A remarkable cycloaddition of bis(arylsulfonyl)iodonium ylide with norbornene derivatives for the direct synthesis of functionalized indanes

Article abstract of DOI:10.1055/s-2003-39894

The reaction of bis(arylsulfonyl)iodonium ylides with a variety of norbornene derivatives 3 affords functionalized indanes 4 in good yields through an unusual cycloaddition. This diastereoselective cycloaddition provides a convenient preparative route to multicyclic structures of well defined stereochemical configuration.

Full text of DOI:10.1055/s-2003-39894

LETTER
1165
A Remarkable Cycloaddition of Bis(arylsulfonyl)iodonium Ylide with
Norbornene Derivatives for the Direct Synthesis of Functionalized Indanes
[3+2]
Cycloaddition of
I
a
odonium
y
l
a
Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg, Germany
b
Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
Fax +30(2651)098799; E-mail: lxatziar@cc.uoi.gr.
Received 24 March 2003
The bis(arylsulfonyl)iodonium ylides 1a,b were prepared
from the corresponding bis(arylsulfonyl)methanes 2 by
treatment with iodobenzene diacetate and KOH as base at
–10 °C (Scheme 2).3 The disulfonyl iodonium ylides are
Abstract: The reaction of bis(arylsulfonyl)iodonium ylides with a
variety of norbornene derivatives 3 affords functionalized indanes 4
in good yields through an unusual cycloaddition. This diastereose-
lective cycloaddition provides a convenient preparative route to
multicyclic structures of well defined stereochemical configuration. labile and may be stored at –30 °C for several weeks with-
out significant decomposition. They are practically insol-
uble in common organic solvents (except DMSO), so that
the reaction of the ylide with the norbornene derivatives 3
was conducted under heterogeneous conditions.
Key words: ylide, [3+2]-cycloaddition, indane
Bis(sulfonyl)iodonium ylides1 are a versatile class of
hypervalent iodine compounds,2 which are related to the
corresponding bis(sulfonyl)diazo compounds and readily
prepared from bis(sulfonyl)methanes.3 Whereas the pho-
tochemical and thermal Cu(acac)2-catalyzed reaction of
bis(sulfonyl)iodonium ylides with olefins affords cyclo-
propanes and thiosulfonates,3 analogous to the bis(sulfo-
nyl)diazomethanes,4 phenylated alkenes and norbornene
lead to substituted indanes (Scheme 1).3,5 In view of the
synthetic value of this unusual cycloaddition, the incen-
tive of the present study was to examine the scope of this
novel process for norbornene derivatives. Provided that
the stereochemical course of this cycloaddition process is
well defined and the arylsulfonyl substituent may be
readily removed by reduction, a potentially useful stereo-
selective synthetic method would become available for
the preparation of highly substituted, functionalized in-
danes.
ArSO2
ArSO2
PhI(OAc)2 / KOH
IPh
CH2
MeOH, -10 °C, 12 h
ArSO2
ArSO2
2
1a: Ar= C6H5
1b: Ar= pC6H5
CH3CN,
Rh2(OAc)4
ca. 20 °C
3
H
Ph
R
H
PhCH CHR
R
ArSO2
4
SO2Ph
Scheme 2
(PhSO2)2C IPh
1
All reactions were run at room temperature (ca. 20 °C),
until complete consumption of the ylide (indicated by the
change from a heterogeneous mixture to a clear solution),
as shown in Scheme 2. The norbornene 3a was selected as
a model substrate and tested with iodonium ylide 1a under
a variety of conditions (Table 1). In CH2Cl2 at 20 °C, a
54:46 mixture of the desired indane 4a and disulfone 2a
was obtained (Table 1, entry 1). Similar results were ob-
served in the absence of light and/or under an inert atmo-
sphere (entries 2–4), albeit at longer reactions times (240
h to 600 h). The addition of catalytic amounts of
Rh2(OAc)4 (0.1 mol%) increased dramatically (ca. 2000
times) the rate of ylide consumption, but still most of the
PhI
+
SO2
H
H
PhSO2
Scheme 1
Synlett 2003, No. 8, Print: 24 06 2003.
