Betaine generation

The last item (S) may explain why the independent betaine generation control experiments gave contradictory results. If betaines are high-energy species that lie above the saddle point leading from the ylide to the oxaphosphetane, then experiments that deliberately generate betaines (Schemes 3-5) may encounter pathways for stereochemical equilibration that are not accessible to typical Wittig reactions. 

There are also some examples where significant reversal and stereochemical equilibration of intermediates has been demonstrated in aldehyde Wittig reactions (Table 7, subset 1). Several additional examples of reversal from betaine generation experiments may also be relevant, depending on whether the same betaines play any role in the Wittig process (Table 7, subset 2). The following generalizations follow from the comparison of Tables 6 and 7. 

Deliberate betaine generation maximizes the risk of reversal. The risk is highest for betaines corresponding to adducts of ArCHO. 

MODIFIED METHOD A BETAINE GENERATION BY KETOPHOSPHONIUM SALT REDUCTION WITH LiBH /THF Me H... 

The simple mesomeric betaine generated from the iodide (101) with an excess of methanolic sodium methoxide at 0°C, reacts with DMAD to give the 2 1 cycloadduct (105) in low yield (Scheme 17) <89JCS(P1)957>. 

Mitsunobu-like Processes. Triphenylphosphonium 3,3-dime-thyl-l,2,5-thiadiazolidine 1,1-dioxide (1) can be conveniently utilized as a stable source of [PhsP+J in the promotion of Mitsunobu-like processes. By analogy with the betaine generated by reaction of DEAD and triphenylphosphine, protonation of zwitterionic species 1 by an acidic component HX generates ion pair 2 which on subsequent reaction with an alcohol (ROH) affords oxyphosphonium species (3) and 3,3-dimethyl-1,2,5-thiadiazolidine-1,1-dioxide (4). Finally, Sn2 displacement reaction, occurring with Walden inversion of the alcohol stereochemistry, leads to the coupled product R-X and triphenylphosphine oxide (TPPO) (eq 1). 

Porco and coworkers used taddol 10 as a chiral H-bond donor in the asymmetric photochemical [3-f2] cycloaddition between oxidopyrylium betaine generated from 11 and methyl cinnamate 12 (Scheme 10.11) [72]. (-)-Methyl rocaglate was obtained... 

More recently, Cheeseman and coworkers have investigated cycloaddition reactions of 2,6-dioxypyrazines (80jCS(Pl)1603). 2,6-Dihydroxy-3,5-diphenylpyrazine (77) reacts with electron deficient dienophiles such as iV-phenylmaleimide, diethyl maleate and diethyl fumarate (Scheme 26) to yield adducts of the 3,8-diazabicyclo[3.2.1]octane class such as (78). This reaction is believed to proceed by way of the betaine (79) and has precedent (69AG(E)604) in that photolysis of the bicyclic aziridine (80) generates analogous betaines which have been trapped in cycloaddition reactions. 

Tnfluoromethyl-substUuted 1,3-dipoles of the propargyl-allenyl type and trifluoromethyl-substituted nitrilium betaines. Tnfluoromethyl- [164, 765] and bis(trifluoromethy])-substituted [166, 167] nitrile ylides have been generated by different methods and trapped with various dipolarophiles to yield [3+2] [768] and [3+1] cycloadducts [769], respectively... 

There are specific associations of various types of dipoles with the four major classes of heterocyclic mesomeric betaines, which have implications in providing a rational foundation for correlating the chemical reactions of these compounds (85T2239). Eight dipole types, systematically generated by union of the heterocations H2C = with carbanions and... 

Dimethylsulfonium methylide is both more reactive and less stable than dimethylsulfoxonium methylide, so it is generated and used at a lower temperature. A sharp distinction between the two ylides emerges in their reactions with a, ( -unsaturated carbonyl compounds. Dimethylsulfonium methylide yields epoxides, whereas dimethylsulfoxonium methylide reacts by conjugate addition and gives cyclopropanes (compare Entries 5 and 6 in Scheme 2.21). It appears that the reason for the difference lies in the relative rates of the two reactions available to the betaine intermediate (a) reversal to starting materials, or (b) intramolecular nucleophilic displacement.284 Presumably both reagents react most rapidly at the carbonyl group. In the case of dimethylsulfonium methylide the intramolecular displacement step is faster than the reverse of the addition, and epoxide formation takes place. 

