Gold-catalyzed stereoselective reaction of tricarbonylchromium complexes of ortho-alkynyl benzaldehydes and benzaldimines with nucleophiles

Article abstract of DOI:10.1016/j.jorganchem.2010.06.005

Gold(I)-catalyzed reaction of ortho-alkynyl benzaldehyde tricarbonylchromium complexes with nucleophiles gave stereoselectively 1-anti-and syn-functionalized 1H-isochromene chromium complexes depending on the nature of nucleophile. By reaction with alcohols, 1-anti-alkoxy 1H-isochromene tricarbonylchromium complexes were obtained via gold benzopyrylium-type intermediates. On the other hand, carbon nucleophiles gave 1-syn-functionalized 1H-isochromene chromium complexes via stereoselective addition of nucleophiles to the activated carbonyl group and following cyclization. Methoxy group of 1-anti-methoxy-1H-isochromene chromium complex was substituted with carbon nucleophiles in the presence of Lewis acid to afford 1-anti-functionalized 1H-isochromene chromium complexes. These methods can be applied to the synthesis of enantiomerically pure trans-and cis-1,3-dimethylisochromans starting from a single planar chiral chromium complex. Similarly, ortho-alkynyl benzaldimine tricarbonylchromium complexes gave stereoselectively 1-syn-and anti-functionalized dihydroisoquinoline chromium complexes by gold(I)-catalyzed reaction with nucleophile.

Full text of DOI:10.1016/j.jorganchem.2010.06.005

Journal of Organometallic Chemistry 695 (2010) 2180e2190
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Gold-catalyzed stereoselective reaction of tricarbonylchromium complexes of
ortho-alkynyl benzaldehydes and benzaldimines with nucleophiles
*
Asami Kotera, Jun’ichi Uenishi, Motokazu Uemura
Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8412, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Gold(I)-catalyzed reaction of ortho-alkynyl benzaldehyde tricarbonylchromium complexes with nucle-
ophiles gave stereoselectively 1-anti- and syn-functionalized 1H-isochromene chromium complexes
depending on the nature of nucleophile. By reaction with alcohols, 1-anti-alkoxy 1H-isochromene tri-
carbonylchromium complexes were obtained via gold benzopyrylium-type intermediates. On the other
hand, carbon nucleophiles gave 1-syn-functionalized 1H-isochromene chromium complexes via ster-
eoselective addition of nucleophiles to the activated carbonyl group and following cyclization. Methoxy
group of 1-anti-methoxy-1H-isochromene chromium complex was substituted with carbon nucleophiles
in the presence of Lewis acid to afford 1-anti-functionalized 1H-isochromene chromium complexes.
These methods can be applied to the synthesis of enantiomerically pure trans- and cis-1,3-dimethyli-
sochromans starting from a single planar chiral chromium complex. Similarly, ortho-alkynyl benzaldi-
mine tricarbonylchromium complexes gave stereoselectively 1-syn- and anti-functionalized
dihydroisoquinoline chromium complexes by gold(I)-catalyzed reaction with nucleophile.
Ó 2010 Elsevier B.V. All rights reserved.
Received 11 May 2010
Received in revised form
31 May 2010
Accepted 3 June 2010
Available online 15 June 2010
Keywords:
Arene chromium complex
Dihydroisoquinoline
Gold catalysis
Isochroman
Planar chirality
1. Introduction
benzaldehydes with nucleophiles giving 1-functionalized-1H-
isochromenes is still attractive reaction. However, the cyclized
Oxygen and nitrogen heterocycles are common structural
components of a wide range of naturally occurring and biologically
active molecules [1]. Development of new and efficient methods for
the synthesis of heterocyclic compounds is of central importance in
organic synthesis. An attractive route to the synthesis of function-
alized heterocycles is via XeH bond of nitrogen or oxygen nucle-
ophile across the carbonecarbon multibond. An activation of the
triple bond is normally required for the achievement of this
process. Thus, halogens [2], ArSeBr, ArSCl, Ipy2BF4 [3] or transition
metals [4] such as palladium, silver, gold or indium catalysts are
employed for the activation of alkyne bond. Transition metal-
catalyzed electrophilic activation of alkynes has attracted much
attention as a useful method, and the generated metal-containing
1-functionalized heterocycles by this methodology are usually
achiral compound, although a chiral center is created. Directed
toward the synthesis of optically active heterocycles, we employed
planar chiral arene chromium complex in this study. In the case of
chromium-complexed o-alkynyl benzaldehydes, the structure of
metal-coordinated interemediates is a significant factor for relative
stereochemistry of the cyclized 1-functionalized 1H-isochromene
tricarbonylchromium complexes. Three activation modes by the
coordination with metal are devised (Fig. 1). In the transition state
A, metal activates the carbonyl group in which carbonyl oxygen is
an anti-conformation with ortho alkyne substituent due to a steric
interaction. On the other hand, the alkyne in the intermediate B is
activated by metal e.g. Au(I) and Pd(II)/Cu(II) systems giving metal-
contained benzopyrylinium ion intermediate [7].
benzopyrylium-type intermediates is considered
a common
process, which upon further treatment with various partners, such
as nucleophiles, alkynes, alkenes and carbonyl compounds, result
in diverse products [5]. In particular, gold has emerged as
a powerful homogeneous catalyst for the electrophilic activation of
alkynes, and has been demonstrated in useful organic transforming
reactions [6]. The metal-catalyzed reaction of o-alkynyl
The transition state C has dual carbophilic and oxophilic activa-
tions [8] with metal such as In(OTf)3 catalyst at the same time. Since
nucleophiles attack the metal-coordinated intermediates from an
opposite side with tricarbonylchromium fragment, the relative
stereochemistryat the benzylic position of cyclized 1-functionalized
1H-isochromene chromium complexes derived from the transition
state A is distinct from the other intermediates B and C. Thus, the
substituent at the benzylic position of cyclized isochromene chro-
mium complexes derived from the transition state Awould be a syn-
configuration with tricarbonylchromium fragment, while the
* Corresponding author.
E-mail address: uemura@mb.kyoto-phi-ac.jp (M. Uemura).
0022-328X/$ e see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2010.06.005

A. Kotera et al. / Journal of Organometallic Chemistry 695 (2010) 2180e2190
2181
C
B
A
H
[M]
H
O
O
[M]
O
H
Cr(CO)3
Cr(CO)3
R
Cr(CO)3
R
R
[M]
carbophilic activation:
dual carbophilic and oxophilic
activation:
oxophilic activation:
anti: C=O / o-alkyne
to benzopyrylium ion
syn: C=O / o-alkyne
intermediate
Fig. 1. Activated form of o-alkynylbenzaldehyde chromium complex with metal.
corresponding substituent arised from the coordination states B or C
is an anti-configuration. Herein, we describe the full details of the
scope and limitations of gold(I)-catalyzed electrophilic cyclization of
the planar chiral chromium complexes of ortho-alkynyl benzalde-
hydes and benzaldimines with nucleophiles [9].
was obtained by detrimethylsilylation, acidic hydrolysis of acetal
and finally Sonogashira coupling with iodobenzene from chro-
mium complex 2.
