Organic Letters
Letter
slow. The reaction in 1.2 mmol scale also successfully gave the
desired product, with 3c isolated in good yield (84%).
A N-tethered 1,7-enyne was subjected to the reaction
conditions next, and the desired product 3-((silyl)methylene)-
piperidine 3i was obtained in 50% yield (Scheme 2).
Cyclopentane derivative 3j was obtained in 49% yield. The
replacement of sulfonamide with an oxygen atom was
compatible, giving the corresponding tetrahydrofurans 3k−
3m in good isolated yields (51−71%). Regarding the alkene of
the enynes, electron-deficient alkenes, such as cyclohexa-2,5-
dienone, containing enynes were subjected to the reaction
conditions and gave the corresponding products 3n−3p in
moderate isolated yields (43−48%).
hydrogen atom transfer being unsuccessful (see Supporting
In order to expand the heteroatom radical scope for this
approach of visible-light mediated synthesis of functionalized
heterocycles, we turned our attention to the phosphorus atom
radicals (Table 2). The replacement of the (TMS)3SiH by
Table 2. Reaction Condition Screening for the
a
Hydrophosphorylative Cyclization
1,6-Dienes for this hydrosilylative cyclization were tested
next, and terminal-alkene-containing dienes were subjected to
the above-mentioned reaction conditions. The corresponding
pyrrolidines 5a−5c (5c, CCDC 1954205) were obtained in
satisfactory yields (43−48%, Scheme 3).19 It should be
b
entry
catalyst loading
x
solvent
yield (%)
1
2
3
4
5
6
7
8
5.0%
5.0%
5.0%
1.0%
2.5%
5.0%
5.0%
5.0%
2.0
2.0
2.0
2.0
2.0
1.0
3.0
4.0
MeCN
THF
DCE
THF
THF
THF
THF
THF
48
58
35
37
49
47
83
Scheme 3. Visible-Light Mediated Hydrosilylative
Cyclization of 1,6-Dienes
c
92(63)
a
Reaction condition: 1a (0.1 mmol), 2a (x mmol), catalyst (5.0%
b
mmol), slovent (2 mL), under an argon atmosphere, 24−48 h. NMR
yield using of 1,3,5-trimethoxybenzene as internal standard. Isolated
c
yield of 9a. THF = tetrahydrofuran; DCE = 1,2-dichloroethane.
diarylphosphine oxide and dialkyl phosphonate were tested,
and to our great delight, when diphenylphosphine oxide was
subjected to the above-mentioned reaction conditions, the
hydrophosphorylative cyclization reactions were observed. The
optimization of reaction conditions was undertaken next, and
the best solvent was proven to be THF, giving the desired
product 9a (CCDC 1967925) in 63% isolated yield (entry 8,
Table 2). Compared with the NMR yield of 9a, the isolated
yield of 9a was much lower due to the loss of the product
during the chromatographic purification step on silica gel.
Under the optimal reaction conditions, the reaction scope
was investigated next. Different enynes were tested, giving the
desired 9a−9f in moderate isolated yields (40−63%, Scheme
5). Different diarylphosphine oxides, such as di-p-tolylphos-
phine oxide and bis(3,5-dimethylphenyl)phosphine oxide,
were subjected to the reaction conditions next, and the
desired products 5g and 5h were isolated in 57% and 48%
yields, respectively. A 1,6-diene also proved to be compatible,
yielding the desired product 9i in 57% yield.
a
Reaction conditions: 4 (0.3 mmol), 2 (1.2 mmol), Eosin Y (5.0 mol
%), MeCN (2 mL), under an argon atmosphere, 24−48 h, isolated
yield of 5a−5c.
mentioned that piperidine products were not observed,
which were found by Wang, Liang, and Yao and co-workers.16
It is due to the cascade reaction being initiated by the silicon
atom radical added to different positions of the alkenes.
The radical cyclization of benzene-tethered 1,6-enynes was
unsuccessful. When 6a and 6b were subjected to the reaction
conditions, no cyclic desired product was obtained (Scheme
4). Alternatively, the hydrosilylation products of 7a and 7b
were obtained in 84% and 71% isolated yield, respectively.
Regarding the silicon atom radical sources, other hydro-
silanes, such as triethylsilane, dimethyl(phenyl)silane, and
triphenylsilane, were tested, and all failed to give the desired
product. It is maybe due to the BDEs of the above-mentioned
hydro-silanes being high and the radical formation by the
It should be mentioned that only Z-isomers were observed
and isolated the hydrosilylative and hydrophosphorylative
cyclizations of the enynes. The high Z-selectivity of the
reaction can be explained by the steric effect, as the cyclization
of the Z radical of the I-1 intermediate occurred more readily
than the E form of I-1 to avoid steric repulsion from the gem-
alkyl groups of the alkene (Scheme 1).20
Scheme 4. Visible-Light Mediated Hydrosilylation of
Benzene-Tethered 1,6-Enynes
In conclusion, we have described a visible-light mediated
intermolecular radical cyclization approach to access hetero-
cycles. The direct hydrogen atom abstraction of the hydro-
silanes and phosphine oxides by the photoexcited catalyst
species allows the silicon and phosphorus atom radicals
generation and the radical addition/cyclization/HAT (hydro-
gen atom transfer) reaction sequence. 1,6-Enynes, 1,7-enynes,
C
Org. Lett. XXXX, XXX, XXX−XXX