a
The reaction was conducted under Method A.
The reaction was conducted under Method B. In this experiment both the
b
methods were applied and the better yields were shown in this table.
N-Methyl p-chloroaniline gave the desired product 16e in only 9%
with corresponding N-cyclopropylated compound (15%). This result
suggested that the presence of an electron-withdrawing group on
the aromatic ring retard the C-cyclopropylation. In contrast to this, it
was suggested that the presence of an electron-donating group
(dimethylamino group) on the aromatic ring activated the C-cyclo-
propylation (entries 8 and 9). Interestingly, 1-aminoanthracene gave
the best yield in Table 1 (entry 11).
Table 2 shows the results for the reaction of cyclopropyl-
magnesium carbenoids having geminal ethyl groups 2d, trimethyl
groups 2e and tetramethyl groups 2f with 4-(dimethylamino)aniline,
1-naphthylamine, and 1-aminoanthracene. As shown in Table 2, the
yields were about 40 to 65%, except in the case of 4-(dimethyl-
amino)aniline with 2f (entry 7). The reaction of 1-naphthylamine and
1-aminoanthracene again gave somewhat better yields compared
with that of the aniline derivatives.
The results shown in entries 3–6 indicate that the reaction of
m-methylaniline and even m-chloroaniline showed the similar
regioselectivity, except the result in entry 3. The yields were again
better when the nitrogen of N-lithio anilines has a methyl group.
N-Lithio anilines having a trifluoromethyl group at the meta-position
showed quite low reactivity toward 2c (entries 7 and 8). From these
results, it was implied that the presence of a strong electron-with-
drawing group on the aromatic ring retards the cyclopropylation.

Y. Yamada et al. / Tetrahedron 65 (2009) 10025–10035
10029
Table 3
charge (for details, see Ref. 13). The regioselectivity observed in the
presented reactions could again be rationalized from the charge of
the N-lithio meta-substituted arylamines.
Reaction of cyclopropylmagnesium carbenoid 2c with N-lithio meta-substituted
arylamines under Method B giving 2-cyclopropylated arylamines 18 and 19
N(Li)R
Next, the reaction of cyclopropylmagnesium carbenoid 2c with
N-lithio ortho-substituted arylamines was investigated and the results
are summarized inTable 4. Very interestingly, as shown in Table 4, the
reactions of 2c with N-lithio ortho-substituted arylamines without
substituent on the nitrogen gave 6-cyclopropylated products 20a and
20b as only isolable products, though the yields were variable (entries
1 and 2). On the other hand, the reactions of 2c with N-lithio ortho-
substituted amines with a methyl group on the nitrogen gave
N-cyclopropylated products 21a-c in up to 42% yield (entries 3–5).
NHR
CH3
CH3
CH3
NHR
CH3
H3C
(2 eq)
H3C
X
Cl
MgCl
Et2O
X
X
2c
18
19
-78 °C ~ r.t.
Entry
Arylamine
18/Yield/%
19/Yield/%
X
R
Table 4
1
2
3
4
5
6
7
8
OCH3
OCH3
CH3
CH3
Cl
Cl
CF3
CF3
H
CH3
H
CH3
H
CH3
H
18a/23
18b/52
18c/16
18d/23
18e/17
18f 29
18g/0
19a/17
19b/21
19c/21
19d/19
19e/8
Reaction of cyclopropylmagnesium carbenoid 2c with N-lithio ortho-substituted
arylamines under Method B giving 2-cyclopropylated arylamines 20 or N-cyclo-
propylated arylamine 21
N(Li)R
H3C
19f/16
19g/9
X
H3C
CH3
NHR
NR
CH3
H3C
(2 eq)
CH3
Complex mixture
H3C
X
X
Cl
Cyclopropylmagnesium carbenoid 2c was generated from 1c with 3 equiv of
i-PrMgCl in diethyl ether at ꢁ78 ꢀC.
MgCl
THF
-78 ~ 0 °C
2c
20
21
The regioselectivity mentioned above is quite interesting. It is
usually said that electrophilic aromatic substitution (such as Frie-
del–Crafts-type alkylation) of meta-substituted aromatic com-
pounds at the 2-position is very difficult because of the position is
too hindered.12 However, as shown in Table 3, our reaction of 2c
with N-lithio meta-substituted anilines gave 2-substituted products
selectively as a main product.
We have observed the similar phenomena in our study for the
reaction of magnesium alkylidene carbenoids with N-lithio meta-
substituted arylamines.13 The reaction gave 2-alkenylated arylamines
as the main products. In order to have the better understanding of
these phenomena, the electrostatic potential-derived charges of
some N-lithio meta-substituted arylamines were calculated and it
was found that the carbon at the 2-position has more negative atom
Entry
Arylamine
20/Yield/%
21/Yield/%
X
R
1
2
3
4
5
CH3
Cl
OCH3
CH3
Cl
H
H
CH3
CH3
CH3
20a/40
20b/14
0
0
0
0
0
21a/37
21b/42
21c/22
Cyclopropylmagnesium carbenoid 2c was generated from 1c with 2.5 equiv of
i-PrMgCl in THF at ꢁ78 ꢀC.
These quite interesting differences for the selective C- and
N-cyclopropylation described in Table 4, and the mechanism of
this reaction are explained as follows (Scheme 5). Thus, N-lithio
CH3
H3C
Cl
H
MgCl
2c
N
N(Li)H
CH3
CH3
NH2
H3C
Li
CH3
CH3
40%
A
20a
CH3
H3C
Cl
MgCl
H3C CH3
2c
H3C Li
N
H3C
Li
N(Li)CH3
CH3
N
NCH3
CH3
CH3
CH3
42%
21b
C
B
CH3
H3C
2c
Cl
MgCl
Li
H
N
CH2
N
CH2
CH3
CH2
N
H3C
Li
54%
22
D
23
Scheme 5. Reaction of cyclopropylmagnesium carbenoid 2c with N-lithio 2-methylanilines and N-lithio indoline 22 giving N-cyclopropylated and C-cyclopropylated products 21b
and 23, respectively. Rationalization for the N- and C-cyclopropylation.

10030
Y. Yamada et al. / Tetrahedron 65 (2009) 10025–10035
o-toluidine is present in the resonance form, lithium
a
-imino
removal of the solvent in vacuo, the product was purified by silica
gel column chromatography to afford a sulfide (2.52 g; 69%) as
colorless oil. IR (neat) 3366 (OH), 2959, 2926, 1584, 1481, 1439,
carbanion A. The carbanion attacks at the carbenoid carbon of 2c to
give ortho-cyclopropylated o-toluidine 20a. On the other hand,
N-lithio N-methyl o-toluidine is present in the resonance form,
1026, 739 cmꢁ1
;
1H NMR
d
1.05 (3H, d, J¼6.7 Hz), 1.56 (1H, br s),
lithium
a-imino carbanion B, in which the methyl group on the
1.91–2.00 (1H, m), 2.85 (1H, dd, J¼12.9, 9.8 Hz), 3.07 (1H, dd,
J¼12.9, 9.8 Hz), 3.59–3.62 (2H, m), 7.16–7.18 (1H, m), 7.22 (2H, d,
J¼7.3 Hz), 7.30–7.35 (2H, m); MS m/z (%) 182 (Mþ, 69), 123 (39), 111
(15), 110 (100). Calcd for C10H14OS: M, 182.0764. Found: m/z
182.0761.
nitrogen must be placed away from the methyl group on the aromatic
ring. As the result, the carbanion is highly hindered by the methyl
group on the nitrogen and the attack of the carbanion to the carbe-
noid carbon must be prevented. This case, N-lithio form C reacts with
2c to give N-cyclopropylated product 21b.
To a solution of the sulfide (2.41 g; 13.2 mmol) in 50 ml of
CH2Cl2 at 0 ꢀC was added m-chloroperbenzoic acid (70% purity;
3.58 g; 14.5 mmol) and the reaction mixture was stirred at 0 ꢀC for
30 min. The reaction was quenched with aq Na2SO3 and the organic
layer was separated. The aqueous layer was extracted with CH2Cl2
and the combined organic layer was washed with 5% aq NaOH
followed by brine. The product was purified by silica gel column
chromatography to give sulfoxide 5 as colorless oil (about 1:1.3
mixture of two diastereomers). IR (neat) 3401 (OH), 2969, 2928,
1647, 1444, 1018 (SO), 752 cmꢁ1; MS m/z (%) 198 (Mþ, 2), 126 (100),
110 (20). Calcd for C10H14O2S: M, 198.0714. Found: m/z 198.0719.
