Stereoselective formation of eight-membered rings by radical cyclization of silylenedioxy-tethered bis-methacrylate derivatives

Article abstract of DOI:10.1021/jo502947k

Radical-initiated addition of CCl₄, Cl₃CBr, PhSH, and (TMS)₃SiH to (bisisopropyl)silylenedioxy-tethered bis-methacrylate derivatives gives the corresponding eight-membered ring cyclic adducts stereoselectively. Hydrolysis

Full text of DOI:10.1021/jo502947k

Note
pubs.acs.org/joc
Stereoselective Formation of Eight-Membered Rings by Radical
Cyclization of Silylenedioxy-Tethered Bis-methacrylate Derivatives
Fan-Yi Meng, Shou-Ling Huang, Yi-Hung Liu, Ziqiang Hu, Guoqiao Lai,* and Tien-Yau Luh*
†
,‡
‡
‡
†
,†
,‡
†Key Laboratory of Organosilicon Chemistry and Technology, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China
‡Department of Chemistry, National Taiwan University, Taipei, Taiwan 106
*
S Supporting Information
ABSTRACT: Radical-initiated addition of CCl , Cl CBr, PhSH, and (TMS) SiH to
4
3
3
(
bisisopropyl)silylenedioxy-tethered bis-methacrylate derivatives gives the corre-
sponding eight-membered ring cyclic adducts stereoselectively. Hydrolysis of halo-
substituted cyclic adducts with HCl in methanol affords the corresponding
valerolactones, and the stereochemistry was determined by the X-ray crystallog-
raphy on a dibromobenzoate derivative. DFT calculation on the eight-membered
radical intermediate offers a plausible rationale for the stereoselectivity of the
reaction.
adical cyclizations have been demonstrated to constitute a
R
powerful arsenal for the construction of cyclic products of a
1
−7
wide range of structural varieties. The reaction is particularly
useful for the synthesis of five- and six-membered rings with well-
1
controlled stereoselectivity. The applications of radical
cyclizations leading to medium-sized rings have also been
2
−6
explored.
Like many other cyclization reactions where germinal
substituents on the tether may facilitate the reactions, known
7
as the Thorpe−Ingold effect, similar behavior has been observed
8
in radical cyclization. Silicon tethers has also been extensively
9
,10
used in cyclization reactions,
cyclization,
particularly in radical
5a,11
and the silicon tethers can readily be removed
afterward. This strategy offers versatile entries for the selective
synthesis of products with fascinating structural complexities.
Since carbon−silicon bonds are longer than those of carbon−
carbon bonds and the rotation barriers for carbon−silicon bonds
12
are much smaller than those of carbon−carbon bonds, little
attention has been paid to the Thorpe−Ingold effect in
13−15
organosilicon derivatives.
We recently found that the
presence of bulky isopropyl substituents on silicon in silylene-
space divinylarene copolymers may exert the Thorpe−Ingold
effect, which can bring two adjacent chromophores to closer
proximity so that the photophysical properties of these
report the stereoselective formation of eight-membered rings by
radical cyclization of silylenedioxy-tethered bis-methacrylate 4.
17
Bis-methacrylate 4 was obtained by silylation of 6 with
i
Pr SiCl . Treatment of 4 with BrCCl (8 equiv) in the presence
2
2
3
14
18
copolymers may be perturbed. In addition, the ATRP-induced
cyclopolymerization of bis-methacrylate 1 tethered by a
substituted silylene moiety has been shown to be somewhat r-
selective for the formation of polymer 2 containing 14-
of AIBN (0.13 equiv) and Cu(TPMA)Cl (7, 0.2 mol %) in
toluene at 60 °C for 24 h afforded 8a as the single diastereomer in
58% yield (eq 2).
1
9,20
Hydrolysis of 8a with methanolic HCl gave
valerolactone 10 in 82% yield. The X-ray structure of the
corresponding dibromobenzoate 12 is shown in Figure 1.
The relative stereochemistries of the asymmetric centers in 8a
1
5,16
membered cyclic monomeric units (eq 1).
Under these
reaction conditions, it would be difficult to stop at cyclization
intermediate 3. It is known that the radical promoted Kharasch
addition and related reactions onto acrylate derivatives to give
were thus assigned. Similarly, reaction of 4 with CCl under the
4
same conditions gave 45% yield of a mixture of 8b and 9b in a
ratio of 97 to 3. Removal of the silylene tether from 8b furnished
16b
the corresponding adducts.
