N-bromosuccinimide (NBS) catalyzed highly chemoselective acetalization of carbonyl compounds using silylated diols and pentaerythritol under neutral aprotic conditions

Article abstract of DOI:10.1055/s-2004-837291

Various types of carbonyl compounds are efficiently converted to their 1,3-dioxanes and pentaerythritol diacetals by the use of either 1,3-bistrimethylsiloxy propane (A) or 1,3-bistrimethylsilanyloxy-2,2- bistrimethylsilanyloxymethyl propane (D) and a catalytic amount of N-bromosuccinimide (3-10 mol%) under essentially neutral aprotic condition, respectively. A variety of functionalities such as both aliphatic and phenolic -OTBDMS, -OMe, -OBz, furan ring, double bonds and more significantly phenolic -OTHP survived under the present reaction condition. The efficient conversion of two α-tertiary ketones to their cyclic acetals was also achieved using the present protocol.

Full text of DOI:10.1055/s-2004-837291

PAPER
279
N-Bromosuccinimide (NBS) Catalyzed Highly Chemoselective Acetalization of
Carbonyl Compounds Using Silylated Diols and Pentaerythritol under Neutral
Aprotic Conditions
N
-Bromosuccinim
a
ide (NBS
)
b
C
atalyzedC
a
hemoselec
k
tive
A
cetalization
o
K
f
Carbonyl
C
om
p
a
ounds rimi,* Hassan Hazarkhani, Jafar Maleki
Institute for Advanced Study in Basic Sciences (IASBS), Department of Chemistry, P.O. Box 45195-159, Gava Zang, Zanjan, Iran
Fax +98(241)4249023; E-mail: karimi@iasbs.ac.ir
Received 9 June 2004; revised 27 September 2004
using this protocol some of the acid sensitive substrates,
Abstract: Various types of carbonyl compounds are efficiently
such as aliphatic THP and TBDMS ethers were stable un-
converted to their 1,3-dioxanes and pentaerythritol diacetals by the
der the described reaction conditions (Scheme 1).
use of either 1,3-bistrimethylsiloxy propane (A) or 1,3-bistrimeth-
ylsilanyloxy-2,2-bistrimethylsilanyloxymethyl propane (D) and a
catalytic amount of N-bromosuccinimide (3–10 mol%) under essen-
tially neutral aprotic condition, respectively. A variety of function-
alities such as both aliphatic and phenolic -OTBDMS, -OMe, -OBz,
furan ring, double bonds and more significantly phenolic -OTHP
survived under the present reaction condition. The efficient conver-
sion of two a-tertiary ketones to their cyclic acetals was also
achieved using the present protocol.
Key Words: N-bromosuccinimide, acetals, aprotic acetalization,
1,3-dioxanes, pentaerythritol diacetals
The electrophilic nature of the carbonyl groups is a domi-
nant feature of their extensive chemistry. One of the major
challenging problems during many multi-step syntheses is
how to protect a carbonyl group from nucleophilic attack
until its electrophilic properties can be exploited. Acetal-
ization is commonly utilized as a protecting method for
carbonyl functions, because, acetals are stable against a
wide rang of nucleophiles under neutral and basic condi-
tions.1–4 Moreover, chiral acetals are particularly impor-
tant precursor for the synthesis of enantiomerically pure
compounds.5 Although, the preparation of acetals has tra-
ditionally been carried out using protonic as well as Lewis
acid catalyst, the methods are not often compatible with
the presence of other acid sensitive functional groups like,
e.g. a protected hydroxyl groups. Among the plethora of
procedures typically developed for the preparation of ac-
etals, only a few work under considerably mild reaction
condition.6–9 Therefore, it seems that developments of
new improved and chemoselective protocols for this
transformation are being pursued. An interesting chal-
lenging problem during many syntheses of reasonable
complexity is how to protect a carbonyl group in the pres-
ence of a wide range of sensitive functional groups. Very
recently, we have discovered that N-bromosuccinimide
(NBS) is a catalyst for the chemoselective conversion of
carbonyl compounds to 1,3-dioxanes in the presence of
triethylorthoformate and a diol under almost neutral reac-
tion conditions.9 Our preliminary observation showed that
Scheme 1
This observation was in sharp contrast to conventional
acid-catalyzed acetalization reactions,10–24 which are not
suitable in most cases for the acetalization of acid-sensi-
tive carbonyl compounds. However, in continuation of
this study, we discovered that the NBS protocol was inef-
fective for the substrates comprising more acid sensitive
functional groups such as phenolic THP and TBDMS
ethers (Scheme 2).
