Chiral N-phosphino sulfinamide ligands in rhodium(I)-catalyzed [2+2+2] cycloaddition reactions

Article abstract of DOI:10.1016/j.tet.2010.09.009

The combination of cationic rhodium(I) complexes with N-phosphino tert-butylsulfinamides (PNSO) ligands is efficient for catalytic intra- and intermolecular [2+2+2] cycloaddition reactions. PNSO ligands are a new class of chiral bidentate ligands, which h

Full text of DOI:10.1016/j.tet.2010.09.009

Tetrahedron 66 (2010) 9032e9040
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Chiral N-phosphino sulfinamide ligands in rhodium(I)-catalyzed [2þ2þ2]
cycloaddition reactions
,
b
b
Sandra Brun a, Magda Parera a, Anna Pla-Quintana a, Anna Roglans a , Thierry León , Thierry Achard ,
*
,
b,
*
Jordi Solà b, Xavier Verdaguer b , Antoni Riera
*
a Department of Chemistry, University of Girona, Campus de Montilivi s/n, 17071 Girona, Spain
b Institute for Research in Biomedicine (IRB Barcelona) and Department de Química Orgànica, Universitat de Barcelona, C/Baldiri Reixac 10, 08028 Barcelona, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 July 2010
Received in revised form 30 August 2010
Accepted 3 September 2010
Available online 15 September 2010
The combination of cationic rhodium(I) complexes with N-phosphino tert-butylsulfinamides (PNSO)
ligands is efficient for catalytic intra- and intermolecular [2þ2þ2] cycloaddition reactions. PNSO ligands
are a new class of chiral bidentate ligands, which have the characteristic of combining the easily
accessible sulfur chirality with the coordinating capacity of phosphorous. Cycloaddition of open-chained
and macrocyclic E-enediynes with these chiral complexes have proved to be highly efficient in terms of
yields, giving moderate enantiomeric excesses of the corresponding cyclohexadiene derivatives. In
addition Rh(I)/PNSO complexes catalyzed the intermolecular cycloaddition of diynes with monoalkynes
in mild reaction conditions and short reaction times.
This manuscript is dedicated to Professor
Carmen Nájera on the occasion of her 60th
birthday
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
[2þ2þ2] Cycloaddition
Rhodium
Sulfinamide ligands
Alkynes
Enediynes
1. Introduction
be conveniently assembled from the commercially available enan-
tiopure tert-butylsulfinamide, an aldehyde, and a chlorophosphine
Transition-metal-catalyzed-[2þ2þ2] cycloadditions are valu-
able strategic reactions in increasing the complexity of target mol-
ecules as theyenable several bond connections tobe madein a single
step.1 This reaction is remarkable in terms of its ability to generate
carbocyclic systems by the involvement of various unsaturated
substrates, such as alkynes and alkenes. In addition, the enantiose-
lective version of these [2þ2þ2] cycloadditions is a powerful syn-
thetic method for the construction of chiral cyclic frameworks.1h,k
Various transition metal catalysts based especially on Ni, Co, Rh,
Ru, and Pd have been developed for cyclotrimerization reactions.
Given the potential of the process, it is extremely interesting to
search for new efficient catalytic systems, which allow us to work,
for example, in mild reaction conditions or with air-stable com-
plexes. Some of us have recently described the synthesis of a new
class of chiral bidentate ligands: N-phosphino tert-butylsulfina-
mides (PNSO, I, Fig. 1). These ligands represent an efficient way
of combining the easily accessible sulfur chirality with the co-
ordinating capacity of phosphorous. Ligands I are modular and can
in two steps. Some of these ligands, such as 1a have proved to be
highly efficient in the intermolecular asymmetric PausoneKhand
reaction acting as bidentate P,S ligands.2 This study was the first
example of a chiral sulfur atom coordinated to a cobalt center.
O
S
R2
P
O
S
N
R2
P
N
R1
Ph
I
1a
Fig. 1. General structure of the N-phosphino tert-butylsulfinamides (PNSO) chiral
ligands.
We recently reported the first rhodium(I) complexes with PNSO
ligands of type I. The reaction of [RhCl(COD)]2 with 1 or 2 equiv of
1a in the presence of 1 equiv of AgOTf, afforded complexes [Rh(1a)
(COD)]OTf and [Rh(1a)2]OTf in good yields.3 We observed that
PNSO ligands, depending on the electronic environment around the
* Corresponding authors. E-mail address: anna.roglans@udg.edu (A. Roglans).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.09.009

S. Brun et al. / Tetrahedron 66 (2010) 9032e9040
9033
metal center can work either as P,O or as P,S chelating ligands. Thus,
N-benzyl-N-diphenylphosphino-tert-butylsulfinamide (1a) provi-
des P,O coordination when olefin ligands (NBD or COD) are attached
to the metal center. Alternatively, rhodium complexes with two
PNSO ligands provide P,S coordination. The thermodynamically
most stable cis configuration is preferentially shown in [Rh(PNSO)2]
OTf complexes (Fig. 2).
Reductive amination with Ti(OEt)4 in the presence of the corre-
sponding aldehyde produced the intermediate sulfinimines,
which were reduced in situ to the corresponding sulfinamides
3aei. Alternatively, depending on the availability of the required
aldehyde, the intermediate sulfinamide 3 could be synthesized
from the metalated amine and Ellman’s thiosulfinate (þ)-5.
From 3, anion formation with n-BuLi at low temperature
followed by the addition of chlorophosphine and the protection
of the phosphine moiety with borane resulted in the corre-
sponding borane/protected ligands 4aei. Protection was neces-
sary to avoid sulfurephosphorous oxygen migration during the
work-up. The borane/free ligand was obtained by deprotection
with DABCO to afford PNSO ligands 1aei in good yields. Once
pure, ligands 1aei were air-stable and could be stored during
weeks. In a few cases, the steric hindrance of the PNSO ligand
prevented protection with borane. However, in this situation, the
ligand was usually resistant to sulfurephosphorous oxygen
transfer (Table 1).
OTf
O O
OTf
O
P
S
S
S
Rh
Ph
N
N
Ph
N
Rh
Ph
P
Ph
P
Ph
Ph
Ph
Ph
Ph
[Rh(1a)(COD)]OTf
[Rh(1a)2]OTf
Fig. 2. Structure of previously described cationic rhodium(I) complexes [Rh(1a)(COD)]
OTf and [Rh(1a)2]OTf.
Table 1
Synthesis of the PNSO ligands
O
S
NH2
i
BH3
O
S
O
S
R2
P
O
S
(+)-2
iii
iv
R2
P
NH
N
R2
N
R2
ii
R1
R1
R1
4a-4i
O
3a-3i
1a-1i
S
S
(+)-5
i) a) R1CHO, Ti(OEt)4 and b) NaBH4; ii) R1CH2NH2, n-BuLi, THF; iii) a) BuLi, R2PCl, -78 ºC and b) BH3•SMe2, -10 ºC; iv) DABCO, r.t., toluene
Entry
R1
Yield of 3 (%)
3a, 91
R2
Yield of 4 (%)
Yield of 1 (%)
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
o-Tolyl
o-Methoxyphenyl
p-(Trifluoromethyl)phenyl
4a, 93
da
1a, 95
1b, 74
1c, 93
1d, 17
1e, 71
1f, 69
1g, 82
1h, 95
1i, 88
4c, 28
da
Ph
3,5-Dimethylphenyl
4e, 68
4f, 90
4g, 79
4h, 82
4i, 88
p-Methoxyphenyl
2-Naphthyl
2,4,6-Trimethylphenyl
p-Fluorophenyl
3f, 34
3g, 79
3h, 65
3i, 60b
Ph
Ph
Ph
Ph
a
Protection with borane did not take place, so 1b and 1d were obtained instead of 4b and 4d.
Synthesized from (þ)-5.
b
We considered that the rhodium complexes of PNSO ligands
2.2. Cycloaddition reactions
might be active in catalytic asymmetric reactions, such as [2þ2þ2]
cycloadditions. The availability and modular nature of these ligands
could be extremely valuable in the optimization of the catalyst.
Here we describe the application of rhodium(I) complexes of
N-phosphino-tert-butylsulfinamide [Rh(PNSO)(COD)]X (X¼OTf or
BF4) in intra- and intermolecular [2þ2þ2] cycloaddition reactions.
We have applied these chiral complexes to the cycloaddition of
open-chained enediynes and macrocyclic enediynes. Furthermore,
we have extended their applicability to the cycloaddition between
diynes and monoalkynes.
The study was initiated using O-tethered (E)-enediyne 6 as
a substrate (Table 2). To the best of our knowledge, there have only
been two significant cases of enantioselective intramolecular
[2þ2þ2] cycloaddition of enediynes reported. Tanaka et al.4 found
that the catalytic system formed by a cationic rhodium(I) complex
with BINAP-type ligands catalyzed enantioselective cycloadditions
of enediyne 6 and its derivatives, which have different terminal
substituents, resulting in good yields and moderate enantiomeric
excesses. Shibata et al.,5 using a similar catalytic system to that used
by Tanaka, performed intramolecular cycloaddition of various car-
bon-, N-tosyl-, and oxygen-tethered enediynes, which gave the
corresponding cyclohexa-1,3-dienes with high enantioselectivity.
However, cycloaddition of enediyne 6 was not reported in this
work.
2. Results and discussion
2.1. Synthesis of the ligands
A family of chiral PNSO ligands 1aei has been synthe-
sized from commercially available tert-butylsulfinamide (þ)-2.
The first reaction was run using the known complex [Rh(1a)
(COD)]OTf in anhydrous dichloromethane at room temperature.

