Design of polyaromatic hydrocarbon-supported tin reagents: A new family of tin reagents easily removable from reaction mixtures

Article abstract of DOI:10.1021/jo049868o

We report in this paper the preparation and use of stannanes 11, 12a, and 12b, compounds whose 3-pyrenylpropyl side chain affinity for activated carbon simplifies tin removal and product isolation. Our pyrene-supported reagents can be used for radical reductions and cyclizations (11), radical and cationic allylations (12a), and Stille couplings (12b) in much the same way as tributyltin derivatives.

Full text of DOI:10.1021/jo049868o

Design of P olya r om a tic Hyd r oca r bon -Su p p or ted Tin Rea gen ts: A
New F a m ily of Tin Rea gen ts Ea sily Rem ova ble fr om Rea ction
Mixtu r es
Didier Stien*,†,‡ and St e´ phane Gastaldi*,§
CNRS-UPS 2561, 16 avenue Andr e´ Aron, 97300 Cayenne, French Guiana, France, LAPP-UMR 5810,
Universit e´ de Montpellier 2, 34095 Montpellier Cedex 5, France, and LCMO-UMR 6517, Universit e´
d’Aix-Marseille III, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
didier.stien@guyane.cnrs.fr; stephane.gastaldi@univ.u-3mrs.fr
Received J anuary 23, 2004
We report in this paper the preparation and use of stannanes 11, 12a , and 12b, compounds whose
3
-pyrenylpropyl side chain affinity for activated carbon simplifies tin removal and product isolation.
Our pyrene-supported reagents can be used for radical reductions and cyclizations (11), radical
and cationic allylations (12a ), and Stille couplings (12b) in much the same way as tributyltin
derivatives.
In tr od u ction
reactions require excesses of reagents on resin support
and up to 3-4 equiv of AIBN.
The usefulness of tin reagents in chemistry is broadly
acknowledged, and to date, most radical reactions are still
conducted using tin hydrides despite the problems of
separation, tin toxicity, and tin disposal. Indeed, radical
chemists have been addressing the problem of purifica-
tion of radical reaction mixtures for more than 10 years.
The methods using tin hydride substitutes such as
silanes or thiols, for example, as well as special workup
procedures allowing for removal of tin have been re-
viewed by Studer and Amrein recently.1
As for our concern, we prospected for alternative
soluble tin hydrides that might allow easy removal of tin
residues from reaction mixtures. Regarding liquid-phase
supported reagents, the innovation lies mostly with the
way reagent-derived side products are separated. A few
of these tin reagents designed with modified alkyl chains
1
4,15
have been reported previously. The methods of Breslow,
Gaston,16 Vedejs, Yoshida, and Collum all use the
17
18
19
1
4-16
side chain of a modified tin reagent as a water-,
acid-
1
7,18
19
,
or base-soluble handle for purification of reaction
The fashionable technique to overcome difficulties
associated with the removal of excess reagent and
reagent-derived side products in general is to use a
mixtures. Polar pyridylstannane described by Clive could
be easily separated by chromatography when radical
reduction led to nonpolar compounds,20 and the second
method of Clive uses a lipophilic tin hydride unstable
under basic and acidic conditions.21 Once decomposed, the
tin residues may be removed by extraction with water.
2
polymer-supported reagent. However, such supported
reagents are usually insoluble, and therefore, reactions
have to be performed under heterogeneous conditions.
Furthermore, although such tin reagents have been
2
2
23
The method of Bergbreiter and Enholm and the
method of Curran24 all attach the molecule of interest to
a solubility control device to remove the undesired
material from the reaction mixtures. In the former cases,
3
-13
synthesized and used with some success,
most of the
†
CNRS-UPS 2561 and Universit e´ de Montpellier 2.
Present address: CNRS-UPS 2561, Cayenne.
Universit e´ d’Aix-Marseille III.
‡
§
(
(
1) Studer, A.; Amreim, S. Synthesis 2002, 835-849.
(12) Chemin, A.; Deleuze, H.; Maillard, B. Eur. Polym. J . 1998, 34,
1395-1404.
2) Ley, S. V.; Baxendale, I. R.; Bream, R. N.; J ackson, P. S.; Leach,
A. G.; Longbottom, D. A.; Nesi, M.; Scott, J . S.; Storer, R. I.; Taylor, S.
J . J . Chem. Soc., Perkin Trans. 1 2000, 3815-4195. See pp 3896-
897 for a list of known polymer supported tin hydrides.
(13) Boussaguet, P.; Delmond, B.; Dumartin, G.; Pereyre, M.
Tetrahedron Lett. 2000, 41, 3377-3380.
3
1
2
(14) Light, J .; Breslow, R. Tetrahedron Lett. 1990, 31, 2957-2958.
(15) Light, J .; Breslow, R. Org. Synth. 1993, 72, 199-207.
(16) Han, X.; Hartmann, G. A.; Brazzale, A.; Gaston, R. D. Tetra-
hedron Lett. 2001, 42, 5837-5839.
(17) Vedejs, E.; Duncan, S. M.; Haight, A. R. J . Org. Chem. 1993,
58, 3046-3050.
(18) Suga, S.; Manabe, T.; Yoshida, J .-i. Chem. Commun. 1999,
1237-1238.
(19) Rai, R.; Collum, D. B. Tetrahedron Lett. 1994, 35, 6221-6224.
(20) Clive, D. L. J .; Yang, W. J . Org. Chem. 1995, 60, 2607-2609.
(21) Clive, D. L. J .; Wang, J . J . Org. Chem. 2002, 67, 1192-1198.
(22) Bergbreiter, D. E.; Walker, S. A. J . Org. Chem. 1989, 54, 5138-
5141.
(23) Enholm, E. J .; Schulte, J . P. Org. Lett. 1999, 1, 1275-1277.
(24) Curran, D. P.; Hadida, S.; Kim, S.-Y.; Luo, Z. J . Am. Chem.
Soc. 1999, 121, 6607-6615 and references therein. See also: http://
fluorous.com/tin.html.
(
3) Weinshenker, N. M.; Crosby, G. A.; Wong, J . Y. J . Org. Chem.
975, 40, 1966-1971.
4) Schumann, H.; Pachaly, B. Angew. Chem., Int. Ed. Engl. 1981,
0, 1043-1044.
