Nickel-Catalyzed Reductive Cross-Coupling of Aryl Triflates and Nonaflates with Alkyl Iodides

Article abstract of DOI:10.1055/s-0036-1588464

A nickel-catalyzed cross-electrophile coupling of aryl triflates and nonaflates with alkyl iodides using manganese(0) as a reductant is described. The method is applicable to the reductive alkylation of various aryl sulfonates, including o -borylaryl triflate, which enabled efficient construction of diverse alkylated arenes under mild conditions.

Full text of DOI:10.1055/s-0036-1588464

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–L
special topic
A
en
Y. Sumida et al.
Special Topic
Synthesis
Nickel-Catalyzed Reductive Cross-Coupling of Aryl Triflates and
Nonaflates with Alkyl Iodides
Yuto Sumida*a
Tomoe Sumidaa
NiBr2·glyme
Ph
Ph
Takamitsu Hosoya*a,b
O
RF
alkyl
N
N
S
alkyl
a Chemical Biology Team, Division of Bio-Function Dynamics Imaging,
RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi,
Chuo-ku, Kobe 650-0047, Japan
+
Ar
Ar
I
O
O
LiBr, Mn0
DMF, 40 °C
RF = CF3, C4F9
27 examples
12–94%
takamitsu.hosoya@riken.jp
yuto.sumida@riken.jp
b Laboratory of Chemical Bioscience, Institute of Biomaterials and Bioengineering,
Tokyo Medical and Dental University (TMDU), 2-3-10 Kanda-Surugadai, Chiyoda-
ku, Tokyo 101-0062, Japan
thosoya.cb@tmd.ac.jp
Dedicated to Professor Teruaki Mukaiyama in celebration of his 90th birthday
(Sotsuju)
Published as part of the Special Topic Advanced Strategies in Synthesis with Nickel
Received: 31.03.2017
Accepted after revision: 20.05.2017
Published online: 28.06.2017
the same starting materials (Scheme 1, C). However, to the
best of our knowledge, cross-electrophile coupling of aryl
sulfonates with alkyl halides has not yet been reported.6
DOI: 10.1055/s-0036-1588464; Art ID: ss-2017-c0215-st
A
Our previous works (Refs 4 and 5)
R' = t-Bu or s-Bu
Abstract A nickel-catalyzed cross-electrophile coupling of aryl triflates
and nonaflates with alkyl iodides using manganese(0) as a reductant is
described. The method is applicable to the reductive alkylation of vari-
ous aryl sulfonates, including o-borylaryl triflate, which enabled effi-
cient construction of diverse alkylated arenes under mild conditions.
R
Li
R'Li
–78 °C
Bpin
O
O
R
B
~ r.t.
TfO
R'
aryne
R
Key words reductive alkylation, cross-electrophile coupling, nickel
OTf
catalysis, aryl triflate, alkyl iodide, aromatic compounds
o-borylaryl triflate
Bpin
Ni
P
P
Ni0/P-ligand
LiBr
t-BuOK
R
Ni
R
P
Transition-metal-catalyzed cross-coupling reactions are
widely used methods for C–C bond formation in the field of
modern organic synthesis.1 In these methods, an organo-
metallic reagent such as organolithium, organomagnesium,
organozinc, organostannane, organoboron, and organosili-
con is generally used along with a carbon electrophile such
as an organo halide. In recent years, the transition-metal-
catalyzed cross-electrophile coupling approach has attract-
ed much attention.2,3 This type of reaction is typically per-
formed in the presence of a reductant such as manga-
nese(0) or zinc(0), thus preventing the use of stoichiometric
amounts of organometallic reagents that are often air- and
moisture-sensitive and usually pre-prepared from the cor-
responding organo halides.
Recently, we reported that o-borylaryl triflates serve as
common precursors of aryne species4 and aryne–nickel
complexes5 (Scheme 1, A), from which a diverse set of func-
tionalized aromatic compounds were synthesizable
(Scheme 1, B). We assumed that cross-electrophile coupling
of o-borylaryl triflates with alkyl halides, providing o-alkyl-
arylboronic acid derivatives, would be effective to further
expand the available aromatic compounds accessible from
Br
P
aryne–Ni complex
Ar–Ni(II) complex
B
Difunctionalization of arynes and aryne–Ni complexes
E
E
R
R
R
R
Nu
Nu
Nu
E
aryne
E
R
R
E
P
P
Nu
E
R
Ni
[Ni]
aryne–Ni complex
E'
C
Another type of derivatization from o-borylaryl triflates
Bpin
Bpin
Ni catalyst ?
alkyl
+
R
R
X
OTf
alkyl
Scheme 1 Diverse sets of transformations from o-borylaryl triflates
Pioneering works on the direct cross-coupling of aryl
halides with alkyl halides were reported independently by
the Weix and Gosmini groups in 2010 using nickel3a and
cobalt3b catalysis, respectively. Thereafter, several groups
have reported various nickel-catalyzed cross-electrophile
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

B
Y. Sumida et al.
Special Topic
Synthesis
couplings,3c–h including a method combining a visible light
photoredox catalyst3i–k that has contributed to the substan-
tial progress in this field (Scheme 2, A). Nevertheless, de-
spite the ready availability of aryl sulfonates, their reductive
alkylation has not yet been reported. Herein, we report a
nickel-catalyzed reductive cross-coupling of aryl sulfonates
with alkyl iodides, which provides a new option for cross-
electrophile coupling (Scheme 2, B).
Table 1 Ni-Catalyzed Reductive Alkylation of 2-Naphthyl Triflate (1a)
with 1-Iodobutane
NiBr2·glyme (5 mol%)
bathophen (6 mol%)
LiBr (1.5 equiv)
OTf
Mn (2.0 equiv)
3
+
I
3
DMF, 40 °C, 14 h
1.5 equiv
1a
2a
Ph
Ph
A
Reported cross-electrophile coupling (Ref 3)
Ni or Co catalyst
with or without
photocatalyst
Ph2P
PPh2
N
N
N
N
X
alkyl
bathophen
dppbz
tmphen
alkyl
+
R
R
X'
t-Bu
t-Bu
X = I, Br, Cl
This work
X' = I, Br, OTs
B
N
N
N
N
dtbpy
phen
alkyl
O
RF
Ni catalyst
S
alkyl
+
R
R
I
O
O
Entry
Change from standard conditions
Yield (%)a
RF = CF3, C4F9
1
2
3
4
5
6
7
8
9
none
77b
13
9
Scheme 2 Transition-metal-catalyzed cross-electrophile coupling
modifiedc Weix’s conditions3a
1-bromobutane instead of 1-iodobutane
dppbz instead of bathophen
tmphen instead of bathophen
dtbpy instead of bathophen
phen instead of bathophen
Zn instead of Mn
Previous reports on the nickel-catalyzed reductive al-
kylation of aryl halides have indicated that a nickel catalyst
with a nitrogen-containing bidentate ligand, such as 4,4′-
di-tert-butyl-2,2′-bipyridine (dtbpy) or 1,10-phenanthro-
line (phen), is effective for this type of transformation.2,3
Furthermore, in our previous work, we found that the addi-
tion of LiBr contributed to the acceleration of oxidative ad-
dition of aryl triflate to the nickel(0) complex, forming a
more stable aryl–nickel(II) complex via ligand exchange.5
Based on these previous studies, we screened for conditions
that promoted the efficient reductive coupling between 2-
naphthyl triflate (1a) and 1-iodobutane. After extensive in-
vestigations, we found that the reaction of 1a with 1-io-
dobutane (1.5 equiv) using NiBr2·glyme (5 mol%) and ba-
thophenanthroline (bathophen; 6 mol%)7 in the presence of
LiBr (1.5 equiv) and Mn (2.0 equiv) in DMF under gentle
heating at 40 °C for 14 hours afforded the desired 2-butyl-
naphthalene (2a) in high yield (Table 1, entry 1). Our initial
attempt using the modified Weix’s conditions3a that were
highly effective for the reductive alkylation of aryl iodides
or aryl bromides was unsuccessful (entry 2). The use of 1-
bromobutane instead of 1-iodobutane significantly lowered
the yield of 2a (entry 3). Using other bidentate phosphorus-
or nitrogen-based ligands, such as 1,2-bis(diphenylphos-
phino)benzene (dppbz), 3,4,7,8-tetramethyl-1,10-phenan-
throline (tmphen), dtbpy, or phen, was less effective than
using bathophen (entries 4–7). The yield of 2a decreased
when zinc(0) was used instead of manganese(0) (entry 8).
The reaction without LiBr also lowered the yield of 2a (en-
try 9).
13
19
28
60
43
55
without LiBr
a GC yields except entry 1.
b Isolated yield.
c NiI2 (10.7 mol%), dppbz (5 mol%), dtbpy (5 mol%), pyridine (10 mol%),
Mn0 (2.0 equiv), DMPU (0.25 M), 80 °C, 14 h.
ble yield of 2a was achieved even when the reaction was
performed without LiBr. On the other hand, the reaction
using 2-naphthyl pivalate, which is a good substrate for
nickel-catalyzed reductive carboxylation8a and amidation,8b
gave no butylated product 2a even performing the reaction
at 80 °C.