9034
S. Brun et al. / Tetrahedron 66 (2010) 9032e9040
(1a)2]BF4, 31P NMR studies were performed in order to find the best
conditions to have [Rh(1a)(COD)]BF4 as the main compound in the
solution. Mixtures containing [Rh(COD)2]BF4 and 1a were prepared
with a molar ratio ranging from 1:1 to 2:1. After hydrogenation, 31P
NMR analysis showed that [Rh(1a)(COD)]BF4 complex was the
main compound (93% yield), the other one being dimeric species
[Rh(1a)2]BF4 (7%) when the ratio was 2:1. ESI-MS studies confirmed
the formation of the two rhodium complexes in solution. A 75%
yield of cyclohexadiene derivative 7 was obtained from the in situ
formed catalyst at reflux of anhydrous dichloromethane after 22 h
of reaction (entry 3, Table 2). The ee was almost the same as using
the preformed catalyst (compare entries 1 and 3, Table 2). As we
and others have found in previous studies,6 running the reaction in
non-dried solvents without degassing gives better results in some
cases. Therefore, the cycloaddition was run in non-dried HPLC
grade CH2Cl2 and the reaction worked at reflux for 3 h to afford
a 92% yield of 7 (entry 4, Table 2). Moreover, running the reaction at
room temperature, a remarkable 78% yield of 7 was achieved in just
15 min (entry 5, Table 2). The ee of 7 in the last two experiments
was similar to previous experiments (compare entries 4 and 5 with
entries 1 and 3). Since some [Rh(COD)2]BF4 remained in solution, it
was necessary to check the catalytic activity of this complex. A
blank experiment using [Rh(COD)2]BF4 without PNSO ligand gave
only a 10% yield of final product 7 under the optimized conditions,
and the yield was only increased to 20% when the reaction was left
to reach completion (entry 6, Table 2). This result demonstrates that
the reaction is PNSO-ligand accelerated. In none of the described
cases was the formation of double-bond-isomerized compounds
detected. Unfortunately the results obtained with ligand 1a could
not be improved with their analogs (entries 7e14, Table 2). Most
interestingly, PNSO ligands with ortho-substitution in the phos-
phine moiety (1b and 1c, entries 7 and 8, Table 2) and ligand 1i
(entry 14, Table 2) bearing an N-p-fluorobenzyl group provided
reversed selectivity. However, we still do not have a proper expla-
nation for this fact.
Table 2
Rh(I)/PNSO catalyzed [2þ2þ2] cycloisomerization reactions of enediyne 6
H H
"Rh(I)"
O
O
O
(10 mol %)
O
7
6
Entry
Catalysta
Reaction conditions
Yield
(%)
[a
]
ee
(%)
23
D
1
[Rh(1a)(COD)]OTf
[Rh(1a)2]OTf
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4
[Rh(COD)2]BF4/1b
[Rh(COD)2]BF4/1c
[Rh(COD)2]BF4/1d
[Rh(COD)2]BF4/1e
[Rh(COD)2]BF4/1f
[Rh(COD)2]BF4/1g
[Rh(COD)2]BF4/1h
[Rh(COD)2]BF4/1i
anh. CH2Cl2, rt, 5 h
anh. CH2Cl2, reflux, 30 h
anh. CH2Cl2, reflux, 22 h
CH2Cl2, reflux, 3 h
CH2Cl2, rt, 15 min
CH2Cl2, reflux, 3 h
CH2Cl2, reflux, 5 h
CH2Cl2, reflux, 5 h
CH2Cl2, reflux, 1 h
CH2Cl2, reflux, 30 min
CH2Cl2, reflux, 5 min
CH2Cl2, reflux, 2 h
CH2Cl2, reflux, 2 h
CH2Cl2, reflux, 3 h
78
0
þ
29
0
27
32
30
e
2
na
þ
3b
75
92
78
10d
20
20
39
42
95
49
87e
98e
4b,c
5b,c
6b
þ
þ
na
ꢀ
7b,c
8b,c
9b,c
10b,c
11b,c
12b,c
13b,c
14b,c
20
20
24
21
18
0
ꢀ
þ
þ
þ
na
na
ꢀ
0
15
a
The ratio [Rh(COD)2]BF4/1 was 2:1.
Hydrogen gas was introduced to the catalyst solution prior to substrate addition.
Non-dried HPLC grade CH2Cl2.
b
c
d
When the reaction was run to completion, only a 20% yield of the product could
be isolated after 20 h of heating in refluxing DCM.
e
Referred to conversion by 1H NMR.
After 5 h, a 78% yield of cyclohexadiene derivative 7 was obtained
with a 29% enantiomeric excess (ee) (entry 1, Table 2). In an attempt
to improve the ee, other solvents, such as toluene, THF, and EtOH
were tested although worse results were obtained. [Rh(1a)2]OTf
was then tested in dichloromethane at reflux for 30 h but only
starting material was recovered (entry 2, Table 2). We concluded
that dimers are not active catalysts in these processes.
To facilitate the testing of the family of ligands 1aei, we studied
the generation of the catalyst in situ. Given that the reaction
between [Rh(COD)2]BF4 and 1a can also give dimeric complex [Rh
We next decided to study the cycloisomerization of macrocyclic
enediynes 8 and 9 (Table 3). Some of us have pioneered the study of
[2þ2þ2] cycloadditions in macrocyclic systems.7 The cycloaddition
of 8 and 9 has previously been reported7d using (bicyclo[2.2.1]
Table 3
Rh(I)-catalyzed [2þ2þ2] cycloisomerization of enediyne macrocycles 8 and 9
NTs
n
"Rh(I)"
(10 mol %)
NTs
n
TsN
TsN
H
H
NTs
n = 1, 8
n = 2, 9
n = 1, 10
n = 2, 11
N
Ts
Entry
1a
Starting compound
Catalyst
Reaction conditions
Toluene, 65 ꢁC, 24h
Product, yield (%)
ee (%)
44
Ph
Ph
Me
P
+
+
-
ClO4
8
10, 95
Rh
P
Me
Me
Ph Ph
Ph
Ph
P
2a
9
Toluene, 65 ꢁC, 24h
11, 46
41
-
Rh
ClO4
P
Me
Ph Ph
3b,c
4c
5
8
8
8
8
9
[Rh(COD)2]BF4/1a
[Rh(1a)(COD)]OTf
[Rh(COD)2]BF4
[Rh(1a)(COD)]OTf
[Rh(1a)(COD)]OTf
CH2Cl2, rt, 2.5 h
CH2Cl2, rt, 28 h
CH2Cl2, rt, 2.5 h
Toluene, rt, 5.5 h
Toluene, rt, 5.5 h
10, 91
10, 77
10, 84
10, 79
11, 94
11
48
d
50
7
6c
7c
a
Ref. 7d.
b
c
The ratio [Rh(COD)2]BF4/1a was 2:1.
The enantiomer obtained in these cases is the opposite of that obtained in entries 1 and 2.

S. Brun et al. / Tetrahedron 66 (2010) 9032e9040
9035
hepta-2,5-diene)[2S,3S]-bis(diphenylphosphino)butane rhodium
(I) perchlorate as a commercial chiral rhodium complex (entries 1
and 2, Table 3). In order to improve on the previously obtained
results, especially the enantiomeric excess, Rh(I)/PNSO, either
generated in situ (entry 3, Table 3) or as an isolated complex (entry
4, Table 3) in CH2Cl2 at room temperature, was used as the catalyst.
In the two cases the reaction worked well but a great difference was
observed in terms of ee. The best result was obtained using the
isolated complex [Rh(1a)(COD)]OTf (compare entries 3 and 4, Table
3). This different behavior of enantioselectivity can be explained
with the blank experiment shown in entry 5 demonstrating that
the [Rh(COD)2]BF4 precursor is also active for these macrocyclic
systems. With the preformed rhodium complex, we then tested
toluene as a solvent and managed to reduce the reaction time
considerably (entry 6, Table 3). A 79% yield of 10 with a slightly
improved 50% of ee was obtained. The same reaction conditions
were applied for macrocycle 9. In this case an excellent yield of 94%
of 11 was obtained although the ee dropped to 7% (entry 7, Table 3).
The enantiomer formed with the new PNSO/Rh complex was the
opposite to that obtained in entries 1 and 2.
Finally, the new catalytic system was tested in intermolecular
[2þ2þ2] cycloaddition reactions of alkynes8,9 (Table 4). We first
investigated the reaction of non-terminal diynes, which are gen-
erally less reactive than their terminal counterparts toward this
reaction. N-Tosyl-tethered diyne 12a was reacted with phenyl-
acetylene 13a in the presence of cationic rhodium(I)/phosphino-
sulfinamide complex as a catalyst generated in situ. An 84% yield of
14aa was obtained in short reaction times in DCE at reflux (entry 1,
Table 4). The catalytic activity of the excess [Rh(COD)2]BF4 present
in the reaction media was evaluated by running a blank experiment
excluding ligand 1a. In the same reaction conditions only a 5% yield
of benzene derivative 14aa was achieved (entry 2, Table 4) as-
suming that the process is PNSO-ligand accelerated and that most
of the catalytic activity is due to our new complex. We then studied
the scope of the reaction by varying the monoyne counterpart.
Monosubstituted alkyne 13b as well as disubstituted alkynes 13c
and 13d effectively participated in the [2þ2þ2] cycloaddition re-
action (entries 3e5, Table 4). It is worth mentioning that monoyne
13d gave high quantities of the trimerization product, hexamethyl
mellitate 15, which was responsible for the decreased yield of the
partially intramolecular reaction. Therefore, a completely inter-
molecular cycloaddition was run with alkyne 13d alone. Hexa-
methyl mellitate 15 was obtained with a 67% yield after 1.5 h of
reaction (entry 6, Table 4). The effect of the tether between the
alkynes was also studied by reacting malonate-linked diyne 12b
with phenylacetylene 13a. The reaction worked effectively at DCE at
reflux achieving a 78% yield of the cycloisomerized product 14ba
after 2 h of reaction.