5) Ueno, Y.; Chino, K.; Watanabe, M.; Moriya, O.; Okawara, M. J .
Am. Chem. Soc. 1982, 104, 5564-5566.
6) Gerick, U.; Gerlach, M.; Neumann, W. P.; Vieler, R.; Weintritt,
(
(
(
V. Synthesis 1990, 448-452.
(
(
(
7) Blanton, J . R.; Salley, J . M. J . Org. Chem. 1991, 56, 490-491.
8) Neumann, W. P.; Peterseim, M. Synlett 1992, 801-802.
9) Ruel, G.; The, N. K.; Dumartin, G.; Delmond, B.; Pereyre, M. J .
Organomet. Chem. 1993, 444, C18-C20.
10) Dumartin, G.; Ruel, G.; Kharboutli, J .; Delmond, B.; Connil,
M.-F.; J ousseaume, B.; Pereyre, M. Synlett 1994, 952-954.
11) Dumartin, G.; Pourcel, M.; Delmond, B.; Donard, O.; Pereyre,
M. Tetrahedron Lett. 1998, 39, 4663-4666.
(
(
1
0.1021/jo049868o CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/21/2004
4
464
J . Org. Chem. 2004, 69, 4464-4470

Design of Polyaromatic Hydrocarbon-Supported Tin Reagents
SCHEME 1 a
tin is linked to soluble polymeric supports that can
precipitate upon cooling or addition of organic cosolvents.
In the latter case, a fluorous phase soluble unit allows
for selective liquid-liquid extraction of the undesired
fluorous reagent derived side products from reaction
mixtures.
With the handle concept in mind, we sought a group
that would have a strong affinity for activated carbon,
strong enough to allow separation on demand.25 Such a
group should be soluble in organic solvents to allow for
immediate use of standard radical chemistry solution-
phase procedures. Herein, we describe our work on the
use of polyaromatic hydrocarbons (PAHs) as soluble
supports for tin reagents and demonstrate how undesired
side products can be efficiently removed from reaction
mixtures by simple treatment with activated carbon.
Resu lts a n d Discu ssion
a
Reagents and conditions: (a) tetrabutylammonium hydroxide,
At first, we concentrated our efforts on the use of
Ramage’s 17H-tetrabenzo[a,c,g,i]fluorenyl (Tbf) moiety as
a polyaromatic tag. Originally, the tetrabenzofluorenyl-
methyl oxycarbonyl group (Tbfmoc) was designed as an
Fmoc-related protecting group and its affinity for char-
dioxane; R-Br, dioxane, 95 °C (1a , 80%; 1b, 62%); (b) NaI (15
equiv), acetone, 50 °C, 12 h (98%, 1c/1b ) 9/1); (c) Bu2SnHCl,
AIBN, CH2Cl2; (d) Bu2SnHPh, Pd(OH)2/C; (e) Bu2SnHLi, THF.
SCHEME 2 a
coal has been used in the purification of peptides,
proteins, and oligonucleotides.2
6-29
Later on, Tbf was also
used as an anchor group for solution phase supported
organic synthesis, and this work was illustrated by the
preparation of the quinolone antibacterial ciprofloxacin.30
With regard to supported synthesis, the authors recom-
mended to choose a 10-carbon alkyl chain as a spacer
between the Tbf moiety and the substrate to limit any
steric effects which the bulky Tbf group may impart.
Preparation and alkylation of Tbf has been very well
described30 and can be easily reproduced. In the synthesis
of Tbf, two regioisomers may be obtained, one with an
endo double bond and the other one with an exo double
bond. The former is the kinetic isomer, and the latter is
the thermodynamic one. Rearrangement occurs sponta-
neously upon heating in the rotary evaporator, but both
isomers react in the same way and give the same product
in the alkylation reaction. 10-Bromodec-1-ene and 1,10-
dibromodecane were treated with Tbf carbanion. This
gave the desired products 1a and 1b, respectively, in good
yields. Unfortunately, many efforts to incorporate tin
starting from 1a or 1b remained unsuccessful (Scheme
a
Reagents and conditions: (a) Bu SnHPh (1.5 equiv), Pd(OH) /C
2
2
(17%); (b) TsCl, pyridine (88%); (c) Tbf/tetrabutylammonium
hydroxide, dioxane (46%); (d) I2, BuOH; NaBH4.
yltin hydride (Lautens’ procedure).32 Finally, halides
substitutions with Bu
2
SnHLi33 starting either from 1b
or 1c were also unsuccessful and led to decomposition
upon forcing conditions. Apparently, the presence of the
Tbf group on one side seems to preclude addition at the
other end of the alkyl chain, even with a 10-carbon
spacer. Even the Finkelstein reaction with NaI on 1b
proved unexpectedly slow and was not completed after
1
2 h at reflux in the presence of a large excess of salt. In
addition, attempted transformation of 1c into the related
alkyllithium with t-BuLi34 resulted in extensive decom-
position of the starting material. A new route to the
desired tin hydride was sought, which would not require
incorporation of tin after ω-alkylation with the Tbf
carbanion.
1
).
For example, attempted radical addition of Bu
2
SnHCl,
generated in situ by mixing an equimolar amount of
dibutyltin dihydride and dibutyltin dichloride, resulted
in no reaction, while we successfully accomplished this
transformation with simple alkenes (vide infra).31 Start-
ing material 1a was also recovered unchanged upon
attempted palladium-catalyzed addition of dibutylphen-
1
-Decen-10-ol was regioselectively hydrostannated with
the tin moiety placed at the terminus following Lautens’
procedure (Scheme 2).32 However, the yield of hydrostan-
nation was low and the purification was very tedious
2
when the reaction was conducted with Bu SnHPh. The
five-step route to the Tbf-supported tin hydride eventu-
ally led to the preparation of the desired compound 4 in
a very small amount and proved very difficult to scale-
up.
(
25) For a preliminary communication, see: Gastaldi, S.; Stien, D.
Tetrahedron Lett. 2002, 43, 4309-4311.
(
26) Ramage, R.; Raphy, G. Tetrahedron Lett. 1992, 33, 385-388.
(27) Brown, A. R.; Irving, S. L.; Ramage, R. Tetrahedron Lett. 1993,
3
7
1
4, 7129-7132.
