Synthesis of axially chiral 1,1′-binaphthalenes by palladium-catalysed cross-coupling reactions of triorganoindium reagents

Article abstract of DOI:10.1002/ejoc.201300042

1,1′-Binaphthalenes and heterocyclic analogues can be efficiently prepared by palladium-catalysed cross-coupling reactions between tri(1-naphthyl)indium reagents and 1-halonaphthalenes and haloisoquinolines. The reactions were usually carried out in THF at 80 °C with a slight excess of the indium reagent (40 mol-%) and a low catalyst loading (4 mol-% Pd) to afford the cross-coupling products in good yields (45-99 %). The method allows the synthesis of sterically hindered 2-substituted and 2,2′-disubstituted 1,1′-binaphthalenes and naphthylisoquinolines. In addition, the coupling reactions can be performed enantioselectively and the best enantiomeric excesses were obtained by using the chiral amino-phosphane ferrocenyl ligand (R,S)-PPFA. 1,1′-Binaphthalenes and heterocyclic derivatives have been synthesized by palladium-catalysed cross-coupling reactions between tri(1-naphthyl)indium reagents and 1-halonaphthalenes and haloisoquinolines, including 2-substituted and 2,2′-disubstituted 1,1′-binaphthyls. The coupling reactions can be performed enantioselectively in the presence of the chiral ligand (R,S)-PPFA. Copyright

Full text of DOI:10.1002/ejoc.201300042

FULL PAPER
DOI: 10.1002/ejoc.201300042
Synthesis of Axially Chiral 1,1Ј-Binaphthalenes by Palladium-Catalysed Cross-
Coupling Reactions of Triorganoindium Reagents
[a]
[a]
[a]
[a]
Ángeles Mosquera, Miguel A. Pena, José Pérez Sestelo,* and Luis A. Sarandeses*
Dedicated to Professor Julio Delgado Martín on the occasion of his 70th birthday
Keywords: Cross-coupling / Indium / Palladium / Biaryls / Asymmetric catalysis
1
,1Ј-Binaphthalenes and heterocyclic analogues can be ef-
(45–99%). The method allows the synthesis of sterically hin-
dered 2-substituted and 2,2Ј-disubstituted 1,1Ј-binaphthal-
enes and naphthylisoquinolines. In addition, the coupling re-
actions can be performed enantioselectively and the best en-
antiomeric excesses were obtained by using the chiral
amino-phosphane ferrocenyl ligand (R,S)-PPFA.
ficiently prepared by palladium-catalysed cross-coupling re-
actions between tri(1-naphthyl)indium reagents and 1-halo-
naphthalenes and haloisoquinolines. The reactions were
usually carried out in THF at 80 °C with a slight excess of the
indium reagent (40 mol-%) and a low catalyst loading (4 mol-
%
Pd) to afford the cross-coupling products in good yields
Introduction
tral-to-axial chirality transfer and cross-coupling reac-
[
6]
tions. Enantioselective coupling has been reported for dif-
ferent organometallic reagents and the first example in-
volved the use of Grignard reagents, nickel catalysis and a
The biaryl unit is a structural motif that is present in a
number of biologically active natural products and pharma-
ceuticals, for example, vancomycin, korupensamine A and
michellamines A and B.[ In addition, the restricted rota-
tion around the aryl–aryl bond can lead to atropisomerism,
and binaphthyls are an important family of chiral ligands
in asymmetric synthesis and organocatalysis.[2]
[
7]
chiral ferrocenylphosphane ligand. It was later shown that
these chiral ligands are useful for the synthesis of chiral
binaphthylic compounds using organozinc reagents,[ and
Suzuki–Miyaura reactions have also been developed by
1]
8]
[
9]
[10]
using different types of ligands, for example, KenPhos
Biaryls can be synthesized by aryl–aryl bond-forming
methodologies, with the Ullmann coupling and metal-cata-
lysed cross-coupling reactions being the most frequently
[
11]
or a chiral ferrocenyl monophosphane.
Recently, chiral
[
12]
[13]
bis-hydrazone and chiral phosphane ligands have also
shown good enantioselectivities with organoboron reagents.
Despite the intensive research in this field, important chal-
lenges remain and these include the optimization of the cat-
alyst loading, the development of milder conditions and the
application of versatile methodologies. Particularly attract-
ive is the enantioselective synthesis of binaphthalenes, espe-
cially those furnished with heteroaromatic structures such
as quinoline derivatives.
[
3]
used. In particular, binaphthalenes can be prepared by
palladium- or nickel-catalysed coupling reactions although
the synthesis of o,oЈ-disubstituted derivatives is sometimes
difficult due to the steric hindrance of the reactive bonds.
In this sense, the development of new catalytic systems and
organometallic reagents has allowed the synthesis of hin-
[
4]
dered derivatives.
The asymmetric synthesis of optically active binaphthylic
structures can be achieved by a diastereoselective ap-
In recent years we have shown that triorganoindium rea-
gents (R In) are useful in metal-catalysed cross-coupling re-
[
5]
3
14]
proach or by enantioselective metal-catalysed transforma-
tions, including the oxidative dimerization of phenols, cen-
[
actions. The main features of these indium organometal-
lics are their high efficiency in transferring the three groups
attached to the metal, their versatility and their chemo- and
[
a] Departamento de Química Fundamental, Universidade da
Coruña,
stereoselectivity. In particular, R In reagents have shown
3
1
5071 A Coruña, Spain
great ability in aryl–aryl bond formation, including the syn-
thesis of hindered biaryls and heterobiaryls following a tan-
dem-directed ortho-metallation/transmetallation/cross-cou-
pling nexus or through selective and/or iterative cross-cou-
Fax: +34-981-167-065
E-mail: qfsarand@udc.es
sestelo@udc.es
Homepage: ciencias.udc.es/investigacion-qf/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300042.
[
15]
pling reactions.
Despite the attractive synthetic features,
Eur. J. Org. Chem. 2013, 2555–2562
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2555

Á. Mosquera, M. A. Pena, J. Pérez Sestelo, L. A. Sarandeses
We then proceeded to assess the reactivity of 2-substi-
FULL PAPER
the utility of indium organometallics in the synthesis of bi-
naphthalenes has not been exploited and there is only one tuted naphthylindium reagents as coupling partners. Under
[
16]
example concerning the use of a naphthylindium reagent.
the previously developed conditions ([Pd dba ], DavePhos,
2 3
In this article, we report the synthesis of axially chiral 1,1Ј- THF, 80 °C), the reaction of tris(2-methylnaphthyl)indium
binaphthalenes by palladium-catalysed coupling reactions (1b) with 1-bromonaphthalene (2) afforded the aforemen-
of triorganoindium reagents with halonaphthalenes tioned binaphthyl 7b in 69% yield (Table 1, entry 2). There-
(Scheme 1).
fore 2-methyl-1,1Ј-binaphthalene (7b) can be prepared by
two procedures, which shows the versatility of organo-
indium reagents in cross-coupling reactions. The lower yield
obtained in the second reaction (69 vs. 92%) can be attrib-
uted to greater steric hindrance in the nucleophilic counter-
part or to side-reactions during the preparation of the trior-
ganoindium reagent. Indeed, the use of larger amounts of
1b (70 mol-%) gave 7b in almost quantitative yield (96%).
