H. Deleuze et al. / Bioorg. Med. Chem. Lett. 12 (2002) 1877–1880
1879
Table 1. Conversion and reaction conditions of radical reduction of 1
(PH-SH/1=0.05; T=70 ꢀC; 1 h)
Entry
Catalyst
Reducing
agent(equiv)
Yield
adamantane (%)
1
2
3
None
C12H25SH
PH-SH
Et3SiH (2)
Et3SiH (2)
Et3SiH (2)
0
100
70
Scheme 3. Radical reduction mechanism of 6-bromohex-1-ene 2.
Table 2. Conversion and reaction conditions of radical reduction of 2
by PH-SH/Et3SiH (PH-SH/2=0.05; T=70 ꢀC; 6 h)
Et3SiH/2
2
10
5
20
55
40
90
100
100
4
0
0
Yield (%)
6
Yield (%)
Unreacted 2 (%)
0
0
0
0
0
Scheme 4. Radical reduction mechanism of -1-allyloxy 2-bromo-
benzene 3.
100
95
45
10
the reductive cyclisation of 2 could be carried outot
completion in 6 h with a one hundred fold excess of
silane relatively to the bromide with PH-SH.
Table 1 summarises the relative and overall yield of
formed products resulting from the reduction of 1, using
various reducing agents and supported catalysts.
The possible use of a catalytic system, even with pri-
mary alkyl bromide, involving an organic reducer
totally soluble in the organic medium (triethylsilane)
and this selectivity are good arguments to select the
thiol/triethylsilane system instead of the tin one.20
Nevertheless, it is important to underline the necessary
use of a high ratio silane/thiol to perform the reduction
of bromide compounds possessing terminal vinyl group.
This could be a drawback when the required reaction
product has a boiling point close to triethylsilane. In
this case, the commercial availability of numerous
silanes would allow to circumvent this problem.
The observation of a relatively high conversion in one
hour proved the efficient regeneration of the hydrogen
transfer agent, the thiol, in the reaction of the inter-
mediate thiyl radical, with the reducing agent employed,
triethylsilane. The first hour conversion using the poly-
HIPE-supported reagent is lower than its solution phase
counterpart (entries 2 and 3). This could be due to
slower elementary reactions rates when one of the reac-
tive species is attached to the polyHIPE; this is certainly
caused by the diffusion of only the small molecules and
radicals towards the backbone of the supported
reagents.
The reductive cyclisation of 3 with the thiol-silane sys-
tem (PH-SH/Et3SiH/ 3=0.05/75/1) is quantitative in
6 h at70 ꢀC. These results confirmed the interest of the
thiol supported reagent over the tin one.
Once the efficiency of the supported hydrogen transfer
was proven, it appeared of interest to study the reduc-
tion of unsaturated bromides. Then, the reduction of 6-
bromohex 1-ene 2 and of 1-allyloxy 2-bromobenzene 3
was investigated using the polyHIPE. These free radical
reactions would produce two major compounds: the
products of reductive cyclisation (4 from 2, 5 from 3)
and the ones arising from the direct reductions (respec-
tively, 6 and 7) (Schemes 3 and 4).
In conclusion, this paper reports an example of appli-
cation in organic synthesis of the new kind of polymer
support, called polyHIPE, we are currently developing
in our group. These polyHIPEs are highly porous
materials easy to synthesise and functionalise which
could become an alternative to conventional resins in
Supported Organic Chemistry.
The treatments of 2 and 3 by triethysilane in the pre-
sence of PH-SH, under the same conditions as the
reduction of 1, did not lead to any of the expected
hydrocarbons 4 or 6 from 2 (about100% of 2 recovered
unchanged), meanwhile the cyclic ether 5 was formed
with a yield of 10% from 3 (90% unchanged) after 6 h.
As pointed out by Roberts,17 the possible addition of
the thiyl radical to the double bonds present in the
medium could be responsible of such an inefficient
reduction. The increase of the concentration of the
silane would allow to direct the reaction of the thiyl
radical towards the regeneration of the thiol by hydro-
gen abstraction to the silane and, then, to allow the free
radical chain reduction of the unsaturated bromide to
occur. The results summarised in Table 2 indicate that
References and Notes
1. Sherrington, D. C. J. Chem. Soc., Chem. Comm. 1998, 2275.
2. Sherrington, D. C. In Synthesis and Separations Using
Functional Polymers; Sherrington, D. C., Hodge, P., Eds.;
Wiley: New York, 1988.
3. Shutteworth, S. J.; Allin, S. M.; Sharma, P. K. Synthesis
1997, 1217.
4. Brown, A. R.; Hermkens, P. H. H.; Ottenheimj, H. C. J.;
Rees, D. C. Synlet 1998, 817.
5. Peters, E. C.; Svec, F.; Frechet, J. M. J. Adv. Mat. 1999, 11,
14.