Thionium

A more recent approach, which also profits from the synthetic versatility of stabilized thionium ions, has been elaborated by Berard and Piras [22]. These authors observed that the cyclobutane thionium ions 1-76 obtained from the cyclopropyl phenyl sulfides 1-75 by treatment with pTsOH under anhydrous conditions can be trapped by an adjacent electron-rich aromatic ring to give the chromane derivatives 1-77 in good to excellent yields (Scheme 1.20). As expected, 1-77 were obtained as single diastereoisomers with a ds-orientation of the methyl and the phenylthio group as a consequence of steric constraints. 

Finally, a sequence consisting of thionium ion formation, thionium ion trapping, an aromatic substitution, and an alkylation, as elaborated by Padwa and coworkers, will be discussed [462]. Since several related sequences have already been mentioned in the foregoing sections, only the total synthesis of ( )-jamtine N-oxide (2-916) will be discussed here (Scheme 2.204). This natural product is an alkaloid from the shrub Cocculus hirsutus, which is commonly found in Pakistan [463]. 

The intramolecular Pummerer reaction has been applied to the synthesis of simple quinolizidine alkaloids like lupinine <2000JOC2368>, and also to arenoquinolizine alkaloids. Thus, the 2-(2-piperidyl)indole 284 was converted to indolo[2,3- ]quinolizidine 287 following a protocol that has as the key step the regioselective cyclization onto the indole 3-position of a thionium ion generated by Pummerer reaction from the appropriately substituted compound... 

Lactam sulfonium salts bearing a dihydrothiopyran skeleton with a sulfonio bridgehead have been synthesized. Tricyclic benzothiazinium salts 87 were prepared by [4+2+]-polar cycloaddition of a thionium intermediate 99, generated from the corresponding a-chloro sulfide 98, in the presence of silver perchlorate in moderate to good yields (see Equation (28) and Table 17) <1997J(P1)309>. Cycloaddition with isoprene 41b gave adducts 87b and 87c as a... 

Table 17 Polar cycloadditions of thionium intermediate 99 with 1,3-butadienes 41 (Equation 28)...

Treatment of a-(benzotriazol-l-yl)alkyl thioethers 831 with ZnBr2 weakens the bond with benzotriazole, and the obtained complex 832 may partially dissociate to thionium cation 835 that can be trapped by even mild nucleophiles. Thus, trimethylsilyl cyanide added to the reaction mixture causes substitution of the benzotriazole moiety by the CN group to give a-(phenylthio)carbonitrile 834. In a similar manner, treatment with allylsilane leads to y,S-unsaturated thioether 833. Addition of species 835 to the double bond of a trimethylsilyl ot-arylvinyl ether followed by hydrolysis of the silyloxy group furnishes (i-(phenylthio)alkyl aryl ketones 836 (Scheme 132) <1996TL6631>. 

Cyclisation of an NH amide toward a cyclic thionium ion was described for the synthesis of a tetrahydropyrrolo-[l,2-tf]pyrimidine-2,6(l//,7//)-dione 351. Compound 349 was transformed to 351 in two steps. The first one is the formation of a transient alkylthio-substituted lactam 350 from amidothioacetal 349 in the presence of dimethyl-(methylthio)sulfonium tetrafluoborate (DMTSF) followed by intramolecular cyclization <2000JOC235>. 

Two step synthesis of medium-ring ethers through the intermediacy of thionium ions followed by sulfide reduction. 

As mentioned in Section 10.1.2, Padwa and co-workers (40,41) employed the Pummerer reaction to generate and trap isomtinchnones. This group (190,191) has now adapted the intramolecular version of this tactic to the synthesis of several alkaloids of the pyridine, quinolizidine, and clavine classes. In each case, a 2-pyridone serves as the keystone intermediate. For example, Kuethe and Padwa (190) employed this Pummerer reaction of imidosulfoxides that contain tethered iz-bonds in a formal synthesis of the frog alkaloid ( )-pumiliotoxin C. They also used this methodology to synthesize the azafluorenone alkaloid onychine (295) (Scheme 10.42) (191). Generation of the thionium ion 291 under standard... 

Addition of allyltins to thioketals.2 The reagent can convert dimethyl thio-ketals to a thionium ion, >=SCH3, which can react with a nucleophile such as an allyltin. 

Addition of methyl iodide to a solution of the aminodithioacrylate 1 in acetone resulted in the rapid formation of the corresponding thionium salt in high yield. Treatment of a solution of 1 in... 

Scheme 48) <1998TL4761>. Further examples of this strategy were also reported <2000JOC2684>. A thionium ion-promoted Mannich reaction of the amide 39 upon treatment with dimethyl(methylthio)sulfonium tetrafluoro-borate yields the extended tetrahydroisoquinoline in excellent yield (Equation 105) <2000JOC235>. 