The reaction of 1b with 3 proceeded similarly, providing
2,2Ј-dimethyl-1,1Ј-binaphthalene (8b) in 60% yield (en-
Scheme 1. Synthetic plan.
try 5), whereas the use of 70 mol-% of R In led to a 90%
3
yield. Analogously, the reactions of organoindium reagent
1b with 1-bromonaphthalenes 4–6 afforded the correspond-
ing cross-coupling products in satisfactory yields (57–65%
yields, entries 8, 11 and 14, respectively). The reaction of
tris(2-methoxybinaphthyl)indium (1c) with 2 in THF at
Results and Discussion
8
0 °C with [Pd dba ] (2 mol-%) and DavePhos (8 mol-%) as
2 3
the catalytic system gave 1,1Ј-binaphthalene 7c in 67% yield
(Table 1, entry 3), a comparable result to that obtained by
inverting the substitution in the coupling partners (76%,
Synthesis of Axially Chiral Binaphthalenes
Our research started with the preparation of tri(naphth- Table 1, entry 7). Interestingly, the binaphthyl 8c, previously
yl)indium reagents and subsequent coupling with 1-bromo- obtained by reaction of the organoindium 1b with bromo-
naphthalenes under palladium catalysis. Triorganoindium naphthalene 4 (65%, entry 8) was also synthesized in 69%
reagents (R In) can be easily prepared from the correspond- yield by the reaction of 1c with 3 (entry 6). In the same way,
3
ing organolithium or Grignard reagents by transmetallation tris(2-methoxynaphthyl)indium (1c) reacted effectively with
with an indium(III) salt.[
14–17]
Accordingly, tri(naphthyl)- 1-bromonaphthlenes 4–6 to afford the corresponding cou-
indium (1a, Table 1), tris(2-methylnaphthyl)indium (1b) and pling products 9c–11c in satisfactory yields (53–69%, en-
tris(2-methoxynaphthyl)indium (1c) were prepared as THF tries 9, 12 and 15). These results show the utility of naphth-
solutions from the corresponding 1-bromonaphthalenes by ylindium reagents in the synthesis of substituted 1,1Ј-bi-
lithiation and transmetallation with InCl . Based on our naphthylic compounds. It is worth highlighting the high
3
previous experience,[
15a]
we found that the reaction of 1a efficiency of the triorganoindium reagents in transferring
(40 mol-%) with 1-bromonaphthalene (2) in the presence of the naphthyl group, even in hindered substrates, because
[
Pd(dppf)Cl ] (4 mol-%) as catalyst in THF at 80 °C pro- only 40 mol-% of these reagents is necessary for completion
2
vided 1,1Ј-binaphthalene (7a) in 84% yield after 16 h of the reactions in good yields.
Table 1, entry 1). This promising result led us to explore Our next step was to explore the reactivity of 1-naphth-
(
the synthesis of functionalized 1,1Ј-binaphthalenes. How- ylindium reagents with haloheteroarenes as electrophiles.
ever, the reaction of 1a with 1-bromo-2-methylnaphthalene Binaphthylic derivatives furnished with heteroaryl moieties,
(
3) only gave the coupling product 2-methyl-1,1Ј-binaphth- for example, quinap, represent an important family of li-
[
19]
alene (7b) in 42% yield, a result that can probably be attrib- gands in asymmetric catalysis,
uted to greater steric hindrance. Interestingly, we found that cross-coupling reactions is less developed. Because of the
but their synthesis by
[
20]
the combination of [Pd dba ] (2 mol-%) and the biarylic li- interest in naphthylisoquinolines, we investigated the cou-
2
3
[
18]
gand DavePhos (8 mol-%) afforded the desired coupling pling of naphthylindium reagents with haloisoquinolines.
product 7b in 92% yield after 12 h in THF at 80 °C (en- Under the previously developed conditions, the reactions of
try 4). Further experiments showed that this catalytic sys- the triorganoindium reagents 1a–c with 4-bromoisoquin-
tem was also effective in the synthesis of 2-substituted 1,1Ј- oline (12) afforded the 4-naphthylisoquinolines 14a–c in
binaphthalenes. For example, the reaction of 1a with 1- good yields (62–79%, Table 2, entries 1–3). Interestingly,
bromo-2-methoxynaphthalene gave the 2-methoxy-1,1Ј-bi- our methodology could also be extended to the use of 1-
naphthalene (7c) in 76% yield (entry 7). As can be seen in haloisoquinolines. The reactions of indium organometallics
Table 1, the reaction of organoindium reagent 1a with 1- 1a–c with 1-chloroisoquinoline (13a) gave 2-naphthyliso-
bromonaphthalenes 5 and 6 provided the corresponding 2- quinolines 15a–c in good yields (60–78%). The coupling re-
substituted 1,1Ј-binaphthalenes 10a and 11a in 89 and 99% actions with 1-iodoisoquinoline (13b) proceeded in shorter
yields (entries 10 and 13, respectively).
reaction times but in similar yields (62–76%, Table 2, en-
2556
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2555–2562

Synthesis of Axially Chiral 1,1Ј-Binaphthalenes
Table 1. Synthesis of 1,1Ј-binaphthalenes by palladium-catalysed cross-coupling reactions of indium organometallics.
2 3
[a] Isolated yield. [b] Reaction performed with [PdCl (dppf)] (4 mol-%) as catalyst. [c] Isolated yield obtained by using 70 mol-% of R In.
tries 4–6). These results demonstrate the usefulness of tri- gand with the same amino-phosphane substitution pattern
organoindium reagents in the synthesis of 1,1Ј-binaphthyls as DavePhos.
and naphthylisoquinolines, including those substituted at
In an effort to minimize racemization during the cou-
the C-2 position, which provides an interesting perspective pling reaction (80 °C, 12–15 h) we focused our attention on
for the development of enantioselective coupling reactions. the synthesis of chiral 2-substituted 1,1Ј-binaphthylic com-
pounds. The reaction of tri(1-naphthyl)indium (1a, 40 mol-
%
) with 1-bromo-2-methylnaphthalene (3) with [Pd dba ]
2 3
(
2 mol-%) and (S)-KenPhos (L1, 8 mol-%) as the catalytic
Enantioselective Synthesis of Axially Chiral 1,1Ј-
Binaphthalenes
system afforded the 2-methyl-1,1Ј-binaphthalene (7b) in
quantitative yield, albeit with low enantioselectivity (18%
Having demonstrated the utility of cross-coupling reac- ee, Table 3, entry 1).[22] This led us to test other available
tions with triorganoindium reagents in the synthesis of axi- P,N ligands for use in the enantioselective synthesis of bi-
[
23]
ally chiral racemic 1,1Ј-binaphthalenes, we turned our at- naphthalenes,
such as amino-phosphane ferrocenyl li-
tention to enantioselective syntheses. The promising results gands. By using the previously described conditions, we
obtained with the ligand DavePhos prompted us to use found that the reaction of tri(1-naphthyl)indium (40 mol-
KenPhos (L1, Table 3),[
10,21]
a chiral 1,1Ј-binaphthylic li- %) with 3 with the (R,S)-Taniaphos ligand (L2) provided
Eur. J. Org. Chem. 2013, 2555–2562
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2557

Á. Mosquera, M. A. Pena, J. Pérez Sestelo, L. A. Sarandeses
FULL PAPER
Table 2. Synthesis of naphthylisoquinolines by palladium-catalysed
cross-coupling reactions of indium organometallics.
Table 3. Enantioselective synthesis of 1,1Ј-binaphthyls by cross-
coupling reactions of triorganoindium reagents.
Entry
3
R In Ar–X
Li- Product Yield [%] ee[b] [%]
gand
[a]
1
2
3
1a
1a
1a
1a
1b
1b
1b
1b
1c
1b
3
3
3
3
3
4
5
12
12
13b
L1
L2
L3
L3
L3
L3
L3
L3
L3
L3
7b
7b
7b
7b
8b
95
81
40
71
70
68
71
73
45
78
18 (R)
0
76 (S)
86 (S)
72 (S)
67 (R)
74 (S)
31 (+)
32 (–)
20 (+)
[
c]
4
[
c]
5
[
c]
6
8c
[
c]
7
10b
14b
14c
15b
[
c]
8
[
c]
9
1
0[c]
[
a] Isolated yield. [b] The yields of reactions with 13b are given in
parentheses.
the coupling product 7b in 81% yield, but with no enantio-
selectivity (entry 2). Interestingly, when the reaction was
carried out in the presence of the chiral ligand (R,S)-PPFA
(
L3), the 1,1Ј-binaphthalene 7b was obtained in an enantio-
[
a] Isolated yield. [b] The enantiomeric ratio was determined by
meric ratio of 88:12 (76% ee), but in only 40% yield (en-
try 3). Encouraged by this result, we aimed to improve the
chemical yield by increasing the amount of indium reagent see the Supporting Information. [c] The reaction was performed by
HPLC and the stereochemistry of the major isomer (in parenthe-
ses) was determined by comparison with reported data. For details,
and found that the use of 100 mol-% of R In increased both using 100 mol-% of R
3
In.
