Aprotic conditions

In aprotic conditions acetic anhydride sodium acetate induces formation of a fused ring through an intra molecular condensation. It results in a pyrrolo[2,l-fc]thiazole (39), which constitutes an interesting intermediate for the synthesis of dyes (Scheme 18) (40). 

The reactions of pyrroles with dimethyl acetylenedicarboxylate (DMAD) have been extensively investigated. In the presence of a proton donor the Michael adducts (125) and (126) are formed. However, under aprotic conditions the reversible formation of the 1 1 Diels-Alder adduct (127) is an important reaction. In the case of the adduct from 1-methylpyrrole, reaction with a further molecule of DMAD can occur to give a dihydroindole (Scheme 48) (82H(19)1915). 

The reaction of A -bromosuccinimide with 5a-cholestan-3-one enol acetate in aprotic conditions, described by Green and Long, is probably free radical in character cf. ref. 69). 

A very efficient method for annulations158 is based on the addition of lithium or silyl enolates to a-silylated enones as a key step. The diastereoselective 1,4-addition is followed by an aldol condensation. This procedure allows Michael additions under aprotic conditions, whereby the silyl substituent stabilizes the enolate of the Michael adduct preventing polymerization of the enone, 59 l63. 

TABLE 5. Analytical and coulometric data concerning some diaryl sulphones and related compounds in aprotic conditions... 

When the substrate contains gem- Z groups, (e.g., 62), bulky groups can be added, if the reaction is carried out under aprotic conditions. For example, addition of... 

When catechol was oxidized with Mn04 under aprotic conditions, a semiquinone radical ion intermediate was involved. For autoxidations (i.e., with atmospheric oxygen) a free-radical mechanism is known to operate. 

Alkyl esters are efficiently dealkylated to trimethylsilyl esters with high concentrations of iodotrimethylsilane either in chloroform or sulfolane solutions at 25-80° or without solvent at 100-110°.Hydrolysis of the trimethylsilyl esters serves to release the carboxylic acid. Amines may be recovered from O-methyl, O-ethyl, and O-benzyl carbamates after reaction with iodotrimethylsilane in chloroform or sulfolane at 50—60° and subsequent methanolysis. The conversion of dimethyl, diethyl, and ethylene acetals and ketals to the parent aldehydes and ketones under aprotic conditions has been accomplished with this reagent. The reactions of alcohols (or the corresponding trimethylsilyl ethers) and aldehydes with iodotrimethylsilane give alkyl iodides and a-iodosilyl ethers,respectively. lodomethyl methyl ether is obtained from cleavage of dimethoxymethane with iodotrimethylsilane. 

The role of the trimethylsilyl group is to stabilize the enolate formed in the conjugate addition. The silyl group is then removed during the dehydration step. Methyl 1-trimethylsilylvinyl ketone can be used under aprotic conditions that are compatible with regiospecific methods for enolate generation. The direction of annulation of unsymmetrical ketones can therefore be controlled by the method of enolate formation. 

Several examples of conjugate addition of carbanions carried out under aprotic conditions are given in Scheme 2.24. The reactions are typically quenched by addition of a proton source to neutralize the enolate. It is also possible to trap the adduct by silylation or, as we will see in Section 2.6.2, to carry out a tandem alkylation. Lithium enolates preformed by reaction with LDA in THF react with enones to give 1,4-diketones (Entries 1 and 2). Entries 3 and 4 involve addition of ester enolates to enones. The reaction in Entry 3 gives the 1,2-addition product at —78°C but isomerizes to the 1,4-product at 25° C. Esters of 1,5-dicarboxylic acids are obtained by addition of ester enolates to a,(3-unsaturated esters (Entry 5). Entries 6 to 8 show cases of... 

When conjugate addition is carried out under aprotic conditions with stoichiometric formation of the enolate, the adduct is present as an enolate until the reaction mixture is quenched with a proton source. It is therefore possible to effect a second reaction of the enolate by addition of an alkyl halide or sulfonate to the solution of the adduct enolate, which results in an alkylation. This reaction sequence permits the formation of two new C-C bonds. 

The initial products of such additions under aprotic conditions are organosamarium reagents and further (tandem) transformations are possible, including addition to ketones, anhydrides, or carbon dioxide. 