A wide range of variously substituted thiochromans has been obtained from the readily accessible ot-(benzotriazo-lyl)methyl thioethers by their Lewis acid-catalyzed reaction with styrenes. Initial loss of the benzotriazole unit generates a thionium cation which undergoes an efficient cationic cycloaddition to the alkene. The reaction, which generally proceeds with high diastereoselectivity, is considered to occur in a stepwise manner rather than as a concerted [4++2] process (Scheme 174) <2001JOC5595>. 

One mechanistic possibility for this thioacetalation reaction invokes furanoside ring-opening of 17, initiated by complexation with boron trifluoride etherate (Scheme 12.9). Oxonium ion 28 could then get intercepted by the ethanethiol to produce 29. After further complexation with BF3, in the manner shown, thionium ion formation can again occur to give 30, which can then engage in yet another nucleophilic addition with the ethanethiol to produce 31 after protonation. 

Several related methods for the preparation of differentially substituted 5-thio-2,3-trisubstituted furans were developed, which involved the formation of a thionium ion and the cyclization of this reactive intermediate into the tethered carbonyl group <02JOC1595>. 

For the intramolecular additive Pummerer reaction, following formation of the oxysulfonium ion (211), nucleophilic attack occurs at the electrophilic P-carbon of the 0-activated substrate producing a saturated p-functionalized thionium species (212). Trapping with a second nucleophilic agent affords a product (213) formally derived by sequential attack of two nucleophiles on an abdication (Fig. 10). 

The finding that thionium ions may serve as electrophiles in electrophilic substitution chemistry has greatly extended the synthetic range of the Pummerer reaction. Padwa and Kuethe used intramolecular versions of this process in the preparation of nitrogen-containing heterocycles. Vinyl amido sulfoxide 217 underwent an additive Pummerer reaction, on treatment with triflic anhydride, to yield product 220 (Scheme 56).123 The critical step in this transformation involves a... 

For the intramolecular vinylogous Pummerer reaction pathway, an electrophilic thionium ion intermediate (222) is formed by y-proton loss from 221 followed by sulfoxide S-O bond scission. This unsaturated thionium ion (222) is then intercepted by a nucleophile at the y-position to yield a vinyl sulfide product (223) (Fig. 11). 

Sequential reduction and cyclisation of a-alkenoyl-a-carboxyl ketene dithioacetals 38 affords 6-substituted 3-ylidene-3,6-dihydropyran-2-ones an intermediate thionium ion is invoked. Further reactions of the products are described <07JOC4401>. 

A convenient method for the synthesis of annulated 2-alkylthio-5-aminofurans has been described by Padwa et al. The reaction sequence involves the formation of a thionium group from readily available dithioacetals upon treatment with dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF). The thionium ion undergoes cyclization with the 7-carbonyl group followed by an elimination step to yield the 2,3,5-trisubstituted furans in good to excellent yields (Equation 29) <2002JOC1595>. The alkylthioaminofuran reaction products can be utilized to constmct polyclic frameworks of natural products in a subsequent Diels-Alder reaction. 

Creation of the 8-membered ring 3 3 of IhxoL by an intramolecular directed aldol reaction failed when the thionium ion intermediate 3 2 underwent intramolecular hydride transfer from a neighbouring p-methoxy benzyl ether instead [Scheme 1.38]. Loss of p-methoxybenzaldehyde and hydrolysis of the enol silane occurred on workup to give the hemiacetal 38,5 in 48% yield. Benzyl ethers can also transfer hydride to proximate carbocationic intermediates.71... 

We have already stressed that acetals are far more susceptible to hydrolysis than thioacetals and Scheme 2.62 attests to the assertion.133-135 The high acid stability of 55-acetals compared with 0,0-acetals may be attributed to the lower Bronsted basicity of sulfur compared with oxygen and the barrier to formation of a thionium ion with its bond. The large number of methods that... 

LTA reacts with enol sulfides,to produce thionium ions, e.g. (106), and thence all)dic acetates (107) or bisacetoxylated products (10, in good yields. Presumably either of Aese compounds could be hydrolyzed to the a-acetoxy ketone. 

In the present review a notation based on that proposed by Cymer-man-Craig and Tate and then by Tozer and Dallas Tuck (last column of Table I) will be used, namely R for phenothiazines, that is, for totally reduced forms of the redox systems, S " for the semiquinonoid radical forms, and T+ for the totally oxidized forms, the phenaza-thionium cations, resulting by the the removal of an electron and a proton from S ". 

BJI250 CAS 61-73-4 HR 3 3,7-BIS(DIMETHYL AMINO)PHENAZA THIONIUM CHLORIDE... 

Figure 5 Diastereoselectivity in nucleophilic additions to chiral thionium ions...

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