28) Ramage, R.; Wahl, F. O. Tetrahedron Lett. 1993, 34, 7133-
136.
(
(32) Lautens, M.; Kumanovic, S.; Meyer, C. Angew. Chem., Int. Ed.
Engl. 1996, 35, 1329-1330.
(29) Brown, A. R.; Irving, S. L.; Ramage, R.; Raphy, G. Tetrahedron
995, 51, 11815-11830.
(
(33) Connil, M.-F.; J ousseaume, B.; Noiret, N.; Pereyre, M. Orga-
nometallics 1994, 13, 24-25.
30) Hay, A. M.; Hobbs-Dewitt, S.; MacDonald, A. A.; Ramage, R.
Synthesis 1999, 1979-1985.
(34) Bailey, W. F.; Punzalan, E. R. J . Org. Chem. 1990, 55, 5404-
5406.
(31) Neumann, W. P.; Pedain, J . Tetrahedron Lett. 1964, 2461-2465.
J . Org. Chem, Vol. 69, No. 13, 2004 4465

Stien and Gastaldib
SCHEME 3 a
SCHEME 4 a
a
Reagents and conditions: (a) Bu2SnHCl, AIBN, CH2Cl2;
NaBH3CN, t-BuOH, reflux (56%).
Owing to the difficulties associated with the prepara-
tion of a Tbf-supported tin hydride on large scale, we
sought other polyaromatic hydrocarbons with good af-
finity for activated carbon. We found that pyrene is
known to exhibit strong affinity for other large aromatic
a
Reagents and conditions: (a) (EtO)2(O)PCH2CO2Et/NaH (88%);
b) NaBH4/CoCl2 (94%); (c) LiAlH4 (96%); (d) PPh3/I2/imidazole
(
(77%); (e) methanesulfonyl chloride, NEt3 (85%); (f) Me Sn /MeLi
(quant from 8a, 73% from 8b); (g) I2/CHCl3 then NaBH4/MeOH
(67%).
6
2
3
5-37
systems such as carbon nanotubes
or activated
carbon.3
8,39
Besides, while our work was in progress,
Warmus and Da Silva’s report confirmed the good
potential of pyrene as a soluble support for the prepara-
carbon spacer)11 are not very stable over time and under
radical conditions. The choice of a three-carbon spacer
appeared to be the best balance between a good similarity
with tributyltin hydride, good stability, and the minimal
number of aliphatic carbons.
tion of a pyrene-supported scavenger reagent for elec-
trophiles.40 When we decided to start working with
pyrene, we first evaluated the relative affinity of alkyl-
pyrenes, alkylphenanthrenes and alkyl-Tbf for activated
carbon. It was found that alkylpyrenes were always
adsorbed faster and more efficiently than the correspond-
ing alkylphenanthrenes or alkyl-Tbf.
Stannane 6 can be prepared straightforwardly follow-
ing the route summarized in Scheme 3. Allylpyrenyl-
methyl ether 5 is readily available on large scale starting
from commercially available pyrenemethanol. It can be
regioselectively hydrostannated in the presence of dibu-
tyltin hydrochloride under radical conditions, and the
resulting trialkyltin chloride can be reduced in situ to
generate the desired tin hydride 6 in 56% unoptimized
yield over two steps.
We discovered that pyrene-supported tin hydride 6
successfully reduces alkyl halides under radical condi-
tions. Unfortunately, removal of the resulting tin halides
from crude reaction mixtures was not satisfactory. In-
deed, the workup with activated carbon (2 g of carbon
per mmol of tin) did not yield tin-free material, and we
observed that product recovery became complicated and
low yielding if much larger quantities of carbon were used
in reaction workup. Instead, we envisioned dropping the
relative proportion of aliphatic carbons in our supported
tin hydride.
Stannane 11 may be prepared in a straightforward
manner from commercially available pyrene carboxalde-
hyde 7 following the route summarized in Scheme 4.
Wittig-Horner olefination followed by reduction of the
4
3
double bond with NaBH
was obtained in two steps from 7 by reduction with
LiAlH and transformation of the resulting primary
alcohol with I /PPh . Alternatively, the alcohol was also
4
/CoCl
2
yielded ester 8. Iodide
9
4
2
3
transformed into its methanesulfonic ester; this route
was found more convenient on larger scale because the
mesylate can be purified by crystallization. Substitution
of the primary iodide or mesylate in 9 with trimethyl-
stannyllithium44 afforded tetraalkylstannane 10 in very
good yield. Treatment of 10 with exactly 1 equiv of I
2
replaces one methyl group selectively. The desired tin
hydride was finally obtained as a white solid after
reduction with sodium borohydride. Compound 11 is
reasonably stable since it was recovered unchanged after
several months at -15 °C (freezer).
Reagent 11 may be used for tin hydride mediated
radical reactions in much the same way as tributyltin
hydride. We have evaluated its performance in the
reduction of various alkyl halides, as exemplified in Table
1.
Therefore, stannane 11 was designed with the smallest
possible alkyl substituents on tin, i.e., methyl groups, and
with the shortest possible spacer between the tin and the
pyrene moiety. Aryltin hydrides (no spacer) are sensitive
and their reactivity is tempered by the delocalization of
Yields are comparable to those obtained with tributyl-
tin hydride mediated reactions, and workup with acti-
vated carbon is quite straightforward and afforded
essentially pure products in all cases (see the Experi-
4
1
1
tin-centered radical into the π-system, and arylmethyl-
mental Section). Indeed, integration of the H NMR
(
one-carbon spacer)42 or 2-arylethyltin hydrides (two-
spectra allowed us to evaluate the amount of residual
tin derivative which was found always to be below 2 mol
% and not even detectable in some samples (Table 1,
entries 1, 2, 5, and 6). Product of typical free radical
(
35) Chen, R. J .; Zhang, Y. G.; Wang, D.; Dai, H. J . Am. Chem. Soc.
001, 123, 3838.
36) G o´ mez, F. J .; Chen, R. J .; Wang, D.; Waymouth, R. M.; Dai, H.
Chem. Commun. 2003, 190-191.