3
the yield and the enantiomeric excess (71% yield and 86%
ee, entry 4). The higher yield can be explained by the larger pling reaction of 1b with 1-bromo-2-methoxynaphthalene
amount of organoindium reagent used, and the higher (4; 68% yield, 67% ee, entry 6). In addition, the reaction of
enantioselectivity by the coordination of the indium species 1b with 1-bromo-4-methylnaphthalene (5) also provided
in the diastereomeric transition state. In the analysis of the (S)-2,4Ј-dimethyl-1,1Ј-binaphthalene (10b) enantioselecti-
results it is important to bear in mind that ligand L3 has vely (74% ee) in 71% yield (entry 7).
also proven useful in previous syntheses of 1,1Ј-binaphth-
Our reaction conditions were also applied to the asym-
ylic compounds by Negishi and Suzuki coupling reac- metric synthesis of heterocyclic analogues of 1,1Ј-binaphth-
[
7,8,11]
tions.
We also extended our research to other related alenes. The reactions of naphthylindium derivatives 1b and
ferrocenyl ligands such as (R,S)-Mandyphos or (R,S)-Jos- 1c with 4-bromoisoquinoline (12) and (R,S)-PPFA (L3) as
iphos, but the coupling products were obtained in variable the chiral ligand gave the 4-naphthylisoquinolines 14b and
yields without significant enantioselectivity. These experi- 14c in yields of 73 and 45%, respectively, with moderate
ments suggest that amino-phosphanes are the catalysts of enantioselectivities (31–32% ee, entries 8 and 9). In an effort
choice for the enantioselective synthesis of 1,1Ј-binaphthal- to synthesize quinap-type 1,1Ј-heterobinaphthyls, we as-
enes by using indium organometallics.
sessed the coupling of 1b with 1-iodoisoquinoline (13b). In
Based on these results, we chose ligand L3 to study the this case, 1-naphthylisoquinoline 15b was obtained in good
enantioselective synthesis of binaphthalene compounds by yield (78%), but with low enantioselectivity (20% ee, en-
using triorganoindium reagents. By using the previous con- try 10). The lower stereoselectivity could be affected by the
ditions, we observed that the reaction of tris(2-methyl- lower steric demand of the nitrogen at C-2 in comparison
naphthyl)indium (1b, 100 mol-%) with 3 gave 2,2Ј-dimethyl- with other substituents. Despite the variable enantiomeric
1,1Ј-binaphthalene (8b) in good yield and with good ratios, our research demonstrates the utility of indium
enantioselectivity (70% yield, 72% ee, entry 5). The feasibil- organometallics for the synthesis of 1,1Ј-binaphthyls and is
ity of this method was also demonstrated in the asymmetric one of the first approaches to the enantioselective synthesis
synthesis of 2,2Ј-disubstituted binaphthalene 8c by the cou- of naphthylisoquinolines by cross-coupling reactions. In
2558
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2555–2562

Synthesis of Axially Chiral 1,1Ј-Binaphthalenes
comparison with related procedures in which the same cata- 1-bromo-2-methylnaphthalene and 1-bromo-2-methoxynaphthal-
ene.
lytic system is employed, the use of indium reagents pro-
vides comparable results to those obtained with boron and
zinc reagents in terms of chemical and optical yields.
General Procedure for the Palladium-Catalysed Cross-Coupling Re-
actions of Tri(1-naphthyl)indium Reagents with 1-Halonaphthalene
Electrophiles: A solution of the tri(2-naphthyl)indium reagent
(
0.20–0.40 mmol, 0.4–1.0 equiv., ca. 0.4 m in dry THF) was added
to a THF (4 mL) solution of the 2-halonaphthalene (0.5 mmol,
equiv.), [Pd dba ] (9 mg, 0.01 mmol, 0.002 equiv.) and the ligand
Conclusions
1
2
3
We have reported herein the first examples of the synthe- [DavePhos (15 mg, 0.04 mmol, 0.08 equiv.) in the racemic coupling
reactions or (R,S)-PPFA (17 mg, 0.04 mmol, 0.08 equiv.) in the
sis of 1,1Ј-binaphthyls and heterocyclic analogues by palla-
enantioselective coupling reactions] in a Schlenk tube filled with
dium-catalysed cross-coupling reactions of tri(1-naphthyl)-
argon. The resulting mixture was heated at 80 °C until the starting
indium reagents with 1-bromonaphthalenes and haloiso-
material was consumed (12–15 h), cooled to room temp., quenched
by the addition of a few drops of MeOH and diluted with Et O
2
quinolines. This methodology is useful for the efficient
preparation of 2-substituted and 2,2Ј-disubstituted 1,1Ј-bi-
naphthyls. The reactions usually proceeded with a small ex-
cess of the indium reagents and low palladium catalyst
(
40 mL). The organic phase was washed successively with aqueous
HCl (5%, 30 mL), a saturated aqueous solution of NaHCO
30 mL) and brine (30 mL), dried and concentrated. The residue
3
(
loading under mild reaction conditions. In addition, when was purified by flash chromatography to afford, after concentration
the cross-coupling reactions were performed in the presence and high-vacuum drying, the corresponding cross-coupling prod-
of a chiral ferrocenyl ligand, binaphthalenes were obtained ucts.
with moderate-to-good enantioselectivities. Moreover, these
results provide new evidence for the utility of indium rea-
gents in cross-coupling reactions and highlight them as an 7.95–7.98 (m, 4 H) ppm. C NMR (75 MHz, CDCl ): δ = 125.4
[24]
1
1
,1Ј-Binaphthalene (7a):
White solid (92 mg, 84%); m.p. 140–
1
42 °C. H NMR (300 MHz, CDCl ): δ = 7.30–7.63 (m, 10 H),
3
1
3
3
alternative to other organometallics used in these reactions. (2 CH), 125.8 (2 CH), 126.0 (2 CH), 126.5 (2 CH), 127.8 (2 CH),
Further studies aimed at finding more efficient reaction 127.9 (2 CH), 128.1 (2 CH), 132.8 (2 C), 133.5 (2 C), 138.5 (2
+
+
C) ppm. MS (EI): m/z (%) = 254 (99) [M] , 253 (100) [M – H] .
conditions and synthesizing new binaphthalenes are un-
derway in our laboratories and will be reported in due
course.
+
HRMS (EI): calcd. for C20H14 [M] 254.1090; found 254.1088.
2-Methyl-1,1Ј-binaphthalene (7b):[11a,25] White solid (93 mg from
the reaction of 1b with 2, 69%; 123 mg from the reaction of 1a
1
with 3, 92%); m.p. 86–89 °C. H NMR (300 MHz, CDCl
3
): δ =
2
2
.15 (s, 3 H), 7.17–7.33 (m, 4 H), 7.40–7.45 (m, 2 H), 7.47–7.54 (m,
H), 7.62–7.67 (m, 1 H), 7.90 (d, J = 8.5 Hz, 2 H), 7.98 (d, J =
Experimental Section
1
3
General Methods: All reactions were carried out in flame-dried
glassware under argon using standard gas-tight syringes, cannulae
and septa. THF was dried by distillation from sodium benzophen-
one ketyl. Reaction temperatures refer to external bath tempera-
tures. Commercially available reagents were used as received with-
out further purification. Butyllithium was titrated prior to use. Or-
3 3
8.5 Hz, 2 H) ppm. C NMR (75 MHz, CDCl ): δ = 20.5 (CH ),
124.8 (CH), 125.6 (CH), 125.8 (CH), 125.9 (CH), 126.0 (CH), 126.1
(CH), 126.2 (CH), 127.5 (CH), 127.6 (CH), 127.72 (CH), 127.74
(CH), 128.2 (CH), 128.6 (CH), 132.0 (C), 132.6 (C), 133.5 (C),
133.7 (C), 134.4 (C), 136.0 (C), 137.5 (C) ppm. MS (EI): m/z (%)
= 268 (100) [M] , 253 (42) [M – CH ] . HRMS (EI): calcd. for
C H [M] 268.1247; found 268.1246.
