Dithioacetals dithiolanes

BF3 Et20, EtSH, 25°, 40 min, 80-90% yield. Addition of sodium sulfate prevents hydrolysis of a dithioacetal group present in the compound replacement of ethanethiol with ethanedithiol prevents cleavage of a dithiolane group. 

The pivotal step in this sequence is an electrophilic substitution on indole. Although the use of l,3-dithian-2-yl carbanions is well documented, it has been shown only recently that 1,3-dithian-2-yl carbenium ions can be used in a Priedel-Crafts type reaction. This was accomplished initially using 2-methoxy-l,3-dithiane [1,3-Dithiane, 2-methoxy-] or 2-metlioxy-l,3-dithiolane [1,3-Dithiolane, 2-methoxy-] and titanium tetrachloride [Titanate(l —), tetrachloro-] as the Lewis acid catalyst.9 2-Substituted lysergic acid derivatives and 3-substituted indoles have been prepared under these conditions, but the method is limited in scope by the difficulties of preparing substituted 2-methoxy-1,3-dithianes. l,3-Dithian-2-yl carbenium ions have also been prepared by protonation of ketene dithioacetals with trifluoroacetic acid,10 but this reaction cannot be used to introduce 1,3-dithiane moieties into indole. 

Acetylquinoxaline gave its cyclic dithioacetal, 2-(2-methyl-l,3-dithiolan-2-yl)quinoxaline (210a) (HSCHjCHjSH BF3, EtjO, CHCI3, 20°C 14%). ... 

The regeneration of carbonyl compounds from dithioacetals and dithiolanes is often done with reagents that oxidize or otherwise activate the sulfur as a leaving... 

Coupling of RMgX with dithioacetals.1 In the presence of Cl2Ni[P(C,H,),]2. Grignard reagents react with 1,3-dithiolanes to give cross-coupled alkenes in moderate yield. 

The stoichiometric equivalents of halofluorides have been recently applied to transform alkylene dithioacetals into gcm-difluorides.70-71 Dithioacetals such as 1,3-dithiolanes and 1,3-dithianes arc readily obtained from the corresponding carbonyl compounds by the reaction with ethane-1,2-dithiol or propane-1,3-dithiol in the presence of the complexes boron trifluoride-bis(acetic acid) or boron trifluoride-diethyl ether. Using a two-step procedure, a range of aldehydes and ketones can be converted into gem-difluorides under mild conditions. 

Dithioacetals (see also dithianes and dithiolanes) alkylation of 98 as acyl anion equivalents 75 carbanions of 87,97-102 cleavage of 14-18,98,102 desulfurization of 78 metal-catalysed coupling 127 reaction with Grignard reagents 127 reductive lithiation of 89 synthesis of 12-19,97-102 Dithioacids synthesis of 40... 

The dithioacetal (0.01 mol) was stirred for a few hours at room temperature with clayfen (4) (10.4 g, 11 mmol of ferric nitrate) or with claycop (12.1 g, 20 mmol of copper nitrate) in toluene, n-pentane or, preferably, dichloromethane (120ml). Evolution of nitrogen oxides occurred rapidly. Stirring was maintained until gas evolution ceased. The clay was then filtered off and washed twice with portions (50 ml) of the solvent. The resulting pale-yellow or slightly green solution was filtered through a small quantity of neutral aluminium oxide and the solvent was evaporated under vacuum. In the case of dithiane and dithiolane derivatives, this afforded the pure carbonyl compound in excellent yield. 

Keywords aldehyde, thiol, lithium bromide, dithioacetalization, 1,3-dithiane, 1,3-dithiolane... 

The reaction of aldehydes or ketones with ethane-1,2-dithiol or propane-1,3-dithiol to form 1,3-dithiolanes or 1,3-dithianes is an important reaction, as these compounds under suitable conditions are acyl anion equivalents (see Section 5.9, p. 626). These cyclic dithioacetals have been less used as protective groups, though when required are formed in high yield in the presence of boron trifluoride-etherate.138... 

Coupling of dithioacetals with RMgX butadienylsilanes.1 This coupling is possible when catalyzed by Ni(H). Thus 2-(2-phenylethenyl)-l, 3-dithiolane (1) couples with (trimethylsilyl)methylmagnesium chloride in THF in the presence of this nickel complex to form (E,E)-trimethyl(4-phenyl-l,3-butadienyl)silane (3) in 91% yield. 

Ring expansion and concomitant chlorination of 1,3-dithiolanes with an enolisable methyl group occurs in DMSO on reaction with silica pre-treated with SOCI2, giving dihydro-1,4-dithiin derivatives. Spirocyclic dithioacetals yield the annulated dithiin <02JOC2572>. 

Heterocycles of this type occur widely. The benzo[l,3]dioxole ring system is often found in natural products and their degradation products, e.g., sesamol 38 lipoic acid 39 is a naturally occurring 1,2-dithiolane derivative. The 1,3-dithiolanes 40 are commonly known as 1,3-dithioacetals and have been extensively used in carbonyl group chemistry. In the absence of cyclic conjugation, ring sulfur atoms can readily exist in higher oxidation states as, for example, in the oxathiole S, -dioxide 41. 1,3,2-Dioxathiolane A-oxides 42 (cyclic sulfites) and 1,3,2-dioxathiolane A,A-dioxides (cyclic sulfates) are useful as synthetic equivalents of epoxides. 

