Pummer reaction

Pumi cites B. pumilis Pummel test Pummerer reactions Pumpingnumber Pumpingnumbers Pumping speed Pumpkin... 

Thermal Stability. Dimethyl sulfoxide decomposes slowly at 189°C to a mixture of products that includes methanethiol, formaldehyde, water, bis(methylthio)methane, dimethyl disulfide, dimethyl sulfone, and dimethyl sulfide. The decomposition is accelerated by acids, glycols, or amides (30). This product mixture suggests a sequence in which DMSO initially undergoes a Pummerer reaction to give (methylthio)methano1, which is labile and reacts according to equations 1—3. Disproportionation (eq. 4) also occurs to a small extent ... 

The reaction is quite general and usually results in 75—90% yields (47). All reactions in which a sulfoxide containing at least one a-hydrogen is reduced to the sulfide and also oxidized at the a-carbon ate referred to as Pummerer reactions (48). 

When DMSO is mixed with concentrated hydrochloric acid, protonated DMSO is in equiUbtium with the chlorodimethylsiilfonium ion. Pummerer reactions and subsequent reaction of the initial products give a complex mixture of products including formaldehyde, bis(methylthio)methane, methanethiol, dimethyl disulfide, dimethyl sulfide, and others. 

A new method for converting a C-20 carboxylic ester to the 21-acetoxy-20-keto group involves the use of the Pummerer reaction... 

Application of Pummerer reaction in the synthesis of complex carbo- and heterocycles 97S1353. 

An alternative approach, which has only been applied to heteroaromatic thiepins, is provided by the Pummerer reaction.70,71 The careful double oxidation of hetarenothicpancs to the corresponding S-oxides, followed by brief treatment with acetic anhydride at 150 °C in the absence of oxygen, gives the heteroaromatic thiepins in moderate yield. 

Due to their thermal instability, this method cannot be applied to the preparation of benzo-thiepins. Although the ft-oxo sulfoxide moiety in precursors such as 5-methoxy-4-phenyl-l-benzothiepin-3(2/7)-one 1-oxide makes them candidates for a Pummerer reaction, treatment with acetic anhydride and triethylamine at - 30 C results in preferential enol acetylation to afford the corresponding 1-benzothiepin 1-oxide.14... 

The sulfoxide 5 on treatment with trifluoroacetic acid in dichloromethane at 20 °C for three hours undergoes a Pummerer reaction (see Houben-Weyl, Vol.Ell, pll89ff) to give the thiazepinone 6 in 79% yield. No further details were reported.48... 

The tetrahydrotrithiepin 1 is oxidized to an 5-oxide of undetermined structure, which undergoes a Pummerer reaction with acetic anhydride to give 1,2,5-trithiepin (2) in low yield.432... 

Horner and Jurgens39 reported that benzoyl peroxides 21 in the presence of sulphides decompose to give sulphoxides and a-acyloxysulphides 22 (equation 8). The latter compounds are undoubtedly formed as a result of the Pummerer reaction. The oxidation reaction leading to sulphoxides has been shown to be an ionic process40. However, till now it has not found wider synthetic applications. Ganem and coworkers41 showed that 2-hydroperoxyhexafluoro-2-propanol 23 formed in situ from hexafluoroacetone and... 

The vinylogous Pummerer reaction of an amido-substituted sulfoxide has been used for the preparation of tetrahydroisoquinoline 83 <95JOC(60)7082>. 

Whereas conversion of sulfoxides to the corresponding a-acyloxysulfides by acid anhydrides, for example acetic anhydride, the Pummerer reaction [1], has been known for quite a time, the conversion of sulfoxides with silylating reagents via the unstable intermediate O-silyl compounds to a-silyloxysulfides, the Sila-Pummerer reaction is a relatively new reaction, which has recently been reviewed [1—4-]. 

Nucleophilic Substitutions and Cyclizations via Sila-Pummerer Reactions... 

For further Pummerer reactions with silylated heterocyclic bases see Refs. 414a—414i in Handbook of Nucleoside Synthesis , H. Vorbruggen, C. Ruh-Pohlenz, Wiley-Inter-science. New York, 2001... 

Sila-Pummerer reaction of the /1-ketosulfoxide 1257 with the enol silyl ether of acetophenone 653 in the presence of BSA 22 a and stannous triflate affords the C-substituted sulfide 1258 in 82% yield and HMDSO 7 [52]. The allylic sulfoxide 1259 reacts with 653 in the presence of TMSOTf 20/DIPEA to give the unsaturated sulfide 1260 in 62% yield or, with the enol silyl ether of cyclohexanone 107a , the unsaturated sulfide 1261 in 63% yield and HMDSO 7 [53] (Scheme 8.21). 

