Organic Letters
Letter
9
e
the potential reactivity of sulfinates as electron donors. It is
worth noting that, as one of the versatile building blocks and
classical isosteres, sulfones possess the ability to participate in a
variety of chemical processes and to alter the biological activity
Scheme 2. Substrate Scope of Sulfinate in This
Photoinduced Transformation
a
11
in a myriad of pharmaceuticals. As such, development of
effective sulfonation methodologies is also a cornerstone of
1
2
medicinal and organic areas. Considering the inherent
electronic properties of α-trifluoromethylstyrenes and sulfi-
nates, we initially wondered whether the electronic features of
α-trifluoromethylstyrenes and sulfinates could be internally
matched up to form the corresponding EDA complex. Given
7b,13
our long-standing interest in fluoro- and photochemistry,
we herein disclose a catalyst-free strategy for sulfonation of α-
trifluoromethylstyrenes, enabling the assembly of densely
functionalized α-trifluoromethyl tertiary alcohols (Scheme 1b).
To validate our hypothesis, we started using 4-(3,3,3-
trifluoroprop-1-en-2-yl)-1,1′-biphenyl (1a) and sodium benze-
nesulfinate as model substrates to test the reaction (Table 1;
a
Table 1. Optimization of the Reaction Conditions
b
entry
variation from the standard conditions
yield (%)
c
1
2
3
4
5
6
7
8
9
−
86 (62 )
63
under air
under O2
nr for 1a
DMF (without purification) instead of DMF/H O
DMF/H O (1/1) instead of DMF/H O (3/1), air
MeCN instead of DMF/H O, air
DMSO instead of DMF/H O, air
purple LEDs instead of blue LEDs
green LEDs instead of blue LEDs
no light
47
52
nr
32
15
nr
nr
2
2
2
a
Standard conditions: 1a (0.2 mmol, 1.0 equiv), 2 (0.6 mmol, 3.0
2
equiv), DMF/H O (2 mL, 3/1, v/v), 10 W blue LEDs, Ar (trace air),
2
2
b
rt, isolated yield. DMF/D O (2 mL, 3/1, v/v) as the solvent. The
2
1
deuterated ratio determined by H NMR analysis is given in
parentheses.
1
0
a
Standard conditions: 1a (0.2 mmol, 1.0 equiv), 2a (0.6 mmol, 3.0
equiv), DMF/H O (2 mL, 3/1, v/v), 10 W blue LEDs, Ar (trace air),
rt, 60 h. Isolated yield. On a 3 mmol scale of 1a.
2
tolerated. It was found that the substrate with substituents at
the para position of sulfinic groups usually gave yields higher
than those of ortho- or meta-substituted substrates, which
might be attributed to steric hindrance. The presence of an
electron-withdrawing group generally gave superior results.
Both 1- and 2-naphthylsulfinic acid sodium also tolerated the
reaction conditions, albeit with lower chemical yields (3k and
3l, respectively). Pleasingly, heterocyclic substrates, including
thiophene and pyridine, also underwent this reaction with
moderate yields (3m and 3n, respectively). Meanwhile,
aliphatic sulfinates were also suitable for this transformation,
and moderate to good yields were obtained. Noticeably, by
simple replacement of H O with D O, deuteriotrifluorinated
b
c
optimization of the reaction conditions, the desired α-
trifluoromethyl-β-sulfonyl tertiary alcohol 3a was successfully
furnished in 86% yield under irradiation with 10 W LEDs in a
DMF/H O mixture [3/1 (v/v)] as the reaction solvent (Table
2
1
analysis (CCDC 2087495) as well as NMR analysis. The inert
atmosphere and water were beneficial to secure a high
chemical yield (Table 1, entries 2−4). However, an excess of
water resulted in a lower yield due to the lower solubility of 1a
2
2
(
Table 1, entry 5). Other solvents such as DMSO and MeCN
products could be facilely obtained in good yields, which will
surely broaden its application in drug development. Surely, this
scope highlights the utility of the developed method in
synthesizing valuable tertiary alcohols.
Thereafter, we shifted our attention to investigate the scope
of α-trifluoromethylstyrenes. A wide range of this type of
substrates have been prepared and subjected to the standard
conditions. As summarized in Scheme 3, all of the tested α-
trifluoromethylstyrenes were compatible with this photo-
induced process. Generally, the electronic nature of the
substitutents on the benzene ring has a weak impact on the
efficacy of this reaction, and comparable chemical yields were
thus secured. Other aryl substrates, including naphthene and
thiophene, also exhibited robust reactivity, delivering the
gave inferior results (Table 1, entries 6 and 7). Finally,
changing the light source to purple or green LEDs resulted in
slightly lower yields of 3a (Table 1, entries 8 and 9).
Obviously, this sulfonation transformation was a photoinduced
process (Table 1, entry 10). The scalability of this protocol was
also successfully demonstrated by performing the reaction on a
gram scale to give a slightly reduced yield (86% vs 62%).
With the optimized reaction conditions in hand, the
versatility and reliability of this developed strategy have been
systematically evaluated (Schemes 2 and 3). Various
arylsulfinates were initially tested by reaction with 1a under
the standard conditions. As illustrated in Scheme 2, a series of
substituted benzenesulfinic acid sodium salts 2a−2j were well
B
Org. Lett. XXXX, XXX, XXX−XXX