To a solution of 5 (2.2 g; 11.1 mmol) in 27 ml of CH2Cl2 at 0 ꢀC
was added triethylamine (1.84 ml; 13.2 mmol) dropwise with stir-
ring. After 10 min, methanesulfonyl chloride (1.5 ml; 13.2 mmol)
The evidence for this assumption is obtained from the reaction
of N-lithio indoline 22 with cyclopropylmagnesium carbenoid 2c.
This reaction gave ortho-cyclopropylated indoline 23 in 54% yield
without any N-cyclopropylated compound. N-Lithio indoline 22 has
alkyl groups on the nitrogen and on the aromatic ring at the ortho-
position; however, as the alkyl groups are bound, the carbanionic
carbon in the resonance form D is not hindered by the alkyl group.
From resonance form D, C-cyclopropylated product 23 was formed.
Finally, the reaction of 2c with N-lithio phenothiazine and
N-lithio phenoxazine was investigated (Scheme 6). These reactions
gave a mixture of N- and C-cyclopropylated compounds 25 and 26
in 40–50% yields and the main products were found to be
N-cyclopropylated ones 25.
CH3
CH3
CH3
CH3
CH3
H3C
Cl
Li
H
N
MgCl
N
2c
N
X
+
X
X
26a X=S (14%)
b X=O (22%)
25a X=S (30%)
b X=O (34%)
24a X=S
b X=O
Scheme 6. Reaction of cyclopropylmagnesium carbenoid 2c with N-lithio phenothiazine and N-lithio phenoxazine.
In conclusion, we found, for the first time, the reaction of
was added and the reaction mixture was stirred at 0 ꢀC for 30 min.
The reaction was quenched with water and the whole was
extracted with CHCl3. The product was purified by short pad of
silica gel to give mesylate (2.43 g; 80%) as colorless oil and it was
used without further purification.
To a solution of LDA (31.5 mmol) in 30 ml of THF at 0 ꢀC was
added a solution of the mesylate (3.5 g; 12.7 mmol) in 30 ml of THF
dropwise with stirring. The reaction mixture was stirred at 0 ꢀC for
30 min and the reaction was quenched by adding satd aq NH4Cl.
The whole was extracted with CHCl3 and the organic layer was
dried over MgSO4. The solvent was removed in vacuo and the
residue was purified by silica gel column chromatography to afford
cyclopropane 6 (1.78 g; 78%).
cyclopropylmagnesium carbenoids 2, generated from 1-chloro-
cyclopropyl phenyl sulfoxides 1 with i-PrMgCl, with N-lithio aryl-
amines gave 2-cyclopropylated arylamines 3 in moderate yields.
We are still uncertain of the reason why the C-cyclopropylation
needs at least one substituent on the cyclopropane ring; however,
the chemistry described in this paper contributes to a synthesis of
2-cyclopropylated arylamines directly from arylamines and to the
chemistry of cyclopropanes.14
3. Experimental
3.1. General
To a solution of 6 (1.78 g; 9.9 mmol) in 30 ml of CCl4 was added
N-chlorosuccinimide (1.47 g; 11 mmol) and the reaction mixture
was stirred at room temperature for overnight. The precipitate was
filtered off and the solvent was removed to give a residue, which
was purified by silica gel column chromatography to give 1b as
colorless oil (1:1 mixture of two diastereomers). IR (neat) 3061,
Melting points were measured on a Yanaco MP-S3 apparatus
and are uncorrected. 1H NMR spectra were measured in a CDCl3
solution with JEOL JNM-LA 500 and BRUKER UltraShield 400, 300
spectrometer. IR spectra were recorded on a Perkin–Elmer spec-
trum One FTIR instrument. Electron-impact mass spectra (MS)
were obtained at 70 eV by direct insertion with JEOL JMS-SX102A.
Silica gel 60N (KANTO CHEMICAL) containing 0.5% fluorescence
reagent 254 and a quartz column were used for column chromato-
graphy and the products having UV absorption were detected by UV
irradiation. In experiments requiring a dry solvent and reagent,
diethyl ether, and THF were distilled from diphenylketyl.
2968, 1444, 1306, 1088, 1056 (SO), 749 cmꢁ1; 1H NMR
d 0.81 (0.5H,
dd, J¼7.7, 6.6 Hz), 0.99 (0.5H, dd, J¼7.7, 6.7 Hz), 1.20 (1.5H, d,
J¼6.1 Hz), 1.29 (1.5H, d, J¼6.1 Hz), 1.74–1.78 (1H, m), 1.82–1.94 (1H,
m), 7.51–7.58 (3H, m), 7.69–7.70 (2H, m). MS m/z (%) 214 (Mþ, 11),
126 (100), 89 (21), 78 (53), 77 (22), 53 (51). Calcd for C10H11ClOS: M,
214.0219. Found: m/z 214.0213.
3.1.2. 1-Chloro-2,2-dimethylcyclopropyl phenyl sulfoxide (1c). To
a solution of ethyl 2-methylacrylate (1.38 ml; 9.6 mmol) and
dichloromethyl phenyl sulfoxide (2.0 g; 9.6 mmol) in 24 ml of THF
at –78 ꢀC was added a solution of NaHMDS (2.0 mol/L solution;
7.2 ml; 14.4 mmol) dropwise with stirring. The temperature of the
3.1.1. 1-Chloro-2-methylcyclopropyl phenyl sulfoxide (1b). To a solu-
tion of 2-methyl-1,3-propanediol (1.8 g; 20 mmol) and diphenyl
disulfide (2.4 g; 11 mmol) in 100 ml of THF was added with stirring
tributylphosphine (2.43 g; 12 mmol) at room temperature. The
reaction mixture was stirred at room temperature for 2 h. After

Y. Yamada et al. / Tetrahedron 65 (2009) 10025–10035
10031
reaction mixture was slowly allowed to warm to 0 ꢀC for 2 h. The
reaction was quenched by adding satd aq NH4Cl and the whole was
extracted with CHCl3. The product was purified by silica gel column
chromatography to give cyclopropylsulfoxide 7 (2.32 g; 84%) as
colorless oil. IR (neat) 2982, 1728 (CO), 1445, 1305, 1180, 1096, 1057
of i-PrMgCl (1.0 mol/L; 0.5 mmol) in 0.5 ml of dry THF in a flame-
dried flask at ꢁ78 ꢀC under argon atmosphere was added a so-
lution of 1b (36.4 mg, 0.2 mmol) in 0.8 ml of dry THF dropwise
with stirring and the reaction mixture was stirred for 10 min to
give cyclopropylmagnesium carbenoid 2b. In another flame-dried
flask, n-BuLi (0.4 mmol) was added to a solution of N-methyl
p-anisidine (0.4 mmol) in 0.5 ml of dry THF at ꢁ78 ꢀC to give
N-lithio N-methyl p-anisidine. This solution was added to the
solution of 2b through a cannula. The temperature of the reaction
mixture was slowly allowed to warm to 0 ꢀC. The reaction was
quenched by satd aq NH4Cl and the whole was extracted with
AcOEt. The organic layer was washed once with water and dried
over MgSO4. After removal of the solvent, the product was pu-
rified by silica gel column chromatography to give 12b (9.5 mg,
25%) and 13b (6.1 mg, 16%). 12b: Colorless oil; IR (neat) 2928,
(SO), 858, 748 cmꢁ1
;
1H NMR
d
1.34 (3H, t, J¼7.0 Hz), 1.40 (1H, d,
J¼7.3 Hz), 1.56 (3H, s), 2.67 (1H, d, J¼7.3 Hz), 4.27 (2H, q, J¼7.0 Hz),
7.51–7.55 (3H, m), 7.65–7.69 (2H, m). MS m/z (%) 286 (Mþ, 9), 241
(24), 161 (65), 133 (100), 126 (54), 105 (25). Calcd for C13H15ClO3S:
M, 286.0430. Found: m/z 286.0429.