37) Petrov, P.; Stassin, F.; Pagnoulle, C.; J e´ r oˆ me, R. Chem. Com-
2
(
(
(41) Neumann, W. P.; Hillg a¨ rtner, H.; Baines, K.; Dicke, R.; Vor-
spohl, K.; Kobs, U.; Nussbeutel, U. Tetrahedron 1989, 45, 951.
(42) Brix, B.; Clark, T. J . Org. Chem. 1988, 53, 3365.
(43) Leutenegger, U.; Madin, A.; Pfaltz, A. Angew. Chem., Int. Ed.
Engl. 1989, 28, 60-61.
mun. 2003, 2904-2905.
(
38) Katz, E. J . Electroanal. Chem. 1994, 365, 157.
(39) J aegfeldt, H.; Kuwana, T.; J ohansson, G. J . Am. Chem. Soc.
1
983, 105, 1805.
40) Warmus, J . S.; Da Silva, M. I. Org. Lett. 2000, 2, 1807-1809.
(
(44) Still, J . C. J . Am. Chem. Soc. 1977, 99, 4836-4838.
4
466 J . Org. Chem., Vol. 69, No. 13, 2004

Design of Polyaromatic Hydrocarbon-Supported Tin Reagents
SCHEME 5 a
TABLE 1. Attem p ted Ha lid es Red u ction w ith 11
a
Reagents and conditions: (a) I2, CDCl3; (b) allyl-MgBr, THF
(12a , 92% for two steps); (c) PhLi, THF (12b, 62% for two steps).
TABLE 2. Allyla tion s w ith 12a a n d Stille Cou p lin gs
w ith 12b
a
Standard procedure: 11 (1.2 equiv), AIBN, benzene, reflux.
b
Catalytic procedure: NaBH3CN, 11 (0.1 equiv), tBuOH, reflux.
c
Only traces (<2%) of uncylized product were detected from the
1
d
H NMR spectrum of the crude reaction mixture. Photochemical
e
initiation: 11, AIBN, benzene, hν, room temperature. Measured
by ICP-MS analysis.
reduction depicted in entry 4 was tested for tin pollution
using ICP-MS analysis. Before any further purification,
we obtained 0.31% of elemental tin in the sample
resulting from treatment with activated carbon. If tin
impurity is the pyrene-supported tin iodide, then the
relative proportion product/tin derivative is 168:1
(99.4:0.6). We can conclude from this measurement that
treatment with activated carbon is able to remove more
than 99% of tin byproducts.
Unfortunately, reagent recovery from activated carbon
is low-yielding.25 On the other hand, we were pleased to
discover that the use of a catalytic amount of 11 following
the procedure described by Stork successfully reduced
methyl 2-bromo-2-phenylacetate (entry 1).45 In addition,
attempted classical cyclizations of an aryl radical led to
the expected benzodihydrofuran in good yields (entries
Our success in the design and use of pyrene-supported
tin hydride 11 prompted us to investigate related tin
47
reagents such as allyltrialkyltin for use in radical, or
48
cationic allylations, or aryltrialkyltin for use in Stille
48
coupling. Such stannanes may be prepared straight-
forwardly from 10 by treatment with 1 equiv of iodine,
followed by trapping of the intermediate tin iodide with
the desired organometallic reagent (Scheme 5).
5
and 6). The photochemically activated cyclization
reaction was also successful (entry 6). Considering how
small the relative proportion of uncyclized product was
in these reactions, we wondered what might be the rate
constant of radical reduction with 11 as compared to that
with tributyltin hydride. Indeed, the same radical reac-
tion (entry 5) conducted with tributyltin hydride under
the same experimental conditions also led to the forma-
tion of cyclized product containing only trace amount of
allyl-phenyl ether. Although the very low relative propor-
tion of uncyclized product does not allow for accurate
measurement of the reduction rate of the aryl radical,
We were pleased to discover that radical and cationic
allylations with 12a give good yields in the desired
products (Table 2, entries 1-3) and, more importantly,
that these products could be purified by treatment with
activated carbon. It can be seen from Table 2 that the
palladium-catalyzed Stille couplings with aryl iodides
were also successful (entries 4-6). In all these reactions,
13
1
C NMR and H NMR indicated no contamination by
tin byproducts (<2 mol %). This observation was further
confirmed by ICP-MS analysis, which provided the same
very low values for tin pollution as that obtained for
radical reduction.
In conclusion, we have reported in this paper the
preparation and use of stannanes 11, 12a , and 12b,
compounds whose 3-pyrenylpropyl side chain simplifies
tin removal and product isolation. Although further
we hypothesized that the order of reactivity of Me
1 and Bu SnH with alkyl radicals is Me SnH < 11 <
Bu SnH. Therefore, since Me
about 0.4 times as fast as Bu
3
SnH,
1
3
3
3
3
3
SnH will react in general
SnH,46 we concluded that
the rate constant of reduction with 11 must be in most
cases within the same order of magnitude than that with
tributyltin hydride.
(
47) Rosenstein I. J . In Radicals in Organic Synthesis Vol.1; Renaud,
(
(
45) Stork, G.; Sher, P. M. J . Am. Chem. Soc. 1986, 108, 303-304.
46) Chatgilialoglu, C.; Newcomb, M. Adv. Organomet. Chem. 1999,
P. and Sibi, M. P., Eds.; Wiley -VCH: New York, 2001; pp 50-69.
(48) Marshall, J . A. in Organometallics in Synthesis A Manual;
Schlosser M., Ed.; J ohn Wiley & Sons: New York, 2002; pp 355-464.
9
9, 90-99.
J . Org. Chem, Vol. 69, No. 13, 2004 4467

Stien and Gastaldib
scribed in the literature (CAS Registry No.: 61098-94-0):51 1
purification may be compulsory if the radical reaction
product is meant for biological assays, the purification
method with activated carbon is very fast and efficient.
It gives satisfying results for organic chemistry purposes.
Our work provides a prototype for rendering a tin reagent
pyrene-supported and pyrene may now be regarded as a
viable alternative to reticulated polystyrene.
H
NMR (CDCl , 300 MHz) δ 2.10 (m, 2H), 3.42 (t, 2H, J ) 7.6),
.76 (t, 2H, J ) 6.3), 7.87 (d, 1H, J ) 7.9), 7.94-8.18 (m, 7H),
, 75.5 MHz) δ 30.4, 35.3,
3
3
8
6
1
.29 (d, 1H, J ) 9.4); 13C NMR (CDCl
3
3.1, 124.1, 125.6, 125.7, 125.7, 125.8, 125.9, 126.6, 127.4,
28.0, 128.1, 128.3, 129.5, 130.7, 131.7, 132.2, 137.0.