An effect of the metal catalyst for activation of the alkyne bond
of 2-(prop-1-ynyl)benzaldehyde chromium complex (3a) was
initially examined. As shown in Table 1, metal such as Ag(I), Pd(II)
and In(OTf)3 gave no cyclization product by reaction of the complex
3a with MeOH, while the corresponding chromium-free o-alkynyl
benzaldehyde afforded cyclized 1-methoxy-1H-isochromene by
reaction with these catalysts [4e6]. With both Au(III) and Au(I)
catalysts, cyclized isochromene chromium complex 5aa was also
not observed (entries 4 and 5). No cyclization product might be
contributed a decreased electron-density of the alkyne bond due to
a strong electron-withdrawing ability of the tricarbonylchromium
fragment. However, an addition of silver salt for de-chlorination of
PPh3AuCl catalyst gave 6-endo-dig cyclization product 5aa as
a single diatereomer in moderate yields (entries 6e8). The best
result was obtained by using of isolated gold bis(tri-
fluoromethanesulfonyl)imidate [11], PPh3AuNTf2, in methylene
chloride at room temperature (entry 9). This catalyst enhances the
Lewis acidity for the coordination to alkyne bonds. It is noteworthy
2. Results and discussion
Gold(I)-catalyzed reaction of o-alkynyl benzaldehyde tricarbonyl-
chromium complexes. ortho-alkynyl benzaldehyde tricarbonylchro-
mium complexes as starting materials in this study were prepared
from benzaldehyde ethyleneacetal chromium complex (Scheme 1).
Sonogashira coupling of o-chlorobenzaldehyde ethyleneacetal
chromium complex 1 with trimethylsilylacetylene gave a coupling
product 2 in good yield. Deprotection of 2 with aqueous NaOH at
ꢀ20 ꢁC followed by methylation and subsequently hydrolysis
produced
[2-(prop-1-ynyl)benzaldehyde]tricarbonylchromium
(3a) in good yield. Other ortho-alkynyl benzaldehyde chromium
complexes 3b and 3c were prepared by Sonogashira coupling of
ortho-chlorobenzaldehyde chromium complex 4 with substituted-
alkynes [10]. 2-Phenylethynyl benzaldehyde chromium complex 3d
O
O
CHO
ii, iii
iv
O
O
i
Cl
Cr(CO)3
Cr(CO)3
Me
3a
Cr(CO)3
SiMe3
1
2
CHO
CHO
Cl
CHO
ii, vi
v
2
vii
Cr(CO)3
Cr(CO)3
Cr(CO)3
Ph
3d
R
4
3
b: R = n-Bu
c: R = SiMe3
Reagents and conditions: i) trimethylsilylacetylene, 5 mol% Pd(PPh3)2Cl2, 5 mol% CuI, Et3N,
THF, reflux, 30 min (87%); ii) 2N NaOH, MeOH, –20 °C (87%); iii) MeLi, THF, –50 °C, then MeI
(85%); iv) 6N HCl, THF, 0° to rt (95%); v) 1-alkyne, 5 mol% Pd(PPh3)2Cl2, 5 mol% CuI, Et3N,
THF (79% for R = n-Bu, 82% for R = SiMe3); vi) 6N HCl, THF (88%); vii) Iodobenzene, 6 mol%
Pd(PPh3)4, 7mol% CuI, THF, NEt3, rt, then 45 °C (99%)
Scheme 1. Synthesis of o-alkynylbenzaldehyde tricarbonylchromium complexes.

2182
A. Kotera et al. / Journal of Organometallic Chemistry 695 (2010) 2180e2190
Table 1
Metal-catalyzed reaction of o-propynylbenzaldehyde chromium complex 3a with MeOH.
HOMe
+
OMe
O
CHO
[M], additive
O
MeOH, CH2Cl2
Me
Me
Cr(CO)3
Cr(CO)3
Me
Cr(CO)3
[Au]–
3a
5aa
6
6-endo-dig
anti; Cr(CO)3 / OMe
Entry
[M]
Additive
Conditions
Yield (%)
1
2
3
4
5
6
7
8
9
Pd(OAc)2
In(OTf)3
AgOTf
Benzoquinone
e
Dioxane, 80 ꢁC
DMF, 50 ꢁC
CH2Cl2, reflux
(CH2Cl)2, 80 ꢁC
CH2Cl2, 40 ꢁC
CH2Cl2, rt
CH2Cl2, rt
CH2Cl2, rt
CH2Cl2, rt
e
e
e
e
AuCl3
e
e
PPh3AuCl
PPh3AuCl
PPh3AuCl
PPh3AuCl
PPh3AuNTf2
e
e
AgOTf
AgSbF6
AgBF4
e
44
59
Trace
80
that the reaction proceeds under mild condition (room tempera-
ture, within 30 min), while the corresponding chromium-free o-
alkynyl benzaldehydes were required high reaction temperature
and long reaction time. The anti-stereochemistry of the methoxy
group of 5aa was determined by X-ray crystallography [12]. The
cyclized isochromene chromium complex 5aa was derived from an
anti-atack of methanol to the generated chromium-complexed
benzopyrinium intermediate 6 derived from the transition state B.
Having established the optimal reaction conditions, we explored
the scope of the methodology by subjecting a range of o-alkynyl
benzaldehyde chromium complexes with various alcohols and the
results are summarized in Table 2. The reaction took place stereo
and regioselectively with primary and secondary alcohols in good
yields. TMS-substituted alkyne chromium complex 3c gave also 6-
endo-dig cyclization product (entry 6), while treatment of 3c with
2 M aqueous NaOH in MeOH at room temperature produced
exclusively 5-exo-dig cyclization product with loss of TMS group
(vide infra). The benzaldehyde chromium complex 3e without
substituent at the alkyne terminus gave a complexed mixture by
gold-catalyzed reaction under same conditions (entry 8).
We next turned our attention to the gold(I)-catalyzed reaction of
o-alkynyl benzaldehyde tricarbonylchromium complexes with
carbon pronucleophiles. Treatment of 3a with allyl tri-n-butyl-
stannane in the presence of 10 mol% gold(I) catalyst at room
temperature for 4.5
h gave interestingly 1-syn-allyl-1H-iso-
chromene chromium complex 9a in 17% yield, along with the
formation of a single diastereomeric allylated benzylalcohol chro-
mium complex 8a in 40% yield (Scheme 2). The corresponding anti-
allyl-1H-isochromene chromium complex was not detected. The
syn stereochemistry of allyl group of the cyclization product 9a was
confirmed by X-ray crystallography [12]. Similarly, ketene trime-
thylsilyl ethyl acetal afforded a mixture of syn-functionalized iso-
chromene chromium complex 9b and benzylalcohol trimethylsilyl
ether 8b in 19% and 38% yields, respectively, by treatment with the
Au(I) catalyst at ꢀ20 ꢁC for 10 min and following reflux for over-
night after addition of 10 equivalent MeOH and H2O. The syn-
functionalized 1H-isochromene chromium complexes 9a and 9b
would be formed via diastereoselective nucleophilc addition to an
anti-oriented carbonyl group in the metal-coordinated interme-
diate A and subsequent intramolecular cyclization of hydroxy
group with metal-activated alkyne group. Different anti- vs syn-
stereoselectivity of the cyclization products depending on the
employing nucleophiles would be fundamentally contributed to
a different ability of nucleophilic addition to the carbonyl group.
With carbon nucleophile, the addition to carbonyl group takes
place exclusively giving a single diastereomeric addition product.
Consequently, the cyclization products are syn-isomers. Thus, gold
bis(trifluoromethanesulfonyl)imidate catalysis in the reaction of
chromium-complexed o-alkynyl benzaldehyde with carbon nucle-
ophile serves as a multicatalysis [13] for the activation of carbonyl
and subsequently alkyne groups with catalytic transformation
stepwise. The low yield of the cyclized isochromene chromium
complexes 9 would be contributed to a slow cleavage of the
generated benzyl alkoxide intermediate, and a decrease of the
activity of the gold catalyst by addition of aqueous methanol.
The low yield of 1-syn-functionalized isochromene chromium
complexes 9 by one pot synthesis was improved by stepwise
reaction via benzylalcohol derivatives as follows. The chromium
Table 2
Gold(I)-catalyzed reactionof o-alkynyl benzaldehyde chromium complexes with
alcohols.