To a solution of 7 (2.86 g; 10 mmol) in 25 ml of THF was added
NaBH4 (0.43 g; 11.5 mmol) and the mixture was heated at reflux for
30 min. During this heating, methanol (2.5 ml) was added dropwise
to the reaction mixture. The reaction was quenched by adding satd
aq NH4Cl and the whole was extracted with CHCl3. The product was
purified by silica gel column chromatography to give an alcohol
1512, 1246, 1044, 819 cmꢁ1; 1H NMR
d
0.53 (1H, q, J¼5.8 Hz), 0.75
(2.44 g; 99%) as crystals. 1H NMR
d
1.20 (1H, d, J¼7.3 Hz), 1.48 (3H,
(1H, m), 0.88–0.96 (1H, m), 1.16 (3H, d, J¼6.4 Hz), 1.95 (1H, m),
2.89 (3H, s), 3.77 (3H, s), 6.84 (2H, d, J¼9.2 Hz), 6.89 (2H, d,
J¼9.2 Hz). MS m/z (%) 191 (Mþ, 34), 190 (20), 176 (100), 160 (15),
135 (18), 121 (19). Calcd for C12H17NO: M, 191.1309. Found: m/z
191.1310. 13b: Colorless oil; IR (neat) 3430 (NH), 2952, 1506, 1419,
s), 1.95 (1H, d, J¼7.3 Hz), 2.63 (1H, t, J¼5.8 Hz, OH), 3.86 (1H, m),
4.10 (1H, m), 7.54 (3H, m), 7.81 (2H, m).
To a solution of the alcohol (2.44 g; 9.98 mmol) in 20 ml of CH2Cl2
was added triethylamine (1.1 ml; 10.3 mmol) at 0 ꢀC with stirring.
After 10 min, methanesulfonyl chloride (11 mmol) was added to the
reaction mixture and the whole mixture was stirred at 0 ꢀC for
30 min. The reaction was quenched by adding satd aq NH4Cl and the
whole was extracted with CHCl3. The product was purified by silica
gel column chromatography to afford mesylate 8 (2.43 g; 84%) as
colorless oil. The mesylate was used immediately in the next step.
To a solution of 8 (71 mg; 0.24 mmol) in 0.8 ml of 1,3-dimethyl-
2-imidazolidinone was added NaBH4 (11 mg; 0.3 mmol) and the
reaction mixture was stirred and heated at 70 ꢀC for 30 min. The
reaction was quenched by adding satd aq NH4Cl and the whole was
extracted with CHCl3. The product was purified by silica gel column
chromatography to give 1c (42 mg; 76%) as colorless crystals. Mp.
66–70 ꢀC (AcOEt–hexane); IR (KBr) 3069, 2959, 1478, 1086, 1049
1286, 1219, 1154, 1035, 798, 757 cmꢁ1 1H NMR
; d 0.64 (1H, m),
0.77 (1H, m), 0.92–0.99 (1H, m), 1.25 (3H, d, J¼6.1 Hz), 1.30–1.34
(1H, m), 2.89 (3H, s), 3.74 (3H, s), 6.54 (1H, d, J¼8.6 Hz), 6.65 (1H,
d, J¼2.7 Hz), 6.72 (1H, dd, J¼8.6, 2.7 Hz). MS m/z (%) 191 (Mþ, 78),
176 (100), 160 (28), 148 (13), 136 (12). Calcd for C12H17NO: M,
191.1309. Found: m/z 191.1302.
3.1.7. N-Methyl-2-(2,2-dimethylcyclopropyl)-para-anisidine (13c)
3.1.7.1. Method A. To
a solution of i-PrMgCl (1.0 mol/L;
0.5 mmol) in 0.5 ml of dry THF in a flame-dried flask at ꢁ78 ꢀC under
argon atmosphere was added a solution of 1c (45.7 mg, 0.2 mmol) in
0.8 ml of dry THF dropwise with stirring and the reaction mixture
was stirred for 10 min to give cyclopropylmagnesium carbenoid 2c.
In another flame-dried flask, n-BuLi (0.4 mmol) was added to a so-
lution of N-methyl p-anisidine (54.8 mg, 0.4 mmol) in 0.5 ml of dry
THF at ꢁ78 ꢀC under argon atmosphere to give N-lithio N-methyl
p-anisidine. This solution was added to a solution of the magnesium
cyclopropylidene 2c through a cannula. Temperature of the reaction
mixture was gradually allowed to warm to 0 ꢀC. The reaction was
quenched by satd aq NH4Cl and the whole was extracted with ethyl
acetate. The organic layer was washed once with water and dried
over MgSO4. After removal of the solvent, the product was purified
by silica gel column chromatography to give 13c (24.2 mg, 59%) as
a colorless oil; IR (neat) 3431 (NH), 2938, 1510, 1452, 1285, 1216,
(SO), 753 cmꢁ1
;
1H NMR
d
1.33 (1H, d, J¼6.8 Hz), 1.35 (3H, s), 1.58
(3H, s), 1.90 (1H, d, J¼6.8 Hz), 7.24–7.56 (3H, m), 7.64–7.67 (2H, m).
MS m/z (%) 228 (Mþ, 5), 211 (12), 170 (7), 126 (100), 103 (29). Calcd
for C11H13ClOS: M, 228.0374. Found; m/z 228.0368. Anal. Calcd for
C11H13ClOS: C, 57.76; H, 5.73; Cl, 15.50; S, 14.02. Found: C, 57.77; H,
5.68; Cl, 15.44; S, 14.00.
3.1.3. 1-Chloro-2,2-diethylcyclopropyl phenyl sulfoxide (1d). Colorless
crystals; mp 100–101 ꢀC (AcOEt–hexane); IR (KBr) 3061, 2972, 1443,
1089, 1055 (SO), 748, 691 cmꢁ1; 1H NMR
d
1.02 (3H, t, J¼7.0 Hz), 1.11
(1H, d, J¼6.9 Hz), 1.12 (3H, t, J¼7.0 Hz), 1.44 (1H, d, J¼6.9 Hz), 1.70
(2H, m), 1.95 (2H, m), 7.51–7.55 (3H, m), 7.64–7.69 (2H, m). Anal.
calcd for C13H17ClOS: C, 60.80; H, 6.67; Cl, 13.81; S, 12.49. Found; C,
60.83; H, 6.70; Cl, 13.67; S, 12.42.
1168, 1053, 1033, 800 cmꢁ1 1H NMR
; d 0.74 (1H, m), 0.76 (3H, s),
0.79–0.83 (1H, m), 1.30 (3H, s), 1.49 (1H, dd, J¼8.3, 5.8 Hz), 2.88 (3H,
s), 3.61 (1H, br s), 3.74 (3H, s), 6.55 (1H, d, J¼8.6 Hz), 6.62 (1H, d,
J¼3.1 Hz), 6.72 (1H, dd, J¼8.6, 3.1 Hz). MS m/z (%) 205 (Mþ, 100), 190
(67),175 (18),174 (23),162 (28),160 (27),150 (32),148 (27). Calcd for
C13H19NO: M, 205.1465. Found: m/z 205.1452.
3.1.4. 1-Chloro-2,2,3-trimethylcyclopropyl phenyl sulfoxide (1e).
Colorless crystals; mp 54.5–55 ꢀC (AcOEt–hexane); IR (KBr) 3063,
2962, 2929, 1442, 1078, 1054 (SO), 749, 689 cmꢁ1 1H NMR
; d 1.14
(3H, s), 1.20 (3H, d, J¼6.0 Hz), 1.56 (3H, s), 1.94 (1H, q, J¼6.0 Hz),
7.51–7.62 (3H, m), 7.64–7.67 (2H, m). Anal. calcd for C12H15ClOS: C,
59.37; H, 6.23; Cl, 14.60; S, 13.21. Found; C, 59.36; H, 6.24; Cl, 14.47;
S, 13.13.
3.1.7.2. Method B. To
a solution of N-methyl p-anisidine
(0.4 mmol) in 0.5 ml of dry THF in a flame-dried flask at 0 ꢀC
under argon atmosphere was added n-BuLi (0.4 mmol) dropwise
with stirring. The reaction mixture was cooled to ꢁ78 ꢀC and
a solution of 1c (45.7 mg, 0.2 mmol) in 0.8 ml of dry THF was
added dropwise with stirring. After 10 min, i-PrMgCl (1.0 mol/L;
0.5 mmol) was added to the reaction mixture and the tempera-
ture of the reaction mixture was slowly allowed to warm to 0 ꢀC.
