1,3-Dithianes, 1,3-Dithiolanes
T. W. Green, P. G. M. Wuts,
Protective Groups in Organic
Synthesis,
Wiley-Interscience, New York, 1999, 329-344, 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-Dithianes and 1,3-dithiolanes can easily be prepared from carbonyl compounds with 1,3-propanedithiol or 1,2-ethanedithiol in the presence of a Brönsted or a Lewis acid catalyst. Removal of a dithiane protection group often requires harsh conditions and is usually performed in the late synthetic stage.
Summary of the use of 1,3-dithianes in synthesis
Protection of Carbonyl Compounds
Carbonyl compounds have been successfully converted into their corresponding
oxathiolane, dithiolane, and dithiane derivatives with 2-mercaptoethanol,
1,2-ethanedithiol, and 1,3-propanedithiol using catalytic amount of yttrium
triflate. In addition, by using this catalyst, highly chemoselective protection
of aldehydes has been achieved.
S. K. De, Tetrahedron Lett., 2004, 45, 2339-3241.
Tungstophosphoric acid (H3PW12O40) was found to
be an effective and highly selective catalyst for the thioacetalization of
aldehydes, ketones, acetals, acylals and O,S-acetals in excellent yields
in the absence of solvent. Chemoselective conversions of α- or β-diketones and a
β-keto ester are described. Sterically hindered carbonyl compounds were
converted to the corresponding thioacetals in refluxing petroleum ether in good
yields.
H. Firouzabadi, N. Iranpoor, K. Amani, Synthesis,
2002, 59-60.
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.
A new procedure for the protection of aldehydes and ketones as thioacetals
promoted by catalytic amount of p-toluenesulfonic acid and silica gel has
been developed. This procedure offers versatility, short reaction time,
excellent yield, and is easy to carry out. A simple filtration followed by
removal of solvent in most cases produces pure product.
M. H. Ali, M. G. Gomes, Synthesis, 2005, 1326-1332.
Perchloric acid adsorbed on silica gel (HClO4-SiO2) has
been found to be an extremely efficient and reusable catalyst for 1,3-dithiolane
and 1,3-dithiane formation under solvent-free conditions at room temperature.
S. Rudrawar, R. C. Besra, A. K. Chakraborti,
Synthesis, 2006, 2767-2771.
Praseodymium triflate is an efficient and recyclable catalyst for chemoselective
protection of aldehydes.
S. K. De, Synthesis,
2004, 2837-2840.
As a non-thiolic, odorless propane-1,3-dithiol equivalent,
3-(1,3-dithian-2-ylidene)pentane-2,4-dione has been investigated in
acid-promoted thioacetalization under solvent-free conditions. A range of
selected aldehydes and aliphatic ketones have been converted into the
corresponding dithioacetals in high yields. The relatively slow reaction rate of
aromatic ketones allows chemoselective protection.
Y. Ouyang, D. Dong, C. Zheng, H. Yu, Q. Liu, Z. Fu,
Synthesis, 2006, 3801-3804.
3-(1,3-dithian-2-ylidene)pentane-2,4-dione has been used as a nonthiolic,
odorless 1,3-propanedithiol equivalent in the p-dodecylbenzenesulfonic
acid-catalyzed thioacetalization of various aldehydes and ketones in water.
D. Dong, Y. Ouyang, H. Yu, Q. Liu, J. Liu, M. Wang, J. Zhu, J. Org. Chem.,
2005,
70, 4535-4537.
Other Syntheses of Dithianes
b-Keto 1,3-dithianes can be generated by the double conjugate addition of
dithiols to propargylic ketones, esters and aldehydes in excellent yields. These
masked 1,3-dicarbonyl systems can be converted to a range of functionalised
oxygen-containing heterocycles that can be used in natural product synthesis.
M. J. Gaunt, H. F. Sneddon, P. R. Hewitt, P. Orsini, D. F. Hook, S. V. Ley,
Org. Biomol. Chem., 2003, 1, 15-16.
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, O,S-acetals and acylals.
H. Firouzabadi, N. Iranpoor, H. Hazarkhani, J. Org. Chem., 2001,
66, 7527-7529.
Deprotection
An efficient and convenient procedure has been developed for the hydrolysis of
thioacetals/thioketals to the corresponding carbonyl compounds in excellent
yields with o-iodoxybenzoic acid (IBX) in presence of β-cyclodextrin
(β-CD) in water under neutral conditions at room temperature.