In a second step, diynes featuring two terminal alkynes were
submitted to the [2þ2þ2] cycloaddition reaction. 1,6-Heptadiyne
12c was reacted with phenylacetylene 13a in the presence of cat-
ionic rhodium(I)/phosphinosulfinamide complex as
a catalyst
generated in situ. A 60% yield of the biphenyl derivative 14ca was
achieved in just 15 min at room temperature (entry 8, Table 4). The
reaction was again shown to be PNSO-ligand accelerated by run-
ning a blank experiment that excluded ligand 1a. In this case (entry
9, Table 4) an 11% yield was obtained in the same reaction condi-
tions, a yield, which was not improved when the reaction was left
to run for 45 min. The monoyne counterpart was varied and slightly
better yields were achieved with propargyl alcohol 13b and 2-
butyn-1,4-diol 13c (entries 10 and 11, Table 4). With respect to the
tethers, N-tosyl-, malonate-, and oxygen-linked diynes could also
be used for this reaction (entries 12e19, Table 4). N-Tosyl-tethered
diyne 12d gave a moderate 44% yield of 14da when reacted with
phenylacetylene 13a for 2 h at room temperature, but the yield
could be increased up to 78% in just 45 min when switching the
reaction media to DCE at reflux. Malonate-tethered diyne 12e
reacted with the three monoynes 13aec with yields above 70%
Table 4
Rh(I)/PNSO catalyzed [2þ2þ2] cycloaddition of 1,6-diynes 12 with monoalkynes 13
R1
R2
"Rh(I)"
R2
R1
R1
(10 mol %)
Z
+
Z
R3
R3
R1
12
13
14
Entry
12 (Z, R1)
13 (R2, R3)
Catalysta
Reaction conditionsb
Product, yield (%)c
1
2
12a (NTs, Me)
12a (NTs, Me)
12a (NTs, Me)
12a (NTs, Me)
12a (NTs, Me)
d
13a (Ph, H)
13a (Ph, H)
13b (CH2OH, H)
13c (CH2OH, CH2OH)
13d (CO2Me, CO2Me)
13d (CO2Me, CO2Me)
13a (Ph, H)
13a (Ph, H)
13a (Ph, H)
13b (CH2OH, H)
13c (CH2OH, CH2OH)
13a (Ph, H)
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4
DCE, reflux, 2 h
DCE, reflux, 2 h
DCE, reflux, 24 h
DCE, reflux, 24 h
DCE, reflux, 5 h
CH2Cl2, reflux, 1.5 h
DCE, reflux, 2 h
CH2Cl2, rt, 15 min
CH2Cl2, rt, 15 min
DCE, reflux, 1 h
DCE, reflux, 2 h
CH2Cl2, rt, 2 h
DCE, reflux, 45 min
DCE, rt, 6 h
14aa, 84
14aa, 5
14ab, 52
14ac, 63
14ad, 44
15, 67
14ba, 78
14ca, 60
14ca, 11
14 cb, 73
14cc, 70
14da, 44
14da, 78
14ea, 71
14eb, 77
14ec, 72
14fa, 60
14fb, 99
14fc, 48
3
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
[Rh(COD)2]BF4/1a
4d
5
6
7
8
12b (C(CO2Et)2, Me)
12c (CH2, H)
12c (CH2, H)
12c (CH2, H)
12c (CH2, H)
12d (NTs, H)
12d (NTs, H)
12e (C(CO2Et)2, H)
12e (C(CO2Et)2, H)
12e (C(CO2Et)2, H)
12f (O, H)
9e
10
11d
12
13
14
15
16d
17
18
19d
13a (Ph, H)
13a (Ph, H)
13b (CH2OH, H)
13c (CH2OH, CH2OH)
13a (Ph, H)
13b (CH2OH, H)
13c (CH2OH, CH2OH)
DCE, reflux, 2 h
DCE, reflux, 7 h
DCE, rt, 3 h
DCE, rt, 5 h
DCE, rt, 8 h
12f (O, H)
12f (O, H)
a
The ratio [Rh(COD)2]BF4/1a was 2:1.
b
Hydrogen gas was bubbled into the catalyst solution for 30 min, the hydrogen and solvent were then removed, the solvent was added again, monoyne 13 was introduced
and finally diyne 12.
c
Isolated yields.
d
Butyne-1,4-diol 13c was added to the reaction mixture dissolved in THF (1 mL).
The reaction did not advance further when performed over 45 min.
e

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S. Brun et al. / Tetrahedron 66 (2010) 9032e9040
(entries 14e16, Table 4). Finally, oxygen-linked diyne 12f was also
shown to participate effectively in the [2þ2þ2] cycloaddition
with monoynes 13aec in DCE at room temperature (entries 17e19,
Table 4).
the solution was stirred for 10 min at room temperature. The al-
dehyde was then added and the crude was heated at reflux tem-
perature. The reaction was followed by TLC. A suspension of NaBH4
in anhydrous THF was canulated to the crude previously cooled to
0 ꢁC. The mixture was then allowed to warm to room temperature.
After 1 h, methanol was added dropwise and stirred strongly. The
resulting crude was poured over icy brine and extracted with
dichloromethane. The crude was then filtered through CeliteÒ,
washed with dichloromethane, and evaporated under reduced
pressure. The resulting oil was purified by column chromatography
through silica gel to obtain the desired sulfinamides.
3. Conclusions
In summary, we have shown that N-phosphino tert-butylsulfi-
namide (PNSO) ligands are efficient in rhodium(I)-catalyzed
[2þ2þ2] cycloaddition reactions. The scope of the cycloadditions
has been evaluated by effectively reacting completely intra-
molecular and macrocyclic enediynes as well as the partially in-
termolecular version of the [2þ2þ2] cycloaddition of alkynes. This
process has been shown to be accelerated by PNSO ligands and in
the case of (E)-enediynes, moderate enantiomeric excesses have
been achieved. The catalytic system presented here is found to be
robust and applicable to a broad range of substrates independently
of the nature of the linker between unsaturations and the sub-
stitution at the termini of the alkynes. We attribute the high activity
of these complexes to the hemilabile nature of the PNSO ligands.
Hemilabile ligands can provide vacant coordination sites to the
substrate, so accelerating the cycloaddition process. The modularity
of PNSO ligands allowed a small library of novel ligands to be
prepared. These new ligands did not improve the enantioselectivity
observed for the parent PNSO ligand 1a. In the PNSO ligands, the
chiral information is located in the hemilabile moiety of the ligand,
which can be far away from the metal center in the crucial CeC
bond formation step. We think that this fact may hamper the
transfer of chiral information from the ligand to the cycloaddition
product. Our groups are currently performing further in-
vestigations to improve the enantioselectivity in the [2þ2þ2]
cycloaddition process by locating the chiral information closer to
the metal center.
4.2.1. (R)-N-(Naphthalen-2-ylmethyl)-2-methyl-2-propane-
sulfinamide, 3g. In accordance with the general procedure for sulfi-
namides, (R)-2-methylpropane-2-sulfinamide (1.00 g, 8.25 mmol), Ti
(OEt)4 (1.73 mL, 8.25 mmol), 2-naphtaldehyde (1.38 g, 8.66 mmol) in
THF (15 mL), and NaBH4 (0.62 g,16.5 mmol) in THF (2 mL) were used.
Column chromatography through silica gel (hexanes/ethyl acetate,
75:25) afforded 1.70 g (79%) of 3g as a colorless foam. [
a
]
23 ꢀ28.4 (c
D
1.00, CHCl3); IR (film) nmax 3189, 2954,1470,1037, 859 cmꢀ1; 1H NMR
(400 MHz, CDCl3)
d
1.27 (s, 9H), 3.52 (br s, NH), 4.42 (d, J¼14 Hz, 1H),
4.52 (d, J¼14 Hz,1H), 7.48 (m, 3H), 7.78 (s, 1H), 7.83 (m, 3H) ppm; 13C
NMR (100 MHz, CDCl3)
d 22.9, 49.9, 56.3, 126.3, 126.4, 126.5,
127.1, 127.9, 128.0, 128.7, 133.1, 133.5, 136.1 ppm; ESI-MS (m/z) 262
[MþH]þ, 284 [MþNa]þ, 545 [2MþNa]þ; ESI-HRMS: calcd m/z for
[C15H20NOSþH]þ 262.1266, found 262.1252.
4.2.2. (R)-N-(2,4,6-Trimethylbenzyl)-2-methyl-2-propanesulfinamide,
3h. In accordance with the general procedure for sulfinamides, (R)-
2-methylpropane-2-sulfinamide (1.00 g, 8.25 mmol), Ti(OEt)4
(1.73 mL, 8.25 mmol), 2,4,6-trimethylbenzaldehyde (1.35 g,
9.08 mmol) in THF (15 mL), and NaBH4 (0.62 g, 16.5 mmol) in THF
(2 mL) were used. Column chromatography through silica gel
(hexanes/ethyl acetate, 75:25) afforded 1.35 g (65%) of 3h as a col-
23
4. Experimental section
4.1. General methods
orless foam. [
a
]
ꢀ8.74 (c 1.35, CHCl3); IR (film) nmax 3208, 2952,
D
1453, 1046, 850 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d 1.19 (s, 9H), 2.26
(s, 3H), 2.36 (s, 6H), 3.08 (d, J¼8 Hz, NH), 4.16 (dd, J¼8 and 12 Hz,1H),
4.37 (dd, J¼3 and 12 Hz, 1H), 6.86 (s, 2H) ppm; 13C NMR (100 MHz,
Unless otherwise noted, materials were obtained from com-
mercial suppliers and used without further purification. [Rh(1a)
(COD)]OTf and [Rh(1a)2]OTf were prepared as described by us.3
Enediyne 6 was prepared following the method described pre-
viously in literature.10 Macrocycles 87b and 9,7d were previously
prepared by us. Cycloisomerized compounds 10,7d 11,7d 14aa,6a and
14ac,6a sulfinamides 3a2a and 3f,2a borane/PNSO ligands 4a2a and
4f,2a and borane/free PNSO ligands 1a2a and 1f2a were previously
characterized by us.