The reaction was quenched by satd aq NH4Cl and the whole was
extracted with AcOEt. The organic layer was washed once with
water and dried over MgSO4. After removal of the solvent, the
product was purified by silica gel column chromatography to give
13c (24.5 mg, 60%).
3.1.5. 1-Chloro-2,2,3,3-tetramethylcyclohexyl phenyl sulfoxide (1f).
Colorless crystals; mp 103–105 ꢀC (AcOEt–hexane); IR (KBr) 3071,
2994, 2958, 2923, 1442, 1380, 1085, 1052 (SO), 754, 688 cmꢁ1 1H
;
NMR
d 1.17, 1.30, 1.57, 1.70 (each 3H, s), 7.50–7.55 (3H, m), 7.60–
7.64 (2H, m). Anal. calcd for C13H17ClOS: C, 60.80; H, 6.67; Cl,
13.81; S, 12.49. Found; C, 60.82; H, 6.73; Cl, 13.78; S, 12.56.
3.1.6. N-(2-Methylcyclopropyl)-N-methyl-para-anisidine (12b) and
N-Methyl-2-(2-methylcyclopropyl)-para-anisidine (13b). To a solution

10032
Y. Yamada et al. / Tetrahedron 65 (2009) 10025–10035
3.1.8. N-Cyclopropyl-N-(4-methoxyphenyl)methylamine (12a).
190 (100), 148 (35), 91 (52). Calcd for C19H23NO: M, 281.1778.
Found: m/z 281.1782.
Colorless oil; IR (neat) 3004, 2933, 1513, 1455, 1361, 1245, 1040,
818 cmꢁ1; 1H NMR
d 0.58 (2H, m), 0.77 (2H, m), 2.27 (1H, m), 2.29
(3H, s), 3.77 (3H, s), 6.84 (2H, d, J¼9.2 Hz), 6.97 (2H, d, J¼9.2 Hz). MS
m/z (%) 177(Mþ, 100), 176(60), 162(80), 146(18), 134(16), 121(57).
Calcd for C11H15NO: M, 177.1154. Found: m/z 177.1135.
3.1.16. [4-Chloro-2-(2,2-dimethylcyclopropyl)phenyl]methylamine
(16e). Colorless oil; IR (neat) 3446 (NH), 2926, 1601, 1510, 1408,
1322, 1165, 805 cmꢁ1 1H NMR
; d 0.73–0.76 (1H, m), 0.76 (3H, s),
0.83 (1H, dd, J¼8.3, 6.5 Hz), 1.30 (3H, s), 1.41 (1H, dd, J¼8.3, 5.5 Hz),
2.89 (3H, s), 3.90 (1H, br s), 6.50 (1H, d, J¼8.6 Hz), 6.92 (1H, d,
J¼2.5 Hz), 7.08 (1H, dd, J¼8.6, 2.5 Hz). MS m/z (%) 209 (Mþ,100),194
(52), 174 (38), 159 (40), 154 (74), 152 (43), 117 (38). Calcd for
C12H16NCl: M, 209.0971. Found: m/z 209.0971.
3.1.9. N-(2-Methylcyclopropyl)naphtalen-1-ylamine(14b). Yellow oil;
IR (neat) 3403 (NH), 2951, 1732, 1582, 1523, 1448, 1406, 1096,
770 cmꢁ1 1H NMR
; d 0.60 (1H, m), 0.78–0.84 (1H, m), 0.94–1.01
(1H, m), 1.22 (3H, d, J¼6.0 Hz), 2.22–2.27 (1H, m), 4.81 (1H, br s),
6.93 (1H, dd, J¼9.0, 1.0 Hz), 7.25 (1H, d, J¼9.0 Hz), 7.39–7.45 (3H,
m), 7.69 (1H, d, J¼7.0 Hz), 7.78 (1H, d, J¼7.0 Hz). This product is
somewhat unstable and reliable data for the mass spectrum could
not be obtained.
3.1.17. 2-(2,2-Dimethylcyclopropyl)-N4,N4-dimethylbenzene-1,4-di-
amine (16f). Colorless oil; IR (neat) 3449 (NH), 3364 (NH), 2926,
2856, 1603, 1508 cmꢁ1 1H NMR
; d 0.66–0.74 (2H, m), 0.75 (3H, s),
1.23 (3H, s), 1.49–1.52 (1H, m), 2.72 (6H, s), 3.24 (2H, br s), 6.45 (1H,
d, J¼2.4 Hz), 6.50 (1H, dd, J¼8.4, 6.5 Hz), 6.55 (1H, d, J¼8.4 Hz). MS
m/z (%) 204(Mþ, 100), 203 (26), 187 (5), 173 (5), 160 (5), 159 (4), 149
(4). Calcd for C13H20N2: M, 204.1626. Found: m/z 204.1633.
3.1.10. 2-(2-Methylcyclopropyl)naphthalen-1-ylamine (15b). Yellow
crystals; mp 100–101 ꢀC (hexane); IR (KBr) 3435 (NH), 3341 (NH),
3054, 2948, 1620, 1400, 806, 799, 739 cmꢁ1 1H NMR
; d 0.71–0.78
(1H, m), 0.85–0.91 (1H, m), 1.02–1.12 (1H, m), 1.32 (3H, d, J¼5.9 Hz),
1.51–1.57 (1H, m), 4.43 (2H, br s), 7.23–7.24 (2H, m), 7.36–7.45 (2H,
m), 7.73–7.81 (2H, m). MS m/z (%) 197 (Mþ, 100), 182 (63), 165 (20),
156 (12). Calcd for C14H15N: M, 197.1204. Found: m/z 197.1206.
3.1.18. 2-(2,2-Dimethylcyclopropyl)-N1,N4,N4-trimethylbenzene-1,4-
diamine (16g). Colorless oil; IR (neat) 3429 (NH), 3061, 2940, 1515,
1312, 1226, 799, 355 cmꢁ1 1H NMR
; d 0.73–0.77 (1H, m), 0.77 (3H,
s), 0.79–0.82 (1H, m), 1.30 (3H, s), 1.48–1.52 (1H, m), 2.81 (6H, s),
2.88 (3H, s), 3.40 (1H, br s), 6.56–6.62 (2H, m), 6.69 (1H, m). MS m/z
(%) 218 (Mþ, 100), 203 (22), 188 (12), 173 (17), 160 (21), 146 (8), 117
(8). Calcd for C14H22N2: M, 218.1781. Found: m/z 218.1781.
3.1.11. 2-(2,2-Dimethylcyclopropyl)naphthalen-1-ylamine
Colorless crystals; mp 188–189 ꢀC (AcOEt–hexane); IR (KBr) 3300
(NH), 3196 (NH), 2950, 1634, 1393, 1365, 1090, 806, 745 cmꢁ1 1H
NMR
1.36 (3H, s), 1.72 (1H, dd, J¼8.6, 5.8 Hz), 4.32 (2H, br s), 7.18 (1H, d,
J¼11.0 Hz), 7.25 (1H, d, J¼12.0 Hz), 7.36–7.46 (2H, m), 7.75–7.82
(2H, m). Anal. calcd for C15H17N: C, 85.26; H, 8.11; N, 6.63. Found;
C, 85.32; H, 8.06; N, 6.59.
(15c).
;
d
0.82 (3H, s), 0.83–0.89 (1H, m), 0.92 (1H, dd, J¼8.6, 4.5 Hz),
3.1.19. [2-(2,2-Dimethylcyclopropyl)naphthalen-1-yl]methylamine
(16h). Yellow oil; IR (neat) 3388 (NH), 3057, 2941, 2885, 1613, 1568,
1509, 1450, 1376, 1122, 830, 807, 748 cmꢁ1 1H NMR
; d 0.79 (3H, s),
0.87–0.98 (2H, m), 1.37 (3H, s), 1.85 (1H, dd, J¼8.4, 6.0 Hz), 3.03 (3H,
d, J¼1.9 Hz), 3.91 (1H, br s), 7.19 (1H, d, J¼8.4 Hz), 7.35–7.48 (3H, m),
7.79 (1H, d, J¼4.1 Hz), 8.13 (1H, d, J¼8.4 Hz). MS m/z (%) 225 (Mþ,
43), 210 (100), 195 (19), 180 (36), 168 (66), 141 (11), 115 (10), 28 (22).
