Convenient preparation of cyclic acetals, using diols, TMS-source, and a catalytic amount of TMSOTf

Article abstract of DOI:10.1021/jo020471z

With use of diol, alkoxysilane, and a catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf), carbonyl compounds are converted to acetals in good yields under mild conditions. This procedure, which was carried out without synthesizing the silylated diols, is a more convenient adaptation of Noyori's method. This acetalization applies to not only simple but also conjugated carbonyl compounds. Moreover, various TMS compounds, including solid supported compounds, are effective for this method instead of alkoxylsilane.

Full text of DOI:10.1021/jo020471z

Con ven ien t P r ep a r a tion of Cyclic Aceta ls, Usin g Diols,
TMS-Sou r ce, a n d a Ca ta lytic Am ou n t of TMSOTf
Masaaki Kurihara* and Wataru Hakamata
Division of Organic Chemistry, National Institute of Health Sciences,
Setagaya-ku, Tokyo 158-8501, J apan
masaaki@nihs.go.jp
Received J uly 15, 2002
With use of diol, alkoxysilane, and a catalytic amount of trimethylsilyl trifluoromethanesulfonate
(TMSOTf), carbonyl compounds are converted to acetals in good yields under mild conditions. This
procedure, which was carried out without synthesizing the silylated diols, is a more convenient
adaptation of Noyori’s method. This acetalization applies to not only simple but also conjugated
carbonyl compounds. Moreover, various TMS compounds, including solid supported compounds,
are effective for this method instead of alkoxylsilane.
In tr od u ction
plication of this method with various “TMS-sources” as
silylating agents.
The utility of acetalization in organic synthesis is well-
recognized for protection of carbonyl compounds1 and the
generation of chiral auxiliaries for asymmetric induction.2
The introduction of new methods and modification of
existing methogology for making acetals is thus an impor-
tant challenge. Among acetalization methods,3 Noyori’s
procedure4 with silylated alcohols and a catalytic amount
of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as
Lewis acid is useful for the synthesis of acetals, under
mild conditions. We reported a facile procedure of acet-
alization using diols, alkoxysilanes, and a catalytic
amount of TMSOTf.5 This modification of the Noyori
procedure uses an alkoxysilane and avoids preparation
of the silylated diols. Recently, Ikegami and co-workers
have succeeded in synthesis of glycosidic spiro-ortho
esters under similar conditions.6 We describe now ap-
Resu lts a n d Discu ssion
Carbonyl compounds were treated with various chiral
and achiral diols, alkoxysilanes, and a catalytic amount
of TMSOTf in CH2Cl2 at -20 °C to prepare the corre-
sponding acetals in high yields under mild conditions
(Table 1). R,â-Unsaturated carbonyl compounds (1f and
1g) were converted to acetals without double bond
migration. Sterically hindered ketones (1d and 1e) were
also converted to acetals in good yield (entries 1 and 2 in
Table 1). Carbamate and ester groups were well-tolerated
under these conditions. Several TMS compounds were
examined as replacements for the alkoxysilane in the
synthesis of acetal 4a . 3-Trimethylsilyl-2-oxazolidinone
(3c), N-(trimethylsilyl)acetamide (3d ), and 2-(trimethyl-
silyloxy)furan (3f) proved effective as TMS-sources for
this acetalization; however, 1-(trimethylsilyl)imidazole
(3e) failed to affect this reaction (Table 2), suggesting that
amines may inactivate the Lewis acid in this reaction. A
solid-supported TMS-source 3h , which was prepared by
trimethylsilylation of Wang resin, also proved effective
(entry 8 in Table 2).
(1) Greene, T. W.; Wuts, P. G. M. Protective Group in Organic
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When diol 2a was treated with isopropoxytrimethyl-
silane 3a in the presence of a catalytic amount of
TMSOTf in dichloromethane at -20 °C, disilylated diol
was shown to be formed by GLC analysis7 (Scheme 1).
Silylation of the diol in situ may thus proceed in the
presence of a catalytic amount of TMSOTf prior to the
acetalization.
Because these conditions were effective for the prepa-
ration of acetals, they may serve in other reactions such
(6) Ohtake, H.; Iimori, T.; Ikegami, S. Tetrahedron Lett. 1997, 38,
3413-3414.
(7) Gas chromatographic analyses were performed with a CBP-1
column (50 m, φ 0.25 mm, carrier gas He, column temperature 100
°C, flow 0.6 mL/min). The retention times of diol 2a and disilylated
diol were 1.97 and 3.29 min, respectively.
(5) Kurihara, M.; Miyata, N. Chem. Lett. 1995, 263.
10.1021/jo020471z CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/28/2003
J . Org. Chem. 2003, 68, 3413-3415
3413