1
-(3-Iod op r op yl)p yr en e (9a ). Iodine (1.35 g, 5.32 mmol)
was added to a solution of PPh (1.395 g, 5.32 mmol) and
imidazole (362 mg, 5.32 mmol) in dichloromethane (8 mL) at
°C. After 20 min stirring, 3-pyren-1-ylpropan-1-ol (1 g, 3.8
3
0
Exp er im en ta l Section
mmol) dissolved in dichloromethane (5 mL) was added. The
resulting solution was stirred for 3 h at room temperature,
diluted with water, washed successively with a 1 N aqueous
1H NMR spectra were recorded at 200 or 300 MHz and 13
C
NMR spectra at 75.5 or 100.6 MHz as indicated. Chemical
shifts (δ) are in ppm downfield from tetramethylsilane, and
coupling constants (J ) are in Hz (s stands for singlet, d for
doublet, t for triplet, q for quadruplet, quint for quintuplet,
and m for multiplet). Satellite signals in NMR refer to
2 2 3 4
Na S O solution and brine, and then dried with MgSO . The
solvent was removed in vacuo, and the crude material was
subjected to column chromatography on silica gel (pentane/
1
dichloromethane, 95:5) to give 9a (1.09 g, 77% yield): H NMR
1
17
119
(CDCl
3
, 300 MHz) δ 2.37 (quint, 2H, J ) 7.2), 3.35 (t, 2H, J )
distinguishable signals obtained for
Sn and
Sn (spin )
1
7.2), 3.45 (t, 2H, J ) 7.2), 7.90 (d, 1H, J ) 7.9), 7.94-8.20 (m,
/
2
), the natural abundance of which is 7.7 and 8.6%, respec-
7
3
1
H), 8.29 (d, 1H, J ) 9.4); 13C NMR (CDCl
, 75.5 MHz) δ 7.6,
3
tively. All solvents were dried and distilled by standard
techniques. Activated carbon was purchased from Aldrich
4.7, 35.9, 123.9, 125.6, 125.7, 125.8, 125.9, 125.9, 126.7, 127.6,
28.2, 128.3, 129.5, 130.9, 131.7, 132.2, 135.4;. MS (FAB+,
(Darco KB-B, 27,810-6).
+
+
NBA matrix) m/z 370 (M , 100), 215 (PyreneCH
2
, 75);. HRMS
3
-P yr en -1-ylp r op ion ic Acid Eth yl Ester (8). Sodium
+
+
calcd for C19
H I (M ) 370.0219, found 370.0231.
15
hydride (0.15 mol) was added portionwise to a solution of
triethylphosphonoacetate (28.5 g, 0.127 mol) in THF (300 mL)
at 0 °C. The mixture was stirred for 1 h at 0 °C. 1-Pyrenecar-
boxaldehyde (20.93 g, 0.091 mol) in THF (150 mL) was slowly
added. The resulting solution was stirred for one night at room
temperature. The mixture was diluted with a 10% HCl
solution, extracted three times with toluene, washed with
Meth a n esu lfon ic Acid 3-P yr en -1-ylp r op yl Ester (9b).
To a solution of 3-pyren-1-ylpropan-1-ol (7.0 g, 26.6 mmol) and
triethylamine (3.54 g, 34.9 mmol) in dichloromethane (100 mL)
at -10 °C was added methanesulfonyl chloride (3.69 g, 32.2
mmol). The reaction mixture was allowed to warm slowly to
room temperature and was then diluted with water, washed
with 1 N aqueous HCl and brine, and dried with MgSO
4
. Pure
water, dried (MgSO
-ylacrylic acid ethyl ester (22.3 g, 81% yield) precipitated upon
4
), and concentrated. The desired 3-pyren-
9
b (7.62 g, 85% yield) solidified by trituration of the crude
1
1
residue with MeOH: H NMR (CDCl
2
3
, 300 MHz) δ 2.32 (m,
trituration of the crude mixture in MeOH. Spectral data were
identical to those previously described in the literature (CAS
H), 3.50 (t, 2H, J ) 7.4), 4.32 (t, 2H, J ) 6.2), 7.87 (d, 1H, J
1
3
4
9 1
) 7.9), 7.96-8.19 (m, 7H), 8.25 (d, 1H, J ) 9.3); C NMR
CDCl , 75.5 MHz) δ 29.6, 31.3, 37.8, 69.7, 123.3, 125.3, 123.3,
25.5, 126.4, 127.3, 127.7, 127.9, 128.1, 129.1, 130.6, 131.2,
Registry No.: 82979-68-8): H NMR (CDCl
(
3
, 300 MHz) δ 1.41
(
1
3
t, 3H, J ) 7.2), 4.36 (q, 2H, J ) 7.2), 7.70 (d, 1H, J ) 15.7),
8
.20-8.30 (m, 8H), 8.47 (d, 1H, J ) 9.3), 8.81 (d, 1H, J ) 15.7);
1
3
131.8, 134.8.
C NMR (CDCl , 75.5 MHz) δ 14.8, 61.0, 120.7, 122.9, 124.2,
3
Tr im eth yl(3-p yr en -1-ylp r op yl)sta n n a n e (10). Methyl-
lithium (9.4 mL, 15 mmol) was added dropwise to a solution
of hexamethylditin (3.11 mL, 15 mmol) in dry and degassed
THF (30 mL) at -40 °C. The reaction mixture was allowed to
warm slowly to -20 °C (45 min) and was then cooled to -80
1
1
24.6, 125.0, 125.3, 125.4, 126.2, 126.4, 126.7, 127.7, 128.7,
28.9, 130.1, 131.1, 131.7, 133.0, 167.5.
