Oxidation nucleophile addition

Oxidative Nucleophilic Addition Starting from 1.2-Dihydro-K-... 

Scheme 28), and vanadium acetylides, formed from acetylenic Grignard or lithium compounds and VCl, react with aldehydes to give a, S-acetylenic ketones via oxidative nucleophilic addition (Scheme... 

Scheme 61 Oxidation - nucleophilic addition - elimination of proton...

Organovanadium compounds exhibit unique reactivities based on the redox characteristics of vanadium. The organovanadium compounds generated in situ couple chemoselectively with acid chlorides or aUyl halides [118]. The reaction with aldehydes gives coupled ketones possibly through oxidative nucleophilic addition (Scheme 2.56) [119, 120]. 

More recently, the focus has been put on formal nucleophilic substitution of —OH or —NH2 groups. To perform this biocatalytic variant of the Mitsunobu reaction, an oxidation-nucleophilic addition-reduction sequence is necessary, for which linked NAD-dependent oxidoreductases are ideally suited. The early contributions from the Forschungszentrum Jiilich [79] have been recently rediscovered by Kroutil and coworkers [80]. By combining a mandelate racemase (MR) with a mandelate dehydrogenase and an L-amino acid dehydrogenase, the authors could completely transform racemic mandelic acid into enantiopure (S)-phenyl-glycine (Scheme 8.16). 

Because of their relative instabiUty, primary phosphine oxides caimot be isolated and must be converted direcdy to derivatives. Primary and secondary phosphine oxides undergo reactions characteristic of the presence of P—H bonds, eg, the base-cataly2ed nucleophilic addition to unsaturated compounds such as olefins, ketones, and isocyanates (95). 

The N-oxides readily undergo nucleophilic addition followed by elimination, which forms the basis of several useful syntheses of 2-substituted pyridines. Chlorination of (13) with POCl to give 2-chloropyridine (17) is a good example (eq. 4) some chlorination may occur also at C-4 (11). 

Many other reactions of ethylene oxide are only of laboratory significance. These iaclude nucleophilic additions of amides, alkaU metal organic compounds, and pyridinyl alcohols (93), and electrophilic reactions with orthoformates, acetals, titanium tetrachloride, sulfenyl chlorides, halo-silanes, and dinitrogen tetroxide (94). 

Nitrile A-oxides, under reaction conditions used for the synthesis of isoxazoles, display four types of reactivity 1,3-cycloaddition 1,3-addition nucleophilic addition and dimerization. The first can give isoxazolines and isoxazoles directly. The second involves the nucleophilic addition of substrates to nitrile A-oxides and can give isoxazolines and isoxazoles indirectly. The third is the nucleophilic addition of undesirable nucleophiles to nitrile A-oxides and can be minimized or even eliminated by the proper selection of substrates and reaction conditions. The fourth is an undesirable side reaction which can often be avoided by generating the nitrile A-oxide in situ and by keeping its concentration low and by using a reactive acceptor (70E1169). 

The mechanism for the redistribution in oxidation states begins similarly to that of the Paal thiophene synthesis. However, upon formation of dithione 38, nucleophilic addition of one thiocarbonyl into the other produces the intermediate zwitterion 39. A 1,3-tautomerization of hydrogen then gives... 

There is some debate in the literature as to the actual mechanism of the Beirut reaction. It is not clear which of the electrophilic nitrogens of BFO is the site of nucleophilic attack or if the reactive species is the dinitroso compound 10. In the case of the unsubstituted benzofurazan oxide (R = H), the product is the same regardless of which nitrogen undergoes the initial condensation step. When R 7 H, the nucleophilic addition step determines the structure of the product and, in fact, isomeric mixtures of quinoxaline-1,4-dioxides are often observed. One report suggests that N-3 of the more stable tautomer is the site of nucleophilic attack in accord with observed reaction products. However, a later study concludes that the product distribution can be best rationalized by invoking the ortho-dinitrosobenzene form 10 as the reactive intermediate. 

In the case of unsubstituted BFO 1 reacting with an enamine, the following mechanism is generally accepted in the literature. The first step is nucleophilic addition of an enamine 2 to electrophilic BFO 1 to form the intermediate 12. Ring closure occurs via condensation of the imino-oxide onto the iminium functionality to give 13. Finally, P-elimination of the dialkyl amine produces the quinoxaline-1,4-dioxide 4. 

Asymmetric nucleophilic addition of dialkylzinc to 3,4-dihydroisoquinoline 1-oxides 98YGK11. 

The isolated cr -adducts 57 undergo oxidation with KMn04 easily, resulting in the corresponding 5-indolyl-1,2,4-triazine 4-oxides 60 (98ZOR429). Separating the nucleophilic addition step from the oxidative aromatization of the intermediate (T -adducts allows the use of such oxidant-sensitive nucleophiles as indoles. 

The initial step of olefin formation is a