Art Id.1437-2096,E;2003,0,08,1165,1169,ftx,en;G06003ST.pdf.
© Georg Thieme Verlag Stuttgart · New York

1166
W. Adam et al.
LETTER
ylide was converted to its disulfonyl methane 2a (entry 5). highest, that is, the decomposition of the ylide is minimal
With CCl4 as solvent and no rhodium catalyst, the reaction under these conditions.
time was significantly (ca. 3 times) prolonged, with no
improvement in the product ratio (entry 6).
The scope of this remarkable cycloaddition was explored
by using other norbornene derivatives. The cycloadducts
4 (Table 2) were isolated by flash chromatography on
silica gel in moderate yields (up to 64%, relative to the
consumed ylide). It should be emphasized that when re-
ferred to the amount of consumed alkene, high yields (up
to 98%) of the adducts 4 were registered. This indicates
that an efficient and clean process operates, except that
Table 1 Optimization of Reaction Conditionsa for the Formation of
Indane 4a
H
1a
(PhSO2)2CH2
substantial amounts (up to 49%) of the ylide decompose
H
to the bis(arylsulfonyl)methane 2.
PhSO2
The reaction of the ylide 1a with norbornene (3a) afforded
exclusively the indane 4a3,6 in 64% yield (Table 2, entry
1). Unexpectedly, a complex non-separable reaction mix-
ture was isolated upon reaction with norbornadiene, while
no reaction was observed with 5-methylene-2-norbornene
(data not shown in Table 2). Dicyclopentadiene (3b) re-
acted exclusively at the norbornene double bond to give a
1:1 mixture of the two regioisomers 4d and 4d¢ in 52%
yield (entry 3). The assigned structures were established
by catalytic hydrogenation of this mixture to afford only
one product, namely the indane 5 in 88% yield
(Scheme 3).
3a
4a
2a
Entry Solvent Catalyst
T
Timeb
(h)
Product ratioc
(°C)
4a:2a
1
2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
20
20
20
20
20
20
20
20
80
20
20
240
600
600
600
54:46
45:55
48:52
42:58
d
d,e
e
3
4
e
5
CH2Cl2 Rh2(OAc)4
0.3 44:56
e
6
CCl4
2160
168
22
45:55
70:30
70:30
7
CH3CNe
H
H
8
CH3CN Rh2(OAc)4
CH3CN Rh2(OAc)4
CH3CN PdCl2
3b
9
1.5 68:32
10
11
60
24
75:25
74:26
(PhSO2)2C IPh 52%
PhSO2
1a
DMSO
Rh2(OAc)4
H
H
H
a All reactions were carried out by stirring a suspension of the ylide
1a (1.0 equiv) and norbornene 3a (7.5 equiv) for the specified time.
b Time required for complete consumption of the ylide 1a.
c The product ratio was determined by 1H NMR-spectral analysis of
the crude reaction mixture, error 5% of the stated value.
d In the absence of light.
+
H
1 : 1
PhSO2
4d
4d'
H2, Pd/C (88%)
H
e Under an argon atmosphere.