Sodium borohydride (5.6 g, 0.148 mol) was added to a
solution of the R,â-unsaturated ester (22.26 g, 0.074 mol) and
cobalt chloride hexahydrate (5.87 g, 0.024 mol) dissolved in a
mixture of MeOH and THF 7/4 (550 mL). The solution was
stirred for 48 h at room temperature. After concentration, the
residue was diluted with a 1 N aqueous HCl, and the aqueous
layer was extracted three times with toluene. The combined
°
C. The iodide (3.72 g, 10 mmol) was added in one portion,
and the reaction mixture was allowed to warm to room
temperature overnight. Alumina was added, the solvent was
evaporated, and the desired product 10 was obtained after
alumina column chromatography (hexane) (4.08 g, quant).
Alternatively, we found accidentally that nice crystals may be
obtained from recrystallization in hexane (reflux to -20 °C).
The same procedure applied to 9b (3.70 g, 10.9 mmol) instead
4
organic fractions were washed with water, dried (MgSO ), and
concentrated. Compound 8 (21.47 g, 96% yield) was precipi-
tated by trituration of the crude residue in MeOH. Spectral
data were identical to those previously described in the
5
0 1
of 9a also yielded the desired tetraalkylstannane (3.25 g, 73%
3
literature (CAS Registry No.: 83671-44-7): H NMR (CDCl ,
1
yield): H NMR (CDCl
3
, 300 MHz) δ 0.10 (s, 9H) (satellite
3
2
8
00 MHz) δ 1.36 (t, 3H, J ) 7.2), 2.82 (t, 2H, J ) 7.7), 3.68 (t,
H, J ) 7.7), 4.25 (q, 2H, J ) 7.2), 7.86 (d, 1H, J ) 7.9), 7.95-
.28 (m, 7H), 8.27 (d, 1H, J ) 9.3); 13C NMR (CDCl
, 75.5 MHz)
2
2
signals: (d, J H-Sn ) 51), (d, J H-Sn ) 52)), 1.00 (m, 2H), 2.05
(m, 2H), 3.35 (pseudo t, 2H, J ) 7.7), 7.87 (d, 1H, J ) 7.7),
3
8
8
.01 (t, 1H, J ) 7.7), 8.03 (AB spectrum, 2H, J ) 8.9), 8.08-
13
δ 15.0, 29.5, 37.0, 61.4, 123.7, 125.6, 125.7, 125.8, 125.9, 126.7,
1
1
3
.18 (m, 4H), 8.29 (d, 1H, J ) 9.5); C NMR (CDCl , 75.5 MHz)
27.6, 127.8, 128.3, 128.4, 129.4, 130.9, 131.6, 132.2, 135.4,
73.8.
1
1
δ -9.4 (satellite signals: (d, J C-Sn ) 321), (d, J C-Sn ) 307)),
1
C-Sn ) 356), (d, 1
1
3
(
2.1 (satellite signals: (d,
J
J C-Sn ) 341)),
3
-P yr en -1-ylp r op a n -1-ol. To a solution of ester 8 (21.47
3
0.2 (satellite signals: (d, J C-Sn ) 18), 38.9 (satellite signals:
g, 0.071 mol) in THF (200 mL) was added AlLiH (3.76 g, 0.099
4
2
d, J C-Sn ) 63), 124.3, 125.4, 125.5, 125.6, 125.9, 126.6, 127.3,
mol). The solution was stirred for 4 h at room temperature.
After dilution with toluene, the reaction mixture was carefully
hydrolyzed with 1 N aqueous HCl. The aqueous phase was
extracted twice with toluene, and the combined organic layers
were washed with brine and dried (MgSO ). The solution was
4
concentrated to give the desired primary alcohol (18.49 g, 100%
yield). Spectral data were identical to those previously de-
1
(
3
27.9, 128.2, 128.3, 129.4, 130.5, 131.7, 132.3, 137.7; MS
+
FAB+, NBA matrix) m/z 408 (M , 2.3, tin isotopic pattern),
93 and 391 (Pyrene(CH
+
2 3 2
) SnMe , 67 and 52%, respectively,
+
tin isotopic pattern), 215 (PyreneCH
2
, 100); HRMS calcd for
24 Sn (M ) 408.0904, found 408.0913.
Dim eth yliod o(3-p yr en -1-ylp r op yl)sta n n a n e. Iodine (405
mg, 1.6 mmol) was added in one portion at 0 °C to a solution
of 10 (650 mg, 1.6 mmol) in CHCl (10 mL). The reaction
1
20
+
+
22
C H
3
(
49) Sinistera, J . V.; Mouloungui, Z.; Delmas, M.; Gasset, A.
Synthesis 1985, 1097-1100.
50) Hayashi, K.; Maruyama, T.; Yachi, T.; Kudo, K.; Ichimura, K.
J . Chem. Soc., Perkin Trans. 2 1998, 981-987.
(
(51) Yang, N.-C. C.; Minsek, D. W.; J ohnson, D. G.; Larson, J . R.;
Petrich, J . W. Tetrahedron 1989, 45, 4669-4682.
4
468 J . Org. Chem., Vol. 69, No. 13, 2004

Design of Polyaromatic Hydrocarbon-Supported Tin Reagents
mixture was allowed to warm slowly to room temperature
overnight. After evaporation of the solvent, H NMR showed
that the expected product was formed in nearly quantitative
yield. The tin iodide was pure enough and was therefore used
7.98-8.06 (m, 4H), 8.29 (d, 1H, J ) 9.3); 13C NMR (C
6
D
6
, 75.5
1
1
1
MHz) δ -11.3 (satellite signals: (d, J C-Sn ) 310), (d, J C-Sn
)
)
)
297)), 10.9 (satellite signals: (d, 1
J
J
C-Sn ) 330), (d,
C-Sn ) 283), (d,
1
J
J
C-Sn
1
1
345)), 17.6 (satellite signals: (d,
C-Sn
1
3
without further purification: H NMR (CDCl
(
1
3
, 300 MHz) δ 0.85
271)), 29.7 (satellite signals: (d, J C-Sn ) 19)), 38.5 (satellite
2
2
2
2
s, 6H) (satellite signals: (d, J H-Sn ) 54), (d, J H-Sn ) 52)),
signals: (d, J C-Sn ) 61)), 110.2 (satellite signals: (d, J C-Sn )
.57 (m, 2H), 2.20 (m, 2H), 3.42 (pseudo t, 2H, J ) 7.6), 7.87
49)), 123.9, 125.2, 125.3, 125.4, 125.9, 126.0, 126.2, 127.1,
127.7, 127.8, 128.0, 129.4, 130.5, 131.6, 132.1, 137.0, 137.8;
(
(
-
(
d, 1H, J ) 7.9), 7.99 (t, 1H, J ) 7.6), 8.03 (s, 2H), 8.09-8.19
13
+
m, 4H), 8.28 (d, 1H, J ) 9.3); C NMR (CDCl
3
, 75.5 MHz) δ
MS (FAB+, NBA matrix) m/z 435 (MH , 2.3, tin isotopic
1
1
+
1.5 (satellite signals: (d, J C-Sn ) 322), (d, J C-Sn ) 307)), 18.3
pattern), 393 (Pyrene(CH
2
)
3
SnMe
2
, 100, tin isotopic pattern),
1
1
+
120
+
+
satellite signals: (d,
J
C-Sn ) 368),(d,
J
C-Sn ) 351)), 29.8
215 (PyreneCH
435.1135, found 435.1138.