To solve this problem, very recently we have reported a
new protocol for efficient acetalization of various types of
HO
OH (3 equiv)
O
O
CHO
(EtO)3CH (1 equiv), NBS (2 mol%)
MeOH (2 equiv), CH2Cl2, r.t., 8.5 h
RO
RO
Yield (%)
Entry
R
1
2
THP
46
30
TBDMS
SYNTHESIS 2005, No. 2, pp 0279–0285
x
x
.
x
x
.2
0
0
4
Advanced online publication: 16.12.2004
DOI: 10.1055/s-2004-837291; Art ID: Z11504SS
© Georg Thieme Verlag Stuttgart · New York
Scheme 2

280
B. Karimi et al.
PAPER
carbonyl compounds including those bearing acid sensi-
tive functional groups using 1,3-bis(trimethylsilyloxy)
propane (A) in the presence of catalytic amounts of iodine
under neutral aprotic conditions.25 However, since in this
protocol the reaction times are prolonged, we thus sought
to find a new modified procedure, which would allow to
circumvent this defect. Based on the previous findings on
the use of NBS as a nearly neutral catalyst for the reac-
tions so traditionally called acid-catalyzed reactions,9,26–30
we hypothesized that this catalyst might be better suited
than I2 in catalyzing the acetalization reactions under
aprotic conditions. Silyl ethers that were used in this study
are shown in Figure 1. Among different solvents such as
THF, CH3CN, CHCl3 and CH2Cl2, both CHCl3 and
CH2Cl2 turned out to be suitable solvents for this transfor-
mation. Therefore, in the subsequent studies we chose an-
hydrous CH2Cl2, although CHCl3 gave equal efficiency in
most cases.
Me3SiO
Me3SiO
OSiMe3
OSiMe3
A
B
Me3SiO
Me3SiO
OSiMe3
OSiMe3
CO2Et
CO2Et
OSiMe3
Me3SiO
D
C
Figure 1
We have observed that 1,3-dioxanes and 1,3-dioxolanes
of simple aromatic as well as aliphatic aldehydes could be
prepared using A or B in the presence of catalytic amounts
of NBS (3 mol%) under neutral and aprotic conditions
(Table 1, entries 1–11).
Table 1 Acetalization of Carbonyl Compounds under Neutral Aprotic Conditions, A, B, and C in the Presence of NBS at Room Temperature
Entry
1
R1
R2
H
H
H
H
H
H
H
H
H
H
H
Silyl ether
Substrate/Silyl ethera/NBS
1:1.3:0.03
1:1.3:0.03
1:1.3:0.03
1:1.3:0.03
1:2:0.03
Time (h)
6.5
5
Yield (%)b
96
Ph
A
B
C
A
A
A
A
A
A
A
A
A
A
C
A
A
A
A
A
2
Ph
95c
96d
95
3
Ph
5.5
5
4
4-(Cl)C6H4
4-(Br)C6H4
4-(CH3)C6H4
4-(MeO)C6H4
4-(NO2)C6H4
3-(CH3)C6H4
n-Butyl
5
6.5
10
85
6
1:1.5:0.03
1:2:0.03
94
7
10
94
8
1:2:0.04
15
87
9
1:1.3:0.03
1:1.3:0.03
1:1.3:0.03
1:1.3:0.03
1:2:0.05
16
89
10
11
12
13
14
15
16
17
18
19
10
91
n-Hexyl
10
92
Citral (E/Z mixture)
Ph
10
93e
94
CH3
CH3
CH3
CH3
CH3
CH3
44
Ph
1:2:0.05
40
90d
79
4-(MeO)C6H4
4-(NO2)C6H4
4-(Ph)C6H4
PhCH2CH2
1:2:0.05
44
1:2:0.05
72
81
1:2:0.05
60
84
1:2:0.05
36
86
1:2:0.05
36
82e
O
20
A
1:2:0.04
36
93
Ph
O
Synthesis 2005, No. 2, 279–285 © Thieme Stuttgart · New York

PAPER
N-Bromosuccinimide (NBS) Catalyzed Chemoselective Acetalization of Carbonyl Compounds
281
Table 1 Acetalization of Carbonyl Compounds under Neutral Aprotic Conditions, A, B, and C in the Presence of NBS at Room Temperature
(continued)
Entry
21
R1
R2
Silyl ether
Substrate/Silyl ethera/NBS
1:5:0.07
Time (h)
168
168
168
12
Yield (%)b
Ph
Ph
A
A
A
A
A
A
A
A
A
A
A
90
22
4-(Cl)C6H4
4-(Cl)C6H4
1:5:0.07
89e
78e
84
23
(–)-Camphor
Furyl
1:5:0.07
24
H
1:1.3:0.03
1:2:0.04
25
4-(PhCO2)C6H4
2-(PhCO2)C6H4
3-(THPO)C6H4
3-(TBDMSO)C6H4
4-(TBDMSO)C6H4
3-(THPO)C6H4
H
12
89
26
H
1:2.5:0.04
1:2:0.04
15
81
27
H
14
90
28
H
1:2:0.04
14
95
29
CH3
CH3
1:2:0.05
63
92
30
1:2:0.05
65
80
31
1:5:0.07
168
40d,e
O
H
TBDMSO
a A was used as silyl ether unless otherwise stated.