+
+
3
+
ganic extracts were dried with anhydrous MgSO
4
, filtered and con-
2
1
16
centrated by using a rotary evaporator under reduced pressure. Re-
actions were monitored by TLC using pre-coated silica gel plates
Enantioselective coupling of 1a with 3 by using L3 as ligand
95 mg, 71%, 86% ee). HPLC (Chiralcel OJ-H, hexane/iPrOH =
(
(0.20 mm thick), UV light as the visualizing agent and ethanolic
9
1
R R
5:5, 0.5 mL/min, 254 nm): t (R, minor) = 13.2, t (S, major) =
9.5 min.
phosphomolybdic acid as the developing agent. Flash column
chromatography was performed with 230–400 mesh silica gel
1
13
2-Methoxy-1,1Ј-binaphthalene (7c):[26] White solid (95 mg from the
packed in glass columns. H and C NMR spectra were recorded
in CDCl at 300 and 75 MHz, respectively, at ambient temperature
reaction of 1c with 2, 67%; 108 mg from the reaction of 1a with 4,
3
1
and calibrated to the solvent peak. DEPT data were used to assign
carbon types. Mass spectra were obtained by EI or FAB ionization
76%); m.p. 107–110 °C. H NMR (300 MHz, CDCl
3
): δ = 3.80 (s,
3 H), 7.21–7.40 (m, 5 H), 7.48–7.54 (m, 3 H), 7.67 (dd, J = 7.1,
8.2 Hz, 1 H), 7.92 (d, J = 8.2 Hz, 1 H), 7.98–8.04 (m, 3 H) ppm.
(matrix for FAB: 3-nitrobenzyl alcohol), as indicated in each case.
1
3
Melting points are uncorrected. Optical rotations were measured
with a digital polarimeter. The enantiomeric ratios of the reactions
were determined by comparison of the chiral stationary phase
HPLC traces with those of the corresponding racemic products.
The absolute configurations of the products were assigned by com-
parison with published data.
3 3
C NMR (75 MHz, CDCl ): δ = 56.7 (CH ), 113.8 (CH), 123.2
(C), 123.5 (CH), 125.47 (CH), 125.54 (CH), 125.7 (CH), 125.8
(CH), 126.2 (CH), 126.4 (CH), 127.7 (CH), 127.8 (CH), 128.2
(CH), 128.4 (CH), 129.0 (C), 129.4 (CH), 132.9 (C), 133.7 (C),
134.2 (C), 134.5 (C), 154.6 (C) ppm. MS (EI): m/z (%) = 284 (100)
+
+
+
[M] , 269 (45) [M – CH
3
] . HRMS (EI): calcd. for C21
H16O [M]
2
84.1196; found 284.1193.
Synthesis of the Tri(1-naphthyl)indium Reagents: Tri(1-naphthyl)in-
dium compounds were prepared by treatment of the corresponding
2,2Ј-Dimethyl-1,1Ј-binaphthalene (8b):[
60%): H NMR (300 MHz, CDCl
7a,9f,27]
Colourless oil (85 mg,
1
1-naphthyllithium reagents (3.0 equiv., ca. 0.5 m in dry THF) with
3
): δ = 2.08 (s, 6 H), 7.09 (d, J =
a solution of InCl in dry THF (1.1 equiv., ca. 0.05 m) at –78 °C
3
8.4 Hz, 2 H), 7.22–7.27 (m, 2 H), 7.40–7.46 (m, 2 H), 7.55 (d, J =
1
3
and warming to room temperature. The required organolithium
reagents were prepared by metal–halogen exchange reactions with
nBuLi (1.0 equiv.) at –78 °C in dry THF from 1-bromonaphthalene,
8.4 Hz, 2 H), 7.92 (dd, J = 4.6, 8.1 Hz, 4 H) ppm. C NMR
(75 MHz, CDCl ): δ = 20.0 (2 CH ), 124.9 (2 CH), 125.6 (2 CH),
126.1 (2 CH), 127.4 (2 CH), 127.9 (2 CH), 128.7 (2 CH), 132.2 (2
3
3
Eur. J. Org. Chem. 2013, 2555–2562
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2559

Á. Mosquera, M. A. Pena, J. Pérez Sestelo, L. A. Sarandeses
FULL PAPER
C), 132.7 (2 C), 134.3 (2 C), 135.1 (2 C) ppm. MS (EI): m/z (%) =
8.5 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl
56.8 (CH ), 113.9 (CH), 123.5 (CH), 124.4 (CH), 125.48 (CH),
125.49 (CH), 125.6 (CH), 126.3 (CH), 126.4 (CH), 126.8 (CH),
3 3
): δ = 19.6 (CH ),
+
+
2
82 (100) [M] , 267 (27) [M – CH
3
] . HRMS (EI): calcd. for
3
+
C
22
H18 [M] 282.1403; found 282.1402.
1
1
27.7 (CH), 128.1 (CH), 129.0 (C), 129.3 (C), 132.7 (C), 132.8 (C),
Enantioselective coupling of 1b with 3 by using L3 as ligand
99 mg, 70%, 72% ee). HPLC (Chiralcel OD-H, hexane, 0.5 mL/
min, 254 nm): t (S, major) = 20.0, t (R, minor) = 24.6 min.
32.9 (C), 133.9 (C), 134.4 (C) ppm. MS (EI): m/z (%) = 298 (100)
(
+
+
+
[
C
M] , 283 (26) [M – CH
3
] , 268 (55) [M – C
O] . HRMS (EI): calcd. for
298.1349.
2
H
6
] , 252 (27) [M –
R
R
+
+
2
H
6
C
22
H
18
O
[M] 298.1352;
2
(
-Methoxy-2Ј-methyl-1,1Ј-binaphthalene (8c):[26b,28] White solid
103 mg from the reaction of 1c with 3, 69%; 97 mg from the reac-
[16]
1
1
7
7
8
1
-(1-Naphthalenyl)pyrene (11a): White solid (162 mg, 99%); m.p.
1
tion of 1b with 4, 65%); m.p. 119–122 °C. H NMR (300 MHz,
CDCl ): δ = 2.17 (s, 3 H), 3.77 (s, 3 H), 7.09 (d, J = 8.5 Hz, 1 H),
.21–7.28 (m, 3 H), 7.34–7.45 (m, 2 H), 7.48 (d, J = 9.1 Hz, 1 H),
.57 (d, J = 8.2 Hz, 1 H), 7.92 (d, J = 8.2 Hz, 3 H), 8.01 (d, J =
.1 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl
): δ = 20.3 (CH ),
6.5 (CH ), 113.8 (CH), 122.0 (C), 123.6 (CH), 124.6 (CH), 125.0
1
3
59–160 °C. H NMR (300 MHz, CDCl ): δ = 7.29–7.32 (m, 1 H),
.41 (d, J = 8.3 Hz, 1 H), 7.49–7.54 (m, 1 H), 7.61–7.71 (m, 3 H),
.91 (d, J = 9.2 Hz, 1 H), 8.00–8.06 (m, 4 H), 8.14–8.26 (m, 4 H),
3
.31 (d, J = 7.8 Hz, 1 H) ppm. C NMR (75 MHz, CDCl ): δ =
3
7
7
9
5
13
3
3
24.5 (CH), 124.7 (CH), 124.8 (CH), 125.0 (CH), 125.2 (CH), 125.4
3
(
(
(
CH), 125.7 (CH), 125.9 (CH), 126.0 (CH), 126.1 (CH), 126.7
CH), 127.41 (CH), 127.44 (CH), 127.5 (CH), 128.0 (CH), 128.2
CH), 128.36 (CH), 128.38 (CH), 129.9 (C), 130.9 (C), 131.0 (C),
(
(
CH), 125.8 (2 CH), 126.5 (CH), 127.4 (CH), 127.88 (CH), 127.91
CH), 128.6 (CH), 129.1 (C), 129.3 (CH), 132.1 (C), 132.3 (C),
1
=
C
33.2 (C), 133.6 (C), 134.9 (C), 154.4 (C) ppm. MS (EI): m/z (%)
131.4 (C), 133.0 (C), 133.6 (C), 135.9 (C), 138.9 (C) ppm. MS (EI):
+
+
298 (100) [M] , 268 (32) [M – CH
3
O] . HRMS (EI): calcd. for
+
+
m/z (%) = 328 (100) [M] . HRMS (EI): calcd. for C26H16 [M]
18O [M]+ 298.1352; found 298.1346.
22
H
328.1247; found 328.1236.
Enantioselective coupling of 1b with 4 by using L3 as ligand
101 mg, 68%, 67% ee). HPLC (Chiralpak AD-H, hexane/EtOH
97:3, 1 mL/min, 254 nm): t (S, minor) = 3.9, t (R, major) =
.2 min.