OR2
CHO
5~10 mol% Ph3PAuNTf2
O
R2OH (7),
CH2Cl2, rt
R1
Cr(CO)3
Cr(CO)3
R1
3
5
Entry
3
R1
R2OH (7)
5
Yield (%)
1
2
3
4
5
6
7
8a
3a
3a
3a
3a
3b
3c
3d
3e
Me
Me
Me
Me
nBu
SiMe3
Ph
MeOH (7a)
5aa
5ab
5ac
5ad
5ba
5ca
5da
5ea
80
60
83
62
71
66
73
e
iPrOH (7b)
CH2]CHCH2OH (7c)
CH]CCH2OH (7d)
MeOH (7a)
MeOH (7a)
MeOH (7a)
MeOH (7a)
H
a
Complexed mixture.

A. Kotera et al. / Journal of Organometallic Chemistry 695 (2010) 2180e2190
2183
Nu
Nu
OX
CHO
10 mol% Ph3PAuNTf2
O
H
+
carbon nucleophile
(Nu–), CH2Cl2
then addition of
Me
Cr(CO)3
Cr(CO)3
Cr(CO)3
Me
Me
3a
8
9
aq MeOH
Nu–; CH2=CHCH2Sn Bu3
n
or CH2=C(OSiMe3)OEt
a: Nu = CH2CH=CH2 a: Nu = CH2CH=CH2
X = H
b: Nu = CH2CO2Et
b: Nu = CH2CO2Et
X = SiMe3
Scheme 2. Gold(I)-catalyzed reaction of o-alkynylbenzaldehyde chromium complex with carbon nucleophile.
complex 3a was reacted with allyl tri-n-butylstannane in the
presence of 10 mol% (Ph3P)AuNTf2 in CH2Cl2 at ꢀ20 ꢁC to give
stereoselectively prepared from a single o-substituted benzalde-
hyde chromium complex. Thus, the gold(I)-catalyzed reaction of o-
alkynyl benzaldehyde chromium complexes with alcohols gave 1-
anti-alkoxy 1H-isochromene chromium complexes which were
subsequently treated with carbon nucleophiles in the presence of
Lewis acid to afford stereoselectively 1-anti-functionalized 1H-
isochromene tricarbonylchromium complexes. On the other hand,
the gold(I)-catalyzed reaction of o-alkynyl benzaldehyde chromium
complexes with carbon nucleophiles produced 1-syn-functional-
ized 1H-isochromene tricarbonylchromium complexes via
secondary benzylalcohol chromium complexes. Both reaction
sequences are useful for stereoselective synthesis of functionalized
isochromans.
a
diastereomerically single allylated secondary benzylalcohol
chromium complex 8a in 73% yield (Table 3, entry 1). Similarly,
ketene enolsilyl acetal and diethylalumium acetylide produced the
corresponding benzyl alcohol chromium complexes 8b, 8c (entries
2, 3). The other hard Lewis acid such as BF3$OEt2 or TiCl4 can be also
employed. Methyl lithium reacted without Lewis acid to afford
a diastereomerically single phenylethyl alcohol chromium complex
in good yield (entry 4). The obtained o-alkynyl benzyl alcohol
chromium complexes 8 were treated with 10 mol% gold(I) catalyst
at room temperature to give 1-syn-functionalized 1H-isochromene
chromium complexes 9 without formation of the corresponding
5-exo-dig cyclization products [14,15b].
We next studied substitution of the alkoxy group of 1-anti-
alkoxy 1H-isochromene chromium complex with carbon nucleo-
philes for further manipulation. Chromium-complexed benzylic
position could be stabilized as benzylic cations and the property
has been widely employed for useful stereoselective
carbonecarbon bond forming reactions [15]. Treatment of 1-anti-
methoxy-1H-isochromene chromium complex (5aa) with carbon
nucleophiles in the presence of Lewis acid gave 1-anti-functional-
ized 1H-isochromene chromium complexes 10 (Table 4). Alkyl,
allyl, ester, nitrile and alkyne groups can be introduced stereo-
selectively. In this manner, both 1-anti- and 1-syn-functionalized
1H-isochromene tricarbonylchromium complexes can be
These reaction sequences could be applied to the synthesis of
enantiomerically pure trans- and cis-1,3- dimethylisochromans as
shown in Scheme 3. Diastereoselective ortho lithiation [16] of
(þ)-(benzylidene)methyl-a-D-glucopyranoside chromium complex
11 followed by bromination with 1,2-dibromo-1,1,2,2-tetra-
fluoroethane gave (þ)-o-brominated chromium complex 12.
(þ)-ortho-brominated chromium complex 12 was converted to
(ꢀ)-o-(prop-1-ynyl)benzaldehyde tricarbonylchromium complex
(13) with 99% ee by several steps. The chromium complex 13 was
reacted with MeOH in the presence PPh3AuNTf2 followed by treat-
ment with Me3Al to give (ꢀ)-1-anti-methyl-3-methyl-1H-iso-
chromene chromium complex (14) in good yield. Reduction of
double bond of the complex 14 with Et3SiH/CF3CO2H followed by air
Table 3
Two steps synthesis of 1-syn-functionalized isochromene tricarbonylchromium complexes.
Nu
Nu
O
carbon nucleophile
OH
10 mol%
(Nu–)
H
O
PPh3AuNTf2
H
CH2Cl2
CH2Cl2, rt
Me
A or B
Cr(CO)3
Cr(CO)3
Me
Cr(CO)3
Me
3a
9
8
A: 10 mol% PPh3AuNTf2
B: Hard Lewis acid
syn-: Nu / Cr(CO)3
Entry
Nuꢀ
Yield 8 (%)
9
Yield 9 (%)
A
B (Lewis acid)
1
CH2]CHCH2Sn(n-Bu)3
CH2]C(OSiMe3)OEt
Et2AlC]CBun
73
56
97
91b
60 (BF3.OEt2)
58 (TiCl4)
9a (Nu ¼ CH2CH]CH2)
9b (Nu ¼ CH2CO2Et)
9c (Nu ¼ C]CBun)
9d (Nu ¼ Me)
68
69
31
80
2a
3
e
4
MeLi
e
a
TBAF was added to the reaction mixture for deprotection of OeSiMe3 bond.
The reaction took place in ether at e78 ꢁC without Au(I) or Lewis acid.
b

2184
A. Kotera et al. / Journal of Organometallic Chemistry 695 (2010) 2180e2190
Table 4
bond and subsequent photo-oxidation. In this way, enantiomerically
pure trans- and both enantiomers of cis-1,3-dimethylisochromans
were stereoselectively prepared from a single planar chiral arene
chromium complex 13 (Scheme 3).
Lewis acid mediated transformation of 1-anti-methoxy iochromene chromium
complex 5aa.