b Yields refer to isolated pure product unless otherwise stated.
c Bistrimethylsilanyloxy ethane B was used.
d C was used.
e Yields are based on NMR data of the crude products.
1
Through careful inspection of the H NMR spectrum of col for synthesis of pentaerythritol diacetals under neutral
the crude product, we found that the double bonds in citral and mild reaction conditions. As summarized in Table 2,
did not undergo any detectable migration during acetal using an almost stoichiometric amount of D in the pres-
formation (Table 1, entry 12). Different types of aliphatic ence of 10 mol% NBS, a variety of aldehydes was effi-
and aromatic ketones were also converted to their acetals ciently converted to the corresponding diacetals under
using A in satisfactory yields although after relatively pro- neutral aprotic conditions and at room temperature
longed reaction time (Table 1, entries 13, 15–20). It is also (Table 2, entries 1–8). Acetophenone was also provided
noteworthy that the reaction of benzaldehyde and ace- 90% yield of the product only in refluxing CHCl3 after
tophenone with C as a model in the presence of 3 mol% five hours in the presence of 10 mol% NBS (Table 2, en-
and 5 mol% of NBS also furnished the corresponding op- try 9). To the best of our knowledge, this method is the
tically active acetals in high yields, respectively (Table 1, first example of preparation of pentaerythritol diacetals
entries 3 and 14). The formation of acetals form diaryl ke- under mild and neutral aprotic conditions.
tones and other types of hindered ketones is difficult to
Amongst acetalization protocols, it has been shown that
achieve under standard acetalization procedure,9,10–24,31
carbonyl compounds comprising acid-sensitive groups
and hence indirect routes have usually been developed for
such as THP ethers are only relatively stable under the
their preparation.32,33 Interestingly, under the described
Noyori’s standard procedure at very low temperature.8
reaction conditions even hindered ketones furnished the
This encouraged us to investigate the ability of the present
corresponding acetals in good to excellent yields at room
NBS protocol for efficient protection of highly acid-sen-
sitive carbonyl compounds at room temperature. In this
temperature (Table 1, entries 21–23).
Among the acetal protecting groups, pentaerythritol respect, we have found that different types of acid-sensi-
diacetals are of some interest since most of them are thor- tive carbonyl compounds were successfully converted to
oughly stable and crystalline substances and have sharp the corresponding 1,3-dioxane and pentaerythritol diace-
melting points. A number of publications have described tals in moderate to excellent yields (Table 1, entries 24–
the preparation of pentaerythritol diacetals under harsh 30; Table 2, entry 8). It is also worth mentioning that
conditions.34–36 However, these methods have not been though owing to the extraordinary repulsion of adjacent
entirely satisfactory, owing to problems of harsh azeotro- axial methyl group, the protection of the steroidal ketone
pic distillation (refluxing toluene) and acidic conditions. 3-b-tert-buthyldimethylsilyloxyandrost-5-ene-17-one did
Thus, we decided to seek the ability of the present proto- not proceed significantly even after one week; interesting-
Synthesis 2005, No. 2, 279–285 © Thieme Stuttgart · New York

282
B. Karimi et al.
PAPER
O
Table 2 Pentaerythrithol Diacetalization of Carbonyl Compounds
under Neutral Aprotic Conditions Using D in the Presence of NBS at
Room Temperature
CHO
O
100
0
A (1.3 equiv), NBS (3 mol%)
O
O
CH2Cl2, r.t., 6.5 h
O
O
O
O
O
R1
R2
R1
R2
O
Silyl ether, NBS (cat.)
CH2Cl2, r.t.
