Ambident, types

Class (2) reactions are performed in the presence of dilute to concentrated aqueous sodium hydroxide, powdered potassium hydroxide, or, at elevated temperatures, soHd potassium carbonate, depending on the acidity of the substrate. Alkylations are possible in the presence of concentrated NaOH and a PT catalyst for substrates with conventional pX values up to - 23. This includes many C—H acidic compounds such as fiuorene, phenylacetylene, simple ketones, phenylacetonittile. Furthermore, alkylations of N—H, O—H, S—H, and P—H bonds, and ambident anions are weU known. Other basic phase-transfer reactions are hydrolyses, saponifications, isomerizations, H/D exchange, Michael-type additions, aldol, Darzens, and similar... 

In addition to reaction sequences of type (66) -> (67), electrophilic reagents can attack at either one of the ring nitrogen atoms in the mesomeric anions formed by proton loss e.g. 70 71 or 72 see Section 4.02.1.3.6). Here we have an ambident anion, and for unsymmetrical cases the composition of the reaction product (71) + (72) is dictated by steric and electronic factors. 

NH form e.g. 505). Most 4- and 5-hydroxy compounds of types (500) and (502) exist largely in these non-aromatic azolinone forms, although the hydroxyl form can be stabilized by chelation e.g. 506). The derived ambident anions react with electrophiles at O or C. Replacement of the hydroxyl group is sometimes possible provided electron-withdrawing groups are present as, for example, in 5-substituted 4-hydroxypyrazoles. 

A mechanism of this type permits substitution of certain aromatic and ahphatic nitro compounds by a variety of nucleophiles. These reactions were discovered as the result of efforts to explain the mechanistic basis for high-yield carbon alkylation of the 2-nitropropane anion by p-nitrobenzyl chloride. p-Nitrobenzyl bromide and iodide and benzyl halides that do not contain a nitro substituent give mainly the unstable oxygen alkylation product with this ambident anion ... 

For a successful application in synthesis, several problems have to be solved regioselectivity, whether the C-C bond is formed with the 1- or 3-position in an unsymmetrical ambident anion, EjZ selectivity in the formation of the double bond, and simple diastereoselectivity, since two new stereogenic centers are created from prostereogenic compounds. Further, different types of induced stereoselectivity or enantioselectivity may be required. Allylmetals with a wide choice of substituents are accessible by various methods (Sections D. 1.3.3.3.1.-10.). 

Some substrates (e.g., 1,3-dichlorobutane) can be attacked at two or more positions. We may call these ambident substrates. In the example given, there happen to be two leaving groups in the molecule, but there are two kinds of substrates that are inherently ambident (unless symmetrical). One of these, the ally lie type, has already been discussed (p. 421). The other is the epoxy (or the similar aziridine" or episulfide) substrate." ... 

Chlorodiphenylphosphine 488 reacts with a-sulphinyl carbanions to give a-sulphinylphosphines 489 which undergo ready isomerization to a-sulphenylphosphine oxides 4W (equation 295). The report of Almog and Weissman that a-sulphinyl carbanions react with phosphorochloridates 491 to give a-phosphoryl sulphoxides 492 calls for correction (equation 296). Actually, the phosphorylation occurs at the oxygen atom of the ambident dimsyl anion, and is followed by the Pummerer-type reaction affording diethylphosphoric acid and tetraethyl pyrophosphate among other products . ... 

At room temperature under photostimulation a-nitrosulfones react with a variety of nucleophiles via radical anion chain reactions interestingly, in none of the cases where the PhSOj group is involved in SrnI type of substitution does the O end of the ambident anion " play a role. This strong regioselectivity is reminiscent of the one reported for other ambident anions involved in these radical chain substitutions. ... 

The intermediacy of a carbocation or complex-equivalent is attractive, if one considers that the nucleophilic ambident cyanide ion may be accomodated on secondary or tertiary cationic sites. Where exceptions (e.g., 125,126,134-136 cf. Sect. 4.3) exist, the cationic intermediate resides on a primary allylic carbon. The following skeletal types are examples of some biogenetic schemes offered in conjunction with the structural determination of isocyanoterpenoids ... 

As far as substrates are concerned, while the usual 1,4-addition and 1,3-substi-tution (Sn2 ) reactions of simple unsaturated substrates have so far predominated, analogous transformations of ambident substrates with extended multiple bond systems (i.e., with two or more reactive positions) have come to attention only recently. Here, systematic investigations have shown that such 1,5-substitutions and even 1,6- and 1,8-addition reactions proceed highly regioselectively and ste-reoselectively, in particular when the substrate contains at least one triple bond besides one or more conjugated double bonds. These unusual reaction types not... 