Nu
OMe
O
As a further extension of the stereoselective gold(I)-catalyzed
reaction of o-alkynyl arene chromium complexes, we examined an
effect of the tricarbonylchromium fragment on the regioselectivity
of 6-endo-dig cyclization of mono tricarbonylchromium complexes
of 1,2-bis(phenyl)acetylene substituted with nuclophilc functional
groups at the ortho position of both arene rings. In the case of biaryl
mono chromium complexes with an identical substituent at the
ortho position of both arene rings, two directions of 6-endo-dig
cyclization (path a or b) might be possible (Table 5, path a or b). If
either of two direction modes takes place predominantly, further
useful organic transformations could be developed. Gold(I)-cata-
lyzed reaction of bis-benzaldehyde acetylene mono chromium
complex 18a in the presence of MeOH resulted in a recovery of the
starting material without formation of the cyclized methoxy iso-
chromene chromium complexes 19a and 20a (entry 1). However,
regioisomeric bis-benzaldehyde chromium complex 18b with para
formyl group on the B-ring afforded an expected 1-anti-methoxy-
1H-isochromene chromium complex 19b under the same condi-
tions (entry 2). On the other hand, bis-dihydroxymethyl substituted
biaryl chromium complex 18c gave a mixture of isochromene
chromium complex 19c as a minor product and a further cyclized
spiro compound 21 as a major product by gold-catalyzed reaction
without MeOH (entry 3). Structural isomeric cyclization product
Nu–
O
Lewis acid, CH2Cl2
Me
Me
Cr(CO)3
10
Cr(CO)3
5aa
Entry Nue
Lewis acid 10
Nu
Yield (%)
99
10b CH2CH]CH2 60
1
2
3
4
5
Me3Al
e
10a Me
CH2]CHCH2Sn(n-Bu)3 BF3$OEt2
CH2]C(OSiMe3)OEt
Me3SiCN
TiCl4
BF3$OEt2
BF3$OEt2
10c
CH2CO2Et
72
56
74
10d CN
Et2AlC]CBun
10e C]CBun
oxidation gave (þ)-trans-1,3-dimethylisochroman (15) [17]. On the
other hand, air oxidation of 14 and subsequent reduction with 10%
Pd/C under 1 atmosphereic hydrogen afforded (ꢀ)-cis-1,3-dime-
thylisochroman (16) [17]. Furthermore, reaction of MeLi with
(þ)-benzaldehyde chromium complex 13 followed by gold(I)-cata-
lyzed cyclization afforded (ꢀ)-1-syn-methyl-3-methyl-1H-iso-
chromene chromium complex (17) in good yield. The chromium
complex 17 was converted to (þ)-ent-16 by reduction of the double
Me
S
d
O
S
Me
Me
15 trans-
[α]D20 +52.2
c
O
(c 1.66, CH2Cl2)
Me
Cr(CO)3
14
Me
S
e
O
H
anti-; Me / Cr(CO)3
[α]D20 –1435.4
(c 0.17, CHCl3)
H
O
OMe
O
OMe
O
CHO
O
a
b
Me
R
16 cis-
O
OMe
O
OMe
H
[α]D20 –162.6
(c 1.30, CH2Cl2)
H
OMe
OMe
Cr(CO)3
Br
Me
Cr(CO)3
Cr(CO)3
11
13
12
[α]D20 68.3
( c, 0.50, CHCl3)
Me
O
[α]D20 –936.8
Me
R
(c 0.15, CHCl3)
g
f
O
>99% ee
Me
Cr(CO)3
17
S Me
ent-16
syn-; Me / Cr(CO)3
[α]D20 –1412.0
(c 0.14, CHCl3)
[α]D20 +160.7
(c 1.23, CH2Cl2)
Reagents and conditions
a) n-BuLi, ether, –78 ° to –40 °C; then BrF2CCF2Br, –40 ° to 0 °C (77%). b) (i) trimethylsilylacetylene, 5 mol% Pd(PPh3)2Cl2, 5 mol%
CuI, Et3N, THF, 80 °C (97%); (ii) n-Bu4NF, THF, 0 °C (97%); (iii) MeLi, ether, –50 °C, 1 h; then MeI, 0 °C (91%); (iv) 50% aq. H2SO4,
acetone, rt (68%); c) (i) 5mol% PPh3AuNTf2, MeOH, CH2Cl2, rt (80%); (ii) Me3Al, CH2Cl2, (72%); d) (i) Et3SiH, CF3CO2H, CH2Cl2, –
20 ~ 0 °C (75%); (ii) hν/air, ether (quantitative); e) (i) hν/air, ether (quantitative); (ii) 10%Pd/C, H2,CH2Cl2, THF (quantitative); f) (i)
MeLi, ether, –78°C (91%); (ii) 5 mol% PPh3AuNTf2, CH2Cl2, rt (80%); g) (i) Et3SiH, CF3CO2H, CH2Cl2 (88%); (ii) hν/air, ether.
Scheme 3. Stereoselective synthesis of enantiomerically pure 1,3-dimethylisochromans.

A. Kotera et al. / Journal of Organometallic Chemistry 695 (2010) 2180e2190
2185
Table 5
Effect of Cr(CO)3 to regioselectivity in gold(I)-catalyzed cyclization.
R1
X
a
A
R1
O
5mol% PPh3AuNTf2
O
Cr(CO)3
CH2Cl2, rt
b
R2
Cr(CO)3
20
B
presence or absence
R3
of 5eq MeOH
Cr(CO)3
19
R3
R2
R3
18
X
a: R1 = R2 = CHO, R3 = H
a: X = OMe, R2 = CHO, R3 = H
b: X = OMe, R2 = H, R3 = CHO
c: X = H, R2 = CH2OH, R3 = H
a: X = OMe, R1 = CHO, R3 = H
b: R1 = R3 = CHO, R2 = H
b: X = H, R1 = CHO, R3 = H
c: R1 = R2 = CH2OH, R3 = H
d: R1 = CHO, R2 = CH2OH, R3 = H
e: R1 = CH2OH, R2 = CHO, R3 = H
c: X = H, R1 = CH2OH, R3 = H
d: X = OMe, R1 = CH2OH, R3 = H
d: X = OMe, R2 = CH2OH, R3 = H
e: X = H, R2 = CHO, R3 = H
O
O
Cr(CO)3
21
Entry
Complex 18
MeOH
Products (yield %)
1a
2
3
18a
18b
18c
18d
18d
18e
18e
þ
þ
e
þ
e
þ
e
e
19b (46)
19c (13), 21 (59)
19d (50)
4
5a,b
6
e
20dc (82)
7b
e
a
Recovery of starting material.
Complexed mixture.
1:1 diastereomeric mixture.
b
c
20c and further cyclized compound were not observed. This result
indicates that the hydroxymethyl group of chromium-coordinated
arene ring operated predominantly as the nucleophile. The regio-
selective cyclization would be contributed to a different electron-
result in a recovery of the starting material without formation of
expected cyclization product 20b (entry 5). On the other hand,
o-alkynyl benzylalcohol chromium complex 18e with formyl group
on the B-ring gave a 1: 1 diastereomeric mixture of the cyclization
product 20d in the presence of MeOH (entry 6), while the complex
18e afforded no cyclization product in the absence of MeOH (entry
7). Thus, the cyclized isochromene derivatives between the
hydroxy group and activated alkyne bond were not formed under
the absence of MeOH. In contrast with above conditions, the
reaction under the presence of methanol as nucleophile gave
expected 1-methoxy-isochromene derivatives in good yields. With
biaryl substituted-alkynes with both formyl and hydroxymethyl
groups at the ortho positions, the formyl group would attacks
predominantly to the activated alkyne to give gold-containing
benzopyrylium-type intermediate which will react with methanol
to afford the cyclized product. In the case of absence of methanol,
the starting materials are recovered since the generated benzo-
pyrinium intermediate could not react with nucleophile.
density at
a- and b-carbons of the alkyne bond. Between two
possible 6-endo-dig cyclized intermediates 23 and 24 generated
from the gold-activated alkyne intermediate 22, the chromium-
complexed benzylic position (a-position) is more stabilized as an
anion character due to the electron-withdrawing ability of the
tricarbonylchromium fragment (Scheme 4) [18].
Furthermore, reactivity of the gold-catalyzed cyclization of bis-
aryl alkyne mono chromium complexes with hydroxyymethyl and
formyl groups under different reaction conditions was studied.
o-Alkynyl benzaldehyde chromium complex 18d with hydrox-
ymethyl group on the B-ring produced expected 6-endo-dig
cyclized 1-methoxy-1H-isochromene chromium complex 19d by
gold-catalyzed-reaction in the presence of methanol (entry 4),
while the complex 18d was treated in the absence of MeOH to
OH
[Au]–
HO
PPh3AuNTf2
18c
OH
O
A
α
β
(CO)3Cr
(CO)3Cr
[Au]–
Cr(CO)3
[Au]
HO
O
B
22
23
24
Scheme 4. Proposed reaction mechanism.