R1
R2
O
Entry R1
R2
Substrate/D/ Time Yield
CHO
O
89
(%)a
95
94
95
93
95
92
94
95
90b
92
A (1.3 equiv), NBS (3 mol%)
NBS
(h)
14
12
12
18
16
16
17
14
5
O
O
CH2Cl2, r.t., 6.5 h
1
2
Ph
H
H
H
H
H
H
H
H
1:0.6:0.1
1:0.6:0.1
1:0.6:0.1
1:0.6:0.1
1:0.6:0.1
1:0.6:0.1
1:0.6:0.1
1:0.6:0.1
11
O
Ph
Ph
4-(CH3)C6H4
3-(PhO)C6H4
4-(Cl)C6H4
4-(Br)C6H4
4-(F)C6H4
4-(MeS)C6H4
4-(i-Pr)C6H4
Ph
3
O
4
100
0
CHO
O
A (1.3 equiv), NBS (3 mol%)
O
O
5
CH2Cl2, r.t., 10 h
O
6
Scheme 3
7
8
was detected by GC analysis, the actual mechanism of this
transformation should be studied in detail.
9
CH3 1:0.6:0.1
1:0.6:0.1
10
4-(TBDMSO)C6H4
H
30
In conclusion, the present protocol demonstrates the po-
tential of NBS, as a cheap and readily available reagent
and effective catalyst for rapid neutral aprotic acetaliza-
tion of a variety of carbonyl compounds. Moreover, the
methodology offers significant improvement over most
existing procedures with regard to yields of products, neu-
trality of the reaction medium to tolerate sensitive moiety,
simplicity in operation, and above all, avoiding expensive,
highly acidic and moisture sensitive TMSOTf. The meth-
od is also superior to our previous acetalization protocol
using iodine as catalyst.25 Further applications of NBS as
a neutral Lewis acid in functional group transformations
are ongoing in our laboratories.
a Yields refer to isolated pure product unless otherwise stated.
b The reaction was performed in refluxing CHCl3.
ly, no deprotection of silyl group was observed and the
residue of the starting substrate was recovered intact
(Table 1, entry 31). These results clearly indicate that
NBS can be considered as a mild and nearly neutral sub-
stitute for highly acidic and moisture sensitive TMSOTf
in catalyzing acetalization reactions under aprotic condi-
tions and at ambient temperature. The protocol is also saf-
er than the previous NBS/ethylorthoformate protocol in
acetalization of highly acid-sensitive carbonyl com-
pounds (Schemes 1 and 2).9
As shown in Table 1, ketones need more time and reagent
to be converted into their 1,3-dioxane. Based on this ob-
servation, we conducted a set of competitive protection
reactions between aldehydes and ketones, the results of
which are shown in Scheme 3.
O
TMSO O
OTMS
TMSO
OTMS
R
R
R
R
NBS
1
SiMe3
TMSO O
O
NBS
Br
These results show that the presented method is potential-
ly applicable for chemoselective conversion of aldehydes
to corresponding acetals in the presence of ketone func-
tions in multi-functional molecules. The actual mecha-
nism for this NBS-catalyzed acetalization is unclear.
However, as we have mentioned in our previous paper,
NBS might act as a Lewis acid.3 Therefore, a plausible
idea is that NBS catalyzes a set of silyl exchange reactions
between A and carbonyl oxygen to produce the intermedi-
ate 4. Irreversible cyclization of this intermediate then
leads to cyclic acetal, hexamethyldisiloxane (HMDS) and
concomitant release of NBS that re-enters the catalytic cy-
cle (Scheme 4).
1
R
R
2
R
R
O
N
TMS
TMSO O
O
O
Br
R
R
O
HMDS
O
Br
3
4
R
R
O
4
O
NBS
The formation of stable HMDS is the driving force for the
progress of the reaction. Though the generation of HMDS
Scheme 4
Synthesis 2005, No. 2, 279–285 © Thieme Stuttgart · New York

PAPER
N-Bromosuccinimide (NBS) Catalyzed Chemoselective Acetalization of Carbonyl Compounds
283
Chemicals were either prepared in our laboratories or purchased
from Merck, Fluka and Aldrich Chemical Companies. All yields re-
fer to isolated products unless otherwise stated. The products were
characterized by comparison of their physical data with those of
2-(4-Nitrophenyl)[1,3]dioxane (Table 1, Entry 8)
1H NMR (250 MHz, CDCl3, 25 °C, TMS): d = 7.98–8.28 (d, J = 9.0
Hz, 2 H), 7.62–7.73 (d, J = 9.0 Hz, 2 H), 5.54 (s, 1 H), 4.24–4.51
(dd, J = J = 5 Hz, 13.8 Hz, 2 H), 3.94–4.05 (pseudo-t, J = 13.8 Hz,
2 H), 2.13–2.25 (tq, J = 5 Hz, J = 13.3 Hz, 1 H), d = 1.43–1.50
(quintd, J = 1.1 Hz, J = 13.3 Hz, 1 H).
