1,3-Dioxanes, 1,3-Dioxolanes
T. W. Green, P. G. M. Wuts,
Protective Groups in Organic Synthesis,
Wiley-Interscience, New York, 1999, 308-322, 724-727.
Stability
| H2O: | pH < 1, 100°C | pH = 1, RT | pH = 4, RT | pH = 9, RT | pH = 12, RT | pH > 12, 100°C |
| Bases: | LDA | NEt3, Py | t-BuOK | Others: | DCC | SOCl2 |
| Nucleophiles: | RLi | RMgX | RCuLi | Enolates | NH3, RNH2 | NaOCH3 |
| Electrophiles: | RCOCl | RCHO | CH3I | Others: | :CCl2 | Bu3SnH |
| Reduction: | H2 / Ni | H2 / Rh | Zn / HCl | Na / NH3 | LiAlH4 | NaBH4 |
| Oxidation: | KMnO4 | OsO4 | CrO3 / Py | RCOOOH | I2, Br2, Cl2 | MnO2 / CH2Cl2 |
General
1,3-Dioxanes and 1,3-dioxolanes can easily be prepared from carbonyl compounds with 1,3-propanediol or 1,2-ethanediol in the presence of a Brönsted or a Lewis acid catalyst. 1,3-Diols give more stable compounds. A standard procedure for protection employs toluenesulfonic acid as catalyst in refluxing toluene, which allows the continuous removal of water from the reaction mixture using a Dean-Stark apparatus. Admixture of orthoesters or molecular sieves can also provide effective water removal through chemical reaction or physical sequestration.
Cyclic acetals offer stability against all types of nucleophiles and bases.
Deprotection is often performed by acid catalyzed transacetalization in acetone or hydrolysis in wet solvents or in aqueous acid. Some strong oxidation agents may cleave acetals such as HClO4 in CH2Cl2. Cyclic ketals and acetals as a rule are stable to mild high-valent chromium reagents (PCC, PDC, Jones, etc.), but strongly acidic reagents will oxidize them to the lactone, or related cleavage products. Addition of strong Lewis acids enhances the sensitivity towards oxidants such as KMnO4, and MCPBA.
Protection of Carbonyl Compounds
Acyclic and cyclic acetals of various carbonyl compounds were obtained in
excellent yields in the presence of trialkyl orthoformate and a catalytic amount
of tetrabutylammonium tribromide (TBATB) in absolute alcohol. This mild,
chemoselective method allows acetalization of an aldehyde in the presence of
ketone, unsymmetrical acetal formation, and tolerates acid-sensitive protecting
groups. Facile isolation of the desired products and the catalytic nature of the
reagent make the present methodology a practical alternative.
R. Gopinath, Sk. J. Haque, B. K. Patel, J. Org. Chem.,
2002,
67, 5842-5845.
Zirconium tetrachloride (ZrCl4) is a highly efficient and
chemoselective catalyst for the acetalization, and in-situ
transacetalization of carbonyl compounds under mild reaction conditions.
H. Firouzabadi, N. Iranpoor, B. Karimi, Synlett, 1999, 321-323.
Various types of carbonyl compounds are efficiently converted to their
1,3-dioxanes by the use of 1,3-bis(trimethylsiloxy)propane (BTSP) and a
catalytic amount of iodine under essentially neutral aprotic condition.
B. Karimi, B. Golshani, Synthesis,
2002, 784-788.
Other Syntheses of Cyclic Acetals
Ammonium salts that can act as hydrogen-bond donors exert a remarkable
acceleration on the rates of the regioselective arylation of electron-rich
olefins by aryl halides in ionic liquids and common solvents.
J. Mo, J. Xiao, Angew. Chem. Int. Ed., 2006,
45, 4152-4157.
A new palladium(0)-catalyzed three-component reaction of salicylic aldehyde
triflates, ethylene glycol vinyl ether, and various secondary nucleophilic
amines involving an initial internal Heck arylation, iminium ion formation, and
subsequent tandem cyclization gives tertiary 3-aminoindan acetals.
A. Arefalk, M. Larhed, A. Hallberg, J. Org. Chem., 2005,
70, 938-942.
Deprotection
Er(OTf)3 is a very gentle Lewis acid catalyst in the chemoselective
cleavage of alkyl and cyclic acetals and ketals at room temperature in wet
nitromethane.
R. Dalpozzo, A. De Nino, L. Maiuolo, M. Nardi, A. Procopio, A. Tagarelli, Synthesis, 2004,
496-498.
A chemoselective method for the cleavage of acetals and ketals at room
temperature in wet nitromethane by using catalytic cerium(III) triflate at
almost neutral pH is presented. High yields and selectivity make this procedure
particularly attractive for multistep synthesis.
R. Dalpozzo, A. De Nino, L. Maiuolo, A. Procopio, A. Tagarelli, G. Sindona, G.
Bartoli, J. Org. Chem.,
2002,
67, 9093-9095.
A convenient method for deprotection of acetals and ketals catalyzed by
molecular iodine in acetone is reported. The deprotection of acyclic or cyclic
O,O-acetals and O,O-ketals is achieved in excellent yields within
minutes under neutral conditions. Double bonds, hydroxyl groups, acetate groups,
and highly acid-sensitive groups such as furyl, tert-butyl ethers, and
ketoximes are tolerated.
J. Sun, Y. Dong, L. Cao, X. Wang, S. Wang, Y. Hu, J. Org. Chem.,
2004,
69, 8932-8934.
Deprotection of acetals and ketals can be achieved by using a catalytic
amount of sodium tetrakis(3,5-trifluoromethylphenyl)borate (NaBArF4)
in water at 30 °C. For example, a quantitative conversion of
2-phenyl-1,3-dioxolane into benzaldehyde was accomplished within five minutes.
C.-C. Chang, B.-S. Liao, S.-T. Liu, Synlett, 2007, 283-287.
Conversion of Cyclic Acetals and Ketals to Other Functional Groups
Aldehydes and ketones were protected as their thioacetals in the presence of a
catalytic amount of iodine. These mild reaction conditions were also applied in
the transthioacetalization of O,O-acetals,
O,O-ketals and O,S-acetals and acylals.
H. Firouzabadi, N. Iranpoor, H. Hazarkhani, J. Org. Chem., 2001,
66, 7527-7529.
An efficient oxidation of various acetals, including open-chain acetals,
1,3-dioxanes and 1,3-dioxalanes, with molecular oxygen in the presence of
catalytic amounts of N-hydroxyphthalimide (NHPI) and Co(OAc)2
as co-catalyst gave esters.
B. Karimi, J. Rajabi, Synthesis,
2003, 2373-2377.
An efficient conversion of cyclic acetals to their corresponding hydroxy alkyl
esters was demonstrated. This oxidation using MCPBA gave products in good to
excellent yields.
J. Y. Kim, H. Rhee, M. Kim, J. Korean Chem. Soc., 2002, 46,
479-483.