2
, 55%); HRMS: calcd for C24H27 Sn (MH )
3
(
satellite signals: (d, J C-Sn ) 24)), 37.7 (satellite signals: (d,
2
J
C-Sn ) 75)), 124.2, 125.6, 125.7, 125.8, 125.8, 125.9, 126.7,
Gen er a l P r oced u r e for Ra d ica l Allyla tion (Ta ble 2,
En tr ies 1 a n d 2). Under inert atmosphere, a solution of
substrate (0.2 mmol), 12a (2 equiv), and AIBN (0.1 equiv) in
dry degassed benzene (200 µL) was stirred under reflux for 5
h (after 2 h, an additional portion of AIBN (0.1 equiv) was
added). The mixture was cooled and evaporated. Methanol/
dichloromethane 3/2 (4 mL) was added to the residue im-
mediately followed by activated carbon (800 mg). The suspen-
sion was stirred for 30 min (the adsorption of pyrene derivatives
was monitored by UV spectroscopy). After filtration, the
activated carbon was washed with MeOH and the combined
filtrates were evaporated, allowing isolation of the radical
reaction product in pure form.
1
27.6, 128.2, 128.3, 129.5, 130.8, 131.7, 132.3, 137.6; HRMS
1
20
+
+
calcd for C21
H
21
I
Sn (M ) 519.9714, found 519.9717.
Dim eth yl(3-p yr en -1-ylp r op yl)sta n n a n e (11). The crude
iodide (1.6 mmol) was dissolved in methanol (40 mL) and
placed under argon at 0 °C. Sodium borohydride (61 mg, 1.6
mmol) was added, and after 30 min, the reaction mixture was
dissolved in EtOAc (40 mL) and water (20 mL). The aqueous
layer was discarded, and the organic phase was further washed
three times with water and dried (MgSO
removed in vacuo, and the crude material was subjected to
flash column chromatography on neutral Al (pentane) to
, 300 MHz) δ 0.20 (s,
4
). The solvent was
2
O
3
1
6 6
give 11 (420 mg, 67%): H NMR (C D
6
(
1
2
2
H) (satellite signals: (d, J H-Sn ) 57), (d, J H-Sn ) 53)), 1.02
m, 2H), 2.08 (m, 2H), 3.29 (t, 2H, J ) 7.4), 4.98 (broad. s,
H), 7.81 (d, 1H, J ) 7.9), 7.86 (t, 1H, J ) 7.4), 7.92 (AB
spectrum, 2H, J ) 9.1), 7.98-8.08 (m, 4H), 8.29 (d, 1H, J )
Gen er a l P r oced u r e for Electr op h ilic Allyla tion . Under
inert atmosphere, a solution of substrate (0.1 mmol) and 12a
(2 equiv) in dry dichloromethane (2 mL) under argon was
cooled to -78 °C. Boron trifluoride etherate (1 equiv) was
added dropwise. The reaction mixture was allowed to warm
to room temperature overnight. After dilution with an aqueous
solution of sodium carbonate, the reaction was extracted twice
with dichloromethane, and the combined organic fractions
1
3
9
6 6
.3); C NMR (C D , 75.5 MHz) δ -12.0 (satellite signals: (d,
1
1
J
C-Sn ) 326), (d, J C-Sn ) 318)), 10.2 (satellite signals: (d,
1
3
C-Sn ) 376),(d, 1J C-Sn ) 359)), 30.6 (satellite signals: (d,
J
J
2
C-Sn ) 20)), 38.6 (satellite signals: (d, J C-Sn ) 58)), 124.3,
1
1
3
25.6, 125.7, 125.8, 126.3, 126.4, 126.6, 127.5, 128.1, 128.5,
4
were washed with brine and dried (MgSO ). After concentra-
29.8, 130.9, 132.0, 132.5, 137.3; MS (FAB+, NBA matrix) m/z
tion, methanol/dichloromethane 3/2 (4 mL) was added to the
residue immediately followed by activated carbon (800 mg).
The suspension was stirred for 30 min (the adsorption of
pyrene derivatives was monitored by UV spectroscopy). After
filtration, the activated carbon was washed with MeOH and
the combined filtrates were evaporated, allowing isolation of
the allylation reaction product in pure form.
Dim eth ylp h en yl(3-p yr en -1-ylp r op yl)sta n n a n e (12b).
Iodine (203 mg, 0.8 mmol) was added in one portion to a 0 °C
cooled solution of trimethylstannane (326 mg, 0.8 mmol) in
+
93 ([M - H] , 56, tin isotopic pattern), 379 and 377 (Pyrene-
+
(CH
2
)
3
SnMeH , 25 and 16, respectively, tin isotopic pattern),
+
120
+
2
15 (PyreneCH , 100); HRMS calcd for C21H21 Sn ([M -
2
+
H] ) 393.0669, found 393.0651.
Gen er a l P r oced u r e for R a d ica l R ed u ct ion (11 St oi-
ch iom etr ic/AIBN/Ben zen e). Under inert atmosphere, a
solution of substrate (0.2 mmol), 11 (1.2 equiv), and AIBN (0.1
equiv) in dry degassed benzene (1-2 mL) was stirred under
reflux for 1 h (TLC monitoring). The mixture was cooled and
evaporated. Methanol/dichloromethane 3/2 (4 mL) was added
to the residue immediately followed by activated carbon (800
mg). The suspension was stirred for 30 min (the adsorption of
pyrene derivatives was monitored by UV spectroscopy of the
supernatant). After filtration, the activated carbon was washed
with MeOH and the combined filtrates were evaporated,
allowing isolation of the radical reaction product in essentially
pure form.
