Dithioacetals ketene dithioacetal

Thioketenes can be prepared in several ways, from carboxyHc acid chlorides by thionation with phosphoms pentasulfide [1314-80-3] 2 5 ketene dithioacetals by -elimination, from l,2,3-thiadia2oles with flash pyrolysis, and from alkynyl sulfides (thioacetylenes). The dimeri2ation of thioketenes to 2,4-bis(alkyHdene)-l,3-dithietane compounds occurs quickly. They can be cleaved back pyrolyticaHy (63). For a review see Reference 18. 

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. 

The use of ethyl ethylthiomethyl sulphoxide in this reaction leads to the desired addition products in much better yields (95-97%). These products were then converted into ketene dithioacetal monoxide derivatives 430 by a sequence of reactions (equation 258)505. Reaction of 2-lithio-l,3-dithiane-l-oxide with benzophenone affords a mixture of the diastereoisomeric tertiary alcohols 431 in a ratio which is temperature dependent (cis trans changes from 3 1 at — 78 °C to 1 1 at room temperature)268. 

Schlessinger and coworkers described a conjugate addition of enolate species to ketene dithioacetal monoxides656 (equation 357). Some of the products obtained were elaborated to dihydrojasmone657, prostaglandins658 and rethrolones659. 

The Knoevenagel condensation of a-lithiosulphoxides with hemiacetal 437 has been used to synthesize PGI2 analogues 438 (equation 261). The Knoevenagel-type condensation of dithioacetal monoxides with substituted benzaldehydes has been performed using Triton B as a base and gave the corresponding ketene dithioacetal monoxides 4395 2,513 (equation 262). 

Ketene dithioacetal 130 reacts with 3-amino-2-pyrazolin-5-one 129 to give the highly functionalized pyrazolopyridine 131, which is converted into the bispyrazolopyridine 132 by reaction with hydrazine hydrate (Scheme 9) <1997JCM256>. 

INVERSE ELECTRON-DEMAND DIELS-ALDER CYCLOADDITION OF A KETENE DITHIOACETAL. COPPER HYDRIDE-PROMOTED REDUCTION OF A CONJUGATED ENONE. 9-DITHIOLANOBICYCLO[3.2.2]NON-6-EN-2-ONE FROM TROPONE... 

Ketene acetals and dithioacetals have been prepared in a solvent-free procedure by base catalyzed / -elimination under PTC conditions. The yields obtained by use of irradiation are much higher than those obtained by use of ultrasound or conventional heating under the same conditions [82] (Scheme 8.58). 

The Lewis acid catalyst 53 is now referred to as the Narasaka catalyst. This catalyst can be generated in situ from the reaction of dichlorodiisopropoxy-titanium and a diol chiral ligand derived from tartaric acid. This compound can also catalyze [2+2] cycloaddition reactions with high enantioselectivity. For example, as depicted in Scheme 5-20, in the reaction of alkenes bearing al-kylthio groups (ketene dithioacetals, alkenyl sulfides, and alkynyl sulfides) with electron-deficient olefins, the corresponding cyclobutane or methylenecyclobu-tene derivatives can be obtained in high enantiomeric excess.18... 

An interesting pyrrolo[l,2-tf]pyrimidine was described as the product of the reaction of the heterocyclic ketene-aminals 236 that was synthesized by cyclocondensation of ketene dithioacetals 237 and 1,3-diamino propane. These compounds reacted with diethyl oxomalonate that behaves as an hetero-enophile, yielding the corresponding products 238 in acceptable to good yield (Scheme 31). A mechanism that involves an aza-ene reaction, via adduct 239 which isomerizes to ketene aminal 240 to produce the lactam ring of 238, has been proposed <1999J(P1)321>. 

Matsuda et al. <1995H(41)2777> described an efficient synthesis of mesoionic [l,2,4]triazolo[4,3-A]pyridazines 390 and 391. The starting compound for the synthesis is the A-aminotriazole 389, which can be treated either with ethyl 2-chloro-3-ethoxyacrylate to yield 390 or with ketene dithioacetals to afford 391. The reactions proceed in good to high yield. 

Ketene dithioacetals are obtained in very good yield (>95%) from the disodium salt of 2-cyanoethene-l,l-dithiolate with a range of alkylating agents in the presence of tetra-n-butylammonium bromide [26]. 

The 3-diketone (50 mmol) and TBA-HS04 (34 mg, 0.1 mmol) in CS2 (50 ml) are stirred with aqueous NaOH (8%, 100 ml) at room temperature for 10 min. The haloalkane (0.15 mol) is added and the mixture stirred for a further 1 h. The organic phase is separated, dried (MgS04), and evaporated to yield the ketene dithioacetal. 

Cyclic ketene acetals, which have utility as co-polymers with functional groups capable of cross-linking, etc., have been prepared by the elimination of HX from 2-halomethyl-l,3-dioxolanes. Milder conditions are used under phase-transfer conditions, compared with traditional procedures, which require a strong base and high temperatures. Solid liquid elimination reactions frequently use potassium f-butoxide [27], but acceptable yields have been achieved with potassium hydroxide and without loss of any chiral centres. The added dimension of sonication reduces reaction times and improves the yields [28, 29]. Microwave irradiation has also been used in the synthesis of methyleneacetals and dithioacetals [30] and yields are superior to those obtained with sonofication. 

The stereoselective intramolecular coupling of a ketene dithioacetal to an oxygen nucleophile to afford (10), was used as a key step in the total synthesis of (+)-nemorensic acid [229]. 

Mukaiyama reported the conjugate addition of a-dithioalkylcuprates to 2-enones (73-94% yields) for the synthesis of 1,4-diketones, and the reaction was exploited in a synthesis of(+)-dihydrojasmone [141]. Few reports on a-thioalkylcuprates have appeared since then. Cuprates formed from lithiated ketene dithioacetals and... 

Alternatively, in an even shorter route through ketene dithioacetal cycloaddition this molecule was obtained (Scheme 8) (10, 21). 

Ketene dithioacetal 237, obtained from acetylacetone, can serve as the initial reactant for the synthesis of aminopyran 238, spiro-annulated with oxazolidine (00SC1269) (Scheme 91). 

The ketene dithioacetal method group has proved useful for the synthesis of a number of biologically interesting molecules <2000BML703, 2004EJM969>, including 5-cyanopyrimidine derivatives which are orally active inhibitors... 

---