CDCl3) d 19.8, 21.2, 22.9, 43.1, 55.9, 129.4, 131.5, 137.7, 137.8 ppm; ESI-
MS (m/z) 254 [MþH]þ, 507 [2MþH]þ; ESI-HRMS: calcd m/z for
[C14H23NOSþH]þ 254.1579, found 254.1573. Anal. Calcd for
C14H23NOS (253.40): C 66.36, H 9.15, N 5.53, S 12.65. Found: C 66.36,
H 9.12, N 5.51, S 12.39.
4.2.3. (R)-(ꢀ)-N-4-Fluorobenzyl-2-methyl-2-propanesulfinamide,
3i. A one-necked round bottomed flask equipped with a magnetic
stirring bar was charged with 4-fluorobenzylamine (2.9 mL,
25 mmol) in THF (10 mL). The solution was cooled at ꢀ78 ꢁC, and
n-BuLi 2.5 M (8.7 mL, 21.8 mmol) was added carefully. After being
stirred for 30 min, a solution of (R)-S-tert-butyl tert-butanethio-
sulfinate (þ)-5 (3.05g, 15.6 mmol) in THF (5 mL) was added. The
crude was left to reach room temperature overnight. Brine (10 mL)
was then added and the layers were separated. The aqueous layer
was extracted with Et2O (2ꢂ10 mL). The organic layer was washed
with HCl 0.1 N (2ꢂ10 mL), dried over anhydrous MgSO4, filtered,
and finally evaporated under reduced pressure. The resulting
crude was purified by column chromatography through silica gel
(SiO2, hexanes/ethyl acetate, 50:50) to afford 2.23 g (60%) of 3i as
an oil that slowly crystallized. The desired product was recrys-
1H, 13C NMR, 31P, and 19F spectra were recorded on a 400 or
300 MHz NMR spectrometer. Chemical shifts (d
) for 1H and 13C
NMR were referenced to internal solvent resonances and reported
relative to SiMe4. 31P NMR spectra were referenced to phosphoric
acid. ESI-MS analyses were recorded on an Esquire 6000 Ion Trap
Mass Spectrometer (Bruker) equipped with an electrospray ion
source.
Optical rotations were recorded on a PerkineElmer polarimeter
at the sodium D line at room temperature (concentration in g/mL).
Melting points were determined using either a Büchi or a Stuart
SMP10 melting point apparatus and were not corrected. IR spectra
were recorded in an FT-IR apparatus.
tallized with hexane affording colorless crystals. [
a]
23 ꢀ43.6 (c 1.0,
D
4.2. General procedure for the synthesis of sulfinamides
CHCl3); IR (film): nmax 3196, 2978, 1510, 1220 cmꢀ1
;
1H NMR
(3g,h)
(400 MHz, CDCl3)
14 Hz, 1H), 4.33 (dd, J¼5 and 14 Hz, 1H), 7.03 (m, 2H), 7.32 (m,
2H) ppm; 13C NMR (100 MHz, CDCl3)
22.8, 48.9, 56.1, 115.6 (d,
d
1.24 (s, 9H), 3.44 (s, 1H), 4.23 (dd, J¼7 and
A one-necked round bottomed flask equipped with a magnetic
stirring bar was charged with (R)-2-methyl-2-propanesulfinamide
under a N2 atmosphere. Ti(OEt)4 in anhydrous THF was added, and
d
JF¼21 Hz), 129.9 (d, JF¼8 Hz) 134.4 (d, JF¼4 Hz), 162.5 (d,
JF¼245 Hz) ppm; 19F NMR (376 MHz, CDCl3)
ꢀ115.1 ppm; MS (CI,
d

S. Brun et al. / Tetrahedron 66 (2010) 9032e9040
9037
NH3) m/z: 460 ([2Mþ2H]þ, 48%), 247 ([MþNH4]þ, 16%), 230
([MþH]þ, 100%).
2.87 mmol) were used. Column chromatography through silica gel
(hexanes/ethyl acetate, 70:30) afforded 0.696 g (79%) of 4g as
23
a colorless foam. [
a
]
D
þ82.43 (c 0.74, CHCl3); IR (film) nmax 3415,
4.3. General procedure for the synthesis of borane/PNSO
2381, 2283, 1628 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d 0.91e1.78 (br,
ligands (4c,e,gei)
BH3), 0.89 (s, 9H), 4.71 (t, J¼17 Hz, 1H), 5.07 (dd, J¼9 and 17 Hz, 1H),
7.29e7.58 (m, 9H), 7.61e7.69 (m, 3H), 7.70e7.90 (m, 5H) ppm; 13C
An oven-dried one-necked round bottomed flask equipped with
a magnetic stirring bar was charged with (R)-N-benzyl-2-methyl-
propane-2-sulfinamide under a N2 atmosphere. Anhydrous THF
was added, and the solution was cooled to ꢀ78 ꢁC. 2.5 M n-BuLi was
added dropwise to the solution. After stirring for 15 min, chlor-
ophosphines were added via syringe. The solution was stirred
for 1 h, during which time the temperature was raised to ꢀ20 ꢁC.
BH3eSMe2 was immediately added and the resulting mixture was
stirred for an additional 20 min. The solution was warmed to 0 ꢁC
and H2O was added carefully. Et2O was then added. The phases
were separated and the aqueous phase was washed with Et2O. The
organic layer was dried over MgSO4, filtered, and finally evaporated
under reduced pressure. The resulting crude mixture was purified
by column chromatography through silica gel to obtain the desired
N-phosphino sulfinamides protected with borane.
NMR (100 MHz, CDCl3)
d
23.6, 44.1 (d, JP¼3 Hz), 66.6 (d, JP¼5 Hz),
125.9, 126.0, 126.5, 127.7 (d, JP¼16 Hz), 127.9 (d, JP¼16 Hz), 128.7 (d,
JP¼8 Hz), 128.8 (d, JP¼8 Hz), 128.9, 129.3, 129.5, 130.0, 131.8 (d,
JP¼2 Hz), 132.3 (d, JP¼2 Hz), 132.6, 132.8 (d, JP¼11 Hz), 132.9, 134.1
(d, JP¼11 Hz), 135.1 (d, JP¼2 Hz) ppm; 31P NMR (121 MHz, CDCl3)
d
78.09 (m); ESI-HRMS: calcd m/z for [C27H31BNOPSꢀHꢀ]þ
458.1879, found 458.1871.
4.3.4. (R)-N-(Diphenylphosphino)-N-(2,4,6-trimethylbenzyl)-2-
methyl-2-propanesulfinamide borane complex, 4h. In accordance
with the general procedure for borane/PNSO ligands, 3h (0.500 g,
1.97 mmol), n-BuLi (0.87 mL, 2.17 mmol), chlorodiphenylphosphine
(0.45 mL, 2.36 mmol) in THF (14 mL), and BH3$SMe2 (0.28 mL,
2.96 mmol) were used. Column chromatography through silica gel
(hexanes/ethyl acetate, 70:30) afforded 0.729 g (82%) of 4h as
23
a colorless foam. [
a
]
D
þ72.36 (c 1.40, CHCl3); IR (film) nmax 2959,
4.3.1. (R)-N-Benzyl-N-(bis(2-methoxyphenyl)phosphino)-2-methyl-
2-propanesulfinamide borane complex, 4c. In accordance with the
general procedure for borane/PNSO ligands, 3a (0.200 g,
0.95 mmol), n-BuLi (0.53 mL, 1.05 mmol), chlorobis(2-methoxy-
phenyl)phosphine (0.33 g, 1.14 mmol) in THF (7 mL), and BH3$SMe2
(0.14 mL, 1.43 mmol) were used. Column chromatography through
silica gel (hexanes/ethyl acetate, 70:30) afforded 0.124 g (28%) of 4c
2391, 1435, 755 cmꢀ1 1H NMR (400 MHz, CDCl3)
; d 0.48 (s, 9H),
0.77e1.81 (br, BH3), 2.21 (s, 3H), 2.52 (s, 6H), 4.69 (dd, J¼2 and
16 Hz, 1H), 4.93 (dd, J¼8 and 16 Hz, 1H), 6.75 (s, 2H), 7.47 (m, 2H),
7.53 (m, 4H), 7.87 (m, 4H) ppm; 13C NMR (100 MHz, CDCl3)
d 21.0,
21.2, 23.6, 43.3 (br), 61.3 (d, JP¼4 Hz), 128.6 (d, JP¼11 Hz), 128.9 (d,
JP¼10 Hz), 129.6, 130.3, 130.8, 130.9, 131.5 (d, JP¼2 Hz), 132.3 (d,
JP¼2 Hz), 132.7 (d, JP¼10 Hz), 134.2 (d, JP¼11 Hz), 138.1, 139.6 ppm;
as a colorless foam. [
a
]
D
23 þ91.04 (c 0.83, CHCl3); IR (film) nmax 2954,
31P NMR (121 MHz, CDCl3)
d 80.74 (m); ESI-HRMS: calcd for
2916, 2353,1483,1451 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
0.96e1.67
[C26H35BNOPSꢀHꢀ]þ 450.2192, found 450.2192.