The reaction of 9 (generated thermally from 7 in toluene) with tetraphenyl-cyclopentadienone is more complex. Both the [6 + 2]-cycloadduct 3416), for which an X-ray structure analysis is available, and the [12 + 2]-cycloadduct 3516), whose constitution has been assigned primarily on the basis of H-NMR evidence, are obtained. The two cycloadducts presumably have a common intermediate which, in accord with the general reactivity of 9, should possess betaine character (.31 - 32) it is caused by nucleophilic attack by the carbonyl oxygen atom on the phosphorus of the heterocumulene. Ring closure of the carbanionic carbon atom... 

Reaction of dimethyl acetylenedicarboxylate (DMAD) with extremely unstable mesomeric betaine 96, generated in situ from 95, gives in 30-36% yield of a 1 2 adduct, the structure of which was originally determined as 97 <1978CL1093>. However, a more recent reinvestigation based on the H and 13C NMR spectroscopy shows that the actual product is pyrazolo[l,5- ]azepine 98, formed probably by mechanism shown in Scheme 6 <1995JCM338>. 

Pyrazolo[l,2- ][l,2,3]triazole mesomeric betaines are generally available by an electrophilic attack of singlet nitrenes on the pyrazole nitrogen atom. When phthalazone derivative 252 is used and the nitrene is generated by reduction with triethyl phosphite, 59% yield of mesomeric betaine 253 is obtained (Equation 40) <2000T5523>. 

The reactions of dichlorocarbene with phosphorus ylides result in the corresponding olefins and phosphines.66-68 In the reaction of dichlorocarbene generated in situ with tributyl- and triphenylmethylenephosphoranes or triphenylethylidenephosphorane, the olefin yield increases as the nucleo-philicity of phosphorus ylide increases. According to,67 the reaction starts from the electrophilic attack of carbene at the a-C atom of phosphorus ylide. Then the intermediately formed betaine (28) (Scheme 14) decomposes to eliminate the phosphine molecule and form dichloroolefin (29). 

The study of the reactivity of betaines I and II is yet far from completion. The data presented show that the scope of their reactions is wide and diverse. Therefore, we can expect that compounds of this type will find various synthetic applications, including those for the preparation and in situ generation of compounds with multiple E14=X bonds. 

The reaction of carbenes 1, generated either thermally or photochemically from the corresponding quinone diazides 2, with pyridine results in the formation of the deeply colored betaines which can be isolated in substance from the reaction mixture.73,62 This alternative synthesis of the betaines opens a general route to pyridine ylides unsubstituted at the pyridine ring. 

About half of the homocysteine so generated is remethylated to methionine, with either betaine or 5-methyltetra-hydrofolic acid (methyl-FH4) serving as methyl donor. 

An improved specificity was observed when FIA-MS-MS in product or parent ion mode was used to perform quantification of the surfactants in the methanolic mixtures. The ions selected for quantitation in product or parent ion mode were C13-AE m/z 71, 85, 99, 113, and 127 from alkyl chain together with 89, 133, and 177 from PEG chain generated from parent ions m/z 394, 526, 658, 790 and 922 alkylbenzyl dimethyl ammonium quat m/z 91 and 58 generated from parent ion m/z 214 FADA m/z 88, 106 and 227 generated from parent ions m/z 232, 260, 288, 316, 344 and 372 while the alkylamido betaine was quantified generating the parent ion m/z 343 obtained from product ion at m/z 240. 

Pyran-4-one (56a) and its benzo derivative (chromone) show chemical properties in agreement with substantial jr-electron delocalization and consistent with a betaine structure 56b (Scheme 27). Experimental data have therefore generated numerous theoretical studies on the aromaticity of pyranones, which have been extensively reviewed.219 Earlier studies suggested that chemical shifts and coupling constants... 

For the reaction of phosphane oxide with isocyanate, the rate-determining step is the formation of the oxazaphosphetane 45 via P—O—bond formation of the intermediate betaine (44), since the stable and energetically favorable P=0 double bond is broken here. Subsequent rapid decomposition of the oxazaphosphetane 45 into iminophosphorane and carbon dioxide occurs. Within the actual aza-Wittig step, the intermediate betaine (46) is generated in a rate-determining step by nucleophilic attack of the iminophosphorane nitrogen on the carbonyl C. By P —O-bond formation, betaine (46) is then converted into an oxazaphosphetane (47), which decomposes... 

Benzyne generated from 2-carboxybenzenediazonium chloride reacted with sulfur monochloiide to give dibenzothiophene 13 (8-10%) and thiantherene 14 (26-35%) (1989SUL83). A mechanism involving the addition of sulfur mono-chloride to benzyne with the formation of betaine 15 followed by the elimination of SCI2 to afford benzothiirene 16 and a further reaction with another benzyne molecule or dimerization to thianthrene 14 is given in Scheme 8. 

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