[12a]
1
5
3
7
-(2-Methyl-1-naphthalenyl)pyrene (11b):
White solid (98 mg,
): δ = 2.15 (s,
(
=
4
1
7%); m.p. 172–173 °C. H NMR (300 MHz, CDCl
H), 7.10–7.14 (m, 1 H), 7.18–7.23 (m, 1 H), 7.40–7.45 (m, 1 H),
.50 (dd, J = 4.2, 9.2 Hz, 1 H), 7.57 (br. d, J = 8.5 Hz, 1 H), 7.88–
7.97 (m, 4 H), 8.03 (t, J = 7.7 Hz, 1 H), 8.14–8.19 (m, 3 H), 8.22–
8.26 (m, 1 H), 8.33 (d, J = 7.7 Hz, 1 H) ppm. C NMR (75 MHz,
CDCl ): δ = 20.7 (CH ), 124.85 (CH), 124.86 (CH), 124.95 (C),
25.02 (CH), 125.1 (CH), 125.3 (CH), 125.97 (CH), 126.01 (CH),
126.4 (CH), 127.4 (CH), 127.5 (CH), 127.6 (CH), 127.7 (CH), 127.8
CH), 128.2 (CH), 128.6 (CH), 129.7 (C), 130.7 (C), 131.1 (C),
31.4 (C), 132.0 (C), 133.7 (C), 134.7 (C), 135.0 (C), 136.5 (C) ppm.
3
R
R
,2Ј-Dimethoxy-1,1Ј-binaphthalene (9c):[
9%); m.p. 196–197 °C. H NMR (300 MHz, CDCl ): δ = 3.79 (s,
29]
2
6
6
6
White solid (108 mg,
1
3
1
3
H), 7.13–7.16 (m, 2 H), 7.21–7.26 (m, 2 H), 7.34 (ddd, J = 1.4,
.7, 8.1 Hz, 2 H), 7.48 (d, J = 9.0 Hz, 2 H), 7.89 (d, J = 8.0 Hz, 2
3
3
1
13
H), 8.00 (d, J = 9.0 Hz, 2 H) ppm. C NMR (75 MHz, CDCl
3
): δ
(
1
=
56.9 (2 CH ), 114.2 (2 CH), 119.6 (2 C), 123.5 (2 CH), 125.2 (2
3
CH), 126.3 (2 CH), 127.9 (2 CH), 129.2 (2 C), 129.4 (2 CH), 134.0
+
+
MS (EI): m/z (%) = 342 (100) [M] . HRMS (EI): calcd. for C H
(
(
2 C), 155.0 (2 C) ppm. MS (EI): m/z (%) = 314 (100) [M] . HRMS
27 18
+
+
[M] 342.1403; found 342.1401.
EI): calcd. for C22
H
18
O
2
[M] 314.1301; found 314.1309.
-Methyl-1,1Ј-binaphthalene (10a):[30] White solid (119 mg, 89%);
1-(2-Methoxy-1-naphthalenyl)pyrene (11c): Yellowish solid (120 mg,
4
1
1
67%); m.p. 194–195 °C. H NMR (300 MHz, CDCl
3
): δ = 3.78 (s,
m.p. 105–108 °C. H NMR (300 MHz, CDCl
3
): δ = 2.86 (s, 3 H),
3
H), 7.12–7.15 (m, 1 H), 7.19–7.24 (m, 1 H), 7.33–7.39 (m, 1 H),
7
8
1
1
(
(
.29–7.36 (m, 2 H), 7.39–7.66 (m, 8 H), 7.97–8.00 (m, 2 H), 8.14–
13
7.53 (d, J = 9.1 Hz, 1 H), 7.58–7.62 (m, 1 H), 7.88–8.08 (m, 5 H),
3 3
.17 (m, 1 H) ppm. C NMR (75 MHz, CDCl ): δ = 19.6 (CH ),
1
3
8
(
(
.13–8.24 (m, 4 H), 8.33 (d, J = 7.8 Hz, 1 H) ppm. C NMR
75 MHz, CDCl ): δ = 56.8 (CH ), 113.9 (CH), 123.6 (CH), 124.7
CH), 124.90 (CH), 124.92 (C), 124.96 (C), 124.98 (CH), 125.6
24.3 (CH), 125.4 (CH), 125.6 (2 CH), 125.7 (CH), 125.9 (CH),
26.2 (CH), 126.7 (CH), 127.2 (CH), 127.5 (CH), 127.7 (CH), 127.9
3
3
CH), 128.1 (CH), 132.6 (C), 132.9 (C), 133.0 (C), 133.5 (C), 134.1
+
(CH), 125.7 (CH), 125.9 (CH), 126.5 (CH), 127.29 (CH), 127.31
(CH), 127.5 (CH), 127.9 (CH), 129.0 (CH), 129.1 (C), 129.6 (CH),
C), 136.8 (C), 138.7 (C) ppm. MS (EI): m/z (%) = 268 (98) [M] ,
+
16 [M]+
2
2
53 (100) [M – CH ] . HRMS (EI): calcd. for C21H
3
1
1
30.2 (C), 130.8 (C), 131.1 (C), 131.4 (C), 132.1 (C), 134.4 (C),
68.1247; found 268.1242.
+
54.9 (C) ppm. MS (EI): m/z (%) = 358 (100) [M] . HRMS (EI):
12a,30]
2
6
3
,4Ј-Dimethyl-1,1Ј-binaphthalene (10b):[
White solid (85 mg,
): δ = 2.13 (s,
18O [M]+ 358.1352; found 358.1353.
H
calcd. for C27
1
0%); m.p. 149–151 °C. H NMR (300 MHz, CDCl
3
4
-(1-Naphthyl)isoquinoline (14a):[ White solid (79 mg, 62%); m.p.
31]
H), 2.84 (s, 3 H), 7.17–7.32 (m, 5 H), 7.37–7.56 (m, 4 H), 7.88
1
dd, J = 2.7, 8.1 Hz, 2 H), 8.12 (d, J = 8.8 Hz, 1 H) ppm. 1 C NMR
3
112–114 °C. H NMR (300 MHz, CDCl
3
): δ = 7.30–7.36 (m, 1 H),
(
(
(
(
(
7
2
1
.40–7.43 (m, 2 H), 7.48–7.56 (m, 3 H), 7.62 (dd, J = 7.3, 8.0 Hz,
3 3 3
75 MHz, CDCl ): δ = 19.6 (CH ), 20.6 (CH ), 124.4 (CH), 124.7
CH), 125.65 (CH), 125.72 (CH), 125.8 (CH), 126.35 (CH), 126.43
CH), 126.6 (CH), 127.4 (2 CH), 127.7 (CH), 128.6 (CH), 132.0
H), 7.99 (t, J = 8.4 Hz, 2 H), 8.09 (d, J = 8.0 Hz, 1 H), 8.59 (s,
1
3
3
H), 9.39 (s, 1 H) ppm. C NMR (75 MHz, CDCl ): δ = 125.3 (2
CH), 126.0 (CH), 126.1 (CH), 126.3 (CH), 127.2 (CH), 127.7 (CH),
128.2 (C), 128.3 (2 CH), 128.6 (CH), 130.4 (CH), 131.7 (C), 132.7
(C), 133.5 (C), 134.5 (C), 135.4 (C), 143.7 (CH), 152.3 (CH) ppm.
C), 132.6 (C), 132.8 (C), 133.6 (C), 133.8 (C), 134.5 (C), 135.7 (C),
+
1
36.3 (C) ppm. MS (EI): m/z (%) = 282 (100) [M] , 267 (24) [M –
+
+
18 [M]+
CH
3
] , 252 (24) [M – C
2
H
6
] . HRMS (EI): calcd. for C22
H
+
MS (FAB): m/z (%) = 256 (20) [M + H] , 154 (100). HRMS (FAB):
2
82.1403; found 282.1404.
Enantioselective coupling of 1b with 5 by using L3 as ligand
100 mg, 71%, 74% ee). HPLC (Chiralcel OD-H, hexane, 1 mL/
min, 254 nm): t (S, major) = 15.9, t (R, minor) = 18.3 min.
-Methoxy-4Ј-methyl-1,1Ј-binaphthalene (10c):[12a] White solid
calcd. for C19H
14N [M + H]+ 256.1121; found 256.1123.