We envisioned that a careful
control of reaction conditions may selectively cyclize a bis-
methacrylate derivative to give the corresponding cyclic product.
In order to test the generality of this cyclization, we now wish to
Received: December 30, 2014
©
XXXX American Chemical Society
A
DOI: 10.1021/jo502947k
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
diastereoselectivities of these reactions were similar to those of
halogen abstractions described above, giving cis-dicarboxylates as
the major products.
It seems likely that the bulky isopropyl groups in 4 may exert
the Thorpe−Ingold effect to favor the syn conformation,
resulting in stereoselective radical cyclization as depicted
above. The incorporation of smaller methyl substituents on
silicon may behave differently. Thus, reaction of 5 with PhSH
t
under the same conditions in BuOH as described above gave a
mixture of 18 and 19 (60:40) in addition to other minor
24
impurities. Apparently, the less sterically hindered methyl
substituents on silicon offer a less hindered environment for
atom-transfer process. The reaction is less stereoselective than
those with isopropyl substituents on silicon.
The stereoselectivity of the radical promoted cyclization for
medium-sized rings, in general, is not satisfactory without
external assistance. Li and co-workers have found that chelation
4j
by Lewis acids may improve the situation significantly. In this
study, the presence of bulky isopropyl substituents apparently
directs the atom-transfer process selectively. Preliminary DFT
calculations on the radical intermediate 20 with the Gaussian 09
Figure 1. ORTEP structure of 12 (50%).
25
26
program using the B3LYP hybrid function and the 6-311G
(d,p) basis sets for all the elements suggest that atom-transfer
+
reaction may preferentially take place from the pseudoequatorial
site, rendering the formation of eight-membered rings stereo-
selectively (Figure 2).
1
1
1 in 97% yield, which was also converted into dibromobenzoate
19
3 in 79% yield.
The high diastereoselectivity of this radical cyclization for the
formation of an eight-membered ring is interesting. Presumably,
18
the halogen atom transfer from the copper catalyst takes place
preferentially from the less hindered pseudoequatorial site,
rendering the stereoselective formation of adduct 8a.
Reaction of 4 with PhSH in the presence of AIBN (6 mol %) in
t
21,22
refluxing BuOH
corresponding adducts 14 and 15 in a ratio of 83 to 17.
The stereochemical assignments were based on ROESY
for 12 h gave 72% yield of the
19,20
1
9
spectra.
Figure 2. DFT calculation of radical intermediate 20.
In summary, we have demonstrated a useful radical cyclization of
a bis-methacrylate derivative tethered by a (bisisopropyl)-
silylenedioxy linker giving the corresponding eight-membered
adducts stereoselectively. Like other cyclization reactions for the
23
4
In a similar manner, (TMS) SiH also added to 4 to afford 16
formation of eight-membered rings, selective 8-endo cyclization
3
and 17 (75:25) in 74% yield. It is worth mentioning that the
was observed in all cases in this study. The isopropyl substituents
B
DOI: 10.1021/jo502947k
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
may not only exert the Thorpe−Ingold effect for the cyclization
11.5, 17.1, 17.2, 17.3, 40.2, 52.1, 52.2, 53.1, 58.1, 60.2, 67.5, 71.0, 96.0,
1
8
+
69.1, 172.2. IR (KBr) ν 2951, 2868, 1746, 1439, 1289, 1249, 1083, 885,
process but also make the atom-transfer process stereoselective.
−1
35
15, 750 cm ; HRMS (ESI) calcd. for C H Cl O Si: 497.0488 ([M
1
7
29
4
6
+
1
H] ), found: 497.0482. 9b: H NMR (500 MHz, CDCl ) δ 0.98−1.01
EXPERIMENTAL SECTION
General Information. High-resolution mass spectroscopy was
obtained by using the FAB method with a magnetic sector analyzer, or
the ESI method with a TOF analyzer.