Calcd for C16H19N: M, 225.1517. Found: m/z 225.1516.
3.1.12. N-[2-(2,2-Dimethylcyclopropyl)phenyl]methyl-amine (16a).
Colorless oil; IR (neat) 3443 (NH), 3066, 2939, 1606, 1582, 1514,
1461, 1321, 1166, 746 cmꢁ1; 1H NMR
d 0.73–0.76 (1H, m), 0.76 (3H,
s), 0.81 (1H, dd, J¼8.3, 4.3 Hz), 1.31 (3H, s), 1.46 (1H, dd, J¼8.3,
5.8 Hz), 2.91 (3H, s), 3.93 (1H, br s), 6.61 (1H, d, J¼7.9 Hz), 6.65 (1H,
dt, J¼7.3, 0.9 Hz), 6.97 (1H, d, J¼7.3 Hz), 7.15 (1H, m). MS m/z (%)
175 (Mþ, 100), 160 (73), 132 (57), 130 (34), 120 (58), 118 (58), 91
(28). Calcd for C12H17N: M, 175.1359. Found: m/z 175.1351.
3.1.20. 2-(2,2-Dimethylcyclopropyl)anthracen-1-ylamine(16i). Orange
crystals; mp 120 ꢀC (Hexane); IR (KBr) 3412 (NH), 3326 (NH), 2932,
1623, 1376, 877, 738 cmꢁ1; 1H NMR
d 0.84–0.88 (1H, m), 0.87 (3H, s),
0.94 (1H, dd, J¼8.6, 4.3 Hz), 1.39 (3H, s), 1.77 (1H, dd, J¼8.6, 6.0 Hz),
4.45 (2H, br s), 7.18–7.39 (2H, m), 7.40–7.44 (2H, m), 7.94–7.99 (2H, m),
8.33 (2H, d, J¼6.0 Hz). Anal. calcd for C19H19N: C, 86.31; H, 7.33; N,
5.36. Found; C, 86.54; H, 7.24; N, 5.26.
3.1.13. N-[2-(2,2-Dimethylcyclopropyl)phenyl]phenylamine (16b).
Colorless oil; IR (neat) 3427 (NH), 3043, 2940, 1596, 1515, 1497,
1456, 1316, 746 cmꢁ1 1H NMR
; d 0.81–0.82 (1H, m), 0.81 (3H, s),
0.87 (1H, dd, J¼8.6, 6.6 Hz), 1.32 (3H, s), 1.65 (1H, dd, J¼8.6, 6.1 Hz),
5.82 (1H, br s), 6.86 (1H, t, J¼7.3 Hz), 6.94 (1H, dt, J¼6.4, 0.90 Hz),
7.08–7.14 (4H, m), 7.24–7.29 (3H, m). MS m/z (%) 237 (Mþ, 100),
222 (48), 194 (40), 182 (50), 180 (75). Calcd for C17H19N: M,
237.1517. Found: m/z 237.1519.
3.1.21. 2-(2,2-Diethylcyclopropyl)-N4,N4-dimethylbenzene-1,4-di-
amine (17a). Colorless oil; IR (neat) 3500 (NH), 3359 (NH), 2961,
1604, 1506, 1457, 1427, 806 cmꢁ1; 1H NMR
d 0.73–0.80 (3H, m), 0.84
(3H, s), 1.02 (3H, t, J¼7.4 Hz), 1.26–1.43 (2H, m), 1.62–1.74 (2H, m),
2.81 (6H, s), 3.48 (2H, br s), 6.54–6.64 (3H,m). MS m/z (%) 232 (Mþ,
100), 203 (26), 159 (12), 149 (17). Calcd for C15H24N2: M, 232.1938.
Found: m/z 232.1938.
3.1.14. 2-(2,2-Dimethylcylcopropyl)-4-methoxyphenylamine (16c).
Colorless oil; IR (neat) 3448 (NH), 3368 (NH), 2941, 1603, 1498,
1283, 1164, 1052, 1035, 810 cmꢁ1
;
1H NMR
d
0.74–0.76 (1H, m),
3.1.22. 2-(2,2-Diethylcyclopropyl)naphtalen-1-ylamine (17b). Colorless
0.80–0.82 (1H, m), 0.81 (3H, s), 1.31 (3H, s), 1.57 (1H, dd, J¼8.3,
5.8 Hz), 3.53 (2H, br s), 3.74 (3H, s), 6.59 (1H, s), 6.62–6.63 (2H, m).
MS m/z (%) 191 (Mþ, 100), 176 (61), 161 (19), 160 (19), 136 (37), 134
(18). Calcd for C12H17NO: M, 191.1308. Found: m/z 191.1308.
crystals; mp 37.5–38.0 ꢀC (AcOEt–hexane); IR (KBr) 3439 (NH), 3342
(NH), 2956, 1626, 1397, 1372, 807, 744 cmꢁ1; 1H NMR
d 0.75–0.80 (1H,
m), 0.78 (3H, s), 0.82–0.87 (2H, m), 1.06–1.09 (3H, m), 1.34–1.43 (2H,
m), 1.71–1.80 (2H, m), 4.37 (2H, br s), 7.16–7.24 (2H, m), 7.35–7.43
(2H,m), 7.73–7.77 (2H, m). Anal. calcd for C17H21N: C, 85.31; H, 8.84; N,
5.85. Found; C, 85.28; H, 8.78; N, 5.79.
3.1.15. Benzyl-[2-(2,2-dimethylcyclopropyl)phenyl]methylamine (16d).
Colorless oil; IR (neat) 3444 (NH), 2939, 1509, 1454, 1286, 1216,
1053, 699 cmꢁ1
;
1H NMR
d
0.74–0.77 (1H, m), 0.79 (3H, s), 0.79–
3.1.23. 2-(2,2-Diethyl-cyclopropyl)-anthracen-1-ylamine (17c).
0.81 (1H, m), 1.21 (3H, s), 1.51 (1H, dd, J¼8.2, 5.5 Hz), 3.69 (3H, s),
3.95 (1H, br s), 4.32 (1H, d, J¼13.8 Hz), 4.37 (1H, d, J¼13.8 Hz), 6.54
(1H, d, J¼8.6 Hz), 6.64 (1H, d, J¼2.5 Hz), 6.67 (1H, dd, J¼8.6,
2.5 Hz), 7.28 (1H, m), 7.36–7.40 (4H, m). MS m/z (%) 281 (Mþ, 45),
Colorless oil; IR (neat) 3476 (NH), 3395 (NH), 3053, 2961, 2932,
1726, 1622, 1429, 1382, 870, 737 cmꢁ1; 1H NMR
d 0.77–0.82 (1H, m),
0.80 (3H, s), 0.83–0.93 (2H, m), 1.11 (3H, t, J¼7.4 Hz), 1.40 (2H, d,
J¼4.3 Hz), 1.77–1.86 (2H, m), 4.55 (2H, br s), 7.22 (2H, t, J¼8.6 Hz),

Y. Yamada et al. / Tetrahedron 65 (2009) 10025–10035
10033
7.39–7.93 (2H, m), 7.94–8.00 (2H,m), 8.34 (2H, d, J¼8.0 Hz). MS m/z
(%) 232 (Mþ, 100), 203 (26), 159 (12), 149 (17). Calcd for C15H24N2:
M, 289.1830. Found: m/z 289.1825.
J¼8.3 Hz). MS m/z (%) 206 (16), 205 (Mþ, 100), 190 (75), 174 (18), 150
(74), 148 (86), 133 (22), 118 (15), 106 (11), 91 (21). Calcd for
C13H19NO: M, 205.1466. Found: m/z 205.1464.