4
-(2-Methyl-1-naphthyl)isoquinoline (14b): Yellow solid (106 mg,
(
1
3
79%); m.p. 95–98 °C. H NMR (300 MHz, CDCl ): δ = 2.15 (s, 3
R
R
H), 7.16 (d, J = 8.5 Hz, 1 H), 7.24–7.29 (m, 2 H), 7.40–7.45 (m, 1
H), 7.50–7.55 (m, 2 H), 7.60–7.65 (m, 1 H), 7.92 (dd, J = 3.4,
8.2 Hz, 2 H), 8.11 (d, J = 8.2 Hz, 1 H), 8.48 (s, 1 H), 9.40 (s, 1
2
1
(
2
7
79 mg, 53%); m.p. 160–162 °C. H NMR (300 MHz, CDCl
3
): δ =
.82 (s, 3 H), 3.77 (s, 3 H), 7.16–7.36 (m, 6 H), 7.44–7.54 (m, 3 H),
.87 (d, J = 8.1 Hz, 1 H), 7.98 (d, J = 9.0 Hz, 1 H), 8.10 (d, J = 125.0 (CH), 125.8 (CH), 126.2 (CH), 127.3 (CH), 127.9 (2 CH),
1
3
3 3
H) ppm. C NMR (75 MHz, CDCl ): δ = 20.6 (CH ), 124.9 (CH),
2560
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2555–2562

Synthesis of Axially Chiral 1,1Ј-Binaphthalenes
28.2 (CH), 128.4 (C), 128.6 (CH), 130.6 (CH), 130.7 (C), 132.0
1
8.03 (d, J = 9.0 Hz, 1 H), 8.76 (d, J = 5.8 Hz, 1 H) ppm. 13C NMR
(75 MHz, CDCl ): δ = 56.6 (CH ), 113.4 (CH), 120.1 (CH), 121.9
(
C), 132.1 (C), 133.4 (C), 135.1 (C), 135.3 (C), 144.0 (CH), 152.2
3
3
+
(CH) ppm. MS (EI): m/z (%) = 269 (100) [M] , 254 (52) [M –
(C), 123.6 (CH), 124.7 (CH), 126.7 (CH), 126.8 (CH), 127.1 (CH),
127.4 (CH), 127.9 (CH), 128.7 (C), 129.0 (C), 130.1 (CH), 130.4
(CH), 133.8 (C), 136.2 (C), 142.7 (CH), 154.7 (C), 158.1 (C) ppm.
+
+
3
CH ] . HRMS (EI): calcd. for C20H15N [M] 269.1199; found
2
69.1195.
Enantioselective coupling of 1b with 12 by using L3 as ligand
98 mg, 73%, 31% ee). HPLC (Chiralpak AD-H, hexane/iPrOH =
+
MS (FAB): m/z (%) = 286 (100) [M + H] . HRMS (FAB): calcd.
for C20H
16ON [M + H]+ 286.1226; found 286.1225.
(
9
2
5:5, 0.5 mL/min, 254 nm): t
R
(minor) = 22.5, t
R
(major) =
Supporting Information (see footnote on the first page of this arti-
cle): NMR spectra and HPLC chromatograms for the compounds
prepared.
6.6 min. [α]2
9
= +6.4 (c = 0.29, CHCl ).
D
3
4
7
3
1
-(2-Methoxy-1-naphthyl)isoquinoline (14c): Yellow solid (110 mg,
1
3
7%); m.p. 113–116 °C. H NMR (300 MHz, CDCl ): δ = 3.79 (s,
H), 7.17–7.20 (m, 1 H), 7.25–7.37 (m, 3 H), 7.46 (d, J = 9.1 Hz,
H), 7.50–7.55 (m, 1 H), 7.61 (ddd, J = 1.2, 6.5, 8.1 Hz, 1 H), 7.90
Acknowledgments
(
1
d, J = 8.1 Hz, 1 H), 8.03 (d, J = 9.1 Hz, 1 H), 8.09 (d, J = 8.0 Hz,
H), 8.51 (s, 1 H), 9.38 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl
):
δ = 56.5 (CH ), 113.4 (CH), 119.1 (C), 123.7 (CH), 125.0 (CH),
25.1 (CH), 126.7 (CH), 127.1 (CH), 127.8 (CH), 127.9 (CH), 128.4
We are grateful to the Spanish Ministerio de Ciencia e Innovación
3
(
MICINN) (grant numbers CTQ2006-06166 and CTQ2009-07180)
3
and the Fondos Europeos para el Desarrollo Regional (FEDER)
funds for financial support. A.M. also thanks the Spanish Minis-
terio de Educación y Ciencia (MEC) for a predoctoral fellowship
1
(
(
C), 128.9 (C), 130.2 (CH), 130.3 (CH), 134.1 (C), 135.7 (C), 144.6
CH), 152.0 (CH), 155.0 (C) ppm. MS (EI): m/z (%) = 285 (100)
(
Formación de Personal Investigador).
+
+
[M] , 270 (27) [M – CH
3
] . HRMS (EI): calcd. for C20
H15NO
+
[M] 285.1148; found 285.1142.
[
1] a) M. C. Kozlowski, B. J. Morgan, E. C. Linton, Chem. Soc.
Rev. 2009, 38, 3193–3207; b) G. Bringmann, T. Gulder,
T. A. M. Gulder, M. Breuning, Chem. Rev. 2011, 111, 563–639.
Enantioselective coupling of 1c with 12 by using L3 as ligand
64 mg, 45%, 32% ee). HPLC (Chiralpak AD-H, hexane/iPrOH =
(
9
4
5:5, 0.5 mL/min, 254 nm): t
R
(major) = 42.5 min, t
R
(minor) =
[2] a) G. Bringmann, A. J. P. Mortimer, P. A. Keller, M. J. Gresser,
J. Garner, M. Breuning, Angew. Chem. 2005, 117, 5518; Angew.
Chem. Int. Ed. 2005, 44, 5384–5427; b) O. Baudoin, Eur. J. Org.
Chem. 2005, 4223–4229; c) T. W. Wallace, Org. Biomol. Chem.
2006, 4, 3197–3210; d) K. Tanaka, Chem. Asian J. 2009, 4,
508–518; e) M. Ogasawara, S. Watanabe, Synthesis 2009, 1761–
1785.
4.0 min. [α]2
7
D
= –18.6 (c = 0.63, CHCl ).
3
1
-(1-Naphthyl)isoquinoline (15a):[20f] Yellow solid (82 mg from the
reaction of 1a with 13a, 64%; 83 mg from the reaction of 1a with
1
1
7
1
2
3
3b, 65%); m.p. 97–100 °C. H NMR (300 MHz, CDCl ): δ = 7.31–
.36 (m, 1 H), 7.39–7.44 (m, 2 H), 7.49 (ddd, J = 1.3, 6.7, 8.1 Hz,
H), 7.59–7.72 (m, 4 H), 7.77 (d, J = 5.6 Hz, 1 H), 7.94–7.97 (m,
H), 8.00 (br. d, J = 8.0 Hz, 1 H), 8.72 (d, J = 5.6 Hz, 1 H) ppm.
[
3] J. Hassan, M. Sévignon, C. Gozzi, E. Schulz, M. Lemaire,
Chem. Rev. 2002, 102, 1359–1469.
1
3
[4] a) J. Yin, M. P. Rainka, X.-X. Zhang, S. L. Buchwald, J. Am.
Chem. Soc. 2002, 124, 1162–1163; b) O. Navarro, R. A. Kelly,
S. P. Nolan, J. Am. Chem. Soc. 2003, 125, 16194–16195; c) G.
Altenhoff, R. Goddard, C. W. Lehmann, F. Glorius, J. Am.
Chem. Soc. 2004, 126, 15195–15201; d) T. E. Barder, S. D.
Walker, J. R. Martinelli, S. L. Buchwald, J. Am. Chem. Soc.
2005, 127, 4685–4696; e) D. S. Surry, S. L. Buchwald, Angew.
Chem. 2008, 120, 6438; Angew. Chem. Int. Ed. 2008, 47, 6338–
3
C NMR (75 MHz, CDCl ): δ = 120.2 (CH), 125.1 (CH), 125.88
(
(
CH), 125.93 (CH), 126.3 (CH), 126.8 (CH), 127.1 (CH), 127.6
CH), 127.7 (CH), 128.21 (CH), 128.24 (C), 128.8 (C), 130.2 (CH),
132.3 (C), 133.7 (C), 136.4 (C), 137.0 (C), 142.4 (CH), 160.4
+
(C) ppm. MS (FAB): m/z (%) = 256 (100) [M + H] . HRMS (FAB):
+
calcd. for C19
-(2-Methyl-1-naphthyl)isoquinoline (15b):[19e] Yellowish oil (81 mg
from the reaction of 1b with 13a, 60%; 102 mg from the reaction
H14N [M + H] 256.1121; found 256.1125.