(br, BH3), 0.92 (s, 9H), 3.29 (s, 3H), 3.66 (s, 3H), 4.52 (dd, J¼13.8 and
17.7 Hz, 1H), 4.97 (dd, J¼9 and 18 Hz, 1H), 6.64 (dd, J¼4 and 8 Hz,
1H), 6.88 (dd, J¼5 and 8 Hz, 1H), 7.05 (m, 7H), 7.44 (dt, J¼8 and
15 Hz, 2H), 7.66 (dd, J¼8 and 12 Hz, 1H), 7.98 (dd, J¼6 and 14 Hz,
4.3.5. (R)-(þ)-N-Diphenylphosphino-N-4-fluorobenzyl-2-methyl-2-
propansulfinamide borane complex, 4i. In accordance with the
general procedure for borane/PNSO ligands, 3i (1.15 g, 5 mmol),
n-BuLi (2.2 mL, 5.5 mmol), chlorodiphenylphosphine (0.98 mL,
0.55 mmol) in THF (20 mL) and BH3$SMe2 (0.58 mL, 6 mmol) were
used. Column chromatography through silica gel (80:20 hexanes/
ethyl acetate) afforded 1.88 g (88%) of 4i as a colorless foam. [a]
þ99.0 (c 1.0, CHCl3); IR (film) nmax 3058, 2963, 2389, 1510, 1437,
1086 cmꢀ1; 1H NMR (400 MHz, CDCl3)
0.88 (s, 9H), 1.00e1.80 (br,
1H) ppm; 13C NMR (100 MHz, CDCl3)
d 23.5, 43.2, 55.0, 55.4, 60.0 (d,
JP¼6 Hz), 111.0 (d, JP¼5 Hz), 111.5 (d, JP¼5 Hz), 118.2, 118.8, 119.4,
121.1 (d, JP¼20 Hz), 121.0 (d, JP¼19 Hz), 126.6, 127.7 (d, JP¼9 Hz),
133.3 (d, JP¼2 Hz), 133.7 (d, JP¼2 Hz), 133.9 (d, JP¼9 Hz), 134.7 (d,
JP¼13 Hz), 139.2 (d, JP¼2 Hz), 160.8 (d, JP¼1 Hz), 161.3 (d,
23
D
JP¼4 Hz) ppm; 31P NMR (121 MHz, CDCl3)
d
75.70 (m); ESI-HRMS:
d
calcd for [C25H33O3BNPSꢀHꢀ]þ: 468.19281, found 468.19259.
BH3), 4.60 (t, J¼17 Hz, 1H), 4.82 (dd, J¼8 and 17 Hz, 1H), 6.84 (m,
2H), 7.35 (m, 2H), 7.38e7.56 (m, 6H), 7.70e7.82 (m, 4H) ppm; 13C
4.3.2. (R)-N-Benzyl-N-(bis(3,5-dimethylphenyl)phosphino)-2-me-
thy-2-lpropanesulfinamide borane complex, 4e. In accordance with
the general procedure for borane/PNSO ligands, 3a (0.200 g,
0.95 mmol), n-BuLi (0.53 mL, 1.05 mmol), chlorobis(3,5-dimethyl-
phenyl)phosphine (0.35 g, 1.14 mmol) in THF (7 mL), and BH3$SMe2
(0.14 mL, 1.43 mmol) were used. Column chromatography through
silica gel (hexanes/ethyl acetate, 70:30) afforded 0.298 g (68%) of 4e
NMR (100 MHz, CDCl3)
d
23.8, 43.9 (d, JP¼4 Hz), 60.8 (d, JP¼5 Hz),
114.8 (d, JF¼21 Hz), 128.6 (d, J¼11 Hz), 128.8 (d, J¼11 Hz), 129.4 (d,
JP¼19 Hz), 129.9, 131.0 (d, J¼8 Hz), 131.8 (d, J¼3 Hz), 132.4
(d, J¼2 Hz), 132.6 (d, J¼11 Hz), 133.1 (m), 134.3 (d, J¼10 Hz), 162.0
(d, JF¼244 Hz) ppm; 31P NMR (121 MHz, CDCl3)
d 76.9 ppm;
19F NMR (376 MHz, CDCl3)
d
ꢀ115.8 ppm; ESI-HRMS: calcd for
[C23H28BFNOPSꢀHꢀ]þ: 426.1628, found 426.1623.
as a colorless foam. [
a]
23 þ80.87 (c 0.69, CHCl3); IR (film) nmax 2919,
D
2381, 2304, 1602 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
0.83e1.74 (br,
4.3.6. (R)-(þ)-N-Benzyl-N-di-o-tolylphosphino-2-methyl-2-pro-
panesulfinamide, 1b. In accordance with the general procedure for
the borane/PNSO ligands, 3a (0.415 g, 1.96 mmol), n-BuLi (0.86 mL,
2.15 mmol), chlorodiphenylphosphine (0.535 mL, 2.15 mmol) in
THF (12 mL) were used. In this case, the ligand is unreactive toward
borane and so P-protection is not necessary. Column chromato-
graphy through silica gel (80:20 hexanes/ethyl acetate) afforded
BH3), 0.89 (s, 9H), 2.28 (s, 6H), 2.34 (s, 6H), 4.54 (t, J¼17 Hz,1H), 4.87
(dd, J¼9 and 17 Hz, 1H), 7.04e7.20 (m, 5H), 7.28e7.35 (m, 4H),
7.37e7.43 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3)
d 21.4, 21.5, 23.7,
44.2 (d, JP¼3 Hz), 60.5 (d, JP¼5 Hz), 127.1, 127.9, 128.7, 129.1, 129.7,
130.4 (d, JP¼11 Hz), 131.6 (d, JP¼11 Hz), 133.6 (d, JP¼2 Hz), 134.0 (d,
JP¼2 Hz), 137.9 (d, JP¼2 Hz), 138.3 (d, JP¼11 Hz), 138.4 (d,
JP¼11 Hz) ppm; 31P NMR (121 MHz, CDCl3)
d
78.70 (m); ESI-HRMS:
0.615 g (74%) of 1b as a colorless solid. [
a]
23 þ26.6 (c 1.0, CHCl3); IR
D
calcd m/z for [C27H37BNOPSꢀHꢀ]þ 464.23428, found 464.23415.
(film) nmax 3056, 2960, 1471, 1453, 1361 cmꢀ1
;
1H NMR (400 MHz,
CDCl3)
J¼15 Hz, 1H), 4.61 (dd, J¼10 and 15 Hz, 1H), 7.02e7.30 (m, 12H), 7.71
(m, 1H) ppm; 13C NMR (100 MHz, CDCl3)
d
0.95 (s, 9H), 2.07 (d, J¼2 Hz, 3H), 2.51 (s, 3H), 4.50 (t,
4.3.3. (R)-N-(Diphenylphosphino)-N-(naphthalen-2-ylmethyl)-2-
methyl-2-propanesulfinamide borane complex, 4g. In accordance
with the general procedure for borane/PNSO ligands, 3g (0.500 g,
1.91 mmol), n-BuLi (0.84 mL, 2.10 mmol), chlorodiphenylphosphine
(0.43 mL, 2.29 mmol) in THF (14 mL) and BH3$SMe2 (0.27 mL,
d
21.0 (d, JP¼21 Hz), 21.7
(d, JP¼23 Hz), 23.5 (d, JP¼2 Hz), 48.7 (d, JP¼15 Hz), 59.6, 125.7, 126.6,
127.2, 128.1, 129.07, 129.12 (d, JP¼2 Hz), 130.1, 130.5 (d, JP¼5 Hz),
130.6 (d, JP¼4 Hz), 131.7 (d, JP¼3 Hz), 134.5, 135.2 (d, JP¼11 Hz),

9038
S. Brun et al. / Tetrahedron 66 (2010) 9032e9040
135.3 (d, JP¼21 Hz), 138.1(d, JP¼3 Hz), 140.6 (d, JP¼27 Hz), 142.6 (d,
138.5 (d, JP¼1 Hz) ppm; 31P NMR (121 MHz, CDCl3)
d 60.25 (s); ESI-
JP¼31 Hz) ppm; 31P NMR (121 MHz, CDCl3)
d
43.4 ppm; ESI-HRMS:
HRMS: calcd m/z for [C27H34NOPSþH]þ 452.2173, found 452.2177.
calcd for [C25H30NOPSþH]þ 424.1864, found 424.1858.
4.4.3. (R)-N-(Diphenylphosphino)-N-(naphthalen-2-ylmethyl)-2-
methyl-2-propanesulfinamide, 1g. In accordance with the general
procedure for borane/free PNSO ligands, 4g (0.200 g, 0.44 mmol),
DABCO (0.074 g, 0.66 mmol) in toluene (1.5 mL) were used. Column
chromatography through silica gel (hexanes/ethyl acetate, 70:30)
4.3.7. (R)-N-Benzy-N-(bis(4-(trifluoromethyl)phenyl)phosphino)-2-
methyl-2-propanesulfinamide, 1d. In accordance with the general
procedure for borane/PNSO ligands, 3a (0.200 g, 0.95 mmol), n-BuLi
(0.53 mL, 1.05 mmol), chlorobis(4-(trifluoromethyl)phenyl)phos-
phine (0.42 g, 1.14 mmol) in THF (6 mL) were used. In this case, the
ligand is unreactive toward borane and so P-protection is not
necessary. Column chromatography through silica gel (hexanes/
ethyl acetate, 90:10) afforded 0.088 g (17%) of 1d as a colorless
afforded 0.160 g (82%) of 1g as a colorless foam. [
a
]
23 þ32.70 (c 1.00,
D
CHCl3); IR (film) nmax 3053, 2959, 2917, 2231, 1428, 1075, 814 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
0.95 (s, 9H), 4.61 (dd, J¼12 and 16 Hz,
1H), 4.78 (dd, J¼9 and 16 Hz, 1H), 7.23e7.27 (m, 1H), 7.30e7.37 (m,
foam. [a]
23 þ56.75 (c 0.615, CHCl3); IR (film) nmax 2958, 2917, 1459,
3H), 7.30e7.43 (m, 5H), 7.52 (s, 1H), 7.55e7.70 (m, 6H), 7.74 (m,
D
1323, 1065 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
0.95 (s, 9H), 4.62 (t,
1H) ppm; 13C NMR (100 MHz, CDCl3)
d
23.7 (d, JP¼2 Hz), 49.3 (d,
J¼17 Hz, 1H), 4.90 (dd, J¼9 and 17 Hz, 1H), 7.09e7.18 (m, 3H), 7.27
JP¼11 Hz), 59.6 (d, JP¼3 Hz), 125.9, 126.0, 126.8 (d, JP¼1 Hz), 127.7,
127.89 (d, JP¼1 Hz), 127.94, 128.5, 128.6, 128.7, 129.1, 130.1, 132.2 (d,
JP¼20 Hz), 132.6, 133.2, 134.4 (d, JP¼22 Hz), 135.8 (d, JP¼2 Hz), 136.9
(d, JP¼18 Hz), 137.4 (d, JP¼15 Hz) ppm; 31P NMR (121 MHz, CDCl3)
(m, 2H), 7.63 (m, 2H), 7.74 (m, 2H), 7.84 (m, 2H), 7.92 (m, 2H) ppm;
13C NMR (100 MHz, CDCl3)
d
23.7, 44.8 (d, JP¼4 Hz), 61.3 (d,
JP¼5 Hz),123.46 (q, JF¼273 Hz),123.50 (q, JF¼273),125.5e125.9 (m),
127.6, 128.2, 128.8, 133.1 (d, JP¼15 Hz), 133.2 (d, JP¼11 Hz), 133.5 (d,
JP¼15 Hz), 133.95 (dq, JF¼2 Hz and JP¼33 Hz),134.4 (dq, JF¼2 Hz and
JP¼33 Hz), 134.5 (d, JP¼11 Hz), 136.5 (d, JP¼2 Hz) ppm; 31P NMR
d
59.77 (s); ESI-HRMS: calcd m/z for [C27H28NOPSþH]þ 446.1708,
found 446.1707.