The yield of indane 4a was improved when the more polar
solvent CH3CN was employed. The reaction time was
now shorter and the product ratio was 70:30 (entry 7). On
addition of catalytic amounts of Rh2(OAc)4 (0.1–0.2
mol%) in CH3CN, the reaction times were again much
shorter (entry 8); a similar improvement was achieved in
DMSO and with catalytic amounts of Rh2(OAc)4 (entry
11). Also at the elevated temperature of 80 °C (entry 9),
the reaction time was shortened considerably. The use of
catalytic amounts of PdCl2 as additive (entry 10) did not
significantly shorten the reaction times. When Cu(acac)2
or CuI was employed as additive, a rather complex reac-
tion mixture was obtained, in which the thiosulfonate was
the major product (data not shown in Table 1). Thus, the
optimal reaction conditions consist of CH3CN as solvent
and Rh2(OAc)4 as additive, since the reaction times are
shortest and the proportion of the indane 4 cycloadduct
H
PhSO2
5
Scheme 3
The cycloaddition of substrate 3a was conducted also with
the iodonium ylide 1b (entry 2), whose p-methyl substitu-
ent of the phenyl-sulfonyl group permitted the determina-
tion of the regioselectivity of the cycloaddition process in
regard to the substitution pattern in the benzo ring of the
indane product (see later). The reaction of the ylide 1b
with all norbornene derivatives was much faster and af-
forded the corresponding indane cycloadducts 4 in good
yields.
Synlett 2003, No. 8, 1165–1169 ISSN 1234-567-89 © Thieme Stuttgart · New York

LETTER
[3+2] Cycloaddition of Iodonium ylides
1167
Table 2 Cycloadditiona of Bis(arylsulfonyl)iodonium Ylides 1a,b with Norbornene Derivatives 3 to Afford the Functionalized Indanes 4
Entry
1
Ylide
Alkene
Time(h)b,c
Conversion(%)d
Product
Yield (%)e
H
1a
22
nd
64
H
PhSO2
3a
3a
4a
Me
H
2
3
1b
1a
240
84
nd
nd
30
52
H
p-TolSO2
4b
H
H
H
H
H
H
PhSO2
3b
4d,4d¢
H
O
O
H
H
4
5
1a
1b
2
22
24
61
58
O
CO2Me
CO2Me
H
H
4e
O
PhSO2
3c
H
O
Me
0.3
CO2Me
CO2Me
H
H
p-TolSO2
O
4f
4f
3c
Me
Me
Me
Me
H
O
6
1a
1.3
25
41
H
O
CO2Me
CO2Me
H
O
H
PhSO2
3d
4g
Me
Me
Me
Me
H
O
O
7
1b
0.5
23
45
Me
H
CO2Me
CO2Me
H
H
p-TolSO2
O
4h
3d
4h
a All reactions were carried out by stirring a suspension of ylide 1 (1 equiv) and alkenes 3 (excess) in CH3CN for the required time.
b Time required for complete consumption of the ylide.
c The reaction was carried out in the presence of a catalytic amount (0.1 mol%) of Rh2(OAc)4, except entry 2 (no additive, CH2Cl2).
d Conversion of the norbornene derivative 3, as determined after isolation by silica-gel chromatography.
e Yield of isolated product (relative to 100% consumption of the ylide) after silica gel chromatography.
This unusual cycloaddition of the bis(arylsulfonyl)-iodo- could not be directly purified by silica gel chromatogra-
nium ylide was extended to the norbornene anhydrides 3c, phy, they were converted to the respective diesters 4e, and
3d (entries 4–7), which gave the corresponding indane de- 4f and fully characterized. For the 7-methylenenor-
rivatives in high yields. Since these anhydride products bornene anhydride 3d (entries 6 and 7), again the ylides
Synlett 2003, No. 8, 1165–1169 ISSN 1234-567-89 © Thieme Stuttgart · New York

1168
W. Adam et al.
LETTER
1a and 1b reacted exclusively with the norbornene double
bond to give after esterification the diesters 4g (41%) and
4h (45%).
3e
The structural assignment of the indanes is exemplified
for the 4b derivative. The 1H NMR spectrum of the 4b cy-
cloadduct displays for the indane ring a doublet at d 4.31
ppm (J = 2.2 Hz for the proton at the C-1 position), a
doublet at d 2.76 ppm (J = 7.3 Hz for the proton at the
C-3 position), and a doublet of doublets at d 2.58 ppm
(J = 2.2 Hz and 7.3 Hz for the proton at the C-2 position).