3
■
(
m, 7 H), 1.07 (d, J = 7.5 Hz, 6 H), 1.22 (hept, J = 7.5 Hz, 1 H), 2.50 (d, J
15.7 Hz, 1 H), 2.57 (d, J = 15.7 Hz, 1 H), 3.13 (d, J = 15.1 Hz, 1 H),
.43 (d, J = 15.1 Hz, 1 H), 3.69 (s, 3 H), 3.80 (s, 3 H), 4.22 (d, J = 12.2
Hz, 1 H), 4.40 (d, J = 12.2 Hz, 1 H), 4.48 (d, J = 13.4 Hz, 1 H), 4.57 (d, J
= 13.4 Hz, 1 H); 13C NMR (125 MHz, CDCl
) δ 11.1, 11.5, 17.0, 17.1,
7.2, 17.3, 37.8, 50.6, 52.2, 53.6, 58.7, 59.4, 66.8, 67.2, 95.9, 170.1, 172.8.
IR (KBr) ν 2954, 2868, 1744, 1462, 1438, 1238, 1127, 1082, 886, 817
=
3
Bis(2-methoxycarbonyl)allyl Diisopropylsilyl Ether (4). To a
16
3
solution of 6 (5.00 g, 43.0 mmol) and imidazole (4.39 g, 64.5 mmol) in
1
DCM (150 mL) was added dropwise dichlorodiisopropylsilane (4.11 g,
2
2.2 mmol) cooled in an ice bath, and the reaction mixture was stirred
−1
35
+
cm ; HRMS (FAB) calcd. for C H Cl O Si: 497.0488 ([M + H] ),
17
29
4
6
overnight at rt. Then, the precipitate was filtered and the filtrate was
found: 497.0493.
R-Bromo-2-hydroxymethyl-4R-(2,2,2-trichloroethyl)-2-
methoxycarbonylvalerolactone and Its Enantiomer (10). To 8a
347 mg, 0.64 mmol) was added 0.1 M HCl in MeOH (30 mL), and the
washed 3 times with brine. After dried (MgSO ), the solvent was
4
2
removed in vacuo, and the residue was chromatographed on silica gel
1
(
hexane/EtOAc = 10/1) to give 4 as a colorless oil (5.4 g, 73%): H
(
NMR (400 MHz, CDCl ) δ1.05−1.09 (m, 14 H), 3.75 (s, 6 H), 4.49 (s,
3
13
mixture was refluxed for 3 h. After cooling to rt, the solvent was removed
in vacuo, and the residue was purified by recrystallization with hexane/
4
H), 5.96 (d, J = 2.4 Hz, 2 H), 6.27 (d, J = 2.4 Hz, 2 H); C NMR (100
MHz, CDCl ) δ 12.0, 17.2, 51.6, 61.1, 123.9, 139.1, 166.1. IR (KBr) ν
3
1
−
1
EtOAc to afford the product 10 (209 mg, 82%): mp 154−155 °C; H
2
997, 2951, 2869, 1727, 1641, 1462, 1392, 1310, 1275, 1096 cm ;
+
NMR (400 MHz, CDCl ) δ 2.63 (m, 1 H), 2.90 (d, J = 16.5 Hz, 1 H),
3
HRMS (ESI) calcd. for C H O SiNa: 367.1547 ([M + Na] ), found:
16
28
6
2
1
.97 (d, J = 16.5 Hz, 1 H), 3.16 (d, J = 15.5 Hz, 1 H), 3.47 (d, J = 15.5 Hz,
H), 3.64 (dd, J = 9.0, 11.7 Hz, 1 H), 3.83 (s, 3 H), 4.32 (dd, J = 6.1, 11.7
3
67.1552.
Bis(2-methoxycarbonyl)allyl Dimethylsilyl Ether (5). To a
solution of 6 (4.4 g, 38.0 mmol) and TEA (5.7 g, 57.0 mmol) in THF
50 mL) was added dropwise dichlorodimethylsilane (2.46 g, 19.0
1
3
Hz, 1 H), 4.83 (d, J = 12.4 Hz, 1 H), 5.24 (d, J = 12.4 Hz, 1 H); C NMR
100 MHz, CDCl ) δ 40.7, 44.8, 51.2, 53.2, 58.6, 67.7, 68.6, 94.8, 167.5,
(
3
(
1
71.4; IR (KBr) ν 3417, 2981, 2954, 2939, 1735, 1469, 1449, 1380,
mmol) cooled in an ice bath, and the mixture was stirred overnight at rt.
The precipitate was then filtered, and the filtrate was washed 3 times
−1
79 35
1
306, 890 cm ; HRMS (FAB) calcd. for C H Br Cl O : 396.9012
10
13
3
5
+
(
[M + H] ), found: 396.9011.