NiBr2·glyme (5 mol%)
bathophen (6 mol%)
LiBr (1.5 equiv)
ONf
Mn (2.0 equiv)
3
+
I
3
DMF, 40 °C, 14 h
1.5 equiv
3a
2a
94%
(85% without LiBr)
Scheme 3 Reductive butylation of 2-naphthyl nonaflate (3a)
Using the optimized reaction conditions, we investigat-
ed the scope of aryl triflates that could react with 1-iodo-
butane or 1-iodooctane (Scheme 4). Reductive alkylation of
phenyl triflates, bearing an electron-withdrawing group
such as acetyl, methoxycarbonyl, trifluoromethyl, or cyano
group at the para-position, which are easier to oxidatively
add to nickel(0), proceeded smoothly to afford alkylated
We also found that using 2-naphthyl nonaflate (3a), in-
stead of triflate 1a, under the optimized conditions afforded
2a in an excellent yield (Scheme 3). In this case, a compara-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

C
Y. Sumida et al.
Special Topic
Synthesis
arenes 2b–e. The same reactions using the corresponding
phenyl nonaflates bearing an electron-withdrawing group
were unsuccessful. 3,5-Disubstituted phenyl triflates with
two electron-withdrawing fluoro or trifluoromethyl groups
also provided the corresponding octylated products 2f and
2g. The reaction was applicable to an ortho-substituted
substrate, such as 2-acetylphenyl triflate, which afforded 2-
butylacetophenone (2h). Similar to 2-naphthyl triflate, π-
extended substrates such as 1-naphthyl triflate and 9-
phenanthryl triflate also participated in this reaction to af-
ford 1-butylnaphthalene (2i) and 9-butylphenanthrene
(2j), respectively. Binaphthyl bistriflate was transformed to
2,2′-dibutyl-1,1′-binaphthalene (2k) by dibutylation using
double the amount of reagents. In contrast to electron-defi-
cient and π-extended substrates, alkylation of phenyl tri-
flate and 4-methoxyphenyl triflate were unsuccessful. At-
tempts using the corresponding nonaflates, with an aim to
facilitate the oxidative addition, afforded 1-octylbenzene
(2l) in low yield. However, only a trace amount of 1-me-
thoxy-4-octylbenzene (2m) was produced, even when the
nonaflate was used at elevated temperature. These results
indicated that electron-rich substrates are unfavorable for
this reaction. Alkylated heteroarenes such as 3-octylpyri-
dine (2n) and 6-butylquinoline (2o) were accessible from
the corresponding triflates without alkylation at the nucleo-
philic nitrogen. The method was also applicable to the syn-
thesis of more complex compounds. For example, albeit the
yield was low, 10-butyl-7-ethylcamptothecin (2p) was ob-
tained by the reductive butylation of triflylated SN-38,
which is a potent anticancer drug and one of the metabo-
lites of irinotecan.9
Various alkyl iodides participated in this reaction (Table
2). The reaction of 2-naphthyl nonaflate (3a) with 1-
iodooctane afforded 2-octylnaphthalene (2q) in excellent
yield (entry 1). However, the reaction with 1-bromooctane
only gave 2q in low yield; a similar tendency toward the
butylation of 2-naphthyl triflate (1a) was found (Table 1,
entries 1 and 3). Iodomethane was an unfavorable substrate
NiBr2·glyme (5 mol%)
bathophen (6 mol%)
LiBr (1.5 equiv)
Mn (2.0 equiv)
n
OSO2RF
Ar
+
Ar
I
n
Table 2 Scope of Alkyl Iodides
DMF
40 °C, 14–21 h
n = 3 or 7
1.5 equiv
1 (RF = CF3)
or
2
NiBr2·glyme (5 mol%)
bathophen (6 mol%)
LiBr (1.5 equiv)
3 (RF = C4F9)
ONf
alkyl
Mn (2.0 equiv)
alkyl
1.5 equiv
+
3
3
I
7
DMF
40 °C, 14–19 h
MeO
F3C
3a
2
O
O
2c
2d
55% (N.D.)a
2b
77% (N.D.)a
73% (6%)a,b
Entry
Alkyl iodide
Product 2
Yield (%)a
F3C
F
7
7
1
2
2q
2r
92 (24)b
12c,d
I
3
NC
I
Me
CF3
F
2e
2g
56%
2f
56%
28% (N.D.)a
OMe
I
3
4
2s
2t
87
3
O
3
3
O
O
2h
2i
2j
62%
28d
39%
quant
I
OMe
NHBoc
7
7
CF3
5
6
2u
2v
8c,d
3
3
I
I
MeO
2l
traceb,d (18%)a
2m
traceb,d (trace)a,b,d
55
2k
37%c
O
N
3
7
8
2w
2x
61
60
7
3
I
I
N
N
N
O
2n
30%
2o
68%
2p
12%
HO
O
Scheme 4 Scope of aryl sulfonates. a Yields from nonaflates in paren-
theses (N.D. = not detected). b Yields determined by 1H NMR analysis. c
1-Iodobutane (3 equiv), NiBr·glyme (10 mol%), bathophen (12 mol%),
LiBr (3 equiv), Mn (4 equiv) were used. d The reactions were performed
at 80 °C.
a Isolated yields unless otherwise noted.
b Yield when 1-bromooctane was used instead of 1-iodooctane in paren-
theses.
c 1H NMR yields.
d The reactions were performed at 80 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

D
Y. Sumida et al.
Special Topic
Synthesis
for this transformation, providing 2-methylnaphthalene in
low yield even when the reaction was conducted at 80 °C
(Table 2, entry 2). The reaction with methyl 4-iodobuta-
noate afforded the corresponding alkylated naphthalene 2s,
bearing an ester moiety, in high yield while the reaction
with a protected β-iodoalanine derivative afforded the de-
sired product 2t in low yield (entries 3 and 4). 1,1,1-Trifluo-
ro-3-iodopropane was also an unsuitable substrate and
only a trace amount of alkylated product 2u was obtained
(entry 5). Secondary alkyl iodides such as 2-iodobutane,
iodocyclopentane, and iodocyclohexane were successfully
coupled with 3a to afford the corresponding alkylated
naphthalenes 2v–x in acceptable yields.
conditions (Scheme 6, A-b). The reactions shown in Scheme
6 A did not proceed when the reactions were conducted
without bathophen. These results indicate that oxidative
addition of aryl triflate to bathophen-ligated nickel(0) is a
key step for this reaction.
(1.5 equiv)
I
3
A
Cy3P
Ni
Br
a
bathophen (1.1 equiv)
LiOTf (0 or 1.0 equiv)
3
PCy3
DMF, 40 °C, 23 h
6
2a
(prepared from
2-naphthyl triflate (1a)
in 85% yield)
47% (without LiOTf)
49% (with LiOTf)
(1.5 equiv)
I
b
7
Cy3P
Br
The nickel-catalyzed reductive alkylation was also ap-
plicable to alkenyl triflates 4 without modifying the reac-
tion conditions, as demonstrated in the synthesis of alkylat-
ed alkenes 5a–c (Scheme 5).10
bathophen (1.1 equiv)
LiOTf (0 or 1.0 equiv)
Ni
7
PCy3
DMF, 80 °C, 2 h
MeO
MeO
7
2m
(prepapred from
4-methoxyphenyl triflate
in 93% yield)
74% (without LiOTf)
71% (with LiOTf)
NiBr2·glyme (5 mol%)
bathophen (6 mol%)
LiBr (1.5 equiv)
Mn (2.0 equiv)
n
B
NiBr2·glyme (5 mol%)
bathophen (6 mol%)
LiBr (1.5 equiv)
Mn (2.0 equiv)
OTf
ONf
+
2-Np
R
R
I
n
2-Np
2-Np
DMF
40 °C, 14 h
n = 3 or 7
1.5 equiv
8
9
3a
5
4
+
DMF, 40 °C, 14 h
I
2-Np
10
11
(1.5 equiv)
48% total yield
3
7
(8/9+10+11 = 8:92)
3
N
Boc
C
NiBr2·glyme (5 mol%)
bathophen (6 mol%)
LiBr (1.5 equiv)
5c
43%a
5a
68%
5b
71%
Mn (2.0 equiv)
50 mol% additive
Scheme 5 Ni-catalyzed reductive alkylation of alkenyl triflates. a Alke-
nyl triflate (1.5 equiv) and 1-iodobutane (1 equiv) were used. Product
5c contained 10% of 2,6-dimethylpentadeca-2,6,10-triene as a regio-
isomeric mixture. The same amount of regioisomer was contained in
the corresponding alkenyl triflate used as the starting material.
ONf
3
+
I
3
DMF, 40 ºC, 17 h
1.5 equiv
3a
2a
BHT: 90%
galvinoxyl: 53%
DHA: 77%
BHT:
galvinoxyl:
OH
t-Bu
t-Bu
t-Bu
t-Bu
TEMPO: trace
Based on several preliminary experiments that were
performed to gain insight into the reaction mechanism, we
currently think that the reductive alkylation of aryl sulfon-
ates proceeds in a similar manner as that of aryl halides, as
proposed by Weix and co-workers,3e although involvement
of a different pathway could not be completely ruled out.
For example, treatment of the aryl–Ni(II)Br complex, 2-
naphthyl–Ni(PCy3)2Br (6), which was efficiently prepared
from 2-naphthyl triflate (1a) based on our previously re-
ported method,5 with 1-iodobutane and bathophen
smoothly afforded the butylated product 2a in 47% yield
with high cross-selectivity even without using manga-
nese(0) (Scheme 6, A-a).11 This result was consistent with
that reported by Weix and co-workers.3e In the catalytic re-
action, electron-rich aryl sulfonates, such as 4-methoxy-
phenyl triflate, were inactive and only a trace amount of al-
kylated product was observed, even when exploiting 4-me-
thoxyphenyl nonaflate (Scheme 4). In contrast, octylated
product 2m was efficiently obtained in the stoichiometric
reaction using aryl–Ni(II)Br complex 7 under same reaction
O
O
t-Bu
t-Bu
DHA:
TEMPO:
O
N
Scheme 6 Mechanistic experiments
The radical clock experiment,12 performing the reaction
of 2-naphthyl nonaflate (3a) with cyclopropylmethyl io-
dide, resulted in a mixture of products; cyclopropylmethyl-
ated naphthalene 8 and ring-opened products 9–11 were
obtained in a 8:92 ratio13 (Scheme 6, B). This result suggest-
ed the involvement of an alkyl radical intermediate in the
reaction. The formation of olefin-isomerized products 10
and 11, which were not observed in the case of aryl ha-
lides,3e indicated the in situ generation of a nickel hydride
species in our case.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

E
Y. Sumida et al.
Special Topic
Synthesis
Although the involvement of an alkyl radical intermedi-
ate was suggested, to our surprise, the reductive butylation
of 2-naphthyl nonaflate (3a) under the optimized condi-
tions was not significantly inhibited, even in the presence
of a radical scavenger. The butylated product 2a was ob-
tained in moderate to excellent yields from the reaction us-
ing 50 mol% of 2,6-di-tert-butyl-4-methylphenol (BHT),
galvinoxyl free radical, or 9,10-dihydroanthracene (DHA)
(Scheme 6, C). Formation of the corresponding radical-
trapped alkylated compounds was not observed in these re-
actions. These results suggest that a free radical species is
not involved in this reaction or that an extremely rapid re-
action occurs between the generated radical and the nickel
species. Although the addition of 2,2,6,6-tetramethylpiperi-
dine 1-oxyl (TEMPO) free radical, which is also a widely
used radical reagent, almost completely inhibited the reac-
tion and a significant amount of 3a was recovered, no alkyl
radical-trapped product was observed, indicating that the
catalyst was deactivated by TEMPO in this case.