Kurihara and Hakamata
TABLE 1.
TABLE 2.
SCHEME 1
a
Entry 13: rt, 16 h.
mmol) in dry CH2Cl2 (10 mL) was added TMSOTf (0.007 mmol)
at -20 °C under argon atmosphere. The reaction mixture was
stirred for 3 h, treated with pyridine (0.5 mL) and evaporated
under reduced pressure to a residue that was purified by silica
gel chromatography to afford acetal.
The acetals 4b,12 4d ,13 4f,14 4g,15 4h ,16 4i,15 4j,17 4k ,3a 4l,3b
4m ,4b and 4p 18 were identified by comparison with the
literature known NMR data.
F IGURE 1.
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625-628. (b) Shiina, I.; Mukaiyama, T. Chem. Lett. 1992, 2319-2320.
(9) Mukaiyama, T.; Izumi, J .; Miyashita, M.; Shiina, I. Chem. Lett.
1993, 907-910.
as esterifications,8 lactonizations,9 and glycosidations10
which employ similar silylated compounds.
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1984, 25, 1379-1382. (b) Tietze, L.-F.; Fischer, R.; Guder, H.-J .
Tetrahedron Lett. 1982, 23, 4661-4664.
Exp er im en ta l Section
(11) Trimethylisopropoxysilane is commercially available from Shin-
etsu silicon Chemicals.
NMR spectra were recorded on a 300-MHz spectrometer.
Alkoxysilanes 3a -c were synthesized with the respective
alcohol, TMSCl, and triethylamine in solvent.11 Other TMS
compounds were obtained from commercial sources. Dry
CH2Cl2 was purchased from a commercial supplier.
(12) Fioravanti, S.; Loreto, M. A.; Pellacani, L.; Tardella, P. A.
Tetrahedron 1991, 47, 5877.
(13) Sugimura, T.; Yoshikawa, M.; Futagawa, T.; Tai, A. Tetrahedron
1990, 46, 5955.
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1990, 393.
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hedron 1989, 45, 507.
Gen er a l P r oced u r e for Aceta liza tion . To a mixture of
ketone (0.672 mmol), diol (0.862 mmol), and TMS-source (2.68
3414 J . Org. Chem., Vol. 68, No. 9, 2003

Convenient Preparation of Cyclic Acetals
6-P h en yl-1,4-dioxaspir o[4,5]decan e (4a). 1H NMR (CDCl3)
δ 1.62-1.88 (8 H, m), 2.51-2.60 (1 H, m), 3.98 (4 H, s), 7.15-
7.31 (5 H, m); 13C NMR (CDCl3) δ 31.50, 35.10, 43.29, 64.24,
64.28, 108.46, 126.82, 128.29, 146.52. HRMS (FAB) calcd for
126.91, 128.28, 146.67. HRMS (FAB) calcd for C18H25O2 (M+
+ H) 273.1855, found 273.1858.
Ben zyl 1,4-Dioxa -7-a za sp ir o[4,5]d eca n e-7-ca r boxyla te
1
(4n ). H NMR (CDCl3) δ 1.74 (4 H, s), 3.43 (4 H, m), 3.95 (4
C
14H19O2 (M+ + H) 219.1385, found 219.1378.
H, m), 5.43 (2 H, s), 7.34 (5 H, m); 13C NMR (CDCl3) δ 22.85,
33.96, 43.68, 49.61, 49.79, 64.52, 66.99, 105.31, 127.72, 127.82,
128.15, 136.76, 155.46. HRMS (FAB) calcd for C15H20O4 (M+
+ H) 278.1392, found 278.1393.
9-P h en yl-1,5-d ioxa sp ir o[5,5]u n d eca n e (4c). 1H NMR
(CDCl3) δ 1.48 (2 H, m), 1.62-1.81 (6 H, m), 2.40 (2 H, m),
2.56 (1 H, m), 3.92 (2 H, t, J ) 5.6 Hz), 3.97 (2 H, t, J ) 5.6
Hz), 7.15-7.32 (5 H, m); 13C NMR (CDCl3) δ 25.70, 29.95,
32.98, 43.90, 59.12, 59.41, 97.36, 125.99, 126.85, 128.29,
146.63. HRMS (FAB) calcd for C15H21O2 (M+ + H) 233.1542,
found 233.1542.
Aceta liza tion w ith Solid Su r p or ted TMS-Sou r ce. Wang
resin (0.6-1.0 mmol/g) 5 g was treated with TMSCl (6 mmol)
and Et3N (6.5 mmol) in CH2Cl2 (40 mL), and then washed with
CH2Cl2 and dried. 3-Phenylcyclohexanone (0.1 mmol) was
treated with ethylene glycol (0.12 mmol), silylated resin 3h
(500 mg), and a catalytic amount of TMSOTf in CH2Cl2 at -20
°C for 3 h. The reaction mixture was filtered and purified by
silica gel chromatography.
Hexah ydr o-4′-ph en yl-tr a n s-spir o[1,3-ben zodioxole-2,1′-
1
cycloh exa n e] (4e). H NMR(CDCl3) δ 1.29 (2 H, m), 1.44 (2
H, m), 1.66-1.99 (10 H, m), 2.15 (2 H, m), 2.57 (1 H, m), 3.31
(2 H, m), 7.15-7.31 (5 H, m); 13C NMR (CDCl3) δ 23.75, 29.02,
31.05, 31.80, 35.90, 37.11, 43.38, 79.74, 80.08, 108.46, 125.97,
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for 4d , 4f, 4g, 4h , 4i, 4j, 4k , 4l, 4m , and 4p . This
material is available free of charge via the Internet at
http://pubs.acs.org.
(16) Suginome, H.; Wang, J . B. J . Chem. Soc., Perkin Trans. 1 1990,
2825.
(17) Arnold, D. R.; Lamout, L. J .; Perrott, A. L. Can. J . Chem. 1991,
69, 225.
(18) Hernandez, A.; Marcos, M.; Rapoport, H. J . Org. Chem. 1995,
60, 2683.
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