Besides direct nucleophilic attack onto the acceptor group, an activated diene may also undergo 1,4- or 1,6-addition in the latter case, capture of the ambident enolate with a soft electrophile can take place at two different positions. Hence, the nucleophilic addition can result in the formation of three regioisomeric alkenes, which may in addition be formed as E/Z isomers. Moreover, depending on the nature of nucleophile and electrophile, the addition products may contain one or two stereogenic centers, and, as a further complication, basic conditions may give rise to the isomerization of the initially formed 8,y-unsaturated carbonyl compounds (and other acceptor-substituted alkenes of this type) to the thermodynamically more stable conjugated isomer (Eq. 4.1). 

Heterocyclic secondary 183-type enamines (exocyclic vinylogous urethanes) show ambident bisnucleophilicity their nucleophilic reaction... 

Hydroxylamines and alkylhydroxylamines possess high nucleophilicity and can react with a variety of primary and secondary alkylating agents. The reactivity of hydroxylamines in the majority of these reactions resembles that of primary and secondary amines. While hydroxylamine and Af-alkylhydroxylamines 1 are ambident nucleophiles, under neutral or weakly basic reaction conditions alkylation proceeds exclusively on nitrogen atom to give products of type 2 (equation 1). Deprotonation of the OH group of hydroxylamines results in O-alkylation products. 

Hydroxamic acids undergo facile nucleophilic Ai-arylation with activated aryl halides such as 31 (equation 22). While hydroxamates are known to be ambident nucleophiles in alkylation reactions, arylation of hydroxylamines results exclusively in Ai-substituted hydroxamates of type 32 (equation 22)". ... 

Phenol-induced oxidative stress mediated by thiol oxidation, antioxidant depletion, and enhanced free radical production plays a key role in the deleterious activities of certain phenols. In this mode of DNA damage, the phenol does not interact with DNA directly and the observed genotoxicity is caused by an indirect mechanism of action induced by ROS. A direct mode of phenol-induced genotoxicity involves covalent DNA adduction derived from electrophilic species of phenols produced by metabolic activation. Oxidative metabolism of phenols can generate quinone intermediates that react covalently with N-1,N of dG to form benzetheno-type adducts. Our laboratory has also recently shown that phenoxyl radicals can participate in direct radical addition reactions with C-8 of dG to form oxygen (O)-adducts. Because the metabolism of phenols can also generate C-adducts at C-8 of dG, a case can be made that phenoxyl radicals display ambident (O vs. C) electrophilicity in DNA adduction. 

In the new structures of type (59) the reactive centre is the methanide site which behaves as a nucleophile. <86JCS(Pi)ii57, 92JCS(P1)1483> (Section 4.17.8). Tautomeric tetrazole-tetrazoline structures of general type (4 R = H) may show ambident reactivity with reactions occurring on the ring or the exocyclic X atom (Sections 4.17.6 and 4.17.7). 

The 1,2,4-triazine ring is an ambident electrophile, and reacts with enamine-type nucleophiles. For example, addition of enamine 78 to a solution of triazine 77 in acetic anhydride furnished the pyrrolotriazine 31 (Equation 24) <2003TL2421>. 

Problem 14.44 Since (CH,)2S==0 is an ambident nucleophile, reaction with CHjI could give ((CH,),s =oir or [(CH3)jS=0—CH,]I. (a) What type of spectroscopy can be used to distinguish between the two products (b) Predict the major product. <... 

This means there are 42 entries that have the words AMBIDENT and NUCLEOPHILE somewhere in them in the titles, keywords, or index entries. We can now, if we wish, display any or all of them. But a particular entry might have these two words in unrelated contexts, e.g., it might be a paper about ambident electrophiles, but which also has NUCLEOPHILE as an index term. We would presumably get fewer papers, but with a higher percentage of relevent ones, if we could ask for AMBIDENT NUCLEOPHILE, and in fact, the system does allow this. If we type S AMBIDENT(W)NUCLEOPHILE, we will get only those papers in which the term NUCLEOPHILE directly follows AMBIDENT, with no words in between.41 This is called proximity searching, and there are other, similar commands. For example, the use of (4A) instead of (W) will give all instances in which the two words appear 4 or fewer words apart, in either order. 

The first example of PTC alkylation of ambident heterocyclic anions of the type N—C—S was by Hassanaly et al.192... 

Ions of this type, which can react at either of two different sites, often are called ambident ions. 

Sulfurdiimines RN=S=NR and thionitrites RN=S=0 (R = alkyl, aryl) have been relatively little investigated as ligands in metal complexes. This lack of attention has been little deserved as both types of ligands have interesting ambident coordination properties, since they may bind via N, S, O, the 7t-N=S or jr-S=0 bond for example. They may be compared with allenes and naturally also with the isostructural and the isoelectronic sulfur dioxide 0=S—O.13 We will first discuss some relevant data concerning RNSNR and RNSO and subsequently the properties of the metal complexes. 

The /-butylthiolate anion exhibits ambident behavior, giving both types of product, complexes 56 and 57 ... 

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