2186
A. Kotera et al. / Journal of Organometallic Chemistry 695 (2010) 2180e2190
R1
syn-isomer 27. The formation of anti-isomer 25 via the intermediate
COR1
OMe
O
26A from the chromium complex 3 takes place concertedly. On the
other hand, the diastereomeric hemiacetal intermediate 26B
attains equilibrium to the parent carbonyl group, since the diaste-
reomer 26B is required a rotation between aryl and benzylic bond
for the syn-isomer 27.
2N NaOH, MeOH
Cr(CO)3
R2
63 ~70%
rt
Cr(CO)3
3
5-exo-dig
25
Gold(I)-catalyzed reaction of o-alkynyl benzaldimine tricarbonyl-
chromium complexes. We furthermore studied the gold(I)-catalyzed
reaction of o-alkynyl benzaldimine tricarbonylchromium
complexes directed toward stereoselective synthesis of optically
active 1,3-difunctionalized 1,2-dihydro- or tetrahydroisoquinoline
derivatives (Table 6). ortho-Alkynyl benzaldimine chromium
complexes 28 as starting materials were easily prepared from
o-alkynyl benzaldehyde tricarbonylchromium 3a and p-methox-
yaniline or p-toluenesulfonamide [20]. Gold(I)-catalyzed reaction
of p-methoxyphenyl substituted imine chromium complex 28a
with methanol or carbon nucleophile gave the corresponding
cyclization or addition products in very low yield [21]. Reduction of
28a with large excess of NaBH4 afforded the corresponding ben-
zylamine chromium complex, which was treated with PPh3AuNTf2
at room temperature to give 1,2-dihydroisoquinoline chromium
complex in good yield. However, as the obtained 1,2-
dihydroisoquinoline chromium complex has no functional group at
C-1 position, gold-catalyzed reaction of an electron-withdrawing
p-tosyl substituted imine chromium complex 28b with nucleo-
philes was examined. Gold(I)-catalyzed reaction of 28b with MeOH
gave expectedly 1-anti-methoxy 1,2-dihydroisoquinoline chro-
mium complex 29 in good yield. Subsequently, Lewis acid medi-
ated-substitution of the methoxy group of 29 with carbon
nucleophiles afforded 1-anti-functionalized 1,2-dihydroisoquino-
line chromium complexes 30 as well as 1-methoxy-isochromene
chromium complex in shown in Table 4.
3c: R1= H, R2 = SiMe3
3e: R1= H, R2 = H
a: R1 = H
b: R1 = Me
3f: R1= Me, R2 = SiMe3
Scheme 5. Reaction of chromium complex with MeOH under basic conditions.
Base-catalyzed reaction of 2-alkynyl benzaldehyde chromium
complexes. As mentioned above, gold(I)-catalyzed reaction of
2-alkynyl benzaldehyde chromium complexes with nucleophiles
gave 6-endo-dig cyclization products. However, base-catalyzed
reaction produced different cyclization mode product as follows.
Thus, the treatment of [2-(trimethylsilylethynyl)benzaldehyde]tri-
carbonylchromium (3c) with aqueous NaOH in MeOH at room
temperature gave regio- and stereoselectively 1-anti-methoxy-
3-methylidene-1,3-dihydroisobenzofuran
tricarbonylchromium
(25a) in 64% yield (Scheme 5). The stereochemistry of OMe group of
25a was determined as an anti-configuration by X-ray
crystallography [12]. Similarly, terminal alkyne chromium
complex 3e afforded also 1-anti-methoxy-3-methylidene-1,3-
dihydroisobenzofuran
tricarbonylchromium
(25a).
Besides
benzaldehyde chromium complexes, 2-alkynyl acetophenone
chromium complex 3f afforded stereoselectively 5-exo-dig mode
cyclization product 25b [12] as a single stereoisomer under the
same conditions. In this way, the cyclization mode of o-alkynyl
benzaldehyde chromium complexes is distinct between Au(I)-
catalyzed reaction and base mediated cyclization.
A mechanism for the stereoselective formation of 5-exo-dig
cyclization product 25 is proposed in Scheme 6. Under the basic
conditions, alkoxide anion attacks the carbonyl group from an
exo-side with the tricarbonylchromium fragment to generate dia-
stereomeric hemiacetal intermediates 26A and 26B [19]. A diaste-
reomeric hemiacetal intermediate 26A will afford the anti-methoxy
isobenzofuran complex 25 by subsequent intramolecular cycliza-
tion, while the other diastereomer 26B produces the corresponding
Reaction of o-alkynyl benzaldimine chromium complex 28b
with carbon pronucleophiles was next examined. Reaction of 28b
with methyl lithium in ether at ꢀ78 ꢁC without gold(I) catalyst gave
a secondary benzylamine chromium complex 31a and the diaste-
reomer in a ratio of 92: 8 in 78% yield (Table 7). Treatment of 31a
with PPh3AuNTf2 in CH2Cl2 at room temperature afforded 1-syn-
methyl 1,2-dihydroisoquinoline chromium complex 32a in 86%
yield. Similarly, ketene silylacetal was reacted with 28b in the
presence of gold catalyst at room temperature to give a sigle dia-
stereomeric addition product 31b in 56% yield. The obtained
OMe
R
OMe
O–
–OMe
R
O–
R
O
2N NaOH, MeOH
Cr(CO)3
26A
Cr(CO)3
26B
Cr(CO)3
H
H
H
3
R
OMe
O
OMe
O
R
Cr(CO)3
25
Cr(CO)3
27
anti;
OMe / Cr(CO)3
syn;
OMe / Cr(CO)3
Scheme 6. Mechanism under basic conditions.

A. Kotera et al. / Journal of Organometallic Chemistry 695 (2010) 2180e2190
2187
Table 6
Synthesis of 1-anti-functionalized 1,2-dihydroisoquinoline chromium complexes.
OMe
N
Nu
R
carbon nucleophile
(Nu–)
R
N
PPh3AuNTf2
R
N
MeOH, CH2Cl2
Lewis acid, CH2Cl2
Me
Me
Cr(CO)3
Me
Cr(CO)3
Cr(CO)3
87% for 29b
28
30
29
a: R = PMP
b: R = Ts
R = Ts
anti; Nu / Cr(CO)3
R = Ts
Entry
Nucleophile (Nuꢀ
Me3Al
CH2]C(OSiMe3)OEt
CH2]CHCH2SnnBu3
Et2AlCN
)
Lewis acid
Nu
Yield (%)
1
2
3
4
5
e
Me
CH2CO2Et
CH2CH]CH2
CN
Et
30a (67)
30b (71)
30c (84)
30d (43)
30e (54)
TiCl4
BF3$OEt2
e
Et2Zn
TiCl4
benzylamine chromium complex 31b was converted to 1-syn-
ethoxycarbonylmethyl 1,2-dihydroisoquinoline chromium complex
32b by further treatment with gold catalyst. However, gold(I)-
catalyzed reaction with allyl n-tributylstanane at room tempera-
arene ring with slightly incline, and NeS bond of the tosyl group is
oriented as an anti-conformation to the tricarbonylchromium
fragment to avoid a nonbonding interaction with syn-oriented
ethyl acetate group. Therefore, 1-anti-functinalized 1,2-dihy-
droisoquinoline chromium complexes 30 and the corresponding
syn-isomers 32 can be distinguished by proton NMR spectra. Thus,
the aromatic protons of tosyl group of syn-isomers appear at higher
ture produced
a mixture of the addition product 31c and
1-anti-allyl-1,2-dihydroisoquinoline chromium complex 30c in 72%
and 17% yields, respectively. Under the reaction condition at 0 ꢁC,
the yield of cyclized 1-anti-allyl-1,2-dihydroisoquinoline chromium
complex 30c decreased (entry 4). The obtained allyl benzylamine
chromium complex 31c afforded 1-syn-allyl-2-tosyl-3-methyl-
isoquinoline chromium complex (32c) in good yield by treatment
with the gold catalyst. The stereochemistry of 1-syn-substituted
1,2-dihydroisoquinoline chromium complex 32b was confirmed by
X-ray crystallography (Fig. 2) [12]. Interestingly, the arene ring of
tosyl group of 32b is stacking with the chromium-coordinated
field (d 7.45 and 7.06 ppm for 32b) than those (d 7.88 and 7.34 ppm
for 30b) of the corresponding anti-isomer.