R-Chloro-2-hydroxymethyl-4S-(2,2,2-trichloroethyl)-2-
methoxycarbonylvalerolactone and Its Enantiomer (11). To 8b
377 mg, 0.76 mmol) was added 0.1 M HCl in MeOH (30 mL), and the
with brine. After dried (MgSO ), the solvent was removed in vacuo, and
4
2
the residue was chromatographed on silica gel (hexane/EtOAc = 10/1,
1
0
.1% TEA added) to give 5 as a colorless oil (2.46 g, 45%): H NMR
(
(
=
400 MHz, CDCl ) δ 0.19 (s, 6 H), 3.75 (s, 6 H), 4.43 (s, 4 H), 5.89 (d, J
3
13
mixture was refluxed for 3 h. After cooling to rt, the solvent was removed
in vacuo, and the residue was purified by recrystallization with hexane/
1.7 Hz, 2 H), 6.27 (d, J = 1.7 Hz, 2 H); C NMR (100 MHz, CDCl ) δ
3
−
3.4, 51.7, 60.9, 124.4, 138.9, 166.2. IR (KBr) ν 3001, 2955, 2908, 2873,
1
−1
EtOAc to afford the product 11 (259 mg, 97%): mp 148−149 °C; H
1
723, 1642, 1439, 1310, 1092, 804 cm ; HRMS (ESI) calcd. for
+
NMR (400 MHz, CDCl ) δ 2.61 (m, 1H), 2.80 (d, J = 16.1 Hz, 1 H),
3
C H O SiNa: 311.0927 ([M + Na] ), found: 311.0919.
1
2
20
6
2
.85 (d, J = 16.1 Hz, 1 H), 3.16 (d, J = 15.5 Hz, 1 H), 3.50 (d, J = 15.5 Hz,
4
,6-cis-Bis(methoxycarbonyl)-4-(2,2,2-trichloroethyl)-6-
1
H), 3.58 (dd, J = 8.0, 11.5 Hz, 1 H), 3.81 (s, 3 H), 4.21 (dd, J = 5.2, 11.5
bromo-1,1-diisopropyl-1-sila-2,8-dioxacyclooctane (8a). To a
solution of 4 (742 mg, 2.15 mmol), AIBN (45 mg, 0.27 mmol),
bromotrichloromethane (3.42 g, 17.3 mmol) in toluene (7 mL) was
added at rt the catalyst solution (70 μL, 0.05 M), prepared by dissolving
CuCl (0.0990 g, 1.00 mmol) and tris(2-pyridylmethyl)amine (TPMA,
1
3
Hz, 1 H), 4.75 (d, J = 12.4 Hz, 1 H), 5.19 (d, J = 12.4 Hz, 1 H); C NMR
100 MHz, CDCl ) δ 40.3, 44.6, 53.2, 58.9, 60.2, 67.3, 69.3, 94.9, 167.3,
(
3
1
1
+
71.6; IR (KBr) ν 3413, 2981, 2954, 2885, 1739, 1445, 1388, 1129,
−1
35
017, 893 cm ; HRMS (FAB) calcd. for C H Cl O : 352.9517 ([M
10 13
4
5
+
H] ), found: 352.9527.
.5-Dibromobenzoate of 2R-Bromo-2-hydroxymethyl-4R-
2,2,2-trichloroethyl)-2-methoxycarbonylvalerolactone and Its
Enantiomer (12). To a solution of 3,5-dibromobenzoic acid (310 mg,
0
.290 g, 1.00 mmol) in methanol (20.0 mL) in a glovebox, and the
3
mixture was stirred at 60 °C for 24 h. The solvent was then evaporated in
vacuo, and the residue was purified by chromatography on silica gel
(
1
(
hexane/EtOAc = 10/1) to afford 8a (673 mg, 58%): H NMR (400
1
2
.1 mmol) in DCM (10 mL) at 0 °C was added oxalyl chloride (0.2 mL,
.3 mmol) and DMF (1 drop). The mixture was gradually warmed to rt
MHz, CDCl ) δ 1.07−1.16 (m, 13 H), 1.26 (hept, J = 7.5 Hz, 1 H), 2.73
3
(
d, J = 14.5 Hz, 1 H), 2.78 (d, J = 14.5 Hz, 1 H), 3.14 (d, J = 15.2 Hz, 1
H), 3.53 (d, J = 15.2 Hz, 1 H), 3.69 (s, 3H), 3.78 (s, 3 H), 4.31 (d, J =
3.2 Hz, 1 H), 4.35 (d, J = 13.2 Hz, 1 H), 4.36 (d, J = 14.2 Hz, 1 H), 4.60
and stirred for 1 h. The solvent was removed in vacuo to give the
corresponding acid chloride, which was used for the next reaction
without further purification. To a mixture of 10 (291 mg, 0.73 mmol),
TEA (0.21 mL, 1.51 mmol), and a trace amount of DMAP in DCM (10
mL) was added the freshly prepared acid chloride (1.1 mmol) described
above in DCM (10 mL) at 0 °C. The mixture was stirred at rt for 12 h.