Based on the results obtained from these mechanistic
experiments, we assume that the nickel-catalyzed reduc-
tive alkylation of aryl sulfonates with alkyl iodides proceeds
by either, or both, of two possible reaction mechanisms in-
volving mono-, di-, and trivalent nickel intermediates
(Scheme 7). One of the possible mechanisms is the one pro-
posed by Weix and co-workers3e (Scheme 7, A). In this
scheme, the reaction starts from the oxidative addition of
aryl sulfonate to the nickel(0) catalyst to form aryl–Ni(II)X
complex I. Thereafter, single-electron transfer occurs from
the Ni complex I to the alkyl iodide to generate an alkyl rad-
ical,14 which rapidly reacts with the aryl–Ni complex I to
form alkyl(aryl)–Ni(III)X complex II. Reductive elimination
from the Ni complex II would smoothly occur to afford the
alkylated product and Ni(I)X complex III,15 from which the
single-electron transfer to alkyl iodide could also occur to
generate an alkyl radical and Ni(II)X2 complex IV. Reduction
of the Ni complex IV with manganese(0) regenerates an ac-
tive nickel(0) complex to complete the catalytic cycle. The
low reactivity observed for methyl iodide (Table 2, entry 2),
as well as the results obtained from stoichiometric experi-
ments (Scheme 6, A) and the formation of ring-opened
products in radical clock experiment (Scheme 6, B) support
this radical-involving mechanism.16 Considering the lower
reactivity of aryl triflate than aryl iodide in the oxidative
addition to nickel(0),15 an alternative mechanism that starts
from the oxidative addition of alkyl iodide to the nickel(0)
catalyst to form alkyl–Ni(II)X complex V is conceivable
(Scheme 7, B). In this scheme, subsequent reduction of the
nickel complex V provides alkyl–Ni(I) complex VI, and the
oxidative addition of aryl sulfonate to this Ni complex VI
with the assistance of LiBr affords the alkyl(aryl)–Ni(III)X
complex VII, from which reductive elimination smoothly
occurs to give the alkylated product. This mechanism, in
which a radical intermediate is not involved, agrees with
the results obtained from the experiments using radical
scavengers (Scheme 6, C). This mechanism can also explain
the formation of ring-opened products, including the ole-
fin-isomerized products that, were observed in the radical
clock experiment (Scheme 6, B).17
A
OSO2RF
MnX2
+
LiBr
N
N
Ni0
Mn0
LiOSO2RF
X
X
N
N
NiII
X
IV
N
N
NiII
I
Alkyl
I
Alkyl
N
N
NiI
X
I
Alkyl
X
NiIII
X
III
X
NiIII
N
N
Alkyl
Alkyl
+
N
Alkyl
N
II
X
N
N
NiI
III
X
B
1/2 MnX2
N
N
I
Alkyl
Ni0
1/2 Mn0
N
NiI
N
X
X
N
VIII
NiII
Alkyl
N
Alkyl
V
X
NiIII
1/2 Mn0
N
Alkyl
N
1/2 MnX2
N
N
VII
NiI
VI
Alkyl
LiOSO2RF
OSO2RF
+
LiBr
Scheme 7 Possible reaction mechanisms (X = Br or I)
The nickel-catalyzed reductive alkylation was also suc-
cessfully applicable to o-silylaryl18,19 and o-borylaryl tri-
flates,4,5 which are widely used aryne precursors, expand-
ing the synthetic utility of the method (Scheme 8). For ex-
ample, 3-(trimethylsilyl)-2-naphthyl triflate (1q) and 3-
(pinacolatoboryl)-2-naphthyl triflate (1r) were butylated
under the standard conditions to afford o-butylated silyl-
naphthalene 2y and borylnaphthalene 2z, respectively, in
good yields. Neither the generation of aryne nor formation
of the aryne–Ni complex was observed in these reactions,
because these transformations require activation with a
base such as fluoride anion,18,19 t-BuLi,4a,b and t-BuOK.5
These alkylated products are potential synthetic intermedi-
ates that can be further transformed using the silyl20 and
boryl21 groups. Indeed, the boryl group of 2z was efficiently
transformed to various functional groups such as azido, hy-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

F
Y. Sumida et al.
Special Topic
Synthesis
droxy, aryl, or iodo group demonstrating an alternative syn-
thetic utility of o-borylaryl triflates besides being aryne and
aryne–Ni precursors (Scheme 8, B).
df) column and He as the carrier gas. 1H NMR (400 MHz), 13C{1H}
NMR (100 MHz), 19F NMR (372.5 MHz), 31P{1H} NMR (160 MHz), and
11B NMR (127 MHz) spectra were taken on a JEOL 400SS spectrometer
at r.t. CDCl3 containing 0.05% TMS (99.8%D, Cambridge Isotope Labo-
ratories, Inc., Cat. No. DLM-7B) and benzene-d6 (C6D6, 99.5%D, Cam-
bridge Isotope Laboratories, Inc., Cat. No. DLM-1) were used as sol-
vents for NMR measurements. 1H NMR measurements are relative to
TMS (δ = 0.00 in CDCl3) or residual benzene (δ = 7.15); 13C{1H} NMR
are relative to CDCl3 (δ = 77.0) or residual benzene (δ = 128.62); 19F
NMR are relative to PhCF3 (δ = –63.0 in CDCl3) used as the external
standard; 31P{1H} NMR are relative to 85% H3PO4 (δ = 0.0 in D2O) used
as the external standard; 11B NMR are given relative to BF3·OEt2 (δ =
0.0 in CDCl3) used as the external standard. IR spectra were measured
by single reflection ATR method on a Shimadzu IRPrestige-21 spec-
trophotometer attached with MIRacle. HRMS were measured on a
Thermo Scientific Exactive Plus Orbitrap under positive (ESI+) condi-
tions at RIKEN CLST.
A
n-BuI (1.5 equiv)
NiBr2·glyme (5 mol%)
bathophen (6 mol%)
LiBr (1.5 equiv)
OTf
Mn (2.0 equiv)
3
DMF, 40 °C, 24 h
TMS
TMS
1q
1r
2y
58%
NaN3
Cu(OAc)2
B
OTf
3
MeOH, 50 °C
under air, 5 h
N3
Bpin
12a 68%
12b 77%
H2O2
NaOH
3
as above
H2O, r.t., 2 h
OH
2-Butyl Naphthalene (2a); Typical Procedure for Nickel-Catalyzed
Reductive Alkylation of Aryl Sulfonates with Alkyl Iodides
3
methyl 4-iodobenzoate
(amphos)2PdCl2
Cs2CO3
Bpin
To a suspension of NiBr2·glyme (3.1 mg, 10 μmol), bathophenanthro-
line (3.9 mg, 12 μmol), manganese (22 mg, 0.40 mmol), and LiBr (26
mg, 0.30 mmol) in DMF (0.4 mL) were added 2-naphthyl nonaflate
(3a; 85.3 mg, 0.200 mmol) and 1-iodobutane (34.2 μL, 0.300 mmol) at
r.t. After stirring for 14 h at 40 °C, the mixture was cooled to r.t. and to
this was added aqueous phosphate buffer (pH 7.4, ca. 2 mL). The mix-
ture was extracted with Et2O (3 × ca. 2 mL) and the combined organic
extracts were dried (Na2SO4) and filtered. The filtrate was concentrat-
ed under reduced pressure. The residue was purified by chromatogra-
phy (silica gel, n-hexane) to give 2a as a colorless oil; yield from 1a:
28.5 mg (0.155 mmol, 77%); yield from 3a: 34.8 mg (0.189 mmol,
94%); Rf = 0.60 (n-hexane).
2z
3
68%
toluene
100 °C, 18 h
12c 93%
12d 41%
CO2Me
NaI
chloramine-T
3
THF, H2O
80 °C, 4 h
I
Scheme 8 Reductive alkylation of o-silylaryl and o-borylaryl triflates
In summary, we have achieved nickel-catalyzed reduc-
tive alkylation of aryl sulfonates with alkyl iodides, offering
a new option for direct cross-electrophile coupling reac-
tion. Since aryl sulfonates are easily prepared from the cor-
responding phenol derivatives, which are frequently found
in natural products and commercially available compounds,
this method would enable the expeditious diversification of
readily available phenol derivatives.
IR (ZnSe): 743, 783, 814, 851, 885, 947, 1125, 1269, 1377, 1454, 1464,
1508, 1601, 2857, 2928, 2955, 3051 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 0.94 (t, J = 7.6 Hz, 3 H, CH3), 1.39 (tq, J =
7.6, 7.6 Hz, 2 H, CH2), 1.69 (tt, J = 7.6, 7.6 Hz, 2 H, CH2), 2.77 (t, J = 7.6
Hz, 2 H, CH2), 7.32 (d, J = 8.4 Hz, 1 H, Harom), 7.37–7.46 (m, 2 H, Harom),
7.60 (s, 1 H, Harom), 7.72–7.81 (m, 3 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.0 (CH3), 22.4 (CH2), 33.5 (CH2),
35.8 (CH2), 124.9 (CH), 125.8 (CH), 126.3 (CH), 127.36 (CH), 127.44
(CH), 127.6 (CH), 127.7 (CH), 131.9 (C), 133.6 (C), 140.4 (C).
HRMS (ESI+): m/z [M]+ calcd for C14H16+: 184.1247; found: 184.1245.