The lack of a ROESY signal between the protons at the
C-1 and C-3 sites and the ROESY signal between the
protons at C-2 and C-3 positions indicate the trans/cis
configuration of the three substituents in the five-mem-
1a
r.t., 3d
15%
Rh2(OAc)4,
CH3CN
1. KOH, MeOH
2. Pb(OAc)4,
pyridine, ∆Τ
CO2Me
CO2Me
H
H
45%
H
H
PhSO2
PhSO2
4e
4c
Scheme 5
bered ring, as was previously established by X-ray analy- As for the mechanism of this remarkable cycloaddition of
sis of the cycloadduct 4a.3a Furthermore, HMBC signals iodonium ylide, a carbene route is unlikely.8 For example,
reveal that the methyl group of the aryl ring and the sulfo- under conditions that generate carbenes,3 such as catalysis
nyl-bearing C-1 position of the five-membered ring are lo- with copper complexes, the reaction of the ylide with nor-
cated meta to one another in the product,5 although bornene (1a) led to a complex reaction mixture. From the
originally this methyl substituent occupied the para posi- latter only the phenyl benzenethiosulfonate (PhSO2SPh),
tion in the para-toluenesulfonyl group of the iodonium the typical product derived from the bis(phenylsulfo-
ylide.
nyl)carbene,3,4,9 was isolated in moderate yield (ca. 40%).
Also a metal-carbenoid intermediate is unlikely to be in-
volved, since the bis(arylsulfonyl)iodonium ylide reacts
with the norbornene (1a) in the absence of metal catalysts
to afford the same indane products, but much longer reac-
tion times are required (Table 1, entry 1). The mechanism
should be analogous to the cycloaddition of the iodonium
ylide to stilbenes.5 The exo configuration is expected and
well documented for cycloadditions with norbornene,10
while the exclusive trans arrangement of the phenylsulfo-
nyl group with respect to the norbornene ring is in accord
with that found for the stilbenes.5
Clearly, these diverse examples of the norbornene deriva-
tives in Table 2 demonstrate that the scope of this remark-
able cycloaddition is broad for the indane synthesis. Since
the required iodonium ylide is readily accessible by con-
densation of bis(arylsulfonyl)methane with the commer-
cially available iodobenzene diacetate, this novel process
constitutes an attractive diastereoselective route for the
preparation of functionalized indanes, in which the three
adjacent stereocenters of the cyclopentane ring are gener-
ated in one step. Moreover, the arylsulfonyl functionality
may be readily removed reductively, as exemplarily illus-
trated for the cycloadduct 4a by treatment with sodium In summary, the work described herein provides a simple
amalgam to afford the indane 6 in 91% yield (Scheme 4). and efficient method for the direct diastereoselective syn-
thesis of functionalized indanes 3 through the cycloaddi-
tion of the bis(benzenesulfonyl)iodonium ylide with a
variety of norbornene derivatives 2. Therewith, complex
multicyclic ring skeletons of well defined configurations
become conveniently accessible.
H
H
H
Na(Hg)
91%
H
PhSO2
4a
6
Acknowledgment
Scheme 4
The authors thank the Deutsche Forschungsgemeinschaft and the
Fonds der Chemischen Industrie for generous funding. EPG also
thanks INTERREG II (Prof. Dr. M. Karayiannis, University of
Ioannina) and DAAD for research scholarships.
We mentioned already, that the reaction of iodonium ylide
1a with norbornadiene (3e) leads to a complex reaction
mixture after stirring at room temperature for 3 days, in
which b-disulfone 1a is the major product, whereas only
a small amount (15%) of the desired cycloadduct 4c was
obtained. Such a cycloadduct 4c could, however, be readi-
ly produced (Scheme 5) by the hydrolysis of the diester 4e
with hot KOH in MeOH, followed by decarboxylation7
with Pb(Oac)4 in hot pyridine (overall 45% yield).
References
(1) Koser, G. F. In The Chemistry of Functional Groups,
Supplement D; Wiley: New York, 1983, Chap. 18.
