2
A. Stikute et al. / Tetrahedron Letters xxx (2015) xxx–xxx
O
S
O
S
O
S
[
R2]
R1
LG
R1
R2
OSiMe3
2
7
1
this work:
LG = OSiR3
SiMe3
O
SiMe3
Ha
O
S
S
SO2
cond.
SiMe3
previous work:
OSiMe3
OH
addition
of the
Me3Si-
group
8
10
LG = OAlk, OAr13
LG = NR2
16
Hb
= SR14
= Ar17
6
SiMe3
SiMe3
15
= OBR2
= C-EWG20
Scheme 1. Sulfoxide synthesis using different sulfinyl transfer agents.
S
S
O
OSiMe3
O
OH
9
11
Conditions:
a) MeCN, Tf2NTMS, -25 °C:
7 (35%), 10 (11%), 11 (4%).
b) MeCN, TMSOTf, +23 °C (bubbling SO2):
7 (46%), 10 (3%), 11 (3%).
c) Toluene, Tf2NTMS, +23 °C (bubbling SO2):
7 (71%), 10 (0%), 11 (0%).
SO2
LA
Si/B
B/Si
S
O
O
3
A > B
A >> C
attack
A
attack
C
O
S
O
S
R-M
Si/B
O
R
attack
B
Scheme 3. Sila-ene and H-ene reactions of 6 with sulfur dioxide.
4
5
Scheme 2. General approach for the synthesis of allyl sulfoxides 5 from allylsilanes
and allylboron derivatives.
O
S
O
S
R-M
SiMe3
O
R
(additive)
7
12a-k
reaction mixture to give products 10 and 11, respectively. The
structures of both 10 and 11 were elucidated from their NMR data
and from analysis of the corresponding sulfoxides (see Scheme 6
and ESI). It was found, that simply bubbling SO2 gas through a
toluene solution of 6 in the presence of Ghosez Lewis acid28
Scheme 4. Synthesis of sulfoxides 12a–k from trimethylsilyl methallylsulfinate (7)
according to Tables 1 and 2.
(trimethylsilyl
bis(trifluoromethanesulfonyl)imide,
Tf2NTMS)
Table 1
resulted in the clean transformation to 7 in 71% isolated yield.27
Next, we turned our attention to the development of experi-
mental conditions for sulfoxide synthesis (Scheme 4, Table 1).
Initially we used silyl sulfinate 7 and phenylmagnesium bro-
mide as the nucleophile to examine the role of solvent, tempera-
ture and additive on the yield of methallyl sulfoxide 12a (R = Ph)
(Table 1). Simple addition of PhMgBr to a solution of 7 in anhy-
drous THF at À78 °C gave methallyl sulfoxide 12a in a moderate
43% yield (Table 1, entry 1). Addition of silicon-based Lewis acids
increased the isolated yields to ꢁ60% (Table 1, entries 2–5).
Encouraged by Knochel’s reports29 on the generation of functional-
ized organometallic reagents in the presence of LiCl as an activator,
we tested this in several experiments (Table 1, entries 6–8). The
addition of LiCl did not give any reasonable improvement when
the reaction was performed in THF. However, when the solvent
system was switched to toluene/THF 15:1–20:1, the isolated yields
of sulfoxide 12a reached 70% and 72% with 10 mol % and 100 mol %
of LiCl, respectively, (Table 1, entry 6 vs entries 7 and 8). Finally,
the addition of 1.0 equiv of PhMgBr/LiCl in toluene/THF at
À100 °C increased the isolated yield of 12a to 79% (Table 1, entry
8). Experiments using various other organometallic reagents
including copper and cerium derivatives showed low reactivity.
Competitive results were obtained when a premixed mixture of
PhMgBr/ZnCl2 was added to sulfinate 7 in toluene/THF at À78 °C
(Table 1, entry 15). We propose that the coordination of lithium
and zinc centers to the Lewis basic sulfinate is more profound in
toluene as a non-coordinating solvent. On the other hand, a recent
study has shown that a metathesis reaction between ZnCl2 and
Grignard reagents leads to the formation of mixed Mg–Zn hybrids
and thus modulates the reactivity of the organometallic species.30
Application of the optimized reaction conditions to other
Grignard reagents gave better yields of sulfoxides 12b–h
(Table 2) in comparison with experiments performed without the
additive. In the cases of 2,4,6-trimethylphenyl-, 4-methylphenyl-,
2-thienyl-, and 1-decylmagnesium substituents the isolated yields
of sulfoxides 12c,d,f,g were over 70%.
Optimization of the reaction conditions for sulfoxide synthesis using trimethylsilyl
methallylsulfinate 7 according to Scheme 4a
Entry
RM (equiv)
Solvent
Additive
(equiv)
Yield of 12a
(R = Ph) (%)
1
2
3
4
5
6
7
8
PhMgBr (1.0)
PhMgBr (1.1)
PhMgBr (1.3)
PhMgBr (1.1)
PhMgBr (1.1)
PhMgBr (1.0)
PhMgBr (1.0)
PhMgBr (1.0)
PhMgBr (1.0)
Ph2CuLi (1.0)
Ph2CuLi (1.1)
PhMgBrÁCeCl3 (1.0)
PhCeCl2ÁLiCl (1.0)
PhMgBr (1.0)
PhMgBrÁZnCl2 (1.0)
THF
THF
THF
Tolb
Tolb
THF
Tolb
Tolb
Tolb
Tol
—
43
57
63
59
54
59
70
TMSOTf (0.1)
TMSOTf (0.3)
TMSOTf (0.1)
TBSOTf (0.1)
LiCl (0.1)
LiCl (0.1)
LiCl (1.0)
BF3ÁOEt2 (0.1)
—
72 (79c)
60
37
27
20
28
9
10
11
12
13
14
15
Tol
TMSOTf (0.1)
—
Tolb
Tol
—
Tolb
Tolb
ZnCl2 (1.0)d
—
17
69
a
b
c
Reactions were carried out at À78 °C unless otherwise stated.
Toluene/THF 15:1–20:1 (see ESI).
The reaction was carried out at À100 °C.
d
Sulfinate 7 was added to a suspension of ZnCl2 in toluene followed by the
addition of PhMgBr.
The addition of LiCl turned out to be quite ineffective when iso-
propyl-, ethyl-, and allylmagnesium halides were used. In most
cases the yields of sulfoxides 12i–k were higher in experiments
without the LiCl additive.
Gratifyingly use of ZnCl2 as the additive gave good yields of sul-
foxides 12i–k (61–77%). Disappointingly experiments with other
organometallic reagents (e.g., BuLi/CeCl3, BuLi/ZnCl2) did not pro-
vide the expected products.
We also tested the ability of commercially available t-
butyldimethylsilyl methallylsulfinate 13 to form sulfoxides
12a,j,k (Scheme 5, Table 3). When the reaction was performed
without additives, the more sterically bulky starting material 13
gave slightly higher yields of sulfoxides 12a,j,k than its