The formation of 1-anti-functionalized-1,2-dihydroisoquinoline
chromium complex 30 by gold(I)-catalyzed reaction of 28b with
allyl stannane is quite interesting, since the reaction of 28b with
other carbon nucleophiles gave 1-syn-functionalized 1,2-
dihydroisoquinoline chromium complexes via stereoselective
addition products of nucleophiles to the imine double bond in
analogy with the reaction of o-alkynyl benzaldehyde chromium
complexes with carbon nucleophiles as shown in Table 3. The
reaction mechanism for the anti-isomer of 1,2-dihydroisoquinoline
chromium complex 30 from the chromium complex 28b is follows.
Nucleophilic ability of the addition of employing reagents to the
imine bond would govern the reaction products. The addition of
allyl tributylstannane to the imine and generation of chromium-
complexed isoquinolinium ion take place competitively. As the
nucleophilicity of the allyl stannane to the imine double bond is not
so strong, the generated chromium-complexed isoquinolinium
ion intermediate would be attacked a part by the allyl group from
exo-side giving 1-anti-allyl-1,2-dihydroisoquinoline chromium
complex 30c. On the other hand, 1-syn-allyl-1,2-dihydroisoquino-
line chromium complex 32c was formed via stereoselective addi-
tion of the allyl to imine double bond.
3. Conclusion
Gold(I)-catalyzed cyclization of o-alkynyl benzaldehyde and
benzaldimine chromium complexes gave stereoselectively 1-anti-
and syn-functionalized heterocycle chromium complexes depend-
ing on the nature of nucleophiles. With alcohol nucleophiles,
1-anti-alkoxy-heterocycle chromium complexes were stereo-
selectively obtained via gold benzopyrylium-type intermediates,
while carbon pronucleophiles gave 1-syn-functionalized hetero-
cycle chromium complexes via stereoselective addition of nucleo-
philes to the activated carbon-heteroatom double bond and
subsequent cyclization. By using these methods, enantiomerically
pure trans- and both enantiomers of cis-1,3-dimethylisochromans
were stereoselectively prepared starting from planar chiral
o-chrorobenzaldehyde tricarbonylchromium complex.
Fig. 2. X-ray crystallography of 32b.

2188
A. Kotera et al. / Journal of Organometallic Chemistry 695 (2010) 2180e2190
Table 7
Synthesis of 1-syn-functionalized 1,2-dihydroisoquinoline chromium complexes.
Nu
Nu
Ts
Ts
Ts
N
10 mol% PPh3AuNTf2
N
H
10 mol% PPh3AuNTf2
N
Nucleophile (Nu–)
CH2Cl2, 0°C ~ rt
CH2Cl2
rt
Me
Cr(CO)3
28b
Cr(CO)3
Me
Cr(CO)3
32
Me
31
syn; Nu / Cr(CO)3
Yield of 31 (%)
Entry
Nue
MeLi
CH2]C(OSiMe3)OEt
CH2]CHCH2Sn(n-Bu)3
CH2]CHCH2Sn(n-Bu)3
Nu
Me
CH2CO2Et
CH2CH]CH2
CH2CH]CH2
Yield 32
1a
2b
3b
4c
31a (78)
31b (56)
31c (72), 30c (15)
31c (69), 30c (3)
32a (86)
32b (68)
32c (86)
e
a
Reaction took place in ether at e78 ꢁC without gold catalyst.
b
c
rt, 2 h.
0
ꢁC, 3 h.
4. Experimental
Allyl tri-n-butylstannane (0.28 mL, 0.89 mmol) was added with
syringe, and the mixture was stirred for 1 h at ꢀ20 ꢁC. Saturated
aqueous KF was added and the reaction mixture was extracted with
ether. The ether was washed with saturated aqueous KF, brine and
dried over MgSO4. The organic layer was evaporated under vacuum,
and purified by SiO2 column chromatography to give the title
compound as yellow crystals in 73% yield.
4.1. General comments
All manipulations involving organometallics were carried out
under an atmosphere of argon or nitrogen with inert gas/vacuum
double-manifold techniques. Diethyl ether and tetrahydrofuran
were distilled from sodium/benzophenone ketyl immediately
before use. Methylene chloride was distilled over P2O5 before use.
Melting points were determined by Yanaco MP micro melting
apparatus and were uncorrected. NMR spectra were recorded in
CDCl3 solvent with tetramethylsilane as an internal reference on
JNM-AL-300 (300 MHz) or Varian Unity Inova (400 MHz). IR spectra
were recorded as a solution in CHCl3 with a JASCO Fourier Trans-
form Spectrometer. Mass spectra were recorded on JEOL GC mate
instruments with EI mode. Optical rotations were measured on
a JASCO DIP-360 automatic polarimeter at 589 nm (sodium D line)
using a 0.5 dm cell.
Method B (reaction with BF3$OEt2): To a mixture of chromium
complex 3a (50 mg, 0.18 mmol) and allyl tri-n-butylstannane
(0.28 mL, 0.89 mmol) in CH2Cl2 (5 mL) was added BF3$OEt2 (44 mL,
0.36 mmol) at ꢀ78 ꢁC under nitrogen. The reaction mixture was
stirred for 1 h and quenched with aqueous NaHCO3 and extracted
with ether. Usual workup gave the title compound in 60% yield. M.
p. 79e80 ꢁC. 1H NMR (300 MHz, CDCl3)
d 5.84e5.98 (1H, m), 5.62
(1H, d, J ¼ 6.4 Hz), 5.47 (1H, d, J ¼ 6.4 Hz), 5.32 (1H, t, J ¼ 6.4 Hz),
5.28 (1H, t, J ¼ 6.4 Hz), 5.11e5.17 (2H, m), 4.85e4.90 (1H, m),
2.61e2.66 (1H, m), 2.32e2.42 (1H, m), 2.05 (3H, s), 1.55 (1H, brs). IR
(CHCl3) 3458, 1971, 1896 cmꢀ1. Anal. Calcd for C16H14CrO4: C, 59.63;
H, 4.38. Found. C, 59.50; H, 4.59.