(2) (a) Varvoglis, A. The Organic Chemistry of
Polycoordinated Iodine; VCH Publishers: New York, 1992.
(b) Varvoglis, A. Hypervalent Iodine in Organic Synthesis;
Academic Press: London, 1997. (c) Moriarty, R. M.; Vaid,
R. K. Synthesis 1990, 431.
Synlett 2003, No. 8, 1165–1169 ISSN 1234-567-89 © Thieme Stuttgart · New York

LETTER
[3+2] Cycloaddition of Iodonium ylides
1169
(3) (a) Hadjiarapoglou, L.; Varvoglis, A.; Alcock, N. W.; Pike,
G. A. J. Chem. Soc., Perkin Trans. 1 1988, 2839.
(b) Hadjiarapoglou, L. P. PhD Thesis; Thessaloniki: Greece,
1987.
(4) Sander, W.; Strehl, A.; Winkler, M. Eur. J. Org. Chem.
2001, 3771.
7.28 (s, 1 H), 7.47 (d, J = 8.2 Hz, 2 H). 13C NMR (100 MHz,
CDCl3) : d = 21.2 (q), 21.6 (q), 28.1 (t), 29.0 (t), 32.8 (t), 42.7
(d), 53.3 (d), 76.1 (d), 124.1 (d), 126.6 (d), 129.2 (d), 129.3
(d), 130.4 (d), 134.0 (s), 135.7 (s), 136.5 (s), 144.3 (s), 145.3
(s). Anal. Calcd for C22H24O2S (352.5): C, 74.96; H, 6.86; S,
9.10. Found: C, 74.66; H, 6.85; S, 9.11.
(5) Adam, W.; Bosio, S. G.; Gogonas, E. P.; Hadjiarapoglou, L.
P. Synthesis 2002, 2084.
Synthesis of 5: To a solution of the indane derivative 4a
(118 mg, 0.36 mmol)in methanol (10 mL), was added in
portions Na2HPO4 (180 mg) and 6% sodium amalgam (1.50
g) and the resulting mixture was stirred at 20 °C for 48 h. The
solvent was evaporated (40 °C at 10 torr), the residue was
dissolved in dichloromethane (30 mL), and extracted with
brine (2 × 50 mL). The organic layer was dried over
magnesium sulfate, the solvent evaporated (20 °C at 10 torr),
and the residue was purified by silica gel chromatography
(CH2Cl2 as eluent) to yield 61 mg (91%) of the indane 5 as
colorless oil. IR (Neat): 2930 cm–1, 2850, 1475, 1450, 830.
1H NMR (400 MHz, CDCl3) : d = 0.98–1.02 (m, 1 H), 1.11–
1.15 (m, 1 H), 1.24–1.30 (m, 1 H), 1.37–1.43 (m, 1 H), 1.50–
1.65 (m, 2 H), 2.10 (d, J = 3.8 Hz, 1 H), 2.29 (d, J = 3.8 Hz,
1 H), 2.36–2.41 (m, 1 H), 2.61 (dd, J = 3.8 Hz, 17.2 Hz, 1 H),
3.14 (d, J = 7.8 Hz, 1 H), 3.26 (dd, J = 10.2 Hz, 17.2 Hz, 1
H), 7.10–7.20 (m, 4 H). 13C NMR (100 MHz, CDCl3) : d =
28.8 (t), 29.0 (t), 32.4 (t), 39.3 (t), 43.4 (d), 43.7 (d), 44.9 (d),
55.5 (d), 124.0 (d), 124.5 (d), 126.1 (d), 126.2 (d), 144.8 (s),
146.3 (s). HRMS (EI): Calcd for C14H16 184.1252 Found:
184.1252.