1
known samples or by their spectral data. H NMR and 13C NMR
spectra were recorded on Bruker 250 MHzor Bruker 500 MHz spec-
trometer in CDCl3 as the solvent and TMS as internal standard.
Most of the products are known. All of the isolated products gave
satisfactory IR and NMR spectra.
13C NMR (63 MHz, CDCl3, 25 °C, TMS): d = 154.5, 147.05,
132.33, 127.50, 102.52, 67.80, 34.5.
2-Methyl-2-phenyl[1,3]dioxane (Table 1, Entry 13)
1H NMR (250 MHz, CDCl3, 25 °C, TMS): d = 7.16–7.37 (m, 5 H),
3.66–3.78 (m, 4 H), 1.94–2.08 (tq, J = 5.4, 12.9 Hz 1 H), 1.44 (s, 3
H), 1.11–1.19 (quintd, J = 1.2, 12.9 Hz, 1 H).
13C NMR (63 MHz, CDCl3, 25 °C, TMS): d = 141.63, 129.10,
128.99, 128.24, 100.92, 61.62, 32.84, 25.89.
Synthesis of Acetals; General Procedure
To a solution of carbonyl compound (2 mmol), A, B, C (2.6–10
mmol), or D (1.2 mmol) in anhyd CH2Cl2 (10 mL), NBS (0.06–0.14
mmol) was added, and the resulting solution was stirred at r.t. After
completion of the reaction (TLC or GC), a cold aq solution of
NaOH (5%, 25 mL) was added and the mixture was extracted with
CH2Cl2 (3 × 15 mL). The organic extracts were washed successive-
ly with NaOH (5%, 15 mL), water (4 × 15 mL) and dried over anhyd
Na2SO4. Evaporation of the solvent under reduced pressure gave al-
most pure product(s). Further purification was carried out by vacu-
um distillation, re-crystallization in appropriate solvent or flash
chromatography using appropriate eluent to afford pure acetals
(Tables 1 and 2).
2-Methyl-2-(2-phenylethyl)[1,3]dioxane (Table 1, Entry 18)
1H NMR (250 MHz, CDCl3, 25 °C, TMS): d = 6.91–7.38 (m, 5 H),
3.79–3.89 (m, 4 H), 2.73–2.79 (m, 2 H), 1.98–2.05 (m, 2 H), 1.97–
1.73 (m, 1 H), 1.48–1.68 (m, 1 H), 1.44 (s, 3 H).
13C NMR (63 MHz, CDCl3, 25 °C, TMS): d = 139.01, 129.63,
129.65, 126.02, 100.85, 58.09, 41.50, 34.13, 23.67 18.27.
Acetalization of Highly Sensitive 3-(tert-Butyldimethylsilyl-
oxy)benzaldehyde; Typical Procedure
2-Furan-2-yl[1,3]dioxane (Table 1, Entry 24)
1H NMR (500 MHz, CDCl3, 25 °C, TMS): d = 7.37–7.38 (t, J = 0.86
Hz, 1 H), 6.41–6.42 (d, J = 3.2 Hz, 1 H), 6.34–6.35 (m, 1 H), 4.21–
4.24 (dd, J = 11.6, 5.0 Hz, 2 H), 3.91–3.97 (pseudo-t, J = 11.6 Hz,
2 H), 2.17–2.26 (tq, J = 5.0, 13.1 Hz, 1 H), 1.41–1.44 (quintd, J =
13.1, 1.9 Hz, 1 H).
