Intermediates anionic

Some Hammett values for reactions in thiazole and in nucleophile are reported in Table V-3. The observed p values for normal substitution processes (methoxy and thiophenoxysubstitution) are high and positive, indicating that the substituent plays an important role in modifying the stability of the intermediate anion. 

The palladium chloride process for oxidizing olefins to aldehydes in aqueous solution (Wacker process) apparendy involves an intermediate anionic complex such as dichloro(ethylene)hydroxopalladate(II) or else a neutral aqua complex PdCl2 (CH2=CH2)(H2 0). The coordinated PdCl2 is reduced to Pd during the olefin oxidation and is reoxidized by the cupric—cuprous chloride couple, which in turn is reoxidized by oxygen, and the net reaction for any olefin (RCH=CH2) is then... 

In a like manner the 6/3-isocyano group can be utilized to activate the C(6) proton (79JCS(P1)2455), an example of which is shown in Scheme 43. It was also possible to introduce the 6a-methylthio substituent by reacting the intermediate anion with methyl methoxycarbonyl disulfide The 6a-methylthio group could subsequently be converted to the 6a-methoxy group by treatment with CI2 and MeOH. 

In the ElcB reaction, C-H bond-breaking occurs first. A base abstracts a proton to give an anion, followed by loss of the leaving group from the adjacent carbon in a second step. The reaction is favored when the leaving group is two carbons removed from a carbonyl, which stabilizes the intermediate anion by resonance. Biological elimination reactions typically occur by this ElcB mechanism. 

Halobenzenes undergo nucleophilic aromatic substitution through either of two mechanisms. If the halobenzene has a strongly electron-withdrawing substituent in the ortho or para position, substitution occurs by addition of a nucleophile to the ring, followed by elimination of halide from the intermediate anion. If the halobenzene is not activated by an electron-withdrawing substituent, substitution can occur by elimination of HX to give a benzyne, followed by addition of a nucleophile. 

Similarly, enamino vinyl sulfones (345) can undergo a thermally allowed electrocyclic reaction between the termini of the enaminic double bond and the allyl sulfonyl portion in the intermediate anion (346) to afford a, /1-unsaturated thiene dioxides (348) as shown in equation 126335. 

In 1995, and regrettably missed in last year s review, Klotgen and Wiirthwein described the formation of the 4,5-dihydroazepine derivatives 2 by lithium induced cyclisation of the triene 1, followed by acylation <95TL7065>. This work has now been extended to the preparation of a number of l-acyl-2,3-dihydroazepines 4 from 3 <96T14801>. The formation of the intermediate anion and its subsequent cyclisation was followed by NMR spectroscopy and the stereochemistry of the final product elucidated by x-ray spectroscopy. The synthesis of optically active 2//-azepines 6 from amino acids has been described <96T10883>. The key step is the cyclisation of the amino acid derived alkene 5 with TFA. These azepines isomerise to the thermodynamically more stable 3//-azepines 7 in solution. 

In contrast to the intermediate anions, an anion without hydrogen atoms no longer has acidic possibilities. 

The addition of eCN is reversible, and tends to lie over in favour of starting materials unless a proton donor is present this pulls the reaction over to the right, as the equilibrium involving the cyanohydrin is more favourable than that involving the intermediate anion (32) ... 

During the reductive cleavage of cyclopolyenes with potassium in liquid ammonia, the intermediate anionic species are quenched with iodine-pentane mixtures. The possibility of formation of explosive nitrogen triiodide and the need for precautions are stressed. 

Ultrafast ESPT from the neutral form readily explains why excitation into the A and B bands of AvGFP leads to a similar green anionic fluorescence emission [84], Simplistic thermodynamic analysis, by way of the Forster cycle, indicates that the excited state protonation pK.J of the chromophore is lowered by about 9 units as compared to its ground state. However, because the green anionic emission is slightly different when it arises from excitation into band A or band B (Fig. 5) and because these differences are even more pronounced at low temperatures [81, 118], fluorescence after excitation of the neutral A state must occur from an intermediate anionic form I not exactly equivalent to B. State I is usually viewed as an excited anionic chromophore surrounded by an unrelaxed, neutral-like protein conformation. The kinetic and thermodynamic system formed by the respective ground and excited states of A, B, and I is sometimes called the three state model (Fig. 7). 

Three possible mechanistic schemes can be suggested for this process. One involves elimination of the proton attached to the p-C atom of nitronate A or A followed by elimination of the OSi group from the intermediate anion (cf. Scheme 3.93). Another mechanism is associated with a 1,4-C,O-transfer of the proton from the p-C atom of nitronate A to the oxygen atom of the N—>0 fragment followed by elimination of silanol from hemiacetal B. The third mechanism is based on the concerted elimination of silanol from the minor cis isomer of SENA. 

Photolysis of nitro-steroids 225 yields the aci-nitronate at 254 nm131. This in turn gives various products, among them are ketone 226 and hydroxamic acid 227 (equation 105) which could be formed from the intermediate anions of the Af-hydroxyoxaziridines, with a possible participation of gem-hydroxynitroso transient (or its anion see Scheme 10). For comparison, IV-butyl spiro-oxaziridine 228 in ethanol is photolysed at 254 nm (equation 106) to give 7V-butyl lactam 229 (50%) and the ketone 230 (25%). The former process is a well-known photoprocess of oxaziridine131. 

