Amide a-anion

Amide a-anions. The Boc-protected secondary amines are readily converted to a-lithio derivatives, which behave in the same way as other organolithium reagents. 7V-Boc-2-methyltetrahydro-l,3-oxazine undergoes regioselective deprotonation at C-4. ... 

Amide a-anions. The BocN(Me)CH2Li species (prepared by lithiation with --BuLi/TMEDA) can be converted into cuprate reagent and coupled with enol triflates. This method is useful for the synthesis of aUyhc amines. ... 

SYNTHESIS OF 5-SUBSTITUTED URIDINES via THE AMIDE a-ANION OF 5,6-DIHYDROURIDINE... 

However, when 5 was lithiated with BuLi and then deuterated, deuterium incorporation occurred with a preference of ca. 2 1 for the C-6 position. Lack of the desired regioselectivity for the C-S in this reaction led us to develop another route to S-substituted uridines. As the C-5 position is alpha to the carbonyl group, we expected that saturation of the 5,6-double bond would provide an "amide a-anion" despite the presence of the acidic N3-H. 

Catalytic hydrogenation effected virtually quantitative conversion of 5 to the 5,6-dihydrouridine derivative 27 (Scheme 9). The amide a-anion generated from 27 using LDA... 

A different route has to be used to synthesize 5-alkyluridines (Scheme 10) because introduction of an electron-donating alkyl group at the C-S position of 27 decreases the acidity of H-S. Thus, while 30 can be prepared in high yield by methylation of the amide a-anion, its reaction with the PhSeCl-pyridine complex only resulted in complete tecoveiy... 

A useful method to synthesize ten and fourteen-membered ring imides 346 involved an initial condensation of macrocyclic -ketoestes 343 with alkyl or aryl isocyanates and carbodiimides, respectively, in the presence of a base [68]. After a nucleophilic attack of the enolate on the isocyanate C, the resultant amide N anion 344 induced a ring closure by addition to the keto group. Then, the intermediately formed four-membered ring 345 underwent a fragmentation... 

The electrochemical cyclization reaction is less successful with the N-(3-phenylallyl)acetanilide 60 which has two potential bond cleavage sites from the radical-anion [173]. Carbon-nitrogen bond cleavage with loss of a 3-phenylallyl radical, leaving an amide nitrogen anion, is favoured over carbon-chlorine bond cleavage. 

The initial conceptualization of the agelastatin A problem took on the form shown below (Scheme 5).17 The key transform in this sequence features intramolecular addition of an amide-derived anion to a tethered alkynyliodonium salt within 33. The alkylidenecarbene generated from this nucleophilic addition, 32, then has a choice of two diastereotopic C-H bonds (Ha or Hb) for 1,5 insertion. Reaction with Ha would provide an advanced intermediate 31 en route to the target 28. Successful execution of this plan would extend alkynyliodonium salt chemistry in three new directions (1) use of an amine derivative as a nucleophile, (2) intramolecularity in the nucleophile addition step, and (3) diastereoselectivity upon alkylidenecarbene C-H insertion. At the initiation of this project, a lack of precedent on any of these topics suggested that focused scouting experiments to assess feasibility would be prudent before beginning work towards the natural product itself. 

Gale, P. A., Camiolo, S., Chapman, C. P., Light, M. E., Hursthouse, M. B. (2001) Hydrogenbonding pyrrolic amide cleft anion receptors, Tetrahedron Lett. 42, 5095-5097. 

The electrodeposition of reactive elements like Al, Si, Ge, Ta and a few others is possible. As discussed in Chapter 4.4 the successful electrodeposition of Ti, Mg, Mo and many others in relevant layer thicknesses has not yet been described, though attempts have been made in some cases. Apart from the availability of suitable precursors there is at least one other issue to consider ionic liquids can be reactive. It was found that magnesium and its alloys can form passivating films in ionic liquids with the bis(trifluoromethylsulfonyl)amide (Tf2N) anion, especially in the presence of water. It was found by two of our groups (Endres, MacFarlane) that, under certain circumstances, the Tf2N ion is subject to cathodic... 

Table 4.4 lists some common bases used in organic chemistry. Although butyl-lithium behaves as a very strong base in many reactions, it also exhibits other chemistry, so it is usually used to prepare other strong bases listed in the table. Lithium diisopropylamide, sodium amide, dimsyl anion, and sodium hydride are often used to prepare the conjugate bases of aldehydes, ketones, and esters for use in reactions. Potassium fert-butoxide is employed when a base somewhat stronger than the conjugate bases of most alcohols is needed. 