4.2. General procedure of gold(I)-catalyzed reaction of o-alkynyl
benzaldehyde chromium complexes with alcohols. Preparation of
(1-anti-methoxy-3-methyl-1H-isochromene)tricarbonylchromium
5aa
4.4. (1-syn-Allyl-3-methyl-1H-isochromene)tricarbonylchromium
9a
A mixture of chromium complex 8a (50 mg, 0.16 mmol) and
PPh3AuNTf2 (11 mg, 0.016 mmol) in CH2Cl2 (1 mL) was stirred for
2 h at room temperature, and the mixture was filtered with celite
washed with ether. The organic layer was evaporated under
vacuum, and purified with SiO2 column chromatography to give the
title compound in 68% yield.yellow crystals; M.p. 68e69 ꢁC. 1H
To a mixture of chromium complex 3a (250 mg, 0.89 mmol) and
PPh3AuNTf2 (33 mg, 44.6 mmol) in CH2Cl2 (9 mL) was added MeOH
(0.18 mL, 4.46 mmol) by a syringe at room temperature under
nitrogen, and the reaction mixture was stirred for 30 min. Filtration
through a layer of celite, wash with ether, concentration of the
organic layer under vacuum and purification by silica gel column
chromatography with ether/hexane gave chromium complex 5aa
as yellow crystals. 80% yield. M.p. 85e86 ꢁC. 1H NMR (300 MHz,
NMR (500 MHz, CDCl3) d 6.01e6.08 (1H, m), 5.48 (1H, m), 5.47 (1H,
d, J ¼ 6.1 Hz), 5.21e5.29 (2H, m), 5.23 (1H, s), 5.00 (1H, d, J ¼ 6.1 Hz),
4.94 (1H, t, J ¼ 6.1 Hz), 4.89 (1H, t, J ¼ 6.1 Hz), 2.75e2.78 (2H, m),
1.94 (3H, s). IR (CHCl3) 1966, 1893 cmꢀ1. Anal. Calcd for C16H14O4Cr:
C, 59.63; H, 4.38. Found. C, 59.63; H, 4.38.
CDCl3)
5.41 (1H, s), 5.17 (1H, d, J ¼ 6.2 Hz), 5.08 (1H, t, J ¼ 6.2 Hz), 3.56 (3H,
s), 2.03 (3H, s). 13C NMR (100 MHz, CDCl3)
232.8, 155.2, 103.3, 98.1,
d
5.62 (1H, s), 5.47 (1H, t, J ¼ 6.2 Hz), 5.46 (1H, d, J ¼ 6.2 Hz),
d
96.6, 96.5, 94.1, 91.1, 88.3, 86.2, 55.9, 19.9. IR (CHCl3) 1969,
1898 cmꢀ1. Anal. Calcd for C14H12O5Cr: C, 53.85; H, 3.87. Found. C,
53.67; H, 3.92.
4.5. (1-Anti-methyl-3-methyl-1H-isochromene)
tricarbonylchromium 10a
To a solution of chromium complex 5aa (430 mg, 1.38 mmol) in
methylene chloride (14 mL) was added Me3Al (2.0 M hexane
solution, 3.4 mL, 6.89 mmol) at ꢀ78 ꢁC under nitrogen, and the
mixture was stirred for 30 min, and warmed to ꢀ40 ꢁC over 45 min.
The reaction mixture was quenched with aqueous NaHCO3 and
extracted with ether. The extract was washed with brine, dried over
MgSO4 and evaporated under vacuum. Purification by silica gel
4.3. [1-(2-(Prop-1-ynyl)phenyl)]but-3-en-1-ol]
tricarbonylchromium 8a
Method A: (reaction with PPh3AuNTf2): A solution of chromium
complex 3a (50 mg, 0.18 mmol) and Ph3AuNTf2 (13 mg,
0.018 mmol) in CH2Cl2 (3 mL) was degassed and cooled to ꢀ20 ꢁC.

A. Kotera et al. / Journal of Organometallic Chemistry 695 (2010) 2180e2190
2189
chromatography gave the title compound in 99% yield. yellow
crystals; M.p. 119e120 ꢁC. 1H NMR (300 MHz, CDCl3)
5.34 (1H, t,
CDCl3) d 232.9, 144.4, 139.8, 137.3, 132.2, 130.0 (2C), 127.6 (2C), 119.7,
d
106.0, 104.8, 103.2, 95.3, 93.2, 85.6, 84.8, 58.6, 41.3, 22.8, 21.6. IR
(CHCl3) 1968, 1898 cmꢀ1; Anal. Calcd for C23H21NO5SCr: C, 58.10; H,
4.45; N, 2.95. Found. C, 58.05; H, 4.26; N, 2.94.
J ¼ 6.4 Hz), 5.30 (1H, d, J ¼ 6.4 Hz), 5.24 (1H, s), 5.07e5.14 (2H, m),
5.03 (1H, q, J ¼ 6.6 Hz), 1.92 (3H, s), 1.52 (3H, d, J ¼ 6.6 Hz). 13C NMR
(100 MHz, CDCl3)
d 233.4, 157.3, 103.6, 102.6, 96.2, 92.9, 89.6, 88.9,
86.6, 72.9, 20.4, 20.2. IR (CHCl3) 1965, 1892 cmꢀ1. Anal. Calcd for
C14H12CrO4: C, 56.76; H, 4.08. Found. C, 56.47; H, 3.89.
4.11. [Ethyl-3-(p-toluenesulfonamido)-3-(2-(prop-1-ynyl)
propanoate)]tricarbonylchromium 31b
yellow crystals. M.p. 141e142 ꢁC. 1H NMR (300 MHz, CDCl3)
4.6. (1-Anti-allyl-3-methyl-1H-isochromene)tricarbonylchromium
10b
d
7.80 (2H, d, J ¼ 8.1 Hz), 7.29 (2H, d, J ¼ 8.1 Hz), 5.97 (1H, d,
J ¼ 9.9 Hz), 5.51 (1H, dd, J ¼ 6.4, 1.1 Hz), 5.31 (1H, ddd, J ¼ 6.4, 6.4,
1.1 Hz), 5.19 (1H, dd, J ¼ 6.4, 1.1 Hz), 5.03 (1H, ddd, J ¼ 6.4, 6.4,
1.1 Hz), 4.72 (1H, ddd, J ¼ 9.9, 4.9, 4.9 Hz), 3.99e4.10 (2H,m), 3.12
(1H, dd, J ¼ 16.9, 7.2 Hz), 2.97 (1H, dd, J ¼ 16.9, 7.2 Hz), 2.41 (3H, s),
2.08 (3H, s), 1.19 (3H, t, J ¼ 7.2 Hz). 13C NMR (100 MHz, CDCl3)
60% yield; yellow liquid; 1H NMR (300 MHz, CDCl3)
d 5.77e5.90
(1H, m), 5.37 (1H, t, J ¼ 5.9 Hz), 5.26 (1H, d, J ¼ 5.9 Hz), 5.20 (1H, s),
5.04e5.16 (4H, m), 4.91 (1H, dd, J ¼ 7.7, 5.9 Hz), 2.66e2.75 (1H, m),
2.41e2.50 (1H, m), 1.91 (3H, s). IR (CHCl3) 1966, 1893 cmꢀ1. EI-MS
(70 eV) m/z (relative intensity fragment) 322 (23, Mþ), 295 (2,
Mþ ꢀ CH]CH2), 266 (5, Mþ e 2CO), 238 (60, Mþ ꢀ 3CO), 145 (34,
Mþ ꢀ Cr(CO)3eOCH]CH2), 52 (100, Cr); HRMS (EIþ) calcd for
C16H14CrO4: 322.0297. Found. 322.0301.
d
231.5, 170.8, 143.9, 136.9, 129.7 (2C), 127.4 (2C), 109.9, 92.8, 92.6,
92.5, 91.2, 87.2, 74.0, 69.8, 61.1, 51.7, 40.2, 21.5, 14.0, 4.5. IR (CHCl3)
1976, 1910, 1719 cmꢀ1. EI-MS (15 eV) m/z (relative intensity, frag-
ment) 521 (23, Mþ), 465 (3, Mþ e 2CO), 437 (15, Mþe 3CO), 385 (2,
Mþe Cr(CO)3), 321 (2, MþeTs e OEt), 306 (18, Mþ ꢀ NHTseOEt).
HRMS (EIþ) Calcd for C24H23CrNO7S: 521.0600; found. 521.0608.
Anal. Calcd for C24H23NO7SCr: C, 55.28; H, 4.45; N, 2.69. Found. C,
55.50; H, 4.55; N, 2.72.