(121 MHz, CDCl3)
d
76.32 (s); ESI-HRMS: calcd m/z for
4.4.4. (R)-N-(Diphenylphosphino)-N-(2,4,6-trimethylbenzyl)-2-
methyl-2-propanesulfinamide, 1h. In accordance with the general
procedure for borane/free PNSO ligands, 4h (0.150 g, 0.33 mmol),
DABCO (0.056 g, 0.50 mmol) in toluene (1.5 mL) were used. Column
chromatography through silica gel (hexanes/ethyl acetate, 90:10)
[C25H24F6NOPSþH]þ 532.12932, found 532.12919.
4.4. General procedure for the synthesis of borane/free PNSO
ligands (1c,e,gei)
afforded 0.138 g (95%) of 1h as a colorless foam. [
a]
23 ꢀ32.80 (c 0.25,
D
An oven-dried one-necked round bottomed flask equipped with
a magnetic stirring bar was charged with the corresponding
N-phosphino sulfinamide borane complex and DABCO under a N2
atmosphere. After adding anhydrous toluene, the reaction took
place at 40 ꢁC. After stirring for 1 h, the crude was evaporated under
reduced pressure. The resulting crude mixture was purified by
column chromatography through silica gel to obtain the desired
N-phosphino sulfinamides.
CHCl3); IR (film) nmax 2910, 1431, 1077, 739 cmꢀ1
;
1H NMR
(400 MHz, CDCl3)
J¼3 and 12 Hz, 1H), 4.85 (m, 1H), 6.80 (s, 2H), 7.28e7.40 (m, 6H),
7.51e7.61 (m, 4H) ppm; 13C NMR (100 MHz, CDCl3)
20.4, 21.2, 24.7
d 0.99 (s, 9H), 2.24 (s, 3H), 2.35 (br s, 6H), 4.10 (dd,
d
(d, JP¼2 Hz), 42.3 (br), 59.6, 127.8 (d, JP¼13 Hz), 128.2 (d, JP¼11 Hz),
128.30 (d, JP¼13 Hz), 128.31, 129.1, 129.7 (d, JP¼7 Hz), 130.2, 131.4
(br, JP¼20 Hz), 133.1 (d, JP¼9 Hz), 135.6 (d, JP¼25 Hz), 137.9, 138.9 (d,
JP¼1 Hz) ppm; 31P NMR (121 MHz, CDCl3)
d 49.01 (s); ESI-HRMS:
calcd m/z for [C26H32NOPSþH]þ 438.2021, found 438.2028.
4.4.1. (R)-N-Benzyl-N-(bis(2-methoxyphenyl)phosphino)-2-methyl-
2-propanesulfinamide, 1c. In accordance with the general pro-
cedure for borane/free PNSO ligands, 4c (0.084 g, 0.18 mmol),
DABCO (0.030 g, 0.27 mmol) in toluene (1.5 mL) were used. Column
chromatography through silica gel (hexanes/ethyl acetate, 70:30)
4.4.5. (R)-(þ)-N-Diphenylphosphino-N-4-fluorobenzyl-2-methyl-2-
propanesulfinamide, 1i. In accordance with the general procedure
for borane/free PNSO ligands, 4i (1.75 g, 4.1 mmol), DABCO (0.690 g,
6.2 mmol) in toluene (30 mL) were used. Column chromatography
afforded 0.076 g (93%) of 1c as a colorless foam. [
a
]
23 ꢀ61.20 (c 0.50,
through silica gel (90:10 hexanes/ethyl acetate) afforded 1.49 g
D
23
CHCl3); IR (film) nmax 2959, 2360, 1472, 1251, 1069 cmꢀ1
;
1H NMR
(88%) of 1i as a colorless foam. [
a
]
þ47.5 (c 1.0, CHCl3); IR (film)
D
(400 MHz, CDCl3)
J¼16 Hz, 1H), 4.74 (t, J¼16 Hz, 1H), 6.76e6.89 (m, 3H), 7.02e7.45 (m,
9H), 7.88 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3)
23.2, 47.0 (d,
d
0.88 (s, 9H), 3.57 (s, 3H), 3.92 (s, 3H), 4.29 (t,
nmax 3054, 2960, 1603, 1509, 1075 cmꢀ1; 1H NMR (400 MHz, CDCl3)
0.95 (s, 9H), 4.50 (d, J¼10 Hz, 2H), 6.86 (m, 2H), 7.11 (m, 2H),
7.30e7.42 (m, 6H), 7.48e7.60 (m, 4H) ppm; 13C NMR (100 MHz,
CDCl3)
d
d
JP¼16 Hz), 55.40, 55.44, 59.2 (d, JP¼2 Hz), 110.1 (d, JP¼2 Hz), 110.3,
120.5, 121.5, 124.3 (d, JP¼10 Hz), 124.6 (d, JP¼26 Hz), 126.9, 128.1,
128.6 (d, JP¼2 Hz), 130.5, 131.7, 132.8 (d, JP¼4 Hz), 134.7, 139.0 (d,
JP¼2 Hz), 160.3 (d, JP¼17 Hz), 161.2 (d, JP¼20 Hz) ppm; 31P NMR
d
23.8 (d, JP¼2 Hz), 48.7 (d, JP¼12 Hz), 59.7 (d, JP¼2 Hz), 115.1
(d, JF¼21 Hz), 128.56 (d, J¼5 Hz), 128.63 (d, J¼5 Hz), 129.1, 130.1,
130.9 (dd, J¼2 and 8 Hz), 132.0 (d, J¼20 Hz), 134.0 (m), 134.5 (d,
J¼23 Hz), 136.8 (d, JP¼18 Hz), 137.3 (d, JP¼14 Hz), 162.1 (d,
(121 MHz, CDCl3)
d
46.90 (s); ESI-HRMS: calcd m/z for
JF¼244 Hz) ppm; 31P NMR (121 MHz, CDCl3)
d
58.4 ppm; 19F NMR
[C25H30NO3PSþH]þ 456.17568, found 456.17577.
(376 MHz, CDCl3)
d
ꢀ115.7 ppm. Anal. Calcd for C23H25FNOPS C
66.81, H 6.09, N 3.39, S 7.75. Found C 66.40, H 6.17, N 3.39, S 7.72.
4.4.2. (R)-N-Benzyl-N-(bis(3,5-dimethylphenyl)phosphino)-2-
methyl-2-propanesulfinamide, 1e. In accordance with the general
procedure for borane/free PNSO ligands, 4e (0.245 g, 0.53 mmol),
DABCO (0.090 g, 0.79 mmol) in toluene (1.5 mL) were used. Column
chromatography through silica gel (hexanes/ethyl acetate, 70:30)
4.5. General procedure for intramolecular [2D2D2]
cycloaddition reactions catalyzed by Rh(I)/PNSO formed in
situ (Tables 2 and 3)
afforded 0.170 g (71%) of 1e as a colorless foam. [
a
]
23 þ57.68 (c 0.69,
In a 25 mL flask, a mixture of [Rh(COD)2]BF4 (0.2 equiv) and
ligand 1a (0.1 equiv) was dissolved in the appropriate solvent
(3 mL) (see Tables 2 and 3). Hydrogen gas was introduced to the
catalyst solution and stirred for 30 min. The resulting mixture was
then concentrated to dryness. Solvent (8 mL) was added and the
solution was stirred under a N2 atmosphere. Enediyne (6, 8, 9)
(1 equiv) in solvent (2 mL) was then added to the previous solution
and the reaction mixture was stirred under N2 until completion
D
CHCl3); IR (film) nmax 2914, 1958, 1451, 1075, 762 cmꢀ1
;
1H NMR
(400 MHz, CDCl3)
J¼12 and 16 Hz, 1H), 4.57 (t, J¼9 and 16 Hz, 1H), 6.94 (s, 1H), 7.03 (s,
1H), 7.09e7.23 (m, 9H) ppm; 13C NMR (100 MHz, CDCl3)
21.4, 21.5,
d 0.96 (s, 9H), 2.27 (s, 6H), 2.31 (s, 6H), 4.42 (dd,
d
23.7 (d, JP¼2 Hz), 49.6 (d, JP¼11 Hz), 59.5 (d, JP¼2 Hz), 127.1, 128.1,
129.1, 129.9 (d, JP¼20 Hz), 130.6, 131.6, 131.9 (d, JP¼23 Hz), 136.6 (d,
JP¼18 Hz), 137.0 (d, JP¼14 Hz), 137.9 (d, JP¼6 Hz), 138.0 (d, JP¼7 Hz),

S. Brun et al. / Tetrahedron 66 (2010) 9032e9040
9039
(for temperatures and reaction times see Tables 2 and 3). The
solvent was evaporated and the residue was purified by column
chromatography through silica gel.