1
(
d, J = 14.2 Hz, 1 H); 13C NMR (100 MHz, CDCl ) δ 11.4, 11.8, 17.3,
3
1
7.4, 17.5, 40.6, 52.3, 53.0, 57.8, 60.2, 64.3, 67.8, 94.3, 95.9, 169.0, 172.0.
IR (KBr) ν 2954, 2869, 1746, 1465, 1438, 1287, 1252, 1083, 886, 778
cm ; HRMS (ESI) calcd. for C H Br Cl O SiNa: 562.9802 ([M +
Na] ), found: 562.9804.
−1
79 35
28
17
3
6
+
Saturated NaHCO aqueous solution was added, and the solution was
3
washed with brine, and then dried over MgSO . The reaction mixture
4
,6-cis- and 4,6-trans-Bis(methoxycarbonyl)-4-(2,2,2-
4
trichloroethyl)-6-chloro-1,1-diisopropyl-1-sila-2,8-dioxacyclo-
was concentrated in vacuo, and the residue was recrystallized by hexane/
1
octane (8b) and (9b). To a solution of 4 (1.81 g, 5.30 mmol), AIBN
EtOAc to give 12 (420 mg, 87%): mp 148−150 °C; H NMR (400
(
87 mg, 0.53 mmol), carbon tetrachloride (6.54 g, 42.5 mmol) in
MHz, CDCl ) δ 2.81 (d, J = 16.5 Hz, 1 H), 3.21 (d, J = 16.5 Hz, 1 H),
3
toluene (12 mL) was at rt added the catalyst solution (200 μL, 0.05 M)
prepared according to a procedure described above, and the mixture was
stirred at 60 °C for 24 h. The precipitate was filtered, and the filtrate was
evaporated in vacuo to give the residue, which was chromatographed on
silica gel (hexane/EtOAc = 10/1) to get a mixture of 8b and 9b (97:3),
and a further purification was proceeded by chromatography on silica gel
3.25 (d, J = 15.5 Hz, 1 H), 3.46 (d, J = 15.5 Hz, 1 H), 3.85 (s, 3 H), 4.68
(d, J = 11.4 Hz 1 H), 4.77 (d, J = 12.4 Hz, 1 H), 4.96 (d, J = 11.4 Hz, 1 H),
5.23 (d, J = 12.4 Hz, 1 H), 7.89 (t, J = 1.8 Hz, 1 H), 8.04 (d, J = 1.8 Hz, 2
H); 13C NMR (100 MHz, CDCl ) δ 40.2, 44.7, 48.4, 53.4, 59.0, 68.4,
3
69.3, 94.7, 123.3, 131.4, 132.0, 139.1, 162.8, 165.4, 171.1; IR (KBr) ν
−1
3078, 2950, 1735, 1565, 1442, 1272, 1241, 1129, 743, 701 cm ; HRMS
7
9
35
+
(
hexane/EtOAc = 15/1) to afford 8b (1.16 g, 44%) and 9b (33 mg, 1%).
(FAB) calcd. for C H Br3 Cl O : 656.7484 ([M + H] ), found:
17 15 3 6
Analytical pure samples were obtained by preparative HPLC (hexane/
THF = 20/1). 8b: H NMR (500 MHz, CDCl ) δ 1.07−1.10 (m, 13 H),
1
656.7485.