1
6
361; f) M. G. Organ, S. Çalimsiz, M. Sayah, K. H. Hoi, A. J.
Lough, Angew. Chem. 2009, 121, 2419; Angew. Chem. Int. Ed.
009, 48, 2383–2387; g) L. Ackermann, H. K. Potukuchi, A.
1
3
of 1b with 13b, 76%). H NMR (300 MHz, CDCl ): δ = 2.12 (s, 3
H), 7.01 (d, J = 8.5 Hz, 1 H), 7.21–7.27 (m, 1 H), 7.36–7.45 (m, 3
H), 7.50 (d, J = 8.2 Hz, 1 H), 7.68 (ddd, J = 2.2, 5.8, 8.2 Hz, 1 H),
7
1
2
Althammer, R. Born, P. Mayer, Org. Lett. 2010, 12, 1004–1007.
[5] a) A. I. Meyers, K. A. Lutomski, J. Am. Chem. Soc. 1982, 104,
879–881; b) J. M. Wilson, D. J. Cram, J. Org. Chem. 1984, 49,
4930–4943; c) B. H. Lipshutz, F. Kayser, Z. P. Liu, Angew.
Chem. 1994, 106, 1962; Angew. Chem. Int. Ed. Engl. 1994, 33,
.78 (d, J = 5.8 Hz, 1 H), 7.88–7.97 (m, 3 H), 8.75 (d, J = 5.8 Hz,
H) ppm. 1 C NMR (75 MHz, CDCl
3
): δ = 20.0 (CH ), 119.9
3 3
(
(
CH), 124.8 (CH), 125.5 (CH), 126.1 (CH), 126.9 (CH), 127.1
CH), 127.3 (CH), 127.8 (CH), 128.2 (C), 128.3 (CH), 128.5 (CH),
1
842–1844; d) S. P. Stanforth, Tetrahedron 1998, 54, 263–303;
e) G. Bringmann, M. Breuning, H. Endress, D. Vitt, K. Peters,
E.-M. Peters, Tetrahedron 1998, 54, 10677–10690; f) P.-E. Brou-
tin, F. Colobert, Org. Lett. 2003, 5, 3281–3284.
1
1
30.2 (CH), 132.0 (C), 132.8 (C), 134.2 (C), 134.7 (C), 136.2 (C),
42.7 (CH), 160.5 (C) ppm. MS (FAB): m/z (%) = 270 (100) [M +
+
+
H] . HRMS (FAB): calcd. for C20
70.1276.
H16N [M + H] 270.1277;
ˇ
[
6] a) M. Smr cˇ ina, J. Polakova, S. Vysko cˇ il, P. Ko cˇ ovský, J. Org.
2
Chem. 1993, 58, 4534–4538; b) R. Irie, K. Masutani, T. Kat-
suki, Synlett 2000, 1433–1436; c) S.-W. Hon, C.-H. Li, J.-H.
Kuo, N. B. Barhate, Y.-H. Liu, Y. Wang, C.-T. Chen, Org. Lett.
Enantioselective coupling of 1b with 13b by using L3 as ligand
105 mg, 78%, 20% ee). HPLC (Chiralpak AD-H, hexane/iPrOH
95:5, 0.5 mL/min, 254 nm): t (major) = 22.8, t (minor) =
= +8.0 (c = 0.47, CHCl ).
-(2-Methoxy-1-naphthyl)isoquinoline (15c):[20a] Yellow solid
(
2
001, 3, 869–872; d) X. Li, J. Yang, M. C. Kozlowski, Org.
=
2
R
R
Lett. 2001, 3, 1137–1140; e) Z. Luo, Q. Q. Liu, L. Gong, X.
Cui, A. Mi, Y. Jiang, Angew. Chem. 2002, 114, 4714; Angew.
Chem. Int. Ed. 2002, 41, 4532–4535; f) X. Li, J. B. Hewgley,
C. A. Mulrooney, J. Yang, M. C. Kozlowski, J. Org. Chem.
4.4 min. [α]2
4
D
3
1
(111 mg from the reaction of 1c with 13a, 78%; 88 mg from the
2
003, 68, 5500–5511; g) F. Guo, L. C. Konkol, R. J. Thomson,
1
reaction of 1c with 13b, 62%); m.p. 99–102 °C. H NMR
300 MHz, CDCl ): δ = 3.79 (s, 3 H), 7.05 (d, J = 8.5 Hz, 1 H),
.23–7.43 (m, 3 H), 7.45 (d, J = 9.0 Hz, 1 H), 7.53 (br. d, J =
J. Am. Chem. Soc. 2011, 133, 18–20; h) L. C. Konkol, F. Guo,
A. A. Sarjeant, R. J. Thomson, Angew. Chem. 2011, 123,
(
3
7
8
5
10105; Angew. Chem. Int. Ed. 2011, 50, 9931–9934.
.3 Hz, 1 H), 7.68 (ddd, J = 1.2, 6.9, 8.2 Hz, 1 H), 7.76 (d, J =
.8 Hz, 1 H), 7.88 (d, J = 7.6 Hz, 1 H), 7.93 (d, J = 8.3 Hz, 1 H),
[7] a) T. Hayashi, K. Hayashizaki, T. Kiyoi, Y. Ito, J. Am. Chem.
Soc. 1988, 110, 8153–8156; b) T. Hayashi, S. Niizuma, T. Kami-
Eur. J. Org. Chem. 2013, 2555–2562
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2561

Á. Mosquera, M. A. Pena, J. Pérez Sestelo, L. A. Sarandeses
FULL PAPER
kawa, N. Suzuki, Y. Uozumi, J. Am. Chem. Soc. 1995, 117,
D. J. Babinski, E. Negishi, Organometallics 2005, 24, 475–478;
e) M. Barbero, S. Cadamuro, S. Dughera, C. Giaveno, Eur. J.
Org. Chem. 2006, 4884–4890; f) E. Font-Sanchis, F. J.
Céspedes-Guirao, A. Sastre-Santos, F. Fernández-Lázaro, J.
Org. Chem. 2007, 72, 3589–3591; g) M. Barbero, S. Cadamuro,
S. Dughera, G. Ghigo, Eur. J. Org. Chem. 2008, 862–868; h) J.-
Y. Lee, P. H. Lee, J. Org. Chem. 2008, 73, 7413–7416; i) L. Jin,
Y. Zhao, L. Zhu, H. Zhang, A. Lei, Adv. Synth. Catal. 2009,
9101–9102.
[
8] a) M. Genov, B. Fuentes, P. Espinet, B. Pelaz, Tetrahedron:
Asymmetry 2006, 17, 2593–2595; b) M. Genov, A. Almorín, P.
Espinet, Tetrahedron: Asymmetry 2007, 18, 625–627.
[
9] a) M. Uemura, K. Kamikawa, J. Chem. Soc. Ch, m. Commun.
1994, 2697–2698; b) A.-S. Castanet, F. Colobert, P.-E. Broutin,
M. Obringer, Tetrahedron: Asymmetry 2002, 13, 659–665; c) A.
Herrbach, A. Marinetti, O. Baudoin, D. Guénard, F. Guéritte,
J. Org. Chem. 2003, 68, 4897–4905; d) J. F. Jensen, M.
Johannsen, Org. Lett. 2003, 5, 3025–3028; e) K. Mikami, T.
Miyamoto, M. Hatano, Chem. Commun. 2004, 2082–2083; f)
M. Genov, A. Almorín, P. Espinet, Chem. Eur. J. 2006, 12,
351, 630–634; j) E. Font-Sanchis, A. Sastre-Santos, F.
Fernández-Lázaro, Dalton Trans. 2009, 2470–2473; k) R. Riv-
eiros, R. Tato, J. Pérez Sestelo, L. A. Sarandeses, Eur. J. Org.
Chem. 2012, 3018–3023.
[
18] DavePhos: 2-dicyclohexylphosphanyl-2Ј-(dimethylamino)bi-
phenyl, see: J. P. Wolfe, R. A. Singer, B. H. Yang, S. L. Buch-
wald, J. Am. Chem. Soc. 1999, 121, 9550–9561.
