Highy Efficient Deprotection of Acetals and Ketals under Neutral and Anhydrous Conditions Using (Trimethylsilyl)bis(fluorosulfuryl)imide

Full text of DOI:10.1021/jo971756s

J . Org. Chem. 1998, 63, 2365-2366
2365
Ta ble 1. Dep r otection of Aceta ls a n d Keta ls w ith
High ly Efficien t Dep r otection of Aceta ls
a n d Keta ls u n d er Neu tr a l a n d An h yd r ou s
Con d ition s Usin g
a
TMSN(SO2F )2
(Tr im eth ylsilyl)bis(flu or osu lfu r yl)im id e
Gurmeet Kaur, Achla Trehan, and Sanjay Trehan*
Department of Chemistry, Panjab University,
Chandigarh-160014, India
Received September 19, 1997
The deprotection of acetals and ketals is an important
transformation in organic synthesis. This transformation
is usually accomplished by aqueous acid hydrolysis.1
Although some methods using less acidic conditions2 have
been developed, the methods using nonacidic and anhy-
drous conditions have gained importance for acid-sensi-
tive substrates. These include use of transition metals
and Lewis acids,3 oxidative methods,4 phosphorus-based
reagents,5 and silicon-based reagents,6 each having their
own advantages. Here, we report a very mild method
for the deprotection of acetals or ketals under neutral
and anhydrous conditions using (trimethylsilyl)bis(fluo-
rosulfuryl)imide [TMSN(SO2F)2].7 Under these condi-
tions, deprotection is achieved at as low as -78 °C for
dimethyl acetals, and only very weak nucleophiles are
present in the reaction mixture.
Benzaldehyde dimethyl acetal in CH2Cl2 was treated
with 5 mol % of TMSN(SO2F)2 at -78 °C, and the reaction
was monitored by TLC. On completion of the reaction
(15 min), the low-temperature bath was removed and the
reaction was quenched by adding saturated aqueous
sodium bicarbonate. Using this procedure, benzaldehyde
was obtained in 92% yield after usual workup.8,9 En-
a
Reactions were carried out at -78 °C using 5 mol % of
TMSN(SO2F)2 unless otherwise stated. b 1.1 equiv of TMSN(SO2F)2
was used. c Reactions carried out at 0 °C.
(1) Greene, T. W.; Wuts, P. G. M. Protecting Groups in Organic
Synthesis, 2nd ed.; J ohn Wiley & Sons, Inc.: New York, 1991.
(2) (a) Oku, A.; Kinugasa, M.; Kamada, T. Chem. Lett. 1993, 165.
(b) Kametani, T.; Kondoh, H.; Honda, T.; Ishizona, H.; Suzuki, Y.; Mori,
W. Chem. Lett. 1989, 901. (c) Huet, F.; Lechevalier, A.; Pellet, M.;
Conia, J . M. Synthesis 1978, 63. (d) Sterzycki, R. Synthesis 1979, 724.
(3) (a) Gros, P.; LePerchec, P.; Senet J . P. J . Chem. Res., Synop.
1995, 196. (b) Wu, S.H.; Biao, D. Z. Synth. Commun. 1994, 24, 2173.
(c) Ma, S.; Venanzi, L. M. Tetrahedron Lett. 1993, 34, 8071. (d) Chang,
C.; Chu, K. C.; Yue, S. Synth. Commun. 1992, 22, 1217. (e) Mandal,
A. K.; Shrotri, P. Y.; Ghogare, A. D. Synthesis 1986, 221. (f) Kim, K.
S.; Song, Y. H.; Lee, B. H.; Hahn, C. S. J . Org. Chem. 1986, 51, 404.
(g) Lipshutz, B. H.; Pollart, D.; Monforte, J .; Kotsuki, H. Tetrahedron
Lett. 1985, 705. (h) Lipshutz, B. H.; Harvey, D. F. Synth. Commun.
1982, 12, 267. (i) Balme, G.; Gore, J . J . Org. Chem. 1983, 48, 3336.
(4) (a) Nishiguchi, T.; Ohosima, T.; Nishida, A.; Fujisaki, S. J . Chem.
Soc., Chem. Commun. 1995, 1121. (b) Tanemura, K.; Suzuki, T.;
Horaguchi, T. J . Chem. Soc. Chem. Commun. 1992, 979. (c) Barton,
D. H. R.; Magnus, P. D.; Smith, G.; Streckert, G.; Zurr, D. J . Chem.
Soc., Perkin Trans 1 1972, 542.
couraged by this result, reactions using various repre-
sentative dimethyl acetals or ketals were carried out. The
results are summarized in Table 1. Acetals and ketals
of aromatic carbonyl compounds underwent deprotection
within 15 min, whereas for those of aliphatic carbonyl
compounds the reaction was relatively slow (4-12 h). The
reaction of aliphatic carbonyl compounds could be ac-
celerated by raising the temperature of the reaction to 0
°C; for example, heptaldehyde dimethyl acetal could be
deprotected in less than 2 h at 0 °C with similar yields.
Isolated yields of deprotected products were very high.
However, the 1,3-dioxolanes of benzaldehyde and cy-
clohexanone only underwent partial deprotection (<15%)
under these conditions even when the temperature was
raised to 25 °C. After some experimentation, it was
found that by using slightly more than 1 equiv of TMSN-
(SO2F)2 at 0 °C benzaldehyde and cyclohexanone could
be isolated in 84% and 79% yield, respectively. Some
unprotected (<10%) 1,3-dioxolane was still present in
both cases.
(5) (a) J ohnstone, C.; Kerr, W. J .; Scott, J . S. J . Chem. Soc. Chem.