3.1.24. N4,N4-Dimethyl-2-(2,2,3-trimethylcyclopropyl)benzene-1,4-
3.1.32. 2-(2,2-Dimethylcyclopropyl)-3-methylphenylamine
Colorless oil; IR (neat) 3547 (NH), 2923, 2852, 1651, 1215, 929,
758 cmꢁ1; 1H NMR
1.01 (1H, m),1.31 (3H, s),1.46 (1H, t, J¼6.5 Hz), 2.29 (3H, s), 3.89 (2H,
brs, NH2), 6.51 (1H, d, J¼7.5 Hz), 6.58 (1H, d, J¼7.5 Hz), 6.92 (1H, t,
J¼7.5 Hz). MS m/z (%) 175 (Mþ, 100), 160 (88), 149 (53), 145 (39), 132
(80), 120 (90), 91 (33), 57 (40), 43 (33). Calcd for C12H17N: M,
175.1361. Found: m/z 175.1359.
(18c).
diamine (17d). Colorless oil; IR (neat) 3445 (NH), 3358 (NH), 2939,
2866, 1603, 1508, 1376, 1340, 804 cmꢁ1; 1H NMR
d
0.81 (3H, s), 1.00
d
0.67 (1H, dd, J¼6.5, 4.3 Hz), 0.88 (3H, s), 0.95–
(1H, q, J¼6.0 Hz), 1.18 (1H, d, J¼6.0 Hz), 1.23 (3H, d, J¼6.0 Hz), 1.27
(3H, s), 2.81 (6H, s), 3.32 (2H, br s), 6.56–6.65 (3H, m). MS m/z (%)
218 (Mþ, 100), 203 (22), 187 (10), 174 (11), 160 (19), 149 (15). Calcd
for C14H22N2: M, 218.1782. Found: m/z 218.1782.
3.1.25. 2-(2,2,3-Trimethylcyclopropyl)naphtalen-1-ylamine (17e).
Colorless oil; IR (neat) 3476 (NH), 3391 (NH), 3055, 2940, 1614,
3.1.33. [2-(2,2-Dimethylcyclopropyl)-3-methylphenyl]methylamine
1401, 805, 751 cmꢁ1
;
1H NMR
d
0.80 (3H, s), 1.11 (1H, q, J¼6.0 Hz),
(18d). Colorless oil; IR (neat) 3458 (NH), 2925, 2812, 1583, 1470,
1.29 (3H, d, J¼6.0 Hz), 1.34 (4H, m), 4.26 (2H, br s), 7.19–7.24 (2H,
m), 7.26–7.45 (2H, m), 7.74–7.82 (2H, m). MS m/z (%) 225 (Mþ, 100),
210 (80), 194 (21), 182 (44), 180 (27), 156 (28), 143 (22), 127 (7), 115
(7). Calcd for C16H19N: M, 225.1517. Found: m/z 225.1517.
1278, 1158, 767 cmꢁ1 1H NMR
; d 0.55–0.65 (1H, m), 0.82 (3H, s),
0.96–0.98 (1H, m), 1.31 (3H, s), 1.33–1.42 (1H, m), 2.29 (3H, s), 2.86
(3H, s), 4.09 (1H, br s), 6.42–6.54 (2H, m), 7.01–7.06 (1H, m). MS m/z
(%) 189 (Mþ, 100), 174 (88), 158 (22), 146 (80), 134 (60), 132 (82), 120
(58). Calcd for C13H19N: M, 189.1517. Found: m/z 189.1517.
3.1.26. 2-(2,2,3-Trimethylcyclopropyl)anthracen-1-ylamine (17f).
Colorless oil; IR (neat) 3456 (NH), 3390 (NH), 2927, 2863, 1609,
3.1.34. 3-Chloro-2-(2,2-dimethylcycloprpyl)phenylamine
Colorless oil; IR (neat) 3394 (NH), 2923, 1610, 1446, 1296, 1123,
761 cmꢁ1 1H NMR
0.69 (1H, m), 0.91 (3H, s), 0.93–1.01 (1H, m),
1.32 (3H, s), 1.50 (1H, m), 3.98 (2H, br s), 6.53 (1H, d, J¼7.9 Hz), 6.76
(1H, d, J¼7.9 Hz), 6.91 (1H, t, J¼7.9 Hz). MS m/z (%) 197 (Mþ, 28), 195
(92), 180 (85), 140 (100), 130 (24), 117 (35). Calcd for C11H14ClN: M,
195.0815. Found: m/z 195.0815.
(18e).
1381, 868, 737 cmꢁ1
;
1H NMR
d
0.84 (3H, s), 1.10 (1H, q, J¼6.0 Hz),
1.30 (3H, d, J¼6.0 Hz),1.36 (4H, m), 4.40 (2H, br s), 7.23 (1H, s), 7.28–
7.44 (3H, m), 7.92–8.00 (2H, m), 8.33 (2H, d, J¼6.7 Hz). MS m/z (%)
275 (Mþ, 100), 260 (55), 244 (17), 232 (24), 217 (20), 193 (18), 178
(9), 165 (9), 115 (8). Calcd for C20H21N: M, 275.1673. Found: m/z
275.1672.
;
d
3.1.27. N4,N4-Dimethyl-2-(2,2,3,3-tetramethylcyclopropyl)benzene-
3.1.35. [3-Chloro-2-(2,2-dimethylcyclopropyl)phenyl]methylamine
1,4-diamine (17g). Colorless oil; IR (neat) 3456 (NH), 3361 (NH),
(18f). Colorless oil; IR (neat) 3458 (NH), 2954, 2867,1592,1455,1312,
2936, 2788, 1602, 1505, 800 cmꢁ1; 1H NMR
d
1.01 (6H, s), 1.25 (1H,
1127, 756 cmꢁ1; 1H NMR
d 0.86 (3H, s), 0.96–1.02 (1H, m),1.31 (3H, s),
s), 1.29 (6H, s), 2.80 (6H, s), 3.46 (2H, br s), 6.57–6.66 (3H, m). MS m/
z (%) 232 (Mþ, 100), 217 (35), 201 (10), 189 (12), 174 (18), 160 (17),
149 (10), 130 (8). Calcd for C15H24N2: M, 232.1937. Found: m/z
232.1937.
1.38–1.41 (1H, m),1.52–1.55 (1H, m), 2.85 (3H, s), 4.34 (1H, br s), 6.46
(1H, d, J¼8.2 Hz), 6.71 (1H, d, J¼8.2 Hz), 7.02 (1H, t, J¼8.2 Hz). MS m/z
(%) 211 (Mþ, 28), 209 (90), 194 (51), 166 (66), 154 (100), 152 (64), 131
(30),117 (40). Calcd for C12H16ClN: M, 209.0971. Found: m/z 209.0973.
3.1.28. 2-(2,2,3,3-Tetramethylcyclopropyl)naphtalen-1-ylamine (17h).
3.1.36. 2-(2,2-Dimethylcyclopropyl)-5-methoxyphenylamine (19a).
Colorless oil; IR (neat) 3476 (NH), 3380 (NH), 2940, 1622, 1512, 1446,
Colorless crystal; mp 76–77 ꢀC (AcOEt–hexane); IR (KBr) 3447 (NH),
3379 (NH), 2934, 1618, 1394, 805, 760 cmꢁ1; 1H NMR
d
1.02 (6H, s),
1294, 1212, 1030, 839 cmꢁ1
;
1H NMR
d
0.69 (1H, dd, J¼5.5, 4.7 Hz),
1.36 (6H, s), 1.39 (1H, s), 4.27 (2H, br s), 7.20–7.25 (2H, m), 7.26–7.45
(2H, m), 7.74–7.82 (2H, m). Anal. calcd for C17H21N: C, 85.31; H, 8.84;
N, 5.85. Found; C, 85.23; H, 8.81; N, 5.78.
0.78(1H, dd, J¼8.5,4.5 Hz), 0.81(3H, s),1.30 (3H, s),1.47(1H, dd, J¼8.5,
5.7 Hz), 3.74 (3H, s), 3.77 (2H, br s), 6.25–6.27 (2H, m), 6.85–6.87 (1H,
m). MS m/z (%) 191 (Mþ, 68), 176 (100), 161 (15), 136 (20), 123 (11).
Calcd for C12H17NO: M, 191.1310. Found: m/z 191.1313.
3.1.29. 2-(2,2,3,3-Tetramethylcyclopropyl)anthracen-1-ylamine (17i).
Colorless oil; IR (neat) 3429 (NH), 3360 (NH), 2938, 1607, 1378, 876,
3.1.37. 2-(2,2-Dimethylcyclopropyl)-5-methoxyphenylamine (19b).
Yellow oil; IR (neat) 3444 (NH), 2939, 1619, 1584, 1521, 1455, 1212,
741 cmꢁ1; 1H NMR
d
1.05 (6H, s), 1.39 (6H, s), 1.45 (1H, s), 4.42 (2H, br
s), 7.26 (1H, s), 7.40–7.44 (3H, m), 7.93–8.01 (2H, m), 8.34 (2H, d,
J¼10.3 Hz). MS m/z (%) 289 (Mþ, 100), 246 (32), 232 (27), 204 (18),
165 (13), 115 (7). Calcd for C21H23N: M, 289.1828. Found: m/z
289.1825.
1172, 1043, 829 cmꢁ1; 1H NMR
d
0.68 (1H, t, J¼5.2 Hz), 0.76 (3H, s),
0.78–0.81 (1H, m), 1.28 (3H, s), 1.38 (1H, dd, J¼8.0, 5.2 Hz), 2.89 (3H,
s), 3.79 (3H, s), 3.96 (1H, br s), 6.18–6.20 (2H, m), 6.86 (1H, d,
J¼8.3 Hz). MS m/z (%) 205 (Mþ, 74), 190 (100), 174 (16), 160 (28), 148
(42), 133 (12), 117 (11), 91 (16). Calcd for C13H19NO: M, 205.1465.
Found: m/z 205.1462.
3.1.30. 2-(2,2-Dimethylcyclopropyl)-3-methoxyphenylamine (18a).
Yellow oil; IR (neat) 3482 (NH), 3385 (NH), 2952, 1612, 1468, 1256,
1132, 1096, 766 cmꢁ1
;
1H NMR
d
0.67–0.72 (1H, m), 0.85 (3H, s),
3.1.38. 2-(2,2-Dimethylcyclopropyl)-5-methylphenylamine (19c).
0.91 (1H, dd, J¼8.6, 4.1 Hz), 1.25 (3H, s), 1.30 (1H, dd, J¼8.6, 6.4 Hz),
3.76 (3H, s), 3.89 (2H, br s), 6.29 (1H, d, J¼8.2 Hz), 6.32 (1H, d,
J¼8.2 Hz), 6.96 (1H, t, J¼8.2 Hz). MS m/z (%) 191 (Mþ, 100), 176 (97),
160 (25), 148 (26), 136 (84), 123 (24), 106 (28). Calcd for C12H17NO:
M, 191.0310. Found: m/z 191.1309.
Colorless oil; IR (neat) 3472 (NH), 3379 (NH), 2940, 1623, 1513,
1445, 1296, 1209, 1036, 805 cmꢁ1 1H NMR
; d 0.70–0.72 (1H, m),
0.76–0.81 (1H, m), 0.81 (3H, s), 1.29 (3H, s), 1.50 (1H, dd, J¼8.2,
6.0 Hz), 2.24 (3H, s), 3.71 (2H, br s), 6.50–6.52 (2H, m), 6.83–6.86
(1H, m). MS m/z (%) 175 (Mþ, 81), 160 (100), 145 (42), 132 (21), 120
(59), 117 (10), 91 (19), 77 (3). Calcd for C12H17N: M, 175.1361. Found:
m/z 175.1360.
3.1.31. [2-(2,2-Dimethylcyclopropyl)-3-methoxyphenyl]methylamine
(18b). Yellow oil; IR (neat) 3450 (NH), 2952, 2833, 1599, 1475, 1255,
1163, 1115, 762 cmꢁ1
;
1H NMR
d
0.66 (1H, br s), 0.81 (3H, s), 0.91
3.1.39. [2-(2,2-Dimethylcyclopropyl)-5-methylphenyl]methylamine
(1H, dd, J¼8.7, 6.3 Hz), 1.19–1.24 (1H, m), 1.28 (3H, s), 2.87 (3H, s),
(19d). Colorless oil; IR (neat) 3443 (NH), 2937, 1579, 1522, 1445,
3.77 (3H, s), 4.23 (1H, br s), 6.29 (2H, d, J¼8.3 Hz), 7.09 (1H, t,
1302, 842, 804 cmꢁ1 1H NMR
; d 0.69–0.72 (1H, m), 0.76 (3H, s),

10034
Y. Yamada et al. / Tetrahedron 65 (2009) 10025–10035
0.76–0.82 (1H, m), 1.28 (3H, s), 1.41 (1H, dd, J¼8.3, 6.0 Hz), 2.31 (3H,
s), 2.89 (3H, s), 3.89 (1H, br s), 6.42–6.48 (2H, m), 6.83–6.85 (1H, m).
MS m/z (%) 189 (Mþ, 93), 174 (100), 159 (30), 144 (34), 134 (44), 132
(62), 117 (17), 91 (10), 77 (8). Calcd for C13H19N: M, 189.1517. Found:
m/z 189.1518.
dd, J¼7.0, 4.5 Hz), 1.04 (3H, s), 1.09 (3H, s), 2.24 (1H, dd, J¼7.0,
4.0 Hz), 2.84 (3H, s), 6.88–6.92 (1H, m), 7.15–7.19 (1H, m), 7.22–7.24
(1H, m), 7.28–7.30 (1H, m). MS m/z (%) 209 (Mþ, 4), 194 (100), (174
91), 158 (21), 144 (20), 138 (11), 111 (10). Calcd for C12H16NCl: M,
209.0971. Found: m/z 209.0969.
3.1.40. 5-Chloro-2-(2,2-dimethylcyclopropyl)phenylamine (19e).
3.1.48. 7-(2,2-Dimethylcyclopropyl)-2,3-dihydro-1H-indole
Colorless oil; IR (neat) 3394 (NH), 3060, 2941, 2864, 1726, 1598,
1453, 1257, 1028, 746 cmꢁ1; 1H NMR
0.73–0.76 (2H, m), 0.82 (3H,
(23).
Colorless oil; IR (neat) 3485 (NH), 3394 (NH), 2942, 1615, 1494,
1418, 1197, 1099, 901, 803 cmꢁ1; 1H NMR
d
0.70–0.74 (1H, m), 0.80
d
(3H, s), 0.80–0.84 (1H, m), 1.30 (3H, s), 1.47 (1H, dd, J¼8.4, 5.8 Hz),
3.83 (2H, br s), 6.63–6.64 (2H, m), 6.85–6.89 (1H, m). MS m/z (%) 195
(Mþ, 97),180 (96),160 (31),145 (100),140 (82),130 (29),117 (23), 77
(10). Calcd for C11H14ClN: M, 195.0815. Found: m/z 195.0817.
s), 1.26 (3H, s), 1.51–1.56 (1H, m), 3.06 (2H, t, J¼8.4 Hz), 3.52–3.61
(2H, m), 3.72 (1H, br s), 6.64 (1H, t, J¼7.4 Hz), 6.76 (1H, d,
J¼7.4 Hz), 6.98 (1H, d, J¼7.4 Hz). MS m/z (%) 187 (Mþ, 82), 172
(100), 157 (20), 144 (18), 132 (31), 117 (10), 91 (5). Calcd for
C13H17N: M, 187.1361. Found: m/z 187.1362.
3.1.41. [5-Chloro-2-(2,2-dimethylcyclopropyl)phenyl]methylamine
(19f). Colorless oil; IR (neat) 3448 (NH), 2925, 1598, 1511, 1407,
3.1.49. 10-(2,2-Dimethylcyclopropyl)-10H-phenothiazine (25a).
1278, 884 cmꢁ1; 1H NMR
d
0.69–0.74 (1H, m), 0.74 (3H, s), 0.81 (1H,
Colorless oil; IR (neat) 3066, 2948, 1573, 1461, 1372, 1309, 1236,
dd, J¼8.4, 4.5 Hz), 1.25 (3H, s), 1.38 (1H, dd, J¼8.4, 5.8 Hz), 2.88 (3H,
m), 4.00 (1H, br s), 6.53–6.61 (2H, m), 6.84–6.89 (1H, m). MS m/z (%)
211 (Mþ, 32), 209 (100), 194 (79), 166 (38), 159 (48), 154 (79), 117
(32). Calcd for C12H16ClN: M, 209.0971. Found: m/z 209.0971.
1127, 1038, 909, 748 cmꢁ1; 1H NMR
d 0.47–0.50 (1H, m), 1.02 (3H, s),
1.05 (1H, dd, J¼6.9, 5.2 Hz), 1.33 (3H, s), 2.64 (1H, dd, J¼6.9, 4.0 Hz),
6.90–6.94 (2H, m), 7.05–7.18 (6H, m). MS m/z (%) 267 (Mþ, 100), 252
(70), 236 (17), 223 (17),198 (65),154 (9), 119 (7). Calcd for C17H17NS:
M, 267.1082. Found: m/z 267.1085.
3.1.42. 2-(2,2-Dimethylcyclopropyl)-5-trifluoromethylphenylamine
(19g). Colorless oil; IR (neat) 3489 (NH), 3400 (NH), 2945, 1623,
3.1.50. 10-(2,2-Dimethylcyclopropyl)-10H-phenoxazine (25b). Colorless
1435, 1336, 1164, 1120, 818 cmꢁ1; 1H NMR
d
0.78–0.82 (1H, m), 0.80
oil; IR (neat) 3065, 2927, 1482, 1338, 1293, 1268, 745 cmꢁ1 1H NMR
;
(3H, s), 0.88 (1H, dd, J¼10.4, 4.6 Hz), 1.33 (3H, s), 1.51–1.53 (1H, m),
3.93 (2H, br s), 6.89–6.93 (2H, m), 7.03–7.25 (1H, m). MS m/z (%) 229
(Mþ, 81), 214 (96), 186 (28), 174 (100), 166 (17), 145 (24). Calcd for
C12H14NF3: M, 229.1079. Found: m/z 229.1076.
d
0.55–0.56 (1H, m), 1.04 (1H, dd, J¼7.1, 5.2 Hz), 1.07 (3H, s), 1.31 (3H, s),
2.17 (1H, dd, J¼7.1, 4.0 Hz), 6.77–6.78 (5H, m), 6.89–6.92 (3H, m). MS
m/z (%) 251 (Mþ, 100), 250 (33), 236 (65), 220 (31), 183 (23), 182 (86).
Calcd for C17H17NO: M, 251.1310. Found: m/z 251.1319.
3.1.43. 2-(2,2-Dimethylcyclopropyl)-6-methylphenylamine (20a).
3.1.51. 1-(2,2-Dimethylcyclopropyl)-10H-phenothiazine (26a). Yellow
Colorless oil; IR (neat) 3482 (NH), 3395 (NH), 2940, 1614, 1465,
oil; IR (neat) 3395 (NH), 2947, 2926, 1568, 1475, 1434, 1292, 1123, 884,
1275, 1123, 872, 746 cmꢁ1; 1H NMR
d
0.75–0.77 (1H, m), 0.80–0.83
741 cmꢁ1 1H NMR
; d 0.73–0.77 (1H, m), 0.79 (3H, s), 0.93 (1H, dd,
(1H, m), 0.80 (3H, s), 1.32 (3H, s), 1.53–1.55 (1H, m), 2.19 (3H, s), 3.74
(2H, br s), 6.63 (1H, t, J¼7.6 Hz), 6.86 (1H, d, J¼7.6 Hz), 6.93 (1H, d,
J¼7.6 Hz). MS m/z (%) 176 (Mþ, 12), 175 (84), 160 (100), 145 (51), 120
(67), 117 (15), 91 (13). Calcd for C12H17N: M, 175.1361. Found: m/z
175.1361.
J¼8.5, 4.6 Hz), 1.40 (3H, s), 1.54 (1H, m), 6.19 (1H, br s), 6.57 (1H, m),
6.82–6.89 (3H, m), 7.01–7.04 (2H, m). MS m/z (%) 267 (Mþ, 100), 252
(26), 273 (20), 224 (42), 211 (63). Calcd for C17H17NS: M, 267.1082.
Found: m/z 267.1083.
3.1.52. 1-(2,2-Dimethylcyclopropyl)-10H-phenoxazine (26b). Colorless
3.1.44. 2-Chloro-6-(2,2-dimethylcyclopropyl)phenylamine (20b).
oil; IR (neat) 3429 (NH), 3063, 2941, 1497, 1467, 1411, 1287, 742 cmꢁ1
;
Colorless oil; IR (neat) 3491 (NH), 3395 (NH), 2943,1611,1455,1279,
1H NMR
d 0.70–0.73 (1H, m), 0.83–0.86 (1H, m), 0.86 (3H, s), 1.33 (3H,
1073, 857, 762 cmꢁ1
;
1H NMR
d
0.75–0.78 (1H, m), 0.80 (3H, s),
s), 1.41 (1H, dd, J¼8.5, 5.8 Hz), 5.22 (1H, br s), 6.41–6.42 (1H, m), 6.54–
6.59 (3H, m), 6.62–6.68 (2H, m), 6.72–6.76 (1H, m). MS m/z (%) 251
(Mþ, 100), 236 (56), 221 (28), 220 (19), 208 (68), 207 (32), 196 (38),
195 (94). Calcd for C17H17NO: M, 251.1308. Found: m/z 251.1308.
0.84–0.86 (1H, m), 1.32 (3H, s), 1.52–1.57 (1H, m), 4.17 (2H, br s),
6.61 (1H, t, J¼7.7 Hz), 6.88 (1H, d, J¼7.7 Hz), 7.12 (1H, d, J¼7.7 Hz).
MS m/z (%) 195 (Mþ, 45), 180 (100), 160 (18), 144 (35), 127 (30).
Calcd for C11H14NCl: M, 195.0815. Found: m/z 195.0824.
Acknowledgements
3.1.45. (2,2-Dimethylcyclopropyl)-(2-methoxyphenyl)methylamine
(21a). Colorless oil; IR (neat) 3065, 2946, 1595, 1503, 1273, 1113,
This work was supported by a Grant-in-Aid for Scientific Re-
search No. 19590018 from the Ministry of Education, Culture,
Sports, Science and Technology, Japan, and TUS Grant for Research
Promotion from Tokyo University of Science, which are gratefully
acknowledged.
1030, 743 cmꢁ1
;
1H NMR
d
0.30–0.33 (1H, m), 0.60 (1H, dd, J¼7.0,
4.6 Hz), 1.00 (3H, s), 1.12 (3H, s), 2.14 (1H, dd, J¼7.0, 4.0 Hz), 2.86
(3H, s), 3.82 (3H, s), 6.83–6.92 (3H, m), 7.09–7.13 (1H, m). MS m/z (%)
205 (Mþ, 10), 190 (100), 174 (75), 134 (22), 121 (12). Calcd for
C13H19NO: M, 205.1467. Found: m/z 205.1467.
References and notes
3.1.46. (2,2-Dimethylcyclopropyl)methyl-o-tolylamine (21b). Colorless
oil; IR (neat) 3066, 2945, 2867, 1599, 1494, 1370, 1300, 1213, 1107, 984,
1. Barton, D. H. R.; Ollis, W. D. In Comprehensive Organic Chemistry; Sutherland, I. O.,
Ed.; Pergamon: Oxford, 1979; Vol. 2, pp 131–184.
842, 761 cmꢁ1
;
1H NMR
d
0.12–0.15 (1H, m), 0.53 (1H, dd, J¼6.9,
4.5 Hz), 1.04 (3H, s), 1.08 (3H, s), 2.20–2.23 (1H, m), 2.24 (3H, s), 2.66
(3H, s), 6.89–6.94 (1H, m), 7.10–7.20 (3H, m). MS m/z (%) 189 (Mþ, 20),
174 (100), 144 (15), 132 (28), 118 (9), 91 (14). Calcd for C13H19N: M,
189.1518. Found: m/z 189.1516.
2. (a) Olah, G. A.; Krishnamurti, R.; Surya Prakash, G. K. In Comprehensive Organic
Chemistry; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3,
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3.1.47. (2-Chloro-phenyl)-(2,2-dimethylcyclopropyl)methylamine
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1052, 983, 876, 753 cmꢁ1
;
1H NMR
d
0.20–0.23 (1H, m), 0.57 (1H,

Y. Yamada et al. / Tetrahedron 65 (2009) 10025–10035
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