9346–9352; g) T. Takemoto, S. Iwasa, H. Hamada, K. Shiba-
tomi, M. Kameyama, Y. Motoyama, H. Nishiyama, Tetrahe-
dron Lett. 2007, 48, 3397–3401; h) R. P. J. Bronger, P. J. Guiry,
Tetrahedron: Asymmetry 2007, 18, 1094–1102; i) K. Sawai, R.
Tatumi, T. Nakahodo, H. Fujihara, Angew. Chem. 2008, 120,
ˇ
[
19] a) P. Ko cˇ ovský, S. Vysko cˇ il, M. Smr cˇ ina, Chem. Rev. 2003, 103,
213–3246; b) G. Chelucci, Tetrahedron 2003, 59, 9471–9515;
c) R. J. Kloetzing, P. Knochel, Tetrahedron: Asymmetry 2006,
7, 116–123; d) X. Li, L. Kong, Y. Gao, X. Wang, Tetrahedron
3
1
7
023; Angew. Chem. Int. Ed. 2008, 47, 6917–6919.
10] a) J. Yin, S. L. Buchwald, J. Am. Chem. Soc. 2000, 122, 12051–
2052; b) X. Shen, G. O. Jones, D. A. Watson, B. Bhayana,
Lett. 2007, 48, 3915–3917; e) A. V. Malkov, P. Ramírez-López,
L. Biedermannová, L. Rulí sˇ ek, L. Dufková, M. Kotora, F.
Zhu, P. Ko cˇ ovský, J. Am. Chem. Soc. 2008, 130, 5341–5348; f)
W. J. Fleming, H. Müller-Bunz, V. Lillo, E. Fernández, P. J.
Guiry, Org. Biomol. Chem. 2009, 7, 2520–2524.
[
[
[
1
S. L. Buchwald, J. Am. Chem. Soc. 2010, 132, 11278–11287.
11] a) A. N. Cammidge, K. V. L. Crépy, Chem. Commun. 2000,
1
723–1724; b) A. N. Cammidge, K. V. L. Crépy, Tetrahedron
[
20] a) N. W. Alcock, J. M. Brown, D. I. Hulmes, Tetrahedron:
Asymmetry 1993, 4, 743–756; b) J.-M. Valk, T. D. W. Claridge,
J. M. Brown, D. Hibbs, M. B. Hursthouse, Tetrahedron: Asym-
metry 1995, 6, 2597–2610; c) G. Chelucci, A. Bacchi, D. Fabbri,
A. Saba, F. Ulgheri, Tetrahedron Lett. 1999, 40, 553–556; d)
A. V. Malkov, L. Dufková, L. Farrugia, P. Ko cˇ ovský, Angew.
Chem. 2003, 115, 3802; Angew. Chem. Int. Ed. 2003, 42, 3674–
3677; e) C. W. Lim, O. Tissot, A. Mattison, M. W. Hooper,
J. M. Brown, A. R. Cowley, D. I. Hulmes, A. J. Blacker, Org.
Process Res. Dev. 2003, 7, 379–384; f) C.-H. Yang, C.-C. Tai,
Y.-T. Huang, I.-W. Sun, Tetrahedron 2005, 61, 4857–4861.
[21] A. Chieffi, K. Kamikawa, J. Åhman, J. M. Fox, S. L. Buch-
wald, Org. Lett. 2001, 3, 1897–1900.
[22] The enantioselectivity was measured by chiral HPLC analysis
of the crude reaction mixture, and the major enantiomer was
determined according to published data.
2004, 60, 4377–4386.
12] a) A. Bermejo, A. Ros, R. Fernández, J. M. Lassaletta, J. Am.
Chem. Soc. 2008, 130, 15798–15799; b) A. Ros, B. Estepa, A.
Bermejo, E. Álvarez, R. Fernández, J. M. Lassaletta, J. Org.
Chem. 2012, 77, 4740–4750.
13] a) Y. Uozumi, Y. Matsuura, T. Arakawa, Y. M. A. Yamada,
Angew. Chem. 2009, 121, 2746; Angew. Chem. Int. Ed. 2009,
[
4
8, 2708–2710; b) S. Wang, J. Li, T. Miao, W. Wu, Q. Li, Y.
Zhuang, Z. Zhou, L. Qiu, Org. Lett. 2012, 14, 1966–1969; c)
W. Tang, N. D. Patel, G. Xu, X. Xu, J. Savoie, S. Ma, M.-H.
Hao, S. Keshipeddy, A. G. Capacci, X. Wei, Y. Zhang, J. J.
Gao, W. Li, S. Rodriguez, B. Z. Lu, N. K. Yee, C. H. Sen-
anayake, Org. Lett. 2012, 14, 2258–2261.
[
14] a) I. Pérez, J. Pérez Sestelo, L. A. Sarandeses, Org. Lett. 1999,
1, 1267–1269; b) I. Pérez, J. Pérez Sestelo, L. A. Sarandeses, J.
Am. Chem. Soc. 2001, 123, 4155–4160; c) M. A. Pena, I. Pérez,
[23] P. J. Guiry, C. P. Saunders, Adv. Synth. Catal. 2004, 346, 497–
J. Pérez Sestelo, L. A. Sarandeses, Chem. Commun. 2002, 2246–
537.
2247; d) M. A. Pena, J. Pérez Sestelo, L. A. Sarandeses, Synthe-
[24] C. F. Nising, U. K. Schmid, M. Nieger, S. Bräse, J. Org. Chem.
2004, 69, 6830–6833.
[25] S. Miyano, S. Okada, T. Suzuki, S. Handa, H. Hashimoto, Bull.
Chem. Soc. Jpn. 1986, 59, 2044–2046.
[26] a) B. H. Lipshutz, K. Siegmann, E. Garcia, F. Kayser, J. Am.
Chem. Soc. 1993, 115, 9276–9282; b) J. Clayden, P. M. Kubin-
ski, F. Sammiceli, M. Helliwell, L. Diorazio, Tetrahedron 2004,
60, 4387–4397.
sis 2003, 780–784; e) M. A. Pena, J. Pérez Sestelo, L. A. Sa-
randeses, Synthesis 2005, 485–492; f) J. Caeiro, J. Pérez Sestelo,
L. A. Sarandeses, Chem. Eur. J. 2008, 14, 741–746; g) R. Riv-
eiros, L. Saya, J. Pérez Sestelo, L. A. Sarandeses, Eur. J. Org.
Chem. 2008, 1959–1966; h) L. Bouissane, J. Pérez Sestelo, L. A.
Sarandeses, Org. Lett. 2009, 11, 1285–1288.
[
15] a) M. A. Pena, J. Pérez Sestelo, L. A. Sarandeses, J. Org. Chem.
2
007, 72, 1271–1275; b) A. Mosquera, R. Riveiros, J. Pérez Ses-
[27] Y.-H. Cho, A. Kina, T. Shimada, T. Hayashi, J. Org. Chem.
2004, 69, 3811–3823.
[28] Y. Tamai, T. Nakano, S. Miyano, J. Chem. Soc. Perkin Trans.
1 1994, 439–445.
telo, L. A. Sarandeses, Org. Lett. 2008, 10, 3745–3748; c)
M. M. Martínez, M. Peña-López, J. Pérez Sestelo, L. A. Sa-
randeses, Org. Biomol. Chem. 2012, 10, 3892–3898; d) M. M.
Martínez, C. Pérez-Caaveiro, M. Peña-López, L. A. Sarand- [29] G. Gottarelli, G. P. Spada, J. Org. Chem. 1991, 56, 2096–2098.
eses, J. Pérez Sestelo, Org. Biomol. Chem. 2012, 10, 9045–9051.
16] W. Lee, Y. Kang, P. H. Lee, J. Org. Chem. 2008, 73, 4326–4329.
17] a) R. Nomura, S.-I. Miyazaki, H. Matsuda, J. Am. Chem. Soc.
[30] S. Yekta, L. Cheung, A. K. Yudin, Tetrahedron Lett. 2007, 48,
[
[
8048–8051.
[31] D. Barbaras, J. Brozio, I. Johannsen, T. Allmendinger, Org.
Process Res. Dev. 2009, 13, 1068–1079.
Received: January 10, 2013
1
992, 114, 2738–2740; b) P. H. Lee, S. W. Lee, K. Lee, Org.
Lett. 2003, 5, 1103–1106; c) U. Lehmann, S. Awasthi, T. Mine-
han, Org. Lett. 2003, 5, 2405–2408; d) Z. Huang, M. Qian,
Published Online: March 8, 2013
2562
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2555–2562