To a solution of 3-(tert-butyldimethylsilyloxy)benzaldehyde (3
mmol, 710 mg), A (6 mmol, 1.32 g), in anhyd CH2Cl2 (15 mL),
NBS (0.12 mmol, 22 mg) was added, and the resulting solution was
stirred magnetically at r.t. After completion of the reaction (TLC),
a cold aq solution of NaOH (5%, 25 mL) was added and the mixture
was extracted with CH2Cl2 (3 × 25 mL). The organic extracts were
washed successively with NaOH (5%, 15 mL), water (4 × 20 mL)
and dried over anhyd Na2SO4. Evaporation of the solvent under re-
duced pressure gave almost pure product(s). Further purification of
the product was achieved using flash chromatography through a
short column of silica gel (2.5 cm × 5 cm) with n-hexane–EtOAc
(15:1) as eluent to afford the corresponding pure tert-butyl-(3-[1,3]-
dioxane-2-ylphenoxy)dimethylsilane as a bright yellow oil.
1H NMR (500 MHz, CDCl3, Me4Si): d = 7.22–7.25 (t, J = 7.9 Hz, 1
H), 7.02–7.11 (d, J = 7.9 Hz, 1 H), 7.01 (t, J = 2.0 Hz, 1 H), 6.82–
6.84 (dd, J = 7.9 Hz, J = 2.0 Hz, 2 H), 5.46 (s, 1 H), 4.24–4.28 (dd,
J = 11.0, 5.0 Hz, 2 H), 3.93–3.99 (pseudo-t, J = 11.0 Hz, 2 H), 2.17–
2.26 (tq, J = 5 Hz, 12.4 Hz), 1.39–1.44 (quintd, J = 2.4 Hz, J = 12.4
Hz, 1 H), 1.02 (s, 9 H), 0.23 (s, 6 H).
13C NMR (125 MHz, CDCl3, 25 °C, TMS): d = 156.20, 144.71,
109.52, 105.68, 102.55, 64.33, 26.29.
2-[4-Benzoyloxyphenyl][1,3]dioxane (Table 1, Entry 25)
1H NMR (500 MHz, CDCl3, 25 °C, TMS): d = 8.20–8.22 (dd, J =
8.4, 1.4 Hz, 2 H), 7.61–7.65 (tt, J = 7.4, 1.4 Hz, 1 H), 7.56–7.59 (d,
J = 8.4 Hz, 2 H), 7.49–7.53 (t, J = 7.4 Hz, 2 H), 7.23–7.26 (dd, J =
8.4 Hz, J = 1.4 Hz, 2 H), 5.54 (s, 1 H), 4.27–4.30 (dd, J = 11.0, 3.6
Hz, 2 H), 3.98–4.03 (pseudo-t, J = 11.0 Hz, 2 H), 2.20–2.27 (tq, J =
5.0, 13.3 Hz, 1 H), 1.44–1.48 (quintd, J = 1.3, 13.3 Hz, 1 H).
13C NMR (125 MHz, CDCl3, 25 °C, TMS): d = 165.08, 151.29,
136.58, 133.68, 130.25, 129.62, 128.65, 127.38, 121.55, 101.05,
67.45, 25.82.
2-[3-(Tetrahydropyran-2-yloxy)phenyl][1,3]dioxane (Table 1,
Entry 27)
13C NMR (125 MHz, CDCl3, 25 °C, TMS): d = 155.62, 140.40,
129.21, 120.22, 119.02, 117.94, 101.38, 67.35, 25.82, 25.76, 18.20,
–4.35.
1H NMR (500 MHz, CDCl3, 25 °C, TMS): d = 7.15–7.17 (t, J = 7.9
Hz, 1 H), 7.01–7.04 (d, J = 7.9 Hz, 1 H), 6.88–6.89 (t, J = 2.2 Hz, 1
H), 6.69–6.71 (dd, J = 7.9 Hz, J = 2.2 Hz, 1 H), 5.38 (s, 1 H), 4.52–
4.53 (m, 1 H), 4.15–4.18 (dd, J = 11.0 Hz, J = 5.0 Hz, 2 H), 4.00–
4.03 (m, 2 H), 3.86–3.91 (pseudo-t, J = 11.0 Hz, 2 H), 2.10–2.15 (tq,
J = 5.0 Hz, J = 12.7 Hz, 1 H), 1.96–2.02 (m, 1 H), 1.81–1.85 (m, 1
H), 1.47–1.50 (m, 3 H), 1.34–1.37 (m, 1 H), 1.23–1.27 (m, 1 H).
2-(4-Chlorophenyl)[1,3]dioxane (Table 1, Entry 4)
1H NMR (250 MHz, CDCl3, 25 °C, TMS): d = 7.40–7.49 (d, J = 8.0
Hz, 2 H), 7.30–7.34 (d, J = 8.0 Hz, 2 H), 5.44 (s, 1 H), 4.20–4.26
(dd, J = 5.0, 11.3 Hz, 2 H), 3.88–3.98 (pseudo-t, J = 11.3 Hz, 2 H),
2.14–2.23 (tq, J = 5 Hz, J = 13.2 Hz, 1 H), 1.37–1.43 (quintd, J =
1.2, 13.2 Hz, 1 H).