All reactions were performed under argon atmosphere unless other-
wise indicated. All manipulations of air- and/or moisture-sensitive
compounds were performed either using standard Schlenk tech-
niques or in a MIWA DBO-1KH-NYWS glovebox under an atmosphere
of argon. Analytical TLC was performed on precoated (0.25 mm) silica
gel plates (Merck, Merck Silica Gel 60 F254, Cat. No. 1.05715.0001). Pre-
parative TLC was carried out using precoated silica gel plates (0.50
mm: Merck, Merck Silica Gel 60 F254, Cat. No. 1.05744.0001. 1.0 mm:
Merck, Merck Silica Gel 60 F254, Cat. No. 1.13895.0001. 2.0 mm: Merck,
Merck Silica Gel 60 F254, Cat. No. 1.05717.0001). Column chromatogra-
phy was conducted by hand using silica gel (SiliCycle Inc., SiliaFlash)
or on a Yamazen Automated Flash Chromatography System that con-
sists of AI-580 and Parallel Frac FR-360 with silica gel packed column
(Universal Column Premium). Recycling preparative HPLC was per-
formed by LC-Forte/R system (YMC Co., Ltd.) with high-resolution gel
permeation chromatography (GPC) columns (YMC Co., Ltd., YMC-GPC
T2000 or YMC-GPC T2000-40). GC analysis was carried out on a Shi-
madzu GC-2014 using an INERT CAP 1 (30 m, 0.32 mm I.D., 0.25 μm
1-(4-Butylphenyl)ethan-1-one (2b)
Colorless oil; yield: 25.6 mg (0.145 mmol, 73%); Rf = 0.30 (n-hexane/
EtOAc, 30:1).
IR (ZnSe): 689, 818, 833, 955, 1016, 1180, 1265, 1356, 1412, 1607,
1680, 2859, 2930, 2957 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 0.93 (t, J = 7.6 Hz, 3 H, CH3), 1.36 (tq, J =
7.6, 7.6 Hz, 2 H, CH2), 1.57–1.66 (m, 2 H, CH2), 2.58 (s, 3 H, CH3), 2.67
(t, J = 7.6 Hz, 2 H, CH2), 7.25–7.29 (AA′BB′, 2 H, Harom), 7.86–7.90
(AA′BB′, 2 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 13.9 (CH3), 22.3 (CH2), 26.5 (CH3),
33.2 (CH2), 35.7 (CH2), 128.4 (2 C, 2 CH), 128.6 (2 C, 2 CH), 134.9 (C),
148.8 (C), 197.9 (CO).
HRMS (ESI+): m/z [M + H]+ calcd for C12H17O+: 177.1274; found:
177.1271.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

G
Y. Sumida et al.
Special Topic
Synthesis
Methyl 4-Butylbenzoate (2c)
19F NMR (CDCl3, 372.5 MHz): δ = –111.4 (dd, J = 8.2, 8.2 Hz).
HRMS (ESI+): m/z [M + H]+ calcd for C14H21F2+: 227.1606; found:
Colorless oil; yield: 29.4 mg (0.153 mmol, 77%); Rf = 0.40 (n-hexane/
EtOAc, 30:1).
227.1605.
IR (ZnSe): 702, 737, 760, 835, 851, 968, 1020, 1105, 1177, 1190, 1273,
1310, 1416, 1435, 1611, 1721, 2930, 2955 cm–1
.
1-Octyl-3,5-bis(trifluoromethyl)benzene (2g)
1H NMR (CDCl3, 400 MHz): δ = 0.93 (t, J = 7.6 Hz, 3 H, CH3), 1.35 (tq, J =
7.6, 7.6 Hz, 2 H, CH2), 1.57–1.66 (m, 2 H, CH2), 2.66 (t, J = 7.6 Hz, 2 H,
CH2), 3.90 (s, 3 H, OCH3), 7.22–7.26 (AA′BB′, 2 H, Harom), 7.93–7.97
(AA′BB′, 2 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 13.9 (CH3), 22.3 (CH2), 33.3 (CH2),
35.7 (CH2), 51.9 (OCH3), 127.6 (C), 128.4 (2 C, 2 CH), 129.6 (2 C, 2 CH),
148.5 (C), 167.2 (CO).
Colorless oil; yield: 36.4 mg (0.112 mmol, 56%); Rf = 0.60 (n-hexane).
IR (ZnSe): 683, 706, 721, 843, 891, 922, 1101, 1128, 1169, 1275, 1379,
1468, 2859, 2928 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 0.88 (t, J = 7.2 Hz, 3 H, CH3), 1.20–1.40
(m, 10 H, 5 CH2), 1.65 (tt, J = 8.0, 8.0 Hz, 2 H, CH2), 2.73 (t, J = 8.0 Hz, 2
H, CH2), 7.62 (s, 2 H, Harom), 7.70 (s, 1 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.1 (CH3), 22.6 (CH2), 29.1 (2 C, 2
HRMS (ESI+): m/z [M + H]+ calcd for C12H17O2+: 193.1223; found:
193.1220.
3
CH2), 29.3 (CH2), 31.1 (CH2), 31.8 (CH2), 35.7 (CH2), 119.7 (sep, JC–F
=
1
3
4.7 Hz, CH), 123.5 (q, JC–F = 274.0 Hz, 2 C, 2 CF3), 128.5 (q, JC–F = 2.8
Hz, 2 C, 2 CH), 131.4 (q, 2JC–F = 33.5 Hz, 2 C, 2 C), 145.2 (C).
1-Octyl-4-(trifluoromethyl)benzene (2d)
19F NMR (CDCl3, 372.5 MHz): δ = –63.1 (s).
Colorless oil; yield: 28.5 mg (0.110 mmol, 55%); Rf = 0.50 (n-hexane);
HRMS (ESI+): m/z [M]+ calcd for C16H20F6+: 326.1464; found: 326.1459.
IR (ZnSe): 723, 754, 820, 843, 1018, 1067, 1119, 1161, 1323, 1418,
1468, 1618, 2857, 2926, 2955 cm–1
.
1-(2-Butylphenyl)ethan-1-one (2h)
1H NMR (CDCl3, 400 MHz): δ = 0.88 (t, J = 6.8 Hz, 3 H, CH3), 1.20–1.37
(m, 10 H, 5 CH2), 1.62 (tt, J = 7.6, 7.6 Hz, 2 H, CH2), 2.65 (t, J = 7.6 Hz, 2
H, CH2), 7.28 (d, J = 8.0 Hz, 2 H, Harom), 7.52 (d, J = 8.0 Hz, 2 H, Harom).
Colorless oil; yield: 13.6 mg (77.2 μmol, 39%); Rf = 0.30 (n-hex-
ane/EtOAc, 30:1).
IR (ZnSe): 756, 955, 1246, 1273, 1354, 1445, 1454, 1485, 1572, 1682,
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.1 (CH3), 22.7 (CH2), 29.2 (2 C, 2
2859, 2930, 2957 cm–1
.
1
CH2), 29.4 (CH2), 31.2 (CH2), 31.8 (CH2), 35.8 (CH2), 124.4 (q, JC–F
=
1H NMR (CDCl3, 400 MHz): δ = 0.93 (t, J = 7.2 Hz, 3 H, CH3), 1.38 (tq, J =
7.2, 7.2 Hz, 2 H, CH2), 1.50–1.59 (m, 2 H, CH2), 2.58 (s, 3 H, CH3), 2.84
(t, J = 7.6 Hz, 2 H, CH2), 7.22–7.28 (m, 2 H, Harom), 7.38 (ddd, J = 1.6, 7.6,
7.6 Hz, 1 H, Harom), 7.62 (dd, J = 1.6, 7.6 Hz, 1 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.0 (CH3), 22.8 (CH2), 30.0 (CH3),
33.7 (CH2), 34.0 (CH2), 125.6 (CH), 128.9 (CH), 131.1 (CH), 131.2 (CH),
138.1 (C), 142.8 (C), 202.4 (CO).
273.0 Hz, CF3), 125.1 (q, 3JC–F = 3.8 Hz, 2 C, 2 CH), 127.9 (q, 2JC–F = 32.5
Hz, C), 128.7 (2 C, 2 CH), 147.0 (C).
19F NMR (CDCl3, 372.5 MHz): δ = –62.5 (s).
HRMS (ESI+): m/z [M + H]+ calcd for C15H22F3+: 259.1668; found:
259.1664.
4-Butylbenzonitrile (2e)
HRMS (ESI+): m/z [M + H]+ calcd for C12H17O+: 177.1274; found:
Colorless oil; yield: 9.0 mg (57 μmol, 28%); Rf = 0.30 (n-hexane/EtOAc,
177.1273.
30:1).
IR (ZnSe): 822, 837, 1020, 1177, 1379, 1416, 1456, 1466, 1504, 1607,
1-Butylnaphthalene (2i)
2226, 2860, 2930, 2957 cm–1
.
Colorless oil; yield: 36.8 mg (0.200 mmol, quantitative); Rf = 0.80 (n-
1H NMR (CDCl3, 400 MHz): δ = 0.93 (t, J = 7.6 Hz, 3 H, CH3), 1.35 (tq, J =
7.6, 7.6 Hz, 2 H, CH2), 1.56–1.65 (m, 2 H, CH2), 2.67 (t, J = 7.6 Hz, 2 H,
CH2), 7.25–7.29 (AA′BB′, 2 H, Harom), 7.54–7.58 (AA′BB′, 2 H, Harom).
hexane).
IR (ZnSe): 691, 712, 729, 746, 773, 1013, 1395, 1456, 1510, 1595,
2860, 2868, 2928, 2955, 3059 cm–1
.
13C{1H} NMR (CDCl3, 100 MHz): δ = 13.8 (CH3), 22.2 (CH2), 33.1 (CH2),
35.8 (CH2), 109.4 (C), 119.2 (C), 129.2 (2 C, 2 CH), 132.1 (2 C, 2 CH),
148.6 (C).
HRMS (ESI+): m/z [M + H]+ calcd for C11H14N+: 160.1121; found:
160.1120.
1H NMR (CDCl3, 400 MHz): δ = 0.97 (t, J = 7.6 Hz, 3 H, CH3), 1.46 (tq, J =
7.6, 7.6 Hz, 2 H, CH2), 1.69–1.78 (m, 2 H, CH2), 3.07 (t, J = 8.0 Hz, 2 H,
CH2), 7.32 (d, J = 6.8 Hz, 1 H, Harom), 7.39 (dd, J = 6.8, 8.4 Hz, 1 H, Harom),
7.43–7.53 (m, 2 H, Harom), 7.70 (d, J = 8.4 Hz, 1 H, Harom), 7.85 (d, J = 8.0
Hz, 1 H, Harom), 8.05 (d, J = 8.0 Hz, 1 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.0 (CH3), 22.9 (CH2), 32.8 (CH2),
33.0 (CH2), 123.9 (CH), 125.3 (CH), 125.5 (CH), 125.6 (CH), 125.8 (CH),
126.3 (CH), 128.7 (CH), 131.9 (C), 133.9 (C), 139.0 (C).