The final type of carbon nucleophile that is discussed in this chapter is a dianion. In some cases, treatment of an anion with a very strong base can remove a second proton to form a dianion. As an example, the reaction of 2,4-pentanedione with one equivalent of base removes a proton from the carbon between the two carbonyl groups. If this anion is treated with a second equivalent of a strong base, such as potassium amide, a second proton can be removed to form a dienolate anion ... 

However, most nucleophiles attack 5-oxazolones at the carbonyl group and the products are derivatives of a-amino acids formed by acyl-oxygen fission. Thus the action of alcohols, thiols, ammonia and amines leads, respectively, to esters, thioesters and amides orthophosphate anion gives acyl phosphates (Scheme 18). The use of a-amino acids in this reaction results in the establishment of a peptide link. Cysteine is acylated at the nitrogen atom in preference to the sulfur atom. Enzymes, e.g. a-chymotrypsin and papain, also readily combine with both saturated and unsaturated azlactones. A useful reagent for the introduction of an a-methylalanine residue is compound (202). Both the trifluoroacetamido and ester groups in the product are hydrolyzed by alkali to give a dipeptide. The alkaline hydrolyzate may be converted into the benzyloxycarbonyl derivative, which forms a new oxazolone on dehydration. Reaction with an ester of an amino acid then yields a protected tripeptide (equation 45). 

This is an example of the first step of an addition-elimination reaction mechanism converting an ester (methyl acetate) to an amide (A - mcth y I acctam ide). For clarity, the anion was repositioned in the scheme. Arrow pushing is illustrated below ... 

Ambident anions are mesomeric, nucleophilic anions which have at least two reactive centers with a substantial fraction of the negative charge distributed over these cen-ters ) ). Such ambident anions are capable of forming two types of products in nucleophilic substitution reactions with electrophilic reactants . Examples of this kind of anion are the enolates of 1,3-dicarbonyl compounds, phenolate, cyanide, thiocyanide, and nitrite ions, the anions of nitro compounds, oximes, amides, the anions of heterocyclic aromatic compounds e.g. pyrrole, hydroxypyridines, hydroxypyrimidines) and others cf. Fig. 5-17. 

The acid and esters do not isomerize in solvents in the absence of strong adds or bases at temperatures up to 100° or higher. Isomerization of the itaconates through basic abstraction of a proton from the a-methylenic position might be ejq>ected to cause difficulty in anionic polymerization. In fact, attempts to polymerize itaconic esters (7) and amides (6) anionically have given little or no polymar, but considerable isomerization. 

Deprotonation of alkylnitriles with LDA or lithium hexamethyldisilazide (LHMDS" ) and treatment of the resultant ambident a-nitrile anions with 1° and 2°-alkyl halides affords C-alkylated products in good yield. However, the a-anions of highly substituted nitriles may undergo N-alkylation to give amides on aqueous workup. 

The Effect of a. Changes of the nature of a are of great importance. For example, one of the requirements for activity in this series appears to be a cyclic urea nitrogen atom having pronounced anionic character (NH-acidity). Analogous cyclic carbamates (a = 0) are considerably less active, whereas cyclic amides (a = CH2) are inactive. 

The affinities observed for complexes between amides and anions are remarkably parallel to those found for the interactions between such anions and carbohydrate models. The data in Tab. 2.1 show the same affinity increase in the sequence r
strong acceptor as the result of two geometrically matching hydrogen bonds with vicinal diols. The formation of two almost linear and parallel hydrogen bonds is also responsible for the efficiency of the guanidinium residue for carboxylate complexation in artificial receptors [101] as well as in proteins (cf. Chapter 6) [102]. 

Secondary amides are versatile and highly accessible hydrogen bond donors that have been used in numerous synthetic receptors, hi the biological arena, there are many examples of proteins that employ amide NH- anion interactions to bind negatively charged guests [5-9]. The first example of a synthetic amide containing receptor, pubUshed in 1986 by Pascal and co-workers, was a crytpand-like tris-amide that was shown to interact with fluoride in DMSO-de [10]. 

This activated base also converts N,N-disubstituted amides into the a-anions, which react with various electrophiles (equation VIII). ... 

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