4.7. 3H-spiro(isobenzofuran-1,30-isochroman)tricarbonylchromium
21
yellow crystals. M.p. 163 ꢁC decomposed. 1H NMR (300 MHz,
CDCl3)
d
7.28e7.53 (4H, m), 5.38 (1H, t, J ¼ 6.2 Hz), 5.35 (1H, d,
4.12. (1-syn-Methyl-3-methyl-2-tosyl-1,2-dihydroisoquinoline)
tricarbonylchromium 32a
J ¼ 6.2 Hz), 5.22e5.30 (2H, m), 5.22 (1H, d, J ¼ 13.0 Hz), 5.08 (2H, d,
J ¼ 13.0 Hz), 4.52 (1H, d, J ¼ 13.0 Hz), 3.56 (1H, d, J ¼ 16.9 Hz), 2.85
(1H, d, J ¼ 16.9 Hz). 13C NMR (100 MHz, CDCl3)
d 233.0, 139.6, 139.4,
Yellow crystals. M.p. 127e128 ꢁC. 1H NMR (500 MHz, CDCl3)
129.6, 128.1, 122.4, 121.1, 106.6, 105.2, 103.0, 92.3, 91.8, 90.5, 89.2,
72.0, 62.1, 35.1. IR (CHCl3) 1969, 1896 cmꢀ1. Anal. C19H14O5Cr: Calcd
for C, 60.97; H, 3.77. Found. C, 60.68; H. 3.78.
d
(ppm): 7.46 (2H, d, J ¼ 7.9 Hz), 7.07 (2H, d, J ¼ 7.9 Hz), 5.95 (1H, s),
5.42 (1H, d, J ¼ 6.4 Hz), 5.22 (1H, t, J ¼ 6.4 Hz), 5.01 (1H, q, J ¼ 7.0 Hz),
4.82 (1H, t, J ¼ 6.4 Hz), 4.60 (1H, d, J ¼ 6.4 Hz), 2.31 (6H, s),1.45 (3H, d,
J ¼ 7.0 Hz). IR (CHCl3) 1968,1896 cmꢀ1; Anal. Calcd for C21H19NO5SCr:
C, 56.12; H, 4.26; N, 3.12. Found. C, 56.27; H, 4.55; N, 2.83.
4.8. [1-Anti-methoxy-3-methyl-2-tosyl-1,2-dihydroisoquinoline]
tricarbonylchromium 29
4.13. [1-syn-(Ethoxycarbonylmethyl)-3-methyl-2-tosyl-1,2-
87% yield. Yellow crystals. M.p. 159 ꢁC decomposed. 1H NMR
dihydroisoquinoline]tricarbonylchromium 32b
(270 MHz, CDCl3)
d
7.88 (2H, d, J ¼ 8.3 Hz), 7.34 (2H, d, J ¼ 8.3 Hz),
Yellow crystals. M.p. 161e162 ꢁC. 1H NMR (300 MHz, CDCl3)
6.28 (1H, s), 5.65 (1H, d, J ¼ 6.4 Hz), 5.60 (1H, t, J ¼ 6.4 Hz), 5.57 (1H,
s), 5.26 (1H, d, J ¼ 6.4 Hz), 5.05 (1H, t, J ¼ 6.4 Hz), 3.51 (3H, s), 2.41
d
7.45 (2H, d, J ¼ 8.3 Hz), 7.06 (2H, d, J ¼ 8.3 Hz), 5.98 (1H, s), 5.66
(3H, s), 2.23 (3H, s). 13C NMR (100 MHz, CDCl3)
d 232.4, 144.9, 138.2,
(1H, d, J ¼ 6.2 Hz), 5.41 (1H, dd, J ¼ 7.3, 7.5 Hz), 5.23 (1H, t,
J ¼ 6.2 Hz), 4.81 (1H, t, J ¼ 6.2 Hz), 4.57 (1H, d, J ¼ 6.2 Hz), 4.23 (1H,
dd, J ¼ 6.8, 14.0 Hz), 4.22 (1H, dd, J ¼ 7.2, 14.0 Hz), 2.86 (1H, dd,
J ¼ 7.3, 16.0 Hz), 2.71 (1H, dd, J ¼ 7.5, 16.0 Hz), 2.33 (3H, s), 2.31 (3H,
136.3, 130.1 (2C), 127.8 (2C), 103.2, 103.2, 100.6, 95.3, 93.0, 86.9,
85.4, 84.6, 54.9, 22.5, 21.6. IR (CHCl3) 1970, 1901 cmꢀ1. Anal. Calcd
for C21H19NO6SCr: C, 54.19; H, 4.11; N, 3.01. Found. C, 54.01; H, 4.19;
N, 2.96.
s), 1.32 (3H, dd, J ¼ 6.8, 7.2 Hz). IR (CHCl3) 1970, 1897, 1727 cmꢀ1
;
Anal. Calcd for C24H23NO7SCr: C, 55.28; H, 4.45; N, 2.69. Found. C,
55.53; H, 4.51; N, 2.67.
4.9. [1-Anti-methyl-3-methyl-2-tosyl-1,2-dihydroisoquinoline]
tricarbonylchromium 30a
Acknowledgments
yellow crystals; M.p. 161e162 ꢁC. 1H NMR (270 MHz, CDCl3)
This work was supported by a Grant-in-Aid for Scientific
Research from Ministry of Education, Culture, Sports, Science and
Technology, Japan. We thank also the support of COE Foundation of
Kyoto Pharmaceutical University.
d
7.88 (2H, d, J ¼ 8.3 Hz), 7.33 (2H, d, J ¼ 8.3 Hz), 5.51 (1H, t,
J ¼ 6.2 Hz), 5.41 (1H, d, J ¼ 6.2 Hz), 5.38 (1H, s), 5.31 (1H, q,
J ¼ 6.7 Hz), 5.00 (1H, d, J ¼ 6.2 Hz), 4.94 (1H, t, J ¼ 6.2 Hz), 2.42 (3H,
s), 2.19 (3H, s), 1.46 (3H, d, J ¼ 6.7 Hz). IR (CHCl3) 1968, 1897 cmꢀ1
;
Anal. Calcd for C21H19NO5SCr: C, 56.12; H, 4.26; N, 3.12. Found. C,
56.35; H, 4.34; N, 3.15.
Appendix A. Supplementary data
CCDC 741238, 741239, 741240, 741214 and 741242 contain the
supplementary crystallographic data for 1, 1a, 2a, 2b and 3b. These
data can be obtained free of charge from The Cambridge Crystal-
lographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
4.10. [1-Anti-allyl-3-methyl-2-tosyl-1,2-dihydroisoquinoline]
tricarbonylchromium 30c
59% yield. yellow crystals. M.p. 154e155 ꢁC. 1H NMR (270 MHz,
CDCl3)
d
7.88 (2H, d, J ¼ 8.2 Hz), 7.33(2H, d, J ¼ 8.2 Hz), 5.76 (1H, ddt,
J ¼ 16.4, 9.9, 6.8 Hz), 5.53 (1H, t, J ¼ 6.4 Hz), 5.41 (1H, d, J ¼ 6.4 Hz),
5.38 (1H, s), 5.24 (1H, t, J ¼ 6.8 Hz), 5.10 (1H, d, J ¼ 9.9 Hz), 5.02 (1H,
d, J ¼ 16.4 Hz), 4.98 (1H, d, J ¼ 6.4 Hz), 4.91 (1H, t, J ¼ 6.4 Hz), 2.51
(2H, dd, J ¼ 6.8, 6.8 Hz), 2.41 (3H, s), 2.18 (3H, s). 13C NMR (100 MHz,
Appendix. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.jorganchem.2010.06.005.

2190
A. Kotera et al. / Journal of Organometallic Chemistry 695 (2010) 2180e2190
[9] A preliminary report; A. KoteraJ. Uenishi, M. Uemura, 51, Tetrahedron Lett.
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