1,3-Difluoro-5-octylbenzene (2f)
Colorless oil; yield: 25.2 mg (0.111 mmol, 56%); Rf = 0.60 (n-hexane).
HRMS (ESI+): m/z [M]+ calcd for C14H16+: 184.1247; found: 184.1243.
IR (ZnSe): 687, 847, 982, 1115, 1310, 1460, 1593, 1626, 2857, 2926
cm–1
.
9-Butylphenanthrene (2j)
1H NMR (CDCl3, 400 MHz): δ = 0.88 (t, J = 7.2 Hz, 3 H, CH3), 1.20–1.36
(m, 10 H, 5 CH2), 1.59 (tt, J = 7.6, 7.6 Hz, 2 H, CH2), 2.58 (t, J = 7.6 Hz, 2
H, CH2), 6.61 (tt, J = 2.4, 9.2 Hz, 1 H, Harom), 6.65–6.72 (m, 2 H, Harom).
Colorless solid; yield: 31.5 mg (0.134 mmol, 62%); mp 79–80 °C; Rf =
0.75 (n-hexane).
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.1 (CH3), 22.7 (CH2), 29.1 (CH2),
IR (ZnSe): 723, 735, 760, 797, 854, 883, 939, 1003, 1036, 1252, 1425,
1449, 2311, 2926, 2951 cm–1
.
29.2 (CH2), 29.4 (CH2), 30.9 (CH2), 31.8 (CH2), 35.7 (CH2), 101.0 (t, 2JC–F
4
2
= 25.9 Hz, CH), 111.0 (dd, JC–F = 6.7 Hz, JC–F = 18.2 Hz, 2 C, 2 CH),
146.8 (t, 3JC–F = 9.5 Hz, C), 162.9 (dd, 3JC–F = 12.5 Hz, 1JC–F = 248.2 Hz, 2
C, 2 C).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

H
Y. Sumida et al.
Special Topic
Synthesis
1H NMR (CDCl3, 400 MHz): δ = 1.00 (t, J = 7.6 Hz, 3 H, CH3), 1.51 (tq, J =
7.6, 7.6 Hz, 2 H, CH2), 1.76–1.85 (m, 2 H, CH2), 3.12 (t, J = 7.6 Hz, 2 H,
CH2), 7.54–7.68 (m, 5 H, Harom), 7.81–7.84 (m, 1 H, Harom), 8.09–8.14
(m, 1 H, Harom), 8.64–8.68 (m, 1 H, Harom), 8.72–8.76 (m, 1 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.0 (CH3), 22.9 (CH2), 32.4 (CH2),
33.2 (CH2), 122.4 (CH), 123.2 (CH), 124.5 (CH), 125.8 (CH), 125.9 (CH),
126.0 (CH), 126.4 (CH), 126.5 (CH), 128.0 (CH), 129.6 (C), 130.7 (C),
131.3 (C), 131.9 (C), 136.9 (C).
IR (ZnSe): 683, 712, 791, 1026, 1188, 1377, 1422, 1456, 1466, 1477,
1574, 2855, 2924, 2955 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 0.88 (t, J = 7.2 Hz, 3 H, CH3), 1.22–1.36
(m, 10 H, 5 CH2), 1.61 (tt, J = 7.6, 7.6 Hz, 2 H, CH2), 2.60 (t, J = 7.6 Hz, 2
H, CH2), 7.20 (ddd, J = 0.8, 4.8, 8.0 Hz, 1 H, Harom), 7.49 (ddd, J = 2.0, 2.0,
8.0 Hz, 1 H, Harom), 8.41–8.46 (m, 2 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.1 (CH3), 22.6 (CH2), 29.1 (CH2),
29.2 (CH2), 29.4 (CH2), 31.1 (CH2), 31.8 (CH2), 33.0 (CH2), 123.2 (CH),
135.7 (CH), 138.0 (C), 147.2 (CH), 150.0 (CH).
HRMS (ESI+): m/z [M]+ calcd for C18H18+: 234.1403; found: 234.1403.
HRMS (ESI+): m/z [M + H]+ calcd for C13H22N+: 192.1747; found:
192.1747.
2,2′-Dibutyl-1,1′-binaphthalene (2k)
Colorless amorphous solid; yield: 27.1 mg (73.9 μmol, 37%); Rf = 0.30
(n-hexane).
6-Butylquinoline (2o)
IR (ZnSe): 748, 777, 816, 862, 1024, 1377, 1454, 1506, 2857, 2926,
Colorless oil; yield: 25.3 mg (0.137 mmol, 68%); Rf = 0.10 (n-hexane/
EtOAc, 10:1).
2953, 3051 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 0.64 (t, J = 7.6 Hz, 6 H, 2 CH3), 1.08 (tq,
J = 7.6, 7.6 Hz, 4 H, 2 CH2), 1.34–1.48 (m, 4 H, 2 CH2), 2.24–2.37 (m, 4
H, 2 CH2), 7.02 (d, J = 8.4 Hz, 2 H, Harom), 7.14–7.20 (m, 2 H, Harom),
7.35–7.40 (m, 2 H, Harom), 7.55 (d, J = 8.8 Hz, 2 H, Harom), 7.87 (d, J = 8.4
Hz, 2 H, Harom), 7.90 (d, J = 8.8 Hz, 2 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 13.7 (2 C, 2 CH3), 22.6 (2 C, 2 CH2),
32.4 (2 C, 2 CH2), 33.3 (2 C, 2 CH2), 124.9 (2 C, 2 CH), 125.7 (2 C, 2 CH),
126.4 (2 C, 2 CH), 127.3 (2 C, 2 CH), 127.5 (2 C, 2 CH), 127.7 (2 C, 2
CH), 132.0 (2 C, 2 C), 133.3 (2 C, 2 C), 134.4 (2 C, 2 C), 139.1 (2 C, 2 C).
IR (ZnSe): 770, 797, 814, 833, 881, 1119, 1377, 1454, 1464, 1499,
1570, 1593, 2857, 2928, 2955 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 0.95 (t, J = 7.6 Hz, 3 H, CH3), 1.40 (tq, J =
7.6, 7.6 Hz, 2 H, CH2), 1.65–1.74 (m, 2 H, CH2), 2.80 (t, J = 7.6 Hz, 2 H,
CH2), 7.36 (dd, J = 4.4, 8.0 Hz, 1 H, Harom), 7.55–7.59 (m, 2 H, Harom),
8.02 (d, J = 9.2 Hz, 1 H, Harom), 8.08 (d, J = 7.6 Hz, 1 H, Harom), 8.85 (dd,
J = 1.6, 4.4 Hz, 1 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 13.9 (CH3), 22.3 (CH2), 33.4 (CH2),
35.6 (CH2), 121.0 (CH), 126.0 (CH), 128.3 (C), 129.1 (CH), 131.0 (CH),
135.5 (CH), 141.3 (C), 147.1 (C), 149.5 (CH).
HRMS (ESI+): m/z [M]+ calcd for C28H30+: 366.2342; found: 366.2339.
HRMS (ESI+): m/z [M + H]+ calcd for C13H16N+: 186.1277; found:
186.1277.
Octylbenzene (2l)
Colorless oil; yield: 6.9 mg (36.3 μmol, 18%); Rf = 0.70 (n-hexane).
10-Butyl-7-ethylcamptothecin (2p)
IR (ZnSe): 696, 721, 745, 1030, 1377, 1454, 1464, 1495, 1605, 1744,
2853, 2924, 2955 cm–1
.
Colorless solid; yield: 10.6 mg (24.5 μmol, 12%); mp 190 °C (dec.); Rf =
0.25 (n-hexane/EtOAc, 1:2).
1H NMR (CDCl3, 400 MHz): δ = 0.88 (t, J = 7.2 Hz, 3 H, CH3), 1.20–1.38
(m, 10 H, 5 CH2), 1.61 (tt, J = 8.0, 8.0 Hz, 2 H, CH2), 2.60 (t, J = 8.0 Hz, 2
H, CH2), 7.14–7.20 (m, 3 H, Harom), 7.24–7.30 (m, 2 H, Harom).
IR (ZnSe): 752, 837, 1032, 1055, 1107, 1157, 1223, 1454, 1557, 1609,
1659, 1751, 2926 cm–1
.
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.1 (CH3), 22.7 (CH2), 29.3 (CH2),
29.4 (CH2), 29.5 (CH2), 31.5 (CH2), 31.9 (CH2), 36.0 (CH2), 125.5 (CH),
128.2 (2 C, 2 CH), 128.4 (2 C, 2 CH), 143.0 (C).
HRMS (ESI+): m/z [M + H]+ calcd for C14H23+: 191.1794; found:
191.1791.
1H NMR (CDCl3, 400 MHz): δ = 0.98 (t, J = 7.6 Hz, 3 H, CH3), 1.04 (t, J =
7.6 Hz, 3 H, CH3), 1.37–1.49 (m, 5 H, CH3 + CH2), 1.74 (tt, J = 7.6, 7.6 Hz,
2 H, CH2), 1.82–1.98 (m, 2 H, CH2), 2.87 (t, J = 7.6 Hz, 2 H, CH2), 3.19 (q,
J = 7.6 Hz, 2 H, CH2), 3.82 (s, 1 H, OH), 5.25 (s, 2 H, NCH2), 5.31 (d, J =
16.4 Hz, 1 H, OCH), 5.76 (d, J = 16.4 Hz, 1 H, OCH), 7.655 (s, 1 H, Harom),
7.658 (dd, J = 2.0, 8.8 Hz, 1 H, Harom), 7.85 (s, 1 H, Harom), 8.15 (d, J = 8.8
Hz, 1 H, Harom).
3C{1H} NMR (CDCl3, 100 MHz): δ = 7.8 (CH3), 13.9 (CH3), 14.0 (CH3),
22.4 (CH2), 23.0 (CH2), 31.6 (CH2), 33.5 (CH2), 36.1 (CH2), 49.4 (CH2),
66.4 (CH2), 72.8 (C), 97.7 (CH), 118.1 (C), 121.7 (CH), 126.8 (C), 126.9
(C), 130.4 (CH), 131.6 (CH), 142.8 (C), 144.8 (C), 147.3 (C), 148.2 (C),
150.2 (C), 151.1 (C), 157.7 (CO), 174.0 (CO).