(6) Representative Experimental Procedure. Synthesis of 4a:
To a suspension of the ylide 1a (1.00 g, 2.0 mmol) and
norbonene 3a (1.40 g, 15.0 mmol) in acetonitrile (10 mL)
was added a catalytic amount (0.1 mol%) of Rh2(OAc)4 and
the mixture was stirred at 20 °C for 22 h until a clear solution
was produced. The solvent was evaporated (40 °C at 10 torr)
and the residue was chromatographed on silica gel (CH2Cl2
as eluent) to yield 419 mg (64%) of the indane derivative 4a;
colorless plates, mp 140–141 °C (lit.3 140–141 °C). IR
(KBr): 3050 cm–1, 2940, 2860, 1580, 1470, 1440, 1330,
1300, 1280, 1250, 1230, 1210, 1200, 1185, 1160, 1120,
1080, 1020, 990, 940, 910, 880, 870, 840, 820. 1H NMR
(250 MHz, CDCl3) : d = 0.82 (d, J = 10.4 Hz, 1 H), 0.93 (d,
J = 10.4 Hz, 1 H), 1.24–1.29 (m, 2 H), 1.48–1.52 (m, 2 H),
2.13 (s, 1 H), 2.62 (dd, J = 1.9 Hz, 7.3 Hz, 1 H), 2.78 (d, J =
7.3 Hz, 1 H), 4.38 (d, J = 1.9 Hz, 1 H), 7.04 (d, J = 7.3 Hz, 1
H), 7.15–7.29 (m, 2 H), 7.35–7.45 (m, 3 H), 7.51–7.59 (m, 3
H). 13C NMR (63 MHz, CDCl3) : d = 28.1 (t), 28.9 (t), 32.7
(t), 42.7 (d), 42.9 (d), 47.8 (d), 53.6 (d), 76.2 (d), 112.6 (s),
124.5 (d), 126.1 (d), 126.8 (d), 128.6 (d), 129.2 (d), 129.5
(d), 133.4 (d), 135.5 (s), 136.7 (d), 148.2 (s).
(7) (a) Cimarusti, C. M.; Wolinsky, J. J. Am. Chem. Soc. 1968,
90, 113. (b) Dauben, W. G.; Schallhorn, C. H.; Whalen, D.
L. J. Am. Chem. Soc. 1971, 93, 1446.
Synthesis of 4b: A suspension of the ylide 1b (1.0 g, 1.9
mmol)and norbonene 3a (2.0 g, 21.0 mmol) in
(8) (a) Moriarty, R. M.; Prakash, O.; Vaid, R. K.; Zhao, L. J. Am.
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(10) For a recent synthesis of similar indanes see: (a) Lautens,
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5981.
dichloromethane (10 mL) was stirred for 240 h until a clear
solution was produced. The solvent was evaporated (40 °C
at 10 torr) and the residue was chromatographed on silica gel
(CH2Cl2 as eluent) to yield 200 mg (30%) of the indane
derivative 4b; colorless plates, mp 181–182 °C. IR (KBr):
2955cm–1, 2920, 2860, 1590, 1490, 1450, 1305, 1285, 1250,
1220, 1210, 1200, 1190, 1175, 1150, 1130, 1120, 1085, 890,
855, 830, 820. 1H NMR (400 MHz, CDCl3) : d = 0.83 (d, J =
10.4 Hz, 1 H), 0.91–0.94 (m, 1 H), 1.19–1.30 (m, 2 H), 1.34–
1.57 (m, 2 H), 2.10 (dd, J = 3.0 Hz, 12.6 Hz, 2 H), 2.33 (s, 3
H), 2.39 (s, 3 H), 2.58 (dd, J = 2.2 Hz, 7.3 Hz, 1 H), 2.76 (d,
J = 7.3 Hz, 1 H), 4.31 (d, J = 2.2 Hz, 1 H), 6.94 (d, J = 7.7
Hz, 1 H), 7.09 (d, J = 7.7 Hz, 1 H), 7.20 (d, J = 8.2 Hz, 2 H),
Synlett 2003, No. 8, 1165–1169 ISSN 1234-567-89 © Thieme Stuttgart · New York