2-Alkyl-l ,3-dithianes

Oxidation of aldehydes to esters and acids Treatment of 2-lithio-2-alkyl-l,3-dithianes (1) with methyl disulfide in THF gives the corresponding orthothioformates (2) in about 90% yield. These are converted in high yield into esters (3) when refluxed in an aqueous alcohol in the presence of mercuric chloride and mercuric oxide as catalysts. Conversion to acids is accomplished by refluxing (2) in aqueous acetone for 24 hr. with catalysis by mercuric chloride and mercuric oxide. Yields in this case are in the range 40-65 %. 

Ethyl acetoacetate, 256, 257, 467, 507 Ethyl 2-alkyl-l, 3-dithiane-2-carboxylates, 230,231... 

Linalool, 51,416 Linde 5A, 345 Lindlar catalyst, 155, 283 2-Lithio-2-alkyl-l,3-dithianes, 216-218 Lithio-/-butylneopentylamine, 310 310... 

Aldehyde synthesis. Vedejs and Fuchs4 report that the usual methods for hydrolysis of a 2,2-dialkyl-1,3-dithiane (HgCL, + HgO or CdCOa) to a ketone give low yields in the hydrolysis of a 2-alkyl-l, 3-dithiane (1) to an aldehyde (2). They... 

The mass spectra of 1,3-dithianes is more complicated. The electron impact (El) mass spectrometry of 2-aryl and 2-alkyl-l,3-dithianes has been investigated with deuterium labeling studies and these showed the loss of S2H to be a common feature. <690MS(2)6l l, 720MS(7)317>. The El mass spectra of... 

High diastereofacial selectivity has been observed in asymmetric Mannich reactions of 2-acyl-2-alkyl-l,3-dithiane 1-oxides, leading to P-amino ketones in good yield [118]. This study is of particular significance since stereoselectiAdty in the Mannich reaction has received relatively little attention [119]. 

Enantiomerically pure DiTOX systems (95) and (96) were used to prepare a-hydroxy acids [132], Page had previously described the stereoselective reduction of 2-acyl-2-alkyl-l,3-dithiane 1-oxides with DIBAL [113], and normally observed [132] a reversal of selectivity upon addition of zinc chloride. In this case (Scheme 4.73), THF solutions of the substrates were treated at -78°C with either DIBAL or DIBAL/ZnCl2 reducing systems. As expected, the DIBAL and DIBAL/ZnClz reducing systems gave products of opposite stereoselectivity in most cases only one product diastereoisomer was observed. 

The concept of umpolung has been developed on the basis of such reactions. It is defined as the change in polarity of an atom in a functional group from electrophilic to nucleophilic character and vice versa. 2-Lithio-2-alkyl-l,3-dithiane 3 behaves like an umpoled ahphatic aldehyde R-CH=0. Aldehydes as electrophiles cannot react with alkyl haUdes, but after transformation of the aldehyde to the dithiane 1 and its litbio derivative 2, alkylation proceeds according to the sequence 1 3 4 5. 

L//-Indole, 3<2-phenyl-l, 3-dithian-2-yl), 10 Indoles, 34 Indoles, 3-acyl-, 8 Indoles, 3 -alkyl, 8 Isocyanate, chlorosulfonyl [Sulfuryl chlonde isocyanate], 41 Isocyanate,2-propyl- [Propane, 2-iso-cyanato-], 96... 

Suda and coworkers described the anodic oxidation of 2-silyl-l,3-dithianes which have two sulfur atoms on the carbon adjacent to silicon [42], In this case, however, the C Si bond is not cleaved, but the C-S bonds are cleaved to give the corresponding acylsilanes (Scheme 12). Although the detailed mechanism has not been clarified as yet, the difference in the anode material seems to be responsible for the different pathway of the reaction. In fact, a platinum plate anode is used in this reaction, although a carbon anode is usually used for the oxidative cleavage of the C-Si bond. In the anodic oxidation of 2-silyl-l,3-dithianes the use of a carbon anode results in a significant decrease in the yield of acylsilanes. The effects of the nature of the solvent and the supporting electrolyte may also be important for the fate of the initially formed cation radical intermediate. Since various 2-alkyl-2-silyl-l,3-dithianes can be readily synthesized, this reaction provides a convenient route to acylsilanes. 