126.7, 128.1, 128.4, 129.5, 130.0, 130.6, 137.8, 139.5, 141.1, 142.0,
172.1 ppm; ESI-HRMS: calcd m/z for [C23H26O4þNa]þ 389.1723,
found 389.1719.
4.5.1. Cyclohexadiene derivative 74. Column chromatography: hex-
anes/ethyl acetate (8:2); colorless solid; mp 187e189 ꢁC; IR (ATR)
4.6.5. Compound 14ca (entries 8 and 9, Table 4). Column chroma-
tography: hexanes/ethyl acetate (24:0.2); colorless solid; mp
nmax 2846, 1366, 1152, 1046 cmꢀ1
;
1H NMR (300 MHz, CDCl3)
74e76 ꢁC (lit.8w mp 75e76 ꢁC); IR (ATR) nmax 2921, 2850,1478 cmꢀ1
;
d
2.71e2.76 (m, 2H), 3.43e3.49 (m, 2H), 4.24e4.30 (m, 2H), 4.35 (d,
1H NMR (400 MHz, CDCl3)
d
2.11 (ap quint, J¼8 Hz, 2H), 2.95 (ap q,
J¼13 Hz, 2H), 4.55 (d, J¼13 Hz, 2H), 5.86 (s, 2H) ppm; 13C NMR
J¼8 Hz, 4H), 7.25e7.48 (m, 6H), 7.54e7.60 (m, 2H) ppm; 13C NMR
(75 MHz, CDCl3)
d
43.5, 69.1, 74.0, 114.3, 141.1 ppm. The ee was
(100 MHz, CDCl3) d 25.6, 32.7, 33.0, 123.3, 124.7, 125.3, 126.9, 127.2,
determined with HPLC analysis using a chiral column (Kromasil 100
TBB column, 4.6ꢂ250 mm, 5 m, rt); eluent: 99% heptane/1% THF,
flow rate:
¼254 nm; tR¼8.4 min (major isomer), tR¼8.1 min (mi-
128.7, 139.5, 141.8, 143.5, 145.0 ppm.
m
l
4.6.6. Compound 14cb (entry 10, Table 4). Column chromatogra-
phy: hexanes/ethyl acetate (16:2); colorless solid; mp 70e72 ꢁC
nor isomer).
(lit.8w mp 71e72 ꢁC); IR (ATR): 3322, 2921, 1345, 1027 cmꢀ1 1H
;
4.6. General procedure for intermolecular [2D2D2]
cycloaddition reactions catalyzed by Rh(I)/PNSO formed in
situ (Table 4)
NMR (400 MHz, CDCl3)
d
1.64 (br abs, 1H), 2.08 (quint, J¼8 Hz, 2H),
2.90 (dt, J¼3 and 8 Hz, 4H), 4.64 (s, 2H), 7.10e7.24 (m, 3H) ppm; 13C
NMR (100 MHz, CDCl3)
138.9, 143.9, 144.8 ppm.
d 25.6, 32.7, 32.9, 65.7, 123.4, 124.5, 125.3,
In a 25 mL flask, a mixture of [Rh(COD)2]BF4 (0.2 equiv) and
ligand 1a (0.1 equiv) was dissolved in the appropriate solvent
(3 mL) (see Table 4). Hydrogen gas was introduced to the catalyst
solution and stirred for 30 min. The resulting mixture was then
concentrated to dryness. Solvent (2 mL) was added and the solution
was stirred under a N2 atmosphere. A solution of alkyne 13
(5 equiv) in the appropriate solvent (3 mL) was then added at room
temperature followed by the diyne 12 (1 equiv) solution (3 mL)
over a 10-min period. The reaction mixture was then stirred until
completion (for temperatures and reaction times see Table 4). The
solvent was evaporated and the residue was purified by column
chromatography through silica gel.
4.6.7. Compound 14cc (entry 11, Table 4). Column chromatography:
hexanes/ethyl acetate (1:1); colorless solid; mp 93e95 ꢁC (lit.12 mp
90e92 ꢁC); IR (ATR) nmax 3211, 2928, 994 cmꢀ1; 1H NMR (400 MHz,
CDCl3)
d
2.07 (quint, J¼7 Hz, 2H), 2.89 (t, J¼7 Hz, 4H), 3.35 (br abs,
2H), 4.64 (s, 4H), 7.19 (s, 2H) ppm; 13C NMR (100 MHz, CDCl3)
32.7, 64.4, 126.0, 137.5, 144.8 ppm.
d 25.5,
4.6.8. Compound 14da13 (entries 12 and 13, Table 4). Column
chromatography: hexanes/dichloromethane (1:1); colorless solid;
mp 170e173 ꢁC; IR (ATR) nmax 2919, 2850,1465,1343,1160 cmꢀ1; 1H
NMR (400 MHz, CDCl3)
d 2.38 (s, 3H), 4.64 (br abs, 4H), 7.20 (d,
J¼8 Hz, 1H), 7.26e7.36 (m, 4H), 7.37e7.44 (m, 3H), 7.45e7.52 (m,
4.6.1. Compound 14ab (entry 3, Table 4). Column chromatography:
hexanes/ethyl acetate (7:3); colorless solid; mp 175e177 ꢁC (dec);
2H), 7.77 (d, J¼8 Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3)
d 21.7,
53.8, 53.9, 121.5, 123.1, 127.1, 127.3, 127.7, 127.8, 129.0, 130.0, 133.9,
135.3, 137.0, 140.7, 141.5, 143.9 ppm; ESI-MS (m/z) 372 [MþNa]þ,
388 [MþK]þ.
IR (ATR) nmax 3493, 2921, 1332, 1158 cmꢀ1 1H NMR (400 MHz,
;
CDCl3) d 1.56 (br abs, 1H), 2.15 (s, 3H), 2.16 (s, 3H), 2.41 (s, 3H), 4.56
(s, 2H), 4.57 (s, 2H), 4.63 (ap d, J¼4 Hz, 2H), 7.05 (s, 1H), 7.32 (AA0
part, AA0BB0 system, J¼8 Hz, 2H), 7.78 (BB0 part, AA0BB0 system,
4.6.9. Compound 14ea (entry 14, Table 4). Column chromatogra-
phy: methylene chloride/hexanes (20:5); yellow oil;14 IR (ATR) nmax
J¼8 Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3)
d 14.7, 18.3, 21.6, 53.5,
53.7, 63.2, 127.6, 128.1, 128.9, 129.9, 133.9, 134.6, 135.9, 138.6,
143.8 ppm; ESI-MS (m/z) 332.1 [MþH]þ, 354.1 [MþNa]þ. Anal.
Calcd for C18H21NO2S: C, 65.23; H, 6.39; N, 4.23. Found: C, 65.46; H,
6.78; N, 4.26.
2979, 2930,1730 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
1.27 (t, J¼7.2 Hz,
6H), 3.63 (s, 2H), 3.65 (s, 2H), 4.22 (q, J¼7 Hz, 4H), 7.24e7.26 (m,1H),
7.29e7.34 (m, 1H), 7.38e7.43 (m, 4H), 7.53e7.57 (m, 2H) ppm; 13C
NMR (100 MHz, CDCl3) d 14.1, 40.3, 40.6, 60.6, 61.9,123.1,124.6,126.2,
127.1, 127.2, 128.8, 139.3, 140.4, 140.8, 141.4, 171.8 ppm.
4.6.2. Compound 14ad (entry 5, Table 4). Column chromatography:
hexanes/ethyl acetate (7:3); colorless solid; mp 193e195 ꢁC; IR
(ATR) nmax 2920, 2850, 1722, 1344, 1319, 1216, 1158 cmꢀ1; 1H NMR
4.6.10. Compound 14eb (entry 15, Table 4). Column chromatogra-
phy: hexanes/ethyl acetate (from 9:1 to 8:2); yellow oil;8w IR (ATR)
(400 MHz, CDCl3)
d
2.20 (s, 6H), 2.42 (s, 3H), 3.84 (s, 6H), 4.61 (s,
nmax 3452, 2981, 1726, 1249 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d 1.25
4H), 7.33 (d, J¼8 Hz, 2H) 7.77 (d, J¼8 Hz, 2H) ppm; 13C NMR
(t, J¼7 Hz, 6H), 1.72 (br abs, 1H), 3.57 (br s, 4H), 4.20 (q, J¼7 Hz, 4H),
(100 MHz, CDCl3)
d 16.7, 21.9, 52.9, 54.3, 127.9, 129.5, 130.4, 132.6,
4.63 (s, 2H), 7.13e7.21 (m, 3H) ppm; 13C NMR (100 MHz, CDCl3)
134.0, 138.5, 144.5, 168.6 ppm; ESI-MS (m/z) 418 [MþH]þ; ESI-
d 14.1, 40.3, 40.5, 60.6, 61.8, 65.5, 123.1, 124.4, 126.1, 139.7, 139.9,
140.6, 171.7 ppm.
HRMS: calcd m/z for [C21H23NSO6þH]þ 418.1319, found 418.1316.