The Sila-Pummerer reaction of a-alkoxy sulfoxides such as 1269 with excess tri-mefhylsilyl cyanide 18 and Znl2 affords, in quantitative yield, the a-cyanoether 1270 and trimethylsilyl methylsulfenate 1271 [58] (Scheme 8.24). 

The Pummerer reaction of conformationally rigid 4-aryl-substituted thiane oxides with acetic anhydride was either stereoselective or stereospecific, and the rearrangement is mainly intermolecular, while the rate-determining step appears to be the E2 1,2-elimination of acetic acid from the acetoxysulfonium intermediates formed in the initial acetylation of the sulfoxide. The thermodynamically controlled product is the axial acetoxy isomer, while the kinetically controlled product is the equatorial isomer that is preferentially formed due to the facile access of the acetate to the equatorial position . The overall mechanism is illustrated in equation 129. 

Ajayaghosh A, George SJ, Schenning APHJ (2005) Hydrogen-Bonded Assemblies of Dyes and Extended jr-Conjugated Systems. 258 83-118 Akai S, Kita Y (2007) Recent Advances in Pummerer Reactions. 274-. 35-76 Albert M, Fensterbank L, l.acote E, Malacria M (2006) Tandem Radical Reactions. 264 1-62 Alberto R (2005) New Organometallic Technetium Complexes for Radiopharmaceutical Imaging. 252 1-44... 

The Pummerer reaction has successfully been applied to the synthesis of some novel thiepins (13) starting from the 4,5-dihydro derivatives 11 and proceeding via the sulfoxide 12 u I2). 

The sequence could even be prolonged by including a Pummerer reaction. Thus, treatment of 4-103 with trifluoroacetic acid (TFA) gave the furan 4-104, which underwent a cycloaddition to furnish 4-105 the erythryna skeleton 4-109 was obtained after subsequent addition of a Lewis acid such as BF3- Et20 (Scheme 4.23) [33]. It can be assumed that 4-106, 4-107 and 4-108 act as intermediates. In a more recent example, these authors also used the procedure for the synthesis of indole alkaloids of the Aspidosperma type [34]. 

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... 

The synthesis of the tetracyclic dibromophakellstatin 362 has been successfully accomplished in 45% yield through an NBS-mediated cyclization of 361 (Equation 97) <2002TL5135>. Another noteworthy approach utilizes a similar precursor, but the cyclization is carried out through an extended Pummerer reaction <20050L929>. 

As depicted in the following scheme, in the presence of sodium iodate and pyridine, several 5,6-dihydroxylated benzofuran derivatives were synthesized via an oxidation-Michael addition of P-dicarbonyl compounds to catechols in a one-pot procedure <06TL2615 06JHC1673>. A novel additive Pummerer reaction of 2-benzo[fc]furan sulfilimines with carbon nucleophiles derived from P-dicarbonyl compounds was also employed to the synthesis of 2,3-disubstituted benzo[b]furans <06TL595>. 

The mechanism of the formation of compound 67 has been studied by Higa and Krubsack [41] in detail, as shown in Scheme 15. Namely, the initial step of the reaction of the cinnamic acid derivative 66 with thionyl chloride is an electrophilic addition of thionyl chloride across the double bond of cin-namoyl chloride to form the sulfinyl chloride intermediate (66a), which is then converted to 68 by the Pummerer reaction. Dehydrochlorination of 68... 

Suppression of the Pummerer reaction (Fig. 24) could also be a manifestation of the stabilization of the persulfoxide which prevents its interconversion to the hydro-peroxysulfonium ylide, HPSY (Fig. 25), which is the intermediate that has been suggested to undergo a 1,2-shift of the hydroperoxy group and ultimately produces the SC bond cleavage products.92 However, the situation is probably more complex since the intrazeolite reaction of /1-chlorosulfide, 29 (Fig. 28A), requires 7-hydrogen abstraction. The complexation motif (Fig. 28B) which favors the extended rather than folded M+-PS may also play an important role. A complete understanding of these reactions will require additional studies. 

In most oases, the fluoro Pummerer reaction can be carried out with 1.33 to 2.0 equiv of DAST and a "catalytic" amount of antimony trichloride in either refluxing methylene chloride or chloroform at room temperature or 50°C. In the synthesis of fluoromethyl phenyl sulfide, however, the induction period makes room temperature conditions the preferred method for large scale synthesis. 

Electron-withdrawing groups decrease the rate of the fluoro Pummerer reaction, which, in certain cases,7 allows a DAST-mediated deoxygenation to compete with the introduction of fluorine alpha to sulfur. The reaction is compatible with a number of functional groups and can readily be carried out with nucleosides. Robins and coworkers4 reported the synthesis of a 5 -fluoro-5 -S-phenyladenosine analog using antimony trichloride as catalyst at room temperature. It should be noted that a-fluoro sulfoxides provide a convenient entry to terminal fluoroalkenes.3 8 9 10... 

---