An intramolecular cycloaddition occurred, when 2-alkylidene-l,3-dithianes having a hydroxy group at an appropriate distant position (3- or 4-atoms) were treated with trifluoromethyl iodide in the presence of SO2. A radical mechanism with 2-alkyl-2-iodo-l,3-dithianes as intermediates is suggested (Equation 37) <1997JOC9107>. 

Stable 2-metalo-l,3-dithianes, such as stannanes or silanes, have also been prepared and reacted with electrophiles. Sequential alkylation of a 2,2-bis-stannyl-l,3-dithiane (i, BuLi, oxirane ii, BuLi, alkyl bromide) furnished the 2,2-dialkylated products in 40% yield (Equation 40) <1997JA2058>. 

The chemistry of chiral 1,3-dithiane 1-oxides, in particular their use as chiral auxiliaries, has been reviewed <19980PP145>. Some further developments in this field are the stereoselective a-alkylation with alkyl halides <1997T13149> or a-hydrazination with di-fert-butyl azodicarboxylate (DBAD) <2000T9683>. The carbonyl group of 2-acyl-l,3-dithiane 1-oxides was also used as an electrophile (Scheme 82). Interestingly, acyclic enolates react with these substrates to give a 95 5 mixture of anti- and ry -adduct, whereas cyclic enolates produce a mixture of anti- and ry -adduct in 8 92 ratio <2000JOC6027>. 

Sterisch gehinderte 1,3-Dialkyl-2-oxo-aziridine (a-Lactame) reagieren mit Alkyl- und Phenyl-lithium und auch mit 2-Lithium-l,3-dithian unter Bildung von (1-Amino-alkyl)-ketonen2,3 ... 

Page et al. (see [298] and references therein) have shown that generally excellent stereocontrol in organic reactions can be obtained by using DITOX (1,3-dithiane-l-oxide) derivatives as chiral auxiliaries. The one-pot stereo-controlled cycloalkanone synthesis given here outlines some aspects of the chemistry worked out for efficient acylation-alkylations steps. Of note are the use of N-acyl imidazoles under mixed base (sodium hexamethyldisilazide/n-butyllithium) conditions to yield the lithium enolates of 2-acyl-l,3-dithiane-l-oxides) and the sequential alkylation-cyclization of the latter (steps (iv) and (v)). 

Acyl silanes by anodic oxidation of2-alkyl-2-trialkylsilyl-l,3-dithianes... 

More reactive anions such as the 2-lithio-l,3-dithiane derivatives, phenyllithium and r-butyllithium do not require a special solvent and proceed in high yield in THF. While HMPA is known to suppress the migratory insertion to CO in anionic complexes,127 it does not deter the CO insertion in these cases no example of direct alkylation is reported. The only electrophile which adds without CO insertion is the proton, as discussed above. Good alkylating agents (primary iodides and triflates, ally bromide, benzyl... 

In our studies, we employed the 2-propionyl-2-ethyl-l,3-dithiane 1-oxide substrates, since our previous work on enolate alkylation had demonstrated optimum levels of stereocontrol with an ethyl group as 2-substituent.22... 

In the case of the enone 142, an intermediate in the synthesis of the anticancer natural product OSW-1, the Michael addition of bis(phenylsulfanyl)methyllithium 126 took place in the presence of HMPA, whereas 2-lithio-l,3-dithiane gave the 1,2-addition product (Scheme 39)150. Unfortunately, this strategy was abandoned because compound 143 could not be further alkylated. 

The reaction of bis(phenylsulfanyl)alkyllithiums with trialkylboranes provides the adduct 144, after elimination of phenylsulfanyllithium. Final oxidation with hydrogen peroxide-dioxane in aqueous sodium acetate afforded aldehydes or ketones in good yields (Scheme 40)151,152. However, this process cannot be carried out with 2-lithio-l,3-dithiane because the initially formed borate did not undergo the spontaneous alkyl migration reaction152. 

All types of electrophiles have been used with 2-lithio-l,3-dithiane derivatives, including alkyl halides, sulfonates, sulfates, allylic alcohols, arene-metal complexes, epoxides, aziridines, carbonyl compounds, imines, Michael-acceptors, carbon dioxide, acyl chlorides, esters and lactones, amides, nitriles, isocyanates, disulfides and chlorotrialkylsilanes or stannanes. The final deprotection of the dithioacetal moiety can be carried out by means of different types of reagents in order to regenerate the carbonyl group by heavy metal coordination, alkylation and oxidation184 or it can be reduced to a methylene group with Raney-nickel, sodium or LiAIII4. 

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