N. S. Krishnaveni, K. Surendra, Y. V. D. Nageswar, K. R. Rao, Synthesis,
2003, 2295-2297.
An efficient, mild and chemoselective method for the deprotection of S,S-acetals
to the corresponding carbonyl compounds using silicasulfuric acid/NaNO3
is reported.
A. R. Hajipour, A. Zarei, L. Khazdooz, A. E. Ruoho,
Synthesis, 2006, 1480-1484.
Different new reactions of IBX with heteroatom-containing substrates were
discovered and their utility was demonstrated. IBX was used for the generation
of imines from secondary amines in notably high yields, for oxidative
aromatization of nitrogen heterocycles and for cleavage of dithianes.
K. C. Nicolaou, C. J. N. Mathison, T. Montagnon, Angew. Chem., 2003,
115, 4211-4216.
A new and efficient method for the cleavage of the PMP, THP and 1,3-dithiane
protecting groups with Selectfluor™ has been developed.
J. Liu, C.-H. Wong, Tetrahedron Lett., 2002, 43, 4037-4039.
Deprotection of several dithiane-containing alkaloids and a nonchromatic
purification cleanly generates corresponding ketoamines. The described procedure
is ideal for labile alkaloids.
F. F. Fleming, L. Funk, R. Altundas, Y. Tu, J. Org. Chem., 2001,
66, 6502 - 6504.
Conversion of Dithianes to Other Functional Groups
Different new reactions of IBX with heteroatom-containing substrates were
discovered and their utility was demonstrated. IBX was used for generation of
imines from secondary amines in notably high yields, for oxidative aromatization
of nitrogen heterocycles and for cleavage of dithianes.
K. C. Nicolaou, C. J. N. Mathison, T. Montagnon, Angew. Chem., 2003,
115, 4211-4216.
Easily prepared 2-alkyl-1,3-dithiane derivatives were reacted with BrF3
to form the corresponding 1,1-difluoromethyl alkanes in good yield. The reaction
proceeds well with primary alkyl halides. The limiting step for secondary alkyl
halides is the relatively low yield of the dithiane preparation.
R. Sasson, A. Hagooly, S. Rozen, Org. Lett., 2003,
5, 3635-3641.
Dithianes in Multi-step Syntheses
A linchpin coupling protocol is based on anion relay chemistry (ARC). The
addition of an anion to an epoxide, bearing on a distal carbon a trialkyl silyl
group and an anion stabilizing group furnishes upon epoxide ring opening an
oxyanion. Addition of HMPA triggers a solvent controlled 1,4-Brook rearrangement
leading to a new distal anion, which reacts with various electrophiles.
A. B. Smtih, III, M. Xiang, J. Am. Chem. Soc., 2006,
128, 66-67.
Arenesulfonates of primary alcohols react smoothly with lithio derivatives of
1,3-dithiane and 2-phenyl-1,3-dithiane at room temperature to give 2-alkyl
derivatives in high yields.
D. Seebach, E.-M. Wilka, Synlett,
1976, 476-477.
While 3,4;5,6-di-O-isopropylidene-N-phthaloyl-D-glucosamine
propane-1,3-diyl dithioacetal underwent fast β-elimination, the corresponding
N-acetyl derivative was easily deprotonated with butyllithium to form the
dilithiated intermediate. Stoichiometry and temperature were crucial factors for
selective C-C coupling with various electrophiles.
Y.-L. Chen, R. Leguijt, H. Redlich, R. Fröhlich,
Synthesis, 2006, 4212-4218.
Multicomponent Linchpin Coupling of Silyl Dithianes Employing an N-Ts
Aziridine as the Second Electrophile: Synthesis of (-)-Indolizidine 223AB
A. B. Smith, D.-S. Kim, Org. Lett., 2004,
6, 1493-1495. DOI:
10.1021/jo035391p
(free Supporting Information)
Total Synthesis of the Boron-Containing Ion Carrier Antibiotic Macrodiolide
Tartrolon B
J. Mulzer, M. Berger, J. Org. Chem., 2004,
69, 891-898. DOI:
10.1021/jo035391p
(free Supporting Information)
Reviews
The role of 1,3-dithianes in natural product synthesis
Miguel Yus, Carmen Nájera and Francisco Foubelo, Tetrahedron,
2003, 59, 6147-6212. DOI:
10.1016/S0040-4020(03)00955-4