13C NMR (125 MHz, CDCl3, 25 °C, TMS): d = 156.58, 140.11,
129.28, 119.13, 117.50, 115.83, 102.29, 98.79, 67.27, 66.81, 30.68,
30.67, 25.44, 19.51.
13C NMR (63 MHz, CDCl3, 25 °C, TMS): d = 137.70, 134.95,
128.81, 127.91, 101.19, 67.78, 26.09.
2-Methyl-2-[3-(tetrahydropyran-2-yloxy)phenyl][1,3]dioxane
(Table 1, Entry 30)
2-(4-Bromophenyl)[1,3]dioxane (Table 1, Entry 5)
1H NMR (500 MHz, CDCl3, 25 °C, TMS): d = 7.49–7.51 (d, J = 8.5
Hz, 2 H), 7.35–7.38 (d, J = 8.5 Hz, 2 H), 5.46 (s, 1 H), 4.24–4.28
(dd, J = 4.9, 10.9 Hz, 2 H), 3.95–4.00 (pseudo-t, J = 10.9 Hz, 2 H),
2.16–2.26 (tq, J = 5.0 Hz, J = 13.3 Hz, 1 H), 1.43–1.47 (quintd, J =
1.3 Hz, J = 13.3 Hz, 1 H).
1H NMR (250 MHz, CDCl3, 25 °C, TMS): d = 7.30 (t, J = 7.60 Hz,
1 H), 7.15–6.95 (m, 3 H), 5.45 (t, J = 3.4 Hz, 1 H), 3.70–3.95 (m, 5
H), 3.60 (m, 1 H), 1.55–2.19 (m, 7 H), 1.47 (s, 3 H), 1.20 (quintd,
J = 1.1, 13.2 Hz, 1 H).
13C NMR (63 MHz, CDCl3, 25 °C, TMS): d = 157.6, 142.9, 129.8,
120.1, 114.9, 114.7, 100.2, 96.4, 61.9, 61.3, 31.9, 30.2, 25.4, 25.2,
18.7.
13C NMR (125 MHz, CDCl3, 25 °C, TMS): d = 138.60, 130.82,
129.60, 124.23, 101.67, 64.30, 24.21.
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B. Karimi et al.
PAPER
1,5-Dioxaspiro[5.11]heptadecane
J = 11.5 Hz, 2 H), 3.80–3.86 (m, 4 H), 3.62–3.64 (d, J = 11.5 Hz, 2
H), 1.03 (s, 18 H), 0.23 (s, 12 H).
13C NMR (125 MHz, CDCl3, 25 °C, TMS): d = 156.79, 131.64,
127.83, 120.45, 115.59, 102.44, 71.49, 70.98, 32.77, 26.16, 18.67,
–4.19.
1H NMR (250 MHz, CDCl3, 25 °C, TMS): d = 3.57–3.79 (m, 4 H),
1.59–1.66 (m, 6 H), 1.16–1.26 (br m, 18 H).
13C NMR (63 MHz, CDCl3, 25 °C, TMS): d = 100.77, 60.28, 60.03,
40.30 (2 ×), 36.50, 30.29 (7 × s), 19.25 (2 × s).
3,9-Bis-m-bromophenyl-2,4,8,10-tetraoxaspiro[5.5]undecane
1H NMR (500 MHz, CDCl3, 25 °C, TMS): d = 7.71 (s, 2 H), 7.51–
7.53 (m, 2 H), 7.44–7.45 (d, J = 7.7 Hz, 2 H), 7.26–7.29 (t, J = 7.7
Hz, 2 H), 5.42 (s, 2 H), 4.82–4.84 (d, J = 11.5 Hz, 2 H), 3.80–3.83
(m, 4 H), 3.60–3.63 (d, J = 11.5 Hz, 2 H).
Acknowledgment
We are thankful to Institute for Advanced Studies in Basic Sciences
(IASBS) Research Council for support of this work.
13C NMR(125 MHz, CDCl3, 25 °C, TMS): d = 140.52, 132.52,
130.40, 129.36, 125.30, 122.82, 101.42, 71.33, 70.82, 32.91.