For the cydative cleavage step, it turned out that aprotic conditions were definitely superior to the use of protic media. Thus, employing N,N-dimethylformamide as solvent at somewhat elevated temperatures furnished the desired compounds in high yields and excellent purities. Having established the optimized conditions, various phthalic acids and amines were employed to prepare a set of phthalimides (Scheme 7.51). However, the nature of the amine was seen to have an effect on the outcome of the reaction. Benzyl derivatives furnished somewhat lower yields, probably due to the reduced activities of these amines. Aromatic amines could not be included in the study as auto-induced ring-closure occurred during the conversion of the polymer-bound phthalic acid. 

Biphenyl catalyses the reductive ring opening of oxetanes with lithium metal under aprotic conditions to give alcohols 14 . 

The subsequent Claisen-Schmidt reaction was originally performed on a 10-pmol scale using 20-fold excess of both acetophenone and LiOH to achieve complete formation of the chalcone 8. This result could be verified on a small scale however, employing the same conditions on a 35-mmol scale resulted in no conversion even after 22 h, as revealed by IR spectroscopy. By cleaving a resin sample with 20% TFA in dichloromethane, only -formylbenzamide 11 was detected by HPLC. This result may be explained by the low solubility of LiOH in DME under dry/aprotic conditions. Therefore, a small amount of EtOH was added, which initiated a fast reaction (Chiu et al. 1999) and the formation of the desired chalcone 8 together with 20% of the Michael adduct 10 (Fig. 2). This was confirmed by sample cleavage from the resin and LC-MS analysis. Short reaction screening resulted in considerable im-... 

Aliphatic nitro compounds exhibit rather different behavior from nitroaromatic compounds. Secondary and primary nitro compounds tend to produce oximes because the intermediate nitroso compound quickly tautomerizes to the oxime (equation 1). Under aprotic conditions the radical anions of primary and secondary nitro compounds are relatively stable those derived from tertiary nitro compounds, on the other hand, eject nitrite ion relatively readily (equation 2)8. 

Under nominally aprotic conditions, 1,2-protonation dominates in naphthalene. Reduction of naphthalene in anhydrous acetonitrile containing tetraethylammo-nium p-toluenesulfonate yields 1,2-di-hydronaphthalene, which is subsequently... 

The addition of protons is certainly the most common nucleophilic reaction of reduced hydrocarbon species due to the almost ubiquitous availability of proton donors, which may or not be wanted. However, under strictly aprotic conditions it is also possible to add other electrophilic reagents such as alkyl halides, acyl halides, CO2, and SO2. 

Under aprotic conditions, prototropic transformations of thiols are relatively slow, so one can observe distinct waves of the oxidation of the protonated form and of its parent base [19, 20]. Normally, the oxidation of thiols (aliphatic, aromatic, and heteroaromatic) affords diorganyl-disulfides. So various aliphatic and aromatic thiols are easily converted into the corresponding disulfides upon oxidation in MeOH/MeONa with the yields ranging... 

Under aprotic conditions, aromatic thioketones are reduced by sodium telluride to the corresponding hydrocarbons. ... 

A related compound was prepared by the reaction of 1,2-diiodoacenaphtalene with sodium telluride under aprotic conditions. ... 

A rhodium-catalyzed asymmetric synthesis of chiral titanium enolates by 1,4-addition of aryltitanium reagents to a,p-enones under aprotic conditions has... 

There is one report of competitive nucleophilic attack at the amide carbonyl in an Ai-acyloxy-A-aUtoxyamide. Shtamburg and coworkers have reported that MeONa reacted with Ai-acetoxy-A-ethoxybenzamide (159) in DME giving methyl and ethyl benzoate (160 and 161) (Scheme 26) . They attributed the formation of methyl benzoate to the direct attack of methoxide ion at the amide carbonyl rather than at nitrogen. The formation of 161 was attributed to a HERON reaction. Though not mentioned by the authors, it seems likely that under these aprotic conditions, 162 could also have been formed by methoxide attack at the acetate carbonyl leading to an anion-induced HERON reaction, by analogy with the reaction of Ai-acyloxy-Ai-alkoxyamides and aqueous hydroxide discussed above (Section IV.C.3.c)... 

A Baeyer-Villiger type oxidation of ketonic substrates occurs exclusively at the carbonyl function under aprotic conditions by use of BTSP and a catalytic amount of McsSiOsCCFs (MesSiOTf) (equation 28). C—C bonds are not affected (Table 5). ... 

Apparently, the mechanisms in protic and aprotic conditions only differ in their early steps, in which the protic system requires additional oxidants to convert luminol to... 

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