1-Methoxy-4-octylbenzene (2m)
Colorless oil; yield: 16.3 mg (74.0 μmol, 74%); Rf = 0.60 (n-hex-
ane/EtOAc, 10:1).
IR (ZnSe): 696, 806, 820, 1040, 1175, 1244, 1300, 1441, 1454, 1464,
1512, 1612, 1744, 2853, 2924, 2953 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 0.88 (t, J = 6.8 Hz, 3 H, CH3), 1.20–1.35
(m, 10 H, 5 CH2), 1.57 (tt, J = 7.6, 7.6 Hz, 2 H, CH2), 2.54 (t, J = 7.6 Hz, 2
H, CH2), 3.79 (s, 3 H, OCH3), 6.80–6.85 (AA′BB′, 2 H, Harom), 7.07–7.12
(AA′BB′, 2 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.1 (CH3), 22.7 (CH2), 29.3 (2 C, 2
CH2), 29.5 (CH2), 31.8 (CH2), 31.9 (CH2), 35.0 (CH2), 55.2 (OCH3), 113.6
(2 C, 2 CH), 129.2 (2 C, 2 CH), 135.1 (C), 157.5 (C).
HRMS (ESI+): m/z [M + H]+ calcd for C26H29N2O4+: 433.2122; found:
433.2122.
2-Octylnaphthalene (2q)
Colorless oil; yield: 44.3 mg (0.184 mmol, 92%); Rf = 0.70 (n-hexane).
IR (ZnSe): 723, 745, 814, 851, 887, 945, 957, 1018, 1242, 1269, 1375,
1454, 1464, 1508, 1601, 1744, 2853, 2924, 2953, 3051 cm–1
.
HRMS (ESI+): m/z [M + H]+ calcd for C15H25O+: 221.1900; found:
221.1896.
1H NMR (CDCl3, 400 MHz): δ = 0.87 (t, J = 6.8 Hz, 3 H, CH3), 1.20–1.40
(m, 10 H, 5 CH2), 1.69 (tt, J = 7.6, 7.6 Hz, 2 H, CH2), 2.75 (t, J = 7.6 Hz, 2
H, CH2), 7.32 (dd, J = 1.6, 8.4 Hz, 1 H, Harom), 7.36–7.45 (m, 2 H, Harom),
7.60 (s, 1 H, Harom), 7.73–7.80 (m, 3 H, Harom).
3-Octylpyridine (2n)
Colorless oil; yield: 11.5 mg (60.1 μmol, 30%); Rf = 0.20 (n-hexane/
EtOAc, 10:1).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

I
Y. Sumida et al.
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Synthesis
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.1 (CH3), 22.7 (CH2), 29.3 (CH2),
29.4 (CH2), 29.5 (CH2), 31.4 (CH2), 31.9 (CH2), 36.1 (CH2), 124.9 (CH),
125.8 (CH), 126.3 (CH), 127.37 (CH), 127.44 (CH), 127.6 (CH), 127.7
(CH), 131.9 (C), 133.6 (C), 140.5 (C).
1H NMR (CDCl3, 400 MHz): δ = 1.64–1.91 (m, 6 H, 3 CH2), 2.09–2.23
(m, 2 H, CH2), 3.16 (tt, J = 8.0, 8.0 Hz, 1 H, CH), 7.37–7.46 (m, 3 H, Har-
om), 7.66 (s, 1 H, Harom), 7.75–7.81 (m, 3 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 25.6 (2 C, 2 CH2), 34.5 (2 C, 2 CH2),
46.0 (CH), 124.8 (CH), 125.0 (CH), 125.8 (CH), 126.2 (CH), 127.48 (CH),
127.52 (CH), 127.7 (CH), 132.0 (C), 133.5 (C), 144.0 (C).
HRMS (ESI+): m/z [M]+ calcd for C18H24+: 240.1873; found: 240.1869.
HRMS (ESI+): m/z [M]+ calcd for C15H16+: 196.1247; found: 196.1244.
Methyl 4-(Naphthalen-2-yl)butanoate (2s)
Colorless oil; yield: 39.5 mg (0.173 mmol, 87%); Rf = 0.20 (n-hex-
ane/EtOAc, 30:1).
2-Cyclohexylnaphthalene (2x)
IR (ZnSe): 746, 791, 818, 853, 1016, 1125, 1144, 1157, 1171, 1196,
Colorless oil; yield: 25.4 mg (0.121 mmol, 60%); Rf = 0.40 (n-hexane).
IR (ZnSe): 654, 745, 787, 814, 851, 881, 943, 953, 1018, 1269, 1447,
1217, 1244, 1364, 1435, 1506, 1732 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 2.04 (tt, J = 7.6, 7.6 Hz, 2 H, CH2), 2.36
(t, J = 7.6 Hz, 2 H, CH2), 2.80 (t, J = 7.6 Hz, 2 H, CH2), 3.65 (s, 3 H, OCH3),
7.31 (dd, J = 1.6, 8.4 Hz, 1 H, Harom), 7.38–7.47 (m, 2 H, Harom), 7.60 (s, 1
H, Harom), 7.74–7.81 (m, 3 H, Harom).
1506, 1601, 2849, 2922 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 1.24–1.36 (m, 1 H, Haliph), 1.38–1.59
(m, 4 H, Haliph), 1.74–1.82 (m, 1 H, Haliph), 1.84–1.92 (m, 2 H, Haliph),
1.93–2.01 (m, 2 H, Haliph), 2.61–2.71 (m, 1 H, Haliph), 7.35–7.46 (m, 3 H,
13C{1H} NMR (CDCl3, 100 MHz): δ = 26.3 (CH2), 33.3 (CH2), 35.2 (CH2),
51.5 (OCH3), 125.2 (CH), 125.9 (CH), 126.5 (CH), 127.2 (CH), 127.4
(CH), 127.5 (CH), 127.9 (CH), 132.0 (C), 133.5 (C), 138.8 (C), 173.9
(CO).
HRMS (ESI+): m/z [M + Na]+ calcd for C15H16O2Na+: 251.1043; found:
251.1040.
Harom), 7.63 (s, 1 H, Harom), 7.74–7.81 (m, 3 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 26.2 (CH2), 26.9 (2 C, 2 CH2), 34.4
(2 C, 2 CH2), 44.6 (CH), 124.5 (CH), 125.0 (CH), 125.7 (CH), 126.2 (CH),
127.5 (CH), 127.6 (CH), 127.7 (CH), 132.1 (C), 133.6 (C), 145.5 (C).
HRMS (ESI+): m/z [M]+ calcd for C16H18+: 210.1403; found: 210.1401.
(3-Butylnaphthalen-2-yl)trimethylsilane (2y)
Methyl (S)-2-[(tert-Butoxycarbonyl)amino]-3-(naphthalen-2-
yl)propanoate (2t)
Colorless oil; yield: 29.6 mg (0.115 mmol, 58%); Rf = 0.60 (n-hexane/
EtOAc, 30:1).
Colorless solid; yield: 18.4 mg (55.9 μmol, 28%); mp 81–83 °C; Rf =
0.15 (n-hexane/EtOAc, 10:1).
IR (ZnSe): 687, 743, 833, 872, 951, 1016, 1028, 1248, 1454, 2928,
2955 cm–1
.
IR (ZnSe): 692, 746, 822, 849, 1007, 1018, 1055, 1167, 1242, 1252,
1283, 1366, 1435, 1514, 1692, 1713, 1730, 2311, 2932, 2953, 3366
1H NMR (CDCl3, 400 MHz): δ = 0.40 (s, 9 H, 3 SiCH3), 0.99 (t, J = 7.2 Hz,
3 H, CH3), 1.49 (tq, J = 7.2, 7.2 Hz, 2 H, CH2), 1.66–1.75 (m, 2 H, CH2),
2.87 (t, J = 8.0 Hz, 2 H, CH2), 7.36–7.47 (m, 2 H, Harom), 7.63 (s, 1 H,
cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 1.40 (s, 9 H, 3 CH3), 3.16–3.34 (m, 2 H,
CH2), 3.72 (s, 3 H, OCH3), 4.67 (dt, J = 7.6, 7.6 Hz, 1 H, CH), 5.00 (d, J =
7.6 Hz, 1 H, NH), 7.26 (dd, J = 1.2, 8.0 Hz, 1 H, Harom), 7.42–7.50 (m, 2
H, Harom), 7.59 (s, 1 H, Harom), 7.76–7.83 (m, 3 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 28.3 (3 C, 3 CH3), 38.5 (CH2), 52.3
(OCH3), 54.4 (CH), 80.0 (C), 125.7 (CH), 126.1 (CH), 127.3 (CH), 127.57
(CH), 127.63 (CH), 128.0 (CH), 128.2 (CH), 132.4 (C), 133.4 (C), 133.5
(C), 155.1 (CO), 172.4 (CO).
H
arom), 7.74 (d, J = 8.0 Hz, 1 H, Harom), 7.79 (d, J = 8.0 Hz, 1 H, Harom),
7.97 (s, 1 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 0.58 (3 C, 3 SiCH3), 14.1 (CH3),
23.0 (CH2), 34.4 (CH2), 35.9 (CH2), 125.0 (CH), 125.9 (CH), 126.3 (CH),
127.0 (CH), 127.8 (CH), 131.2 (C), 133.9 (C), 135.2 (CH), 137.6 (C),
145.0 (C).
HRMS (ESI+): m/z [M]+ calcd for C17H24Si+: 256.1642; found: 256.1641.
HRMS (ESI+): m/z [M + Na]+ calcd for C19H23NNaO4+: 352.1519; found:
352.1518.
(3-Butylnaphthalen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lane (2z)
Colorless oil; yield: 420 mg (1.35 mmol, 68%); Rf = 0.30 (n-hex-
ane/EtOAc, 30:1).
2-sec-Butylnaphthalene (2v)
Colorless oil; yield: 20.3 mg (0.110 mmol, 55%); Rf = 0.60 (n-hexane).
IR (ZnSe): 746, 858, 961, 1032, 1132, 1144, 1209, 1275, 1288, 1327,
IR (ZnSe): 658, 743, 797, 816, 854, 889, 947, 961, 1018, 1377, 1454,
1344, 1371, 1462, 1593, 1630, 2928, 2955, 2976 cm–1
.