1
3
3.5-Dibromobenzoate of 2R-Chloro-2-hydroxymethyl-4S-
(2,2,2-trichloroethyl)-2-methoxycarbonylvalerolactone and Its
Enantiomer (13). To a mixture of 11 (150 mg, 0.42 mmol), TEA (0.10
mL, 0.72 mmol), and a trace amount of DMAP in DCM (10 mL) was
added the freshly prepared acid chloride (1.0 mmol) described above in
.23 (hept, J = 7.5 Hz, 1 H), 2.58 (ABq, J = 14.9 Hz, 2 H), 3.14 (d, J =
5.3 Hz, 1 H), 3.43 (d, J = 15.3 Hz, 1 H), 3.65 (s, 3 H), 3.75 (s, 3 H), 4.19
1
(
d, J = 13.7 Hz, 1 H), 4.28 (d, J = 13.0 Hz, 1 H), 4.35 (d, J = 13.0 Hz, 1
13
H), 4.62 (d, J = 13.7 Hz, 1 H); C NMR (125 MHz, CDCl ) δ 11.2,
3
C
DOI: 10.1021/jo502947k
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
DCM (10 mL) at 0 °C. The mixture was stirred at rt for 12 h. Saturated
4,6-cis- and 4,6-trans-Bis(methoxycarbonyl)-4-(phenyl-
NaHCO aqueous solution was added, and the solution was washed
mercaptomethyl)-1,1-di-methyl-1-sila-2,8-dioxacyclooctanes
3
(
18) and (19). To a mixture of 5 (400 mg, 1.4 mmol) and AIBN (20 mg,
with brine, and then dried over MgSO . The reaction mixture was
4
t
0
.12 mmol) in BuOH (15 mL) was added thiophenol (300 mg, 2.7
concentrated in vacuo, and the residue was recrystallized by hexane/
1
mmol), and the mixture was refluxed for 12 h. After cooling to rt, the
solvent was removed in vacuo to give a mixture of 18 and 19 in addition
to other unidentified products. The ratio of 18 and 19 was estimated to
be 60% and 40% based on the integration of the peaks of the NMR
spectrum of the crude mixture at δ 2.20 (dd, 1 H for 18, relative
integration = 1.00) and δ 2.83 (m, 1 H for both 18 and 19, relative
integration = 1.65). Attempts to purify 18 and/or 19 by column
chromatography on silica gel were unsuccessful, 18 and 19 being
decomposed under these conditions.
EtOAc to give 13 (205 mg, 79%): mp 169−171 °C; H NMR (400
MHz, CDCl ) δ 2.72 (d, J = 16.0 Hz, 1 H), 3.13 (d, J = 16.0 Hz, 1 H),
3
3
.25 (d, J = 15.4 Hz, 1 H), 3.50 (d, J = 15.4 Hz, 1 H), 3.85 (s, 3 H), 4.61
(
d, J = 11.4 Hz, 1 H), 4.70 (d, J = 12.3 Hz, 1 H), 4.88 (d, J = 11.4 Hz, 1
H), 5.20 (d, J = 12.3 Hz, 1 H), 7.89 (t, J = 1.8 Hz, 1 H), 8.04 (d, J = 1.8
Hz, 2 H); 13C NMR (125 MHz, CDCl ) δ 39.8, 44.6, 55.4, 58.6, 59.4,
3
6
8.0, 69.9, 94.8, 123.3, 131.4, 132.0, 139.1, 162.9, 164.9, 171.1. IR (KBr)
−1;
ν 3097, 3074, 2954, 1735, 1565, 1442, 1272, 1206, 1129, 701 cm
HRMS (FAB) calcd. for C H Br2 Cl O : 612.7989 ([M + H] ),
79
15
35
+
17
4
6
found: 612.7979.
,6-cis- and 4,6-trans-Bis(methoxycarbonyl)-4-(Phenyl-
mercaptomethyl)-1,1-diisopropyl-1-sila-2,8-dioxacyclooctane
14) and (15). To a mixture of 4 (345 mg, 1.0 mmol) and AIBN (10 mg,
ASSOCIATED CONTENT
4
■
*
S
Supporting Information
(
1
13
t
H and C NMR spectra of new compounds and/or 2D ROESY
0
.06 mmol) in BuOH (10 mL) was added thiophenol (220 mg, 2.0
of 14−17, Cartesian coordinates of 20 by DFT calculation, and
crystal data of 12. This material is available free of charge via the
Internet at http://pubs.acs.org.
mmol), and the mixture was refluxed for 12 h. After cooling to rt, the
solvent was removed in vacuo, and the residue was chromatographed on
silica gel (hexane/EtOAc = 10/1) to get a mixture of 14 and 15 (83:17).