Commun. 1996, 341. (b) Denis, J . N.; Krief, A. Angew Chem., Int. Ed.
Engl. 1980, 19, 1006.
(6) (a) Olah, G. A.; Husain, A.; Singh, B. P.; Mehrotra, A. K. J . Org.
Chem. 1983, 48, 3667. (b) J ung, M. E.; Andrus, W. A.; Ornstein, P. L.
Tetrahedron Lett. 1977, 4175.
(7) Trehan, A.; Vij, A.; Walia, M.; Kaur, G.; Verma, R. D.; Trehan,
S. Tetrahedron Lett. 1993, 7335.
(8) Trimethylsilyl trifluoromethanesulfonate (TMSOTf) has been
used for the deprotection of oxathiolanes; see: Ravindernathan, T.;
Chavan, S. P.; Dantale, S. W. Tetrahedron Lett. 1995, 2285.
(9) When same reaction was carried out using TMSOTf (up to 25
mol %) as a catalyst instead of TMSN(SO2F)2 some benzaldehyde
formation (5-10%) was observed. However, when the reaction was
carried out at 40 °C for 8 h only 46% benzaldehyde was isolated and
rest was nonpolar byproducts. This experiment showed that TMSOTf
is inferior to TMSN(SO2F)2 for this type of deprotection.
These results can be rationalized by the catalytic cycle
shown in Scheme 1. TMSN(SO2F)2 silylates one of the
oxygens of the acetal or ketal to give 2, which loses
TMSOCH3 to give oxonium ion 3. The TMSOCH3 then
attacks the methyl of the oxonium ion to give dimethyl
ether and free carbonyl compound. Trimethylsilyl cation
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2366 J . Org. Chem., Vol. 63, No. 7, 1998
Notes
Sch em e 1
to this likely equilibrium, complete deprotection is not
observed for 1,3-dioxolanes.
In conclusion, this work demonstrates TMSN(SO2F)2
as a highly efficient catalyst for the deprotection of
dimethyl acetals or ketals. Only 5 mol % of catalyst at
-78 °C is sufficient for complete conversion. Due to the
-
non-nucleophilic nature of N(SO2F)2 the catalyst is
regenerated. Thus, TMSN(SO2F)2 is an alternative
catalyst for silyl iodides, which are used in stoichiometric
amounts. Also, silyl iodides do not deprotect 1,3-dioxo-
lanes, whereas TMSN(SO2F)2 when used in a stoichio-
metric amount can be used for their deprotection.
Exp er im en ta l Section
Ma ter ia ls. Acetals or ketals were prepared by reaction of
aldehydes or ketones with methanol in the presence of 1.5 equiv
of trimethyl orthoformate and a catalytic amount of p-toluene-
sulfonic acid under refluxing conditions. On completion of the
reaction, it was neutralized by adding methanolic NaOH. Excess
methanol and trimethyl orthoformate were evaporated to dry-
ness using a rotary evaporator, and the residue was purified
either by distillation or by flash chromatography. TMSN(SO2F)2
was prepared as described in the literature.7
Gen er a l P r oced u r e for Dep r otection . A solution of acetal
(1 equiv) in dichloromethane (4 mL/mmol) under nitrogen
atmosphere at the temperature shown in Table 1 was treated
with TMSN(SO2F)2 (5 mol %). The reaction was monitored by
TLC. On completion of the reaction the low-temperature bath
was removed in the cases where it was done at -78 °C. The
reaction was quenched by adding saturated aqueous sodium
bicarbonate, and the product was extracted into ether. The ether
layer was washed with brine and was dried (Na2SO4). Removal
of the solvent gave a residue that was pure by NMR or TLC in
all cases. The products could be further purified by flash
chromatography and were identified by comparison of their
NMR, IR, TLC, and mixed TLC analysis with the authentic
samples.
-
formed in the process combines with the N(SO2F)2 to
regenerate the catalyst.10 Another possibility could be
that oxonium ion pair 3 collapses to give CH3N(SO2F)2
and free carbonyl compound. Subsequent deprotection
may then be catalyzed by CH3N(SO2F)2. To check this
possibility, CH3N(SO2F)2 was prepared11 and was treated
with benzaldehyde dimethyl acetal. It did not give any
deprotected product even at 0 °C, and starting material
was recovered. This clearly indicates that TMSN(SO2F)2
is the true catalyst.12
In the case of 1,3-dioxolanes, one would expect ethylene
oxide formation instead of dimethyl ether, and under
these conditions the ethylene oxide may be reacting with
the carbonyl compound to give back 1,3-dioxolane.13 Due
(10) When silyl iodides are used for the deprotection of dimethyl
acetals, the oxonium ion of type 3 is formed, but iodide ion being a
stronger nuclephile than silylmethoxide reacts preferentially with
methyl group of 3 to give methyl iodide and free carbonyl compound.6
As a result, silyl iodides get consumed during the process and at least
1 equiv of the reagent is required for complete deprotection.6
(11) (a) Ruff, J . K. Inorg. Chem. 1965, 4, 1446. (b) Ruff, J . K.; Lustig,
M. Inorg. Synth. 1968, 11, 138.
Ack n ow led gm en t. We are thankful to CSIR for the
financial support of our research program and for
fellowships to G.K. and A.T.
(12) A reaction of heptaldehyde dimethyl acetal with TMSN(SO2F)2
J O971756S
in dichloromethane was monitored by 19F NMR. No peak corresponding
-
to CH3N(SO2F)2 was observed. This clearly indicates that N(SO2F)2
does not remove methyl group from the oxonium ion 3 to generate
CH3N(SO2F)2.
(13) Torok, D. S.; Figueroa, J . F.; Scott, W. J . J . Org. Chem. 1993,
58, 7274.