1506, 1599, 2872, 2926, 2959 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 0.95 (t, J = 7.6 Hz, 3 H, CH3), 1.38 (s, 12
H, 4 CH3), 1.42 (tq, J = 7.6, 7.6 Hz, 2 H, CH2), 1.56–1.65 (m, 2 H, CH2),
3.02 (t, J = 7.6 Hz, 2 H, CH2), 7.38 (ddd, J = 0.4, 8.0, 8.0 Hz, 1 H, Harom),
7.45 (ddd, J = 0.4, 8.0, 8.0 Hz, 1 H, Harom), 7.58 (s, 1 H, Harom), 7.73 (dd,
J = 0.4, 8.0 Hz, 1 H, Harom), 7.83 (dd, J = 0.4, 8.0 Hz, 1 H, Harom), 8.33 (s, 1
H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.1 (CH3), 22.8 (CH2), 24.9 (4 C, 4
CH3), 35.5 (CH2), 35.8 (CH2), 83.5 (2 C, 2 C), 124.9 (CH), 126.7 (CH),
126.9 (CH), 127.0 (CH), 128.2 (CH), 131.1 (C), 134.9 (C), 137.5 (CH),
145.6 (C). The signal for the carbon attached to the boron atom was
not observed.
1H NMR (CDCl3, 400 MHz): δ = 0.85 (t, J = 7.2 Hz, 3 H, CH3), 1.32 (d, J =
7.2 Hz, 3 H, CH3), 1.63–1.75 (m, 2 H, CH2), 2.76 (tq, J = 7.2, 7.2 Hz, 1 H,
CH), 7.34 (dd, J = 1.6, 8.8 Hz, 1 H, Harom), 7.38–7.46 (m, 2 H, Harom), 7.60
(s, 1 H, Harom), 7.76–7.81 (m, 3 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 12.3 (CH3), 21.9 (CH3), 31.0 (CH2),
41.8 (CH), 125.0 (CH), 125.2 (CH), 125.7 (CH), 125.9 (CH), 127.5 (CH),
127.6 (CH), 127.8 (CH), 132.1 (C), 133.6 (C), 145.1 (C).
HRMS (ESI+): m/z [M]+ calcd for C14H16+: 184.1247; found: 184.1245.
2-Cyclopentylnaphthalene (2w)
11B NMR (CDCl3, 127 MHz): δ = 31.3 (br).
Colorless oil; yield: 24.1 mg (0.123 mmol, 61%); Rf = 0.50 (n-hexane).
HRMS (ESI+): m/z [M + H]+ calcd for C20H28BO2+: 311.2177; found:
311.2174.
IR (ZnSe): 743, 777, 797, 814, 853, 887, 945, 961, 1018, 1269, 1450,
1506, 1601, 2866, 2909, 2949 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

J
Y. Sumida et al.
Special Topic
Synthesis
1-Octylcyclohexene (5a)
IR (ZnSe): 731, 818, 849, 935, 1003, 1026, 1173, 1202, 1445, 1572,
1748, 2845, 2924 cm–1
.
Colorless oil; yield: 26.6 mg (0.137 mmol, 68%); Rf = 0.95 (n-hexane).
1H NMR (C6D6, 400 MHz): δ = 0.85–1.30 (m, 18 H, Haliph), 1.47–1.57
(m, 6 H, Haliph), 1.60–1.88 (m, 24 H, Haliph), 2.05–2.23 (m, 18 H, Haliph),
7.13–7.19 (m, 1 H, Harom), 7.29 (dd, J = 8.0, 8.0 Hz, 1 H, Harom), 7.40 (d,
J = 8.0 Hz, 1 H, Harom), 7.59 (d, J = 8.0 Hz, 1 H, Harom), 7.65 (d, J = 8.0 Hz,
1 H, Harom), 8.05 (s, 1 H, Harom), 8.15 (d, J = 8.0 Hz, 1 H, Harom).
IR (ZnSe): 723, 916, 943, 966, 1302, 1327, 1341, 1348, 1377, 1418,
1439, 1454, 1651, 1659, 2855, 2922 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 0.88 (t, J = 7.2 Hz, 3 H, CH3), 1.20–1.41
(m, 12 H, 6 CH2), 1.50–1.64 (m, 4 H, 2 CH2), 1.87–1.94 (m, 4 H, 2 CH2),
1.94–2.01 (m, 2 H, CH2), 5.36–5.39 (m, 1 H, Holefin).
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.1 (CH3), 22.6 (CH2), 22.7 (CH2),
23.1 (CH2), 25.2 (CH2), 27.7 (CH2), 28.3 (CH2), 29.3 (CH2), 29.4 (CH2),
29.5 (CH2), 31.9 (CH2), 38.1 (CH2), 120.4 (CH), 138.2 (C).
13C{1H} NMR (C6D6, 100 MHz): δ = 27.5 (6 C, 6 CH2), 28.67 (6 C, 6 CH2),
28.71 (6 C, 6 CH2), 31.0 (6 C, 6 CH2), 31.1 (6 C, 6 CH2), 35.4 (t, 1JC–P = 8.7
Hz, 6 C, 6 PCH), 123.9 (CH), 124.3 (CH), 126.1 (2 C, 2 CH), 131.3 (C),
2
133.6 (C), 138.2 (CH), 138.6 (CH), 150.1 (t, JC–P = 33.5 Hz, NiC). One
HRMS (ESI+): m/z [M + H]+ calcd for C14H27+: 195.2107; found:
195.2107.
signal for aromatic CH carbon overlapped with the solvent peak.
31P{1H} NMR (C6D6, 160 MHz): δ = 11.6 (s).
HRMS (ESI+): m/z [M – Br]+ calcd for C46H73NiP2+: 745.4535; found:
745.4520.
tert-Butyl 4-Butyl-3,6-dihydropyridine-1(2H)-carboxylate (5b)
Colorless oil; yield: 33.8 mg (0.141 mmol, 71%); Rf = 0.50 (n-hexane/
EtOAc, 10:1).
trans-Bromo(4-methoxyphenyl)bis(tricyclohexylphosphine)nick-
el(II) (7)
IR (ZnSe): 770, 866, 961, 984, 1113, 1157, 1173, 1238, 1285, 1339,
1364, 1393, 1416, 1454, 1697, 2859, 2928, 2959 cm–1
.
To a solution of 4-methoxyphenyl triflate (1m, 128 mg, 500 μmol)
and LiBr (47.8 mg, 550 μmol) in THF (5 mL) were added PCy3 (421 mg,
1.50 mmol) and Ni(cod)2 (138 mg, 502 μmol) at r.t. After stirring for 3
h at this temperature, the solution was concentrated under reduced
pressure. The residue was washed with MeOH/n-hexane (5:1) to give
7 as a yellow solid; yield: 376 mg (466 μmol, 93%); mp 118 °C (dec.).
1H NMR (CDCl3, 400 MHz, 50 °C): δ = 0.90 (t, J = 7.6 Hz, 3 H, CH3), 1.30
(tq, J = 7.6, 7.6 Hz, 2 H, CH2), 1.33–1.43 (m, 2 H, CH2), 1.46 (s, 9 H, 3
CH3), 1.94–2.05 (m, 4 H, 2 CH2), 3.47 (t, J = 6.0 Hz, 2 H, NCH2), 3.83 (br
s, 2 H, NCH2), 5.33 (br s, 1 H, Holefin).
13C{1H} NMR (CDCl3, 100 MHz, 50 °C): δ = 13.8 (CH3), 22.3 (CH2), 28.4
(CH2), 28.5 (3 C, 3 CH3), 29.6 (CH2), 36.9 (CH2), 40.6 (CH2), 43.4 (CH2),
79.3 (C), 117.7 (CH), 136.9 (C), 155.0 (CO).
IR (ZnSe): 700, 731, 787, 804, 824, 849, 889, 1003, 1024, 1173, 1227,
1258, 1445, 1477, 2847, 2922 cm–1
.
HRMS (ESI+): m/z [M + H]+ calcd for C14H26NO2+: 240.1958; found:
240.1955.
1H NMR (C6D6, 400 MHz): δ = 1.07–1.29 (m, 18 H, Haliph), 1.58–1.67
(m, 6 H, Haliph), 1.69–1.89 (m, 24 H, Haliph), 2.06–2.21 (m, 18 H, Haliph),
3.46 (s, 3 H, OCH3), 6.72 (d, J = 8.4 Hz, 2 H, Harom), 7.53 (d, J = 8.4 Hz, 2
H, Harom).
2,6-Dimethyl-10-methylenetetradeca-2,6-diene (5c)
13C{1H} NMR (C6D6, 100 MHz): δ = 27.6 (6 C, 6 CH2), 28.6–29.0 (m, 12
Colorless oil; yield: 20.2 mg (86.2 μmol, 43%); mixture of stereo- and
regioisomers; Rf = 0.80 (n-hexane).
C, 12 CH2), 31.1 (12 C, 12 CH2), 35.3 (t, 1JC–P = 8.7 Hz, 6 C, 6 PCH), 55.7
2
(OCH3), 113.5 (2 C, 2 CH), 135.9 (t, JC–P = 33.5 Hz, NiC), 140.0 (2 C, 2
IR (ZnSe): 829, 885, 978, 1107, 1377, 1452, 1643, 2859, 2928, 2959
cm–1
.
CH), 157.3 (C).
31P{1H} NMR (C6D6, 160 MHz): δ = 11.4 (s).
HRMS (ESI+): m/z [M – Br]+ calcd for C43H73NiOP2+: 725.4485; found:
Since minor regioisomers were difficult to assign, only two major ste-
reoisomers were assigned.
1H NMR (CDCl3, 400 MHz): δ = 0.91 (t, J = 7.2 Hz, 6 H, 2 CH3), 1.25–
1.45 (m, 8 H, 4 CH2), 1.59–1.63 (m, 9 H, 3 CH3), 1.66–1.70 (m, 9 H, 3
CH3), 1.95–2.16 (m, 20 H, 10 CH2), 4.71 (s, 4 H, 2 =CH2), 5.06–5.16 (m,
4 H, 4 CHolefin).
725.4470.