The formation of cyclopropanes from 7C-deficient alkenes via an initial Michael-type reaction followed by nucleophilic ring closure of the intermediate anion (Scheme 6.26, see also Section 7.3), is catalysed by the addition of quaternary ammonium phase-transfer catalysts [46,47] which affect the stereochemistry of the ring closure (see Chapter 12). For example, equal amounts of (4) and (5) (X1, X2 = CN) are produced in the presence of benzyltriethylammonium chloride, whereas compound (4) predominates in the absence of the catalyst. In contrast, a,p-unsatu-rated ketones or esters and a-chloroacetic esters [e.g. 48] produce the cyclopropanes (6) (Scheme 6.27) stereoselectively under phase-transfer catalysed conditions and in the absence of the catalyst. Phenyl vinyl sulphone reacts with a-chloroacetonitriles to give the non-cyclized Michael adducts (80%) to the almost complete exclusion of the cyclopropanes. 

A degree of stereoselective control of the course of a reaction, which is absent or different from that prevalent when the reaction is conducted in the absence of quaternary ammonium salts, may be achieved under standard phase-transfer catalysed reaction conditions. The reactions, which are influenced most by the phase-transfer catalyst, are those involving anionic intermediates whose preferred conformations or configurations can be controlled by the cationic species across the interface of the two-phase system. For example, in the base-catalysed Darzens condensation of aromatic aldehydes with a-chloroacetonitriles to produce oxiranes (Section 6.3), the intermediate anion may adopt either of the two conformations, (la) or (lb) which are stabilized by interaction across the interface by the cations (Scheme 12.1) [1-4]. 

Reduction in liquid NH3 and NaCl at Pt electrodes gives a 90% yield of a mixture consisting of 85% (A) (Fig. 60) and 14% (C) [329]. The hydrogenations in methy-lamine or ammonia are cathodic Birch reductions in which the final protonation of the intermediate anion leads to the thermodynamically more favorable trans product. 

C=X bonds The stereochemistry of the reduction of carbonyl compounds has been intensely studied with regard to synthetic and mechanistic aspects. The reduction of 1,2-diphenyl-l-propanone at a Hg cathode in aqueous EtOH and pH 8 affords the erythro alcohol as the major diastereomer (erythro threo = 5 to 1.4 1) [332]. This selectivity is in accord with a protonation of the intermediate anion, formed in an ECE sequence, from the least hindered side (Fig. 61). 

The keto radical is reduced and further protonated. The function of yohimbine-H+ is to catalyze the tautomerization and to enantioselectively protonate the final carbanion. It is also concluded that the hydrophobic yohimbine is enriched near the hydrophobic cathode surface. Quantum chemical calculations demonstrate that si protonation of the intermediate anion by yohimbine-H+ to give the (i )-dihydroproduct is energetically favored [389, 390]. Similarly, 3-methylinden-l-one in the presence of strychnine yields 71% 3-methylindan-1-one with 35% ee (S -enantiomer). 

HCCl2C00Me could be used instead of CHCI3 with similar results [128]. For (43a), cyclization by intramolecular Sn2 reaction competes with protonation, and when stoichiometric amounts of EGB and CHCI3 were used, the cyclopropane derivative was the main product. Scheme 32, since protonation of the intermediate anion now has to be from (33H), which is less acidic than CHCI3 [128],... 

Nucleophilic acyl complexes can be 0-alkylated with hard electrophiles to yield the corresponding alkoxy- or (acyloxy)carbene complexes. The first carbene complex ever isolated [61] was prepared by this route the intermediate, anionic acyl complex was generated by addition of phenyllithium to tungsten hexacarbonyl (Figure 2.3). 

As MO calculations show (Vilar et al. 1982), the energy levels for pairs (Ar + TePh) and (ArTe + Ph ) are equal. This makes a dual direction of decomposition possible for the intermediate anion-radical as follows ... 

Thus, if the concerted pathway has a stronger driving force than that of the first step of the stepwise pathway, the cleavage of anion-radical is thermodynamically favorable. Stepwise mechanisms are considered viable when the intermediate (anion-radical in the preceding schemes) has a lifetime that is longer than the time for a bond vibration (ca. 10 s). Concerted mechanisms occur under... 

Amide formation involved the same considerations. Thus, esters are readily converted into amides by treatment with ammonia (see Section 7.10). The intermediate anion has two potential leaving groups, alkoxide RO and amide NH2, and alkojdde is the better leaving group. The converse of this is that treatment of an amide with an alcohol does not lead to an amide we generate the same intermediate anion, so the reverse reaction, loss of alkoxide, predominates. 

Alkene polymers such as poly(methyl methacrylate) and polyacrylonitrile are easily formed via anionic polymerization because the intermediate anions are resonance stabilized by the additional functional group, the ester or the nitrile. The process is initiated by a suitable anionic species, a nucleophile that can add to the monomer through conjugate addition in Michael fashion. The intermediate resonance-stabilized addition anion can then act as a nucleophile in further conjugate addition processes, eventually giving a polymer. The process will terminate by proton abstraction, probably from solvent. 

Similar resonance structures may be drawn in the case of 4-chloropyridine, and this will also undergo nucleophilic substitution. However, 3-chloropyridine, despite having the same favourable leaving group, does not undergo substitution. This may be deduced from consideration of the intermediate anion resonance... 

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