3
CDCl (10 mL). The reaction mixture was allowed to warm
1
slowly to room temperature overnight. H NMR showed that
the expected iodide was formed in nearly quantitative yield.
CDCl
dry and degassed THF (4 mL), and the solution was cooled to
80 °C. A PhLi solution (prepared by adding BuLi (1.4 M, 1.15
3
was evaporated, the crude tin iodide was dissolved in
-
mL, 1.6 mmol) over PhI (179 µL, 1.6 mmol) in THF (2.5 mL)
at -80 °C and stirring for 30 min) was added dropwise to the
tin iodide solution. The reaction mixture was allowed to warm
to room temperature overnight, neutral alumina was added,
and the THF was evaporated. Column chromatography over
neutral alumina (hexane) allowed isolation of the desired
Allyld im eth yl(3-p yr en -1-yl-p r op yl)sta n n a n e (12a ). In-
termediate tin iodide (dimethyliodo(3-pyren-1-ylpropyl)stan-
nane) was prepared prior to being needed in the same way as
described for the synthesis of tin hydride 11. Crude tin iodide
1
(2.39 mmol) was dissolved in dry degassed THF (10 mL), and
product 12b as a viscous colorless oil (233 mg, 62%): H NMR
2
the solution was placed under argon at -78 °C. Allylmagne-
sium bromide (4.78 mL of a 1.0 M solution in diethyl ether,
(CDCl
3
, 200 MHz) δ 0.48 (s, 6H) (satellite signals: (d, J H-Sn
2
) 53), (d, J H-Sn ) 51)), 1.29 (m, 2H), 2.16 (m, 2H), 3.40 (broad
t, 2H, J ) 7.7), 7.35-7.46 (m, 3H), 7.51-7.60 (m, 2H), 7.87 (d,
1H, J ) 7.8), 8.07 (s, 2H), 7.99-8.28 (superimposed m, 6H);
4
.78 mmol) was added dropwise. The reaction mixture was
allowed to warm to room temperature overnight. After dilution
with toluene, the reaction mixture was hydrolyzed with water
and extracted twice with toluene. The combined organic
1
1
1
3
3
C NMR (CDCl
C-Sn ) 334), (d,
C-Sn ) 368), (d, 1
3
, 100.6 MHz) δ -10.2 (satellite signals: (d,
1
J
J
J
J
J
C-Sn ) 320)), 11.8 (satellite signals: (d,
fractions were washed with brine and dried (MgSO
solvent was removed in vacuo, and the crude material was
subjected to flash column chromatography on neutral Al
4
). The
C-Sn ) 351)), 29.6 (satellite signals: (d,
2
C-Sn ) 19)), 38.4 (satellite signals: (d, J C-Sn ) 62)), 123.9,
2
O
3
125.0, 125.1, 125.2, 125.5, 126.2, 126.9, 127.5, 127.8, 127.9,
128.6, 128.7, 129.1, 130.2, 131.3, 131.9, 136.5 (satellite sig-
1
(
6 6
pentane) to give 12a (950 mg, 92%): H NMR (C D , 300 MHz)
2
2
2
δ 0.15 (s, 6H) (satellite signals: (d, J H-Sn ) 49), (d, J H-Sn
1)), 1.00 (m, 2H), 1.80 (d, 2H, J ) 8.6), 2.07 (m, 2H), 3.29
pseudo t, 2H, J ) 7.6), 4.84 (bd, 1H, J ) 10.0), 4.97 (bd, 1H,
J ) 10.0), 6.00 (ddt, 1H, J ) 17.0, 10.0, 8.6), 7.82 (d, 1H, J )
.7), 7.85 (t, 1H, J ) 7.6), 7.90 (AB spectrum, 2H, J ) 9.0),
)
nals: (d, J C-Sn ) 34), 137.1, 142.2; MS (FAB+, NBA matrix)
m/z 470 (C27
and 453 (C26
isotopic pattern of tin (M - CH
50, and C21
1
20
+
+
5
(
H26 Sn (M ), 10, isotopic pattern of tin), 455
1
20
118
H
23 Sn, 55, and C26
H
23 Sn, 45, respectively,
+
120
3
)), 393 and 391 (C21
H
20 Sn,
1
18
7
H
20 Sn, 38, respectively, isotopic pattern of tin
J . Org. Chem, Vol. 69, No. 13, 2004 4469

Stien and Gastaldib
120
10118Sn,
(
6
(
4
M+ - Ph), 227 and 225 (C
8
H
10 Sn, 100, and C
8
H
Cl
2
(3/2, 1 mL) and treated with activated carbon (200 mg).
+
8, respectively, isotopic pattern of tin (M - [pyrene-
After 30 min, charcoal was removed by filtration over Celite
and was washed with MeOH. Evaporation gave the desired
product tin-free, but still containing high-boiling tributyl-
amine, which could be easily removed by chromatography.
1
20
+
CH
2
)
3
])); HRMS calcd for C27
70.1052.
Gen er a l P r oced u r e for Stille Cou p lin gs (Ta ble 2,
H27 Sn (MH ) 470.1056, found
En tr ies 4-6). A mixture of stannane 12b (1.5 equiv) and aryl
iodide (50 µmol) was thoroughly degassed by repeated vacuum/
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
nitrogen cycles. Methanol-d
4
(6 equiv), tributylamine (2 equiv),
1
13
cedures and spectral data ( H NMR, C NMR and HRMS) for
compounds 1a -c, 2, 3, 5, and 6 and all compounds described
in Tables 1 and 2. This material is available free of charge via
the Internet at http://pubs.acs.org.
and PdCl (dppf) (0.1 equiv) were then successively added, and
2
the reaction mixture was sealed and heated at 60 °C for 12 h.
At the end of the reaction, 1H NMR of the crude mixture
(CDCl
3
) showed complete disappearance of the starting mate-
rial. The crude reaction mixture was diluted with MeOH/CH
2
-
J O049868O
4
470 J . Org. Chem., Vol. 69, No. 13, 2004