References
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9-Phenyl-1,5-dioxaspiro[5.5]undecane (Table 2, Entry 1)
1H NMR (500 MHz, CDCl3, 25 °C, TMS): d = 7.29–7.32 (m, 2 H),
7.24–7.26 (m, 2 H), 7.18–7.22 (tt, J = 1.4, 7.2 Hz, 5 H), 3.97–4.00
(t, J = 5.7 Hz, 2 H), 3.93–3.95 (t, J = 5.7 Hz, 2 H), 2.56–2.60 (tt,
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6 H), 1.47–1.54 (m, 2 H).
13C NMR (125 MHz, CDCl3, 25 °C, TMS): d = 154.93, 128.23,
126.57, 98.36, 55.01, 66.81, 33.73, 29.76, 28.36, 28.35.
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3,9-Di-m-phenoxyphenyl-2,4,8,10-tetraoxaspiro[5.5]undecane
(Table 2, Entry 3)
1H NMR (500 MHz, CDCl3, 25 °C, TMS): d = 7.40–7.44 (m, 6 H),
7.35–7.37 (d, J = 7.15 Hz, 2 H), 7.32 (s, 2 H), 7.18–7.21 (t, J = 7.5
Hz, 2 H), 7.09–7.13 (m, 6 H), 5.45 (s, 2 H), 4.88–4.90 (d, J = 11.25
Hz, 2 H), 3.80–3.84 (m, 4 H), 3.59–3.61 (d, J = 11.25 Hz, 2 H).
13C NMR (125 MHz, CDCl3, 25 °C, TMS): d = 157.76 (2 × s),
140.59, 130.28 (2 × s), 123.92, 121.56, 119.88, 119.23, 117.32,
102.08, 71.41, 70.86, 32.88.
3,9-Bis-p-fluorophenyl-2,4,8,10-tetraoxaspiro[5.5]undecane
(Table 2, Entry 6)
1H NMR (500 MHz, CDCl3, 25 °C, TMS): d = 7.49–7.52 (dd, J =
8.5, 5.5 Hz, 4 H), 7.08–7.12 (t, J = 8.5 Hz, 4 H), 5.46 (s, 2 H), 4.86–
4.88 (d, J = 11.5 Hz, 2 H), 3.83–3.88 (m, 4 H), 3.66–3.68 (d, J =
11.5 Hz, 2 H).
13C NMR (125 MHz, CDCl3, 25 °C, TMS): d = 164.51, 162.55,
134.36, 128.45, 115.56, 102.02, 71.43, 70.94, 32.83.
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3,9-Di-p-methylthiophenyl-2,4,8,10-tetraoxaspiro[5.5]unde-
cane (Table 2, Entry 7)
1H NMR (500 MHz, CDCl3, 25 °C, TMS): d = 7.42–7.43 (d, J = 8.3
Hz, 4 H), 7.27–7.29 (d, J = 8.3 Hz, 4 H), 5.44 (s, 2 H), 4.85–4.87 (d,
J = 11.6 Hz, 2 H), 3.82–3.86 (m, 4 H), 3.65–3.67 (d, J = 11.6 Hz, 2
H), 2.50 (s, 3 H).
13C NMR (125 MHz, CDCl3, 25 °C, TMS): d = 140.03, 135.25,
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3,9-Di-p-isopropylphenyl-2,4,8,10-tetraoxaspiro[5.5]undecane
(Table 2, Entry 8)
1H NMR (500 MHz, CDCl3, 25 °C, TMS): d = 7.49–7.50 (d, J = 8.1
Hz, 4 H), 7.31–7.32 (d, J = 8.1 Hz, 4 H), 5.50 (s, 2 H), 4.92–4.94 (d,
J = 11.6 Hz, 2 H), 3.80–3.89 (m, 4 H), 3.66–3.68 (d, J = 11.6 Hz, 2
H), 2.93–3.02 (sept, J = 6.9 Hz, 2 H), 1.30–1.32 (d, J = 6.9 Hz, 12
H).
13C NMR (125 MHz, CDCl3, 25 °C, TMS): d = 150.32, 136.01,
126.88, 126.49, 102.73, 71.52, 71.04, 34.46, 32.88, 24.43.
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3,9-Bis-[4-(tert-butyldimethylsilanyloxy)phenyl]-2,4,8,10-tetra-
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1H NMR (500 MHz, CDCl3, 25 °C, TMS): d = 7.40–7.42 (d, J = 8.3
Hz, 4 H), 6.89–6.90 (d, J = 8.3 Hz, 4 H), 5.43 (s, 2 H), 4.89–4.91 (d,
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