4.6.3. Hexamethyl ester benzene derivative, 1511 (entry 6, Table 4).
Column chromatography hexanes/ethyl acetate (7:3); colorless
solid; mp 181e183 ꢁC (lit.11 mp 186 ꢁC); IR (ATR) nmax 2921, 1726,
4.6.11. Compound 14ec (Entry 16, Table 4). Column chromatogra-
phy: methylene chloride/hexanes/ethyl acetate (8:5:7); colorless
solid; mp 84e86 ꢁC (lit.9d oil); IR (ATR) nmax 3272, 2919, 1725, 1267,
1442,1225 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
3.88 (s,18H) ppm; 13
C
1194, 1065 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
1.25 (t, J¼7 Hz, 6H),
NMR (100 MHz, CDCl3)
d
53.5, 133.9, 165.1 ppm; ESI-MS (m/z) 427
3.21 (br abs, 2H), 3.56 (s, 4H), 4.19 (t, J¼7 Hz, 4H), 4.65 (s, 4H), 7.17
[MþH]þ, 444 [MþNH4]þ, 449 [MþNa]þ.
(s, 2H) ppm; 13C NMR (100 MHz, CDCl3)
125.7, 138.5, 140.5, 171.7 ppm.
d 14.1, 40.3, 60.6, 61.9, 64.3,
4.6.4. Compound 14ba (entry 7, Table 4). Column chromatography:
methylene chloride/hexanes (6:4); orange pale oil; IR (ATR) nmax
4.6.12. Compound 14fa (entry 17, Table 4). Column chromatogra-
phy: methylene chloride/hexanes (1:1); colorless solid; mp
80e82 ꢁC (lit.15 yellow oil); IR (ATR) nmax 2855, 1479, 1037 cmꢀ1; 1H
2924, 1730, 1243 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
1.28 (t, J¼7 Hz,
6H), 2.13 (s, 3H), 2.25 (s, 3H), 3.58 (s, 2H), 3.59 (s, 2H), 4.23 (q,
J¼7 Hz, 4H), 6.90 (s, 1H), 7.25e7.33 (m, 3H), 7.36e7.41 (m, 2H) ppm;
NMR (400 MHz, CDCl3)
1H), 7.32e7.38 (m, 1H), 7.41e7.51 (m, 4H), 7.55e7.59 (m, 2H) ppm;
d
5.16 (s, 2H), 5.17 (s, 2H), 7.30 (d, J¼8 Hz,
13C NMR (100 MHz, CDCl3)
d 14.2, 16.8, 18.7, 39.7, 40.3, 59.7, 61.9,

9040
S. Brun et al. / Tetrahedron 66 (2010) 9032e9040
7. (a) Pla-Quintana, A.; Roglans, A.; Torrent, A.; Moreno-Mañas, M.; Benet-Buch-
13C NMR (100 MHz, CDCl3)
127.4, 128.9, 138.3, 140.0, 140.9, 141.1 ppm.
d
73.5, 73.6, 119.8, 121.3, 126.6, 127.3,
holz, J. Organometallics 2004, 23, 2762e2767; (b) Torrent, A.; González, I.;
Pla-Quintana, A.; Roglans, A.; Moreno-Mañas, M.; Parella, T.; Benet-Buchholz, J.
J. Org. Chem. 2005, 70, 2033e2041; (c) González, I.; Bouquillon, S.; Roglans, A.;
Muzart, J. Tetrahedron Lett. 2007, 48, 6425e6428; (d) Brun, S.; Garcia, L.; Gon-
zález, I.; Torrent, A.; Dachs, A.; Pla-Quintana, A.; Parella, T.; Roglans, A. Chem.
Commun. 2008, 4339e4341; (e) Ref. 6a; (f) Dachs, A.; Torrent, A.; Roglans, A.;
Parella, T.; Osuna, S.; Solà, M. Chem.dEur. J. 2009, 15, 5289e5300.
4.6.13. Compound 14fb (entry 18, Table 4). Column chromatogra-
phy: methylene chloride/hexanes/ethyl acetate (from 20:16:2 to
20:12:2); colorless solid; mp 69e71 ꢁC (lit.8w mp 70e71 ꢁC); IR
(ATR) nmax 3318, 2919, 1367, 1034 cmꢀ1; 1H NMR (400 MHz, CDCl3)
8. For selected examples of [2þ2þ2] cycloadditions of diynes with monoynes
using rhodium catalysts, see: (a) Sedlák, D.; Novák, P.; Kotora, M.; Bartunek, P.
J. Med. Chem. 2010, 53, 4290e4294; (b) Wu, W.; Zhang, X. Y.; Kang, S. X. Chin.
Chem. Lett. 2010, 21, 18e22; (c) Tanaka, K.; Sawada, Y.; Aida, Y.; Thammathevo,
M.; Tanaka, R.; Sagae, H.; Otake, Y. Tetrahedron 2010, 66,1563e1569; (d) Garcia, L.;
Pla-Quintana, A.; Roglans, A. Org. Biomol. Chem. 2009, 7, 5020e5027; (e) Kotha, S.;
Khedkhar, P. Eur. J. Org. Chem. 2009, 730e738; (f) Komine, Y.; Kamisawa, A.;
Tanaka, K. Org. Lett. 2009, 11, 2361e2364; (g) Suda, T.; Noguchi, K.; Hirano, M.;
Tanaka, K. Chem.dEur. J. 2008, 14, 6593e6596; (h) Novák, P.; Cíhalová, S.;
Otmar, M.; Hocek, M.; Kotora, M. Tetrahedron 2008, 64, 5200e5207; (i) Nishida, G.;
Noguchi, K.; Hirano, M.; Tanaka, K. Angew. Chem., Int. Ed. 2007, 46, 3951e3954; (j)
Oppenheimer, J.; Hsung, R. P.; Figueroa, R.; Johnson, W. L. Org. Lett. 2007, 9,
3969e3972; (k) Clayden, J.; Moran, W. J. Org. Biomol. Chem. 2007, 5,1028e1030; (l)
Taylor, M. S.; Swager, T. M. Org. Lett. 2007, 9, 3695e3697; (m) Young, D. D.;
Senaiar, R. S.; Deiters, A. Chem.dEur. J. 2006, 12, 5563e5568; (n) Wu, Y.-T.;
Hayama, T.; Baldridge, K. K.; Linden, A.; Siegel, J. S. J. Am. Chem. Soc. 2006, 128,
6870e6884; (o) Tanaka, K.; Sagae, H.; Toyoda, K.; Noguchi, K. Eur. J. Org. Chem.
2006, 3575e3581; (p) Dufková, L.; Císarová, I.; Stepnicka, P.; Kotora, M. Eur. J. Org.
Chem. 2003, 2882e2887; (q) Witulski, B.; Zimmermann, A. Synlett 2002,
1855e1859; (r)Kotha, S.;Brahmachary, E. Bioorg.Med. Chem.2002,10, 2291e2295;
(s) Kotha, S.; Sreenivasachary, N. Eur. J. Org. Chem. 2001, 3375e3383; (t) Grigg, R.;
Savic, V.; Tambyrajah, V. Tetrahedron Lett. 2000, 41, 3003e3006; (u) Witulski, B.;
Stengel, T. Angew. Chem., Int. Ed. 1999, 38, 2426e2430; (v) McDonald, F. E.;
Zhu, H. Y. H.; Holmquist, C. R. J. Am. Chem. Soc.1995,117, 6605e6606; (w) Grigg, R.;
Scott, R.; Stevenson, P. J. Chem. Soc., Perkin Trans. 11988, 1357e1364.
d
2.16 (br abs, 1H), 4.68 (s, 2H), 5.06 (s, 2H), 5.07 (s, 2H), 7.18e7.26
(m, 3H) ppm; 13C NMR (100 MHz, CDCl3)
126.3, 138.5, 139.6, 140.4 ppm.
d 65.2, 73.4, 119.7, 121.1,
4.6.14. Compound 14fc (entry 19, Table 4). Column chromatogra-
phy: methylene chloride/hexanes/ethyl acetate (5:1:4); colorless
solid; mp 108e110 ꢁC (lit.16 thick gum); IR (ATR) nmax 3244, 2853,
1068, 995 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
3.12 (br abs, 2H), 4.73
(s, 4H), 5.07 (s, 4H), 7.22 (s, 2H) ppm; 13C NMR (100 MHz, CDCl3)
64.3, 73.5, 122.4, 138.9, 139.5 ppm.
d
Acknowledgements
ꢀ
ꢀ
ꢀ
We would like to thank the Spanish MICINN (projects CTQ2008-
05409 and CTQ2008-00763), IRB Barcelona, and the Generalitat de
Catalunya (projects 2009SGR637 and 2009SGR00901) for their
financial support. S.B. thanks University of Girona (UdG) and T.L.
thanks AGAUR for a predoctoral fellowship. We also acknowledge
the Research Technical Services of the UdG for spectral data.
9. For selected examples of [2þ2þ2] cycloadditions of diynes with monoynes
using other metals, see: Cobalt: (a) Saino, N.; Kawaji, T.; Ito, T.; Matsushita, Y.;
Okamoto, S. Tetrahedron Lett. 2010, 51, 1313e1316; (b) Young, D. D.; Teske, J. A.;
Deiters, A. Synthesis 2009, 3785e3790; (c) Doszczak, L.; Tacke, R. Organome-
tallics 2007, 26, 5722e5723; (d) Saino, N.; Amemiya, F.; Tanabe, E.; Kase, K.;
Okamoto, S. Org. Lett. 2006, 8, 1439e1442; (e) Gandon, V.; Leca, D.; Aechtner, T.;
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Supplementary data
NMR spectra of PNSO ligands 1bei, cyclohexadiene derivative 7,
and benzene derivatives 14 and 15. Supplementary data associated
with this article can be found in online version at doi:10.1016/
j.tet.2010.09.009.
References and notes
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ꢀ
ꢀ
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ꢀ
ꢀ
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