Further purification was proceeded by chromatography (hexane/EtOAc
=
15/1) to afford 14 (276 mg, 61%) and 15 (52 mg, 11%). Analytical
AUTHOR INFORMATION
Corresponding Authors
E-mail: tyluh@ntu.edu.tw (T.-Y.L.).
E-mail: laiguoqiao@aliyun.com (G.L.).
■
*
*
pure samples were obtained by preparative HPLC (hexane/THF = 20/
1
1
). 14: H NMR (400 MHz, CDCl ) δ 0.97−1.12 (m, 14 H), 2.24 (dd, J
3
=
5.5, 15.6 Hz, 1 H), 2.58 (dd, J = 2.9, 15.6 Hz, 1 H), 2.78 (m, 1 H), 3.11
d, J = 13.2 Hz, 1 H), 3.27 (d, J = 13.2 Hz, 1 H), 3.49 (s, 3 H), 3.65 (s, 3
H), 3.85−3.90 (m, 2 H), 4.11−4.15 (m, 2 H), 7.16−7.20 (m, 1 H),
(
Notes
13
7
.24−7.28 (m, 2 H), 7.38−7.41 (m, 2 H); C NMR (100 MHz, CDCl )
The authors declare no competing financial interest.
3
δ 11.6, 12.1, 17.2, 17.31, 17.34, 17.36, 31.8, 37.3, 42.1, 51.9, 52.0, 52.3,
6
2
5.3, 66.1, 126.5, 128.8, 130.6, 136.1, 173.7. IR (KBr) ν 2947, 2892,
ACKNOWLEDGMENTS
−1
■
865, 1743, 1466, 1439, 1248, 1193, 1096, 1065 cm ; HRMS (FAB)
+
1
T.-Y.L. thanks the Ministry of Science and Technology, Taipei,
and National Taiwan University for support. We are grateful to
the Computer and Information Networking Center, National
Taiwan University, for the support of high-performance
computing facilities. G.L. and Z.H. thank the Natural Science
Fund of China (Grant No. 51353003) and the Zhejiang
Provincial Natural Science Foundation of China (Grant No.
LY12B04006), respectively, for support.
calcd. for C H O SSi: 455.1924 ([M + H] ), found: 455.1924. 15: H
NMR (400 MHz, CDCl3) δ 0.97 (m, 1 H), 1.02 (s, 6 H), 1.07 (m, 7 H),
22
35
6
1
.86 (dd, J = 6.1, 14.9 Hz, 1 H), 2.47 (dd, J = 2.4, 14.9 Hz, 1 H), 2.69 (m,
1
H), 3.24 (ABq, J = 13.4 Hz, 2 H), 3.47 (s, 3 H), 3.67 (s, 3 H), 3.80 (m, 1
H), 4.03 (m, 1 H), 4.12 (m, 2 H), 7.14−7.18 (m, 1 H), 7.23−7.27 (m, 2
13
H), 7.40−7.42 (m, 2H); C NMR (125 MHz, CDCl ) δ 11.6, 12.2,
3
1
1
1
7.33, 17.36, 17.5, 34.7, 39.9, 43.9, 51.7, 52.1, 52.8, 61.8, 66.7, 126.3,
28.8, 130.1, 136.4, 173.0, 173.9. IR (KBr) ν 2951, 2896, 2869, 1735,
466, 1439, 1264, 1135, 1080, 886 cm ; HRMS (FAB) calcd. for
−1
+
C H O SSi: 455.1924 ([M + H] ), found: 455.1920.
2
2
35
6
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4
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■
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1
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3
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3
4
2
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−1
+
1
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57
6
5
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(
d, J = 14.4 Hz, 1 H), 1.36 (d, J = 14.4 Hz, 1 H), 1.82 (dd, J = 5.9, 14.9
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3
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5
1
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−
1
303, 1244, 1131, 1069, 835 cm ; HRMS (FAB) calcd. for
+
C H O Si : 593.3001 ([M + H] ), found: 593.2996.
2
5
57
6
5
D
DOI: 10.1021/jo502947k
J. Org. Chem. XXXX, XXX, XXX−XXX

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