A convenient three-component coupling reaction of Meldrum s acid, acrolein, and thioacetic acid was described <1997TL5785> for the synthesis of 2-(l,2-dithiolan-3-yl)acetic acid 315 (Scheme 58). As shown, diacetylthiolated propyl Meldrum s acid 311 was refluxed in methanol affording ester acid dithioacetate 312, which without purification was transformed upon acid-catalyzed methanolysis into diester 313. The subsequent oxidation step led to ester 314 which afforded the final acid 315 by a hydrolysis-decarboxylation sequence. 

Dithiolanes, also named five-membered 1,3-dithioacetals or A,3 -acetals, find wide applications in organic synthesis, particularly in protection of carbonyl functions and their reductive conversion to hydrocarbons or olefins. Due to the stability of 1,3-dithiolanes toward various reagents and reaction conditions, they have attained an important position in this area despite the fact that dedithioacetalization to the corresponding carbonyl compounds is sometimes not an easy process. There are three general strategies that can be used for deprotection of 1,3-dithiolanes involving... 

Among a variety of methods reported for constmction of 1,3-dithiolanes, the most important play a role in conversions involving carbonyl compounds. For this reason, this group of compounds is also named five-membered 1,3-dithioacetals or A,A-acetals. 1,3-Dithiolanes can he easily prepared hy condensation of carhonyl compounds with 1,2-ethanedithiol in... 

One of the effective reagents for highly chemoselective dithioacetalization of carbonyl compounds is ceric ammonium nitrate (CAN) in chloroform. When a mixture of benzaldehyde and acetophenone was allowed to react with 1,2-ethanedithiol and a catalytic amount of CAN, the 1,3-dithiolane derived from the aldehyde was obtained in 84% yield while the ketone was recovered unchanged. It is noteworthy that aromatic ketones, 7-lactones, and acylic ketones did not react at all under these conditions and even at elevated temperatures for longer reaction times <1995T7823>. 

The ionic liquid based on the l- -butyl-3-methylimidazolium cation was also used as an efficient catalytic medium for the chemoselective dithioacetalization of carbonyl compounds. This reaction proceeded with both activated and weakly activated aromatic aldehydes in almost quantitative yields in short reaction times. In addition, an acid-sensitive substrate such as furfural also gave the corresponding 1,3-dithiolane without a formation of any side products (Table 8). Moreover, aromatic ketones did not produce dithioketals under the same reaction conditions (room temperature, 10-20 min) or even after a prolonged reaction time <2004ASC579>. 

One of the most common routes to this class, already described in CHEC-II(1996), is dithioacetalization (deacetaliza-tion/dithioacetalization) of 1,3-dioxolanes 641 to 1,3-dithiolanes 642, usually carried out under acidic conditions. In the reviewed period, new Lewis acids used in catalytic amounts were employed in this transformation WCls... 

The reaction of aldehydes or ketones with thiols, usually with a Lewis acid catalyst, leads to dithioacetals or dithioketals. The most common catalyst used is probably boron trifluoride etherate (BF3 OEt2). Similarly reactions that use 1,2-ethanedithiol or 1,3-propanedithiolleadto 1,3-dithiolanes, such as 18 or l,3-dithianes. " Dithioa-cetals can also be prepared from aldehydes or ketones by treatment with thiols in the presence of TiCU, SiCU, LiBp4, AKOTfls, with a disulfide RSSR (R = alkyl or aryl), or with methylthiotrimethylsilane (MeSSiMe3). " ... 

Desulfurization of 1,3-dithiolanes.9 Selective hydrogenolysis of dithioketals and dithioacetals is possible with 4 equivalent of this hydride in the presence of AIBN. Yields are 75-95%. The other products are ethane and (Bu5Sn)2S. 

Cyclopropanecarbaldehydes, 1,1-dialkoxy-l-cyclopropylalkanes and cyclopropyl ketones reacted readily with ethanedithiol " " " and propanedithioP to give the corresponding 1,3-dithiolanes and 1,3-dithianes, respectively, in excellent yield. Boron trifluoride diethyl ether complex, in the presence or absence of acetic acid, has generally been used as the catalyst, but hydrogen chloride has also been utilized.An example of this reaction is the formation of the dithioacetal of cyclopropanecarbaldehyde 3. ... 

The Friedel-Crafts reaction has been used to introduce an acyl group at the a-position of phosphonoketene dithioacetals. " Under classical conditions using diethyl (l,3-dithiolan-2-ylidene)meth-ylphosphonate and MeCOCl/AlCl3 in CH2CI2, the expected a-(acetyl)phosphonoketene dithioacetal is isolated in modest yield (38%). By contrast, the use of a-silylated phosphonoketene dithioacetals improves the yield up to 89% (Scheme... 

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