2-Azido-3-butylnaphthalene (12a)
To a solution of 2z (31.0 mg, 0.100 mmol, 1 equiv) in MeOH (1 mL)
were added NaN3 (19.5 mg, 0.300 mmol, 3.0 equiv) and Cu(OAc)2 (7.3
mg, 40 μmol, 0.20 equiv) at r.t. After stirring for 5 h with heating at 50
°C under air, the mixture was cooled to r.t. To the mixture was added
aq phosphate buffer (pH 7.4, ca. 1 mL) and it was extracted with Et2O
(3 × ca. 1 mL). The combined organic extracts were dried (Na2SO4) and
filtered through a short pad of silica gel; the filtrate was concentrated
under reduced pressure. The residue was purified by column chroma-
tography (silica gel, n-hexane) to give 12a as a pale yellow oil; yield:
15.3 mg (67.9 μmol, 68%); Rf = 0.70 (n-hexane).
3C{1H} NMR (CDCl3, 100 MHz): δ = 14.0 (2 C, 2 CH3), 16.0 (CH3), 17.6
(CH3), 17.7 (CH3), 22.5 (2 C, 2 CH2), 23.4 (CH3), 25.70 (CH3), 25.72
(CH3), 26.3 (CH2), 26.4 (CH2), 26.6 (CH2), 26.7 (CH2), 30.0 (2 C, 2 CH2),
32.0 (CH2), 35.9 (2 C, 2 CH2), 36.1 (CH2), 36.3 (CH2), 39.7 (CH2), 108.6
(2 C, 2 =CH2), 124.2 (CH), 124.3 (CH), 124.4 (CH), 124.9 (CH), 131.3
(C), 131.6 (C), 135.1 (C), 135.3 (C), 150.0 (2 C, 2 C).
HRMS (ESI+): m/z [M + H]+ calcd for C17H31+: 235.2420; found:
235.2418.
IR (ZnSe): 743, 835, 864, 949, 1140, 1209, 1279, 1445, 1454, 1464,
trans-Bromo(naphthalen-2-yl)bis(tricyclohexylphosphine)nick-
el(II) (6)
1501, 2099, 2859, 2928, 2955, 4195 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 0.95 (t, J = 7.6 Hz, 3 H, CH3), 1.40 (tq, J =
7.6, 7.6 Hz, 2 H, CH2), 1.58–1.68 (m, 2 H, CH2), 2.70 (t, J = 7.6 Hz, 2 H,
CH2), 7.36–7.45 (m, 2 H, Harom), 7.50 (s, 1 H, Harom), 7.59 (s, 1 H, Harom),
7.73 (dd, J = 1.6, 7.6 Hz, 2 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.0 (CH3), 22.5 (CH2), 31.3 (CH2),
32.4 (CH2), 115.2 (CH), 125.3 (CH), 126.0 (CH), 126.3 (CH), 127.2 (CH),
128.7 (CH), 131.1 (C), 132.5 (C), 133.8 (C), 137.3 (C).
To a solution of 2-naphthyl triflate (1a; 1.38 g, 5.00 mmol) and LiBr
(478 mg, 5.50 mmol) in THF (20 mL) were added PCy3 (4.21 g, 15.0
mmol) and Ni(cod)2 (1.38 g, 5.02 mmol) at r.t. After stirring for 2 h at
this temperature, the solution was concentrated under reduced pres-
sure. The residue was washed with n-hexane and MeOH to give 6 as a
yellow solid; yield: 3.50 g (4.23 mmol, 85%); mp 122 °C (dec.).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

K
Y. Sumida et al.
Special Topic
Synthesis
+
HRMS (ESI+): m/z [M]+ calcd for C14H15N3
225.1272.
:
225.1260; found:
mixture was added a solution of pH 7.4 aq phosphate buffer (ca. 1 mL)
and it was extracted with Et2O (3 × ca. 1 mL). The combined organic
extracts were dried (Na2SO4) and filtered through a short pad of silica
gel; the filtrate was concentrated under reduced pressure. The residue
was purified by column chromatography (silica gel, n-hexane) to give
12d as a colorless oil; yield: 12.8 mg (41.3 μmol, 41%); Rf = 0.70 (n-
hexane).
3-Butyl-2-naphthol (12b)
To a solution of 2z (31.0 mg, 0.100 mmol, 1 equiv) in THF (10 mL) was
added 30% aq H2O2 (0.6 mL) and 15% aq NaOH (1.3 mL) at r.t. The mix-
ture was stirred for 2 h at this temperature, and then aq phosphate
buffer (pH 7.4, ca. 2 mL) was added. The mixture was extracted with
Et2O (3 × ca. 1 mL), and the combined organic extracts were dried
(Na2SO4), filtered, and concentrated under reduced pressure. The resi-
due was purified by column chromatography (silica gel, n-hexane/
EtOAc, 10:1) to give 12b as a colorless solid; yield: 15.4 mg (76.9
μmol, 77%); mp 83–84 °C; Rf = 0.20 (n-hexane/EtOAc, 10:1).
IR (ZnSe): 743, 876, 951, 966, 1128, 1427, 1445, 1489, 1582, 2857,
2926, 2953, 3051 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 0.99 (t, J = 7.6 Hz, 3 H, CH3), 1.46 (tq, J =
7.6, 7.6 Hz, 2 H, CH2), 1.62–1.71 (m, 2 H, CH2), 2.85 (t, J = 7.6 Hz, 2 H,
CH2), 7.39–7.48 (m, 2 H, Harom), 7.64 (s, 1 H, Harom), 7.68 (d, J = 8.0 Hz, 1
H, Harom), 7.73 (d, J = 8.0 Hz, 1 H, Harom), 8.37 (s, 1 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.0 (CH3), 22.5 (CH2), 32.6 (CH2),
40.4 (CH2), 99.2 (C), 125.8 (CH), 126.3 (CH), 126.4 (CH), 127.0 (CH),
127.3 (CH), 133.1 (C), 133.4 (C), 138.6 (CH), 141.6 (C).
IR (ZnSe): 681, 719, 743, 756, 849, 870, 951, 1101, 1140, 1152, 1180,
1244, 1352, 1396, 1449, 1514, 1601, 1632, 2857, 2936, 2953, 3514
cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 0.97 (t, J = 7.6 Hz, 3 H, CH3), 1.44 (tq, J =
7.6, 7.6 Hz, 2 H, CH2), 1.65–1.74 (m, 2 H, CH2), 2.78 (t, J = 7.6 Hz, 2 H,
CH2), 4.91 (s, 1 H, OH), 7.09 (s, 1 H, Harom), 7.30 (dd, J = 8.0, 8.0 Hz, 1 H,
HRMS (ESI+): m/z [M]+ calcd for C14H15I+: 310.0213; found: 310.0215.
H
arom), 7.36 (dd, J = 8.0, 8.0 Hz, 1 H, Harom), 7.58 (s, 1 H, Harom), 7.64 (d,
Funding Information
J = 8.0 Hz, 1 H, Harom), 7.71 (d, J = 8.0 Hz, 1 H, Harom).
13C{1H} NMR (CDCl3, 100 MHz): δ = 14.0 (CH3), 22.6 (CH2), 30.2 (CH2),
31.8 (CH2), 109.3 (CH), 123.5 (CH), 125.6 (CH), 125.8 (CH), 127.1 (CH),
128.6 (CH), 129.2 (C), 131.0 (C), 133.2 (C), 152.4 (C).
This research was supported by JSPS KAKENHI Grant Number
16K17907 (Y.S.); Japan Prize Foundation (Y.S.); the Incentive Research
Grant from RIKEN (Y.S.).
S
JPS
K
A
K
E
N
H
I
1(
6
K
1
7
9
0
7)
HRMS (ESI+): m/z [M + H]+ calcd for C14H17O+: 201.1274; found:
201.1265.
Acknowledgment
Methyl 4-(3-Butylnaphthalen-2-yl)benzoate (12c)
The authors thank Central Glass Co., Ltd. for providing Tf2O.
To a solution of 2z (31.0 mg, 0.100 mmol, 1 equiv) in toluene (0.5 mL)
and water (0.1 mL) were added methyl 4-iodobenzoate (52.4 mg,
0.200 mmol, 2.0 equiv), (amphos)2PdCl2 (3.54 mg, 5.00 μmol, 0.05
equiv), and Cs2CO3 (97.9 mg, 0.300 mmol, 3.0 equiv) at r.t. The mix-
ture was stirred and heated at 100 °C for 18 h and then it was cooled
to r.t. To the mixture was added water (ca. 1 mL) and it was extracted
with Et2O (3 × ca. 1 mL). The combined organic extracts were dried
(Na2SO4) and filtered through a short pad of silica gel; the filtrate was
concentrated under reduced pressure. The residue was purified by
column chromatography (silica gel, n-hexane/EtOAc, 20:1) to give 12c
as a colorless oil; yield: 29.5 mg (92.6 μmol, 93%); Rf = 0.40 (n-hex-
ane/EtOAc, 10:1).
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1588464.
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u
p
p
o
nrtogI
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p
ortiInfogrmoaitn
References
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13C{1H} NMR (CDCl3, 100 MHz): δ = 13.8 (CH3), 22.4 (CH2), 33.1 (CH2),
33.2 (CH2), 52.1 (OCH3), 125.6 (CH), 126.1 (CH), 127.1 (CH), 127.5
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319.1691.
2-Butyl-3-iodonaphthalene (12d)
To a solution of 2z (31.0 mg, 0.100 mmol, 1 equiv) in THF (0.5 mL) and
water (0.5 mL) were added NaI (75 mg, 0.50 mmol, 5.0 equiv) and
chloramine-T (68.3 mg, 0.300 mmol, 3.0 equiv) at r.t. The mixture was
stirred and heated at 80 °C for 4 h, and then it was cooled to r.t. To the
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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Y. Sumida et al.
Special Topic
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(16) Another mechanism (Figure S3), wherein a free alkyl radical is
uninvolved, is also conceivable. See the Supporting Information
for details. We appreciate the reviewer for the suggestion.
(17) Proposed mechanism for olefin isomerization (Scheme 9):
β-C
elimination
I
I
I
N
N
N
N
N
N
NiII
Ni0
NiII
i
ii
β-H
elimination
I
N
N
2-Np
I
N
re-insertion
NiII
10
NiII
H
N
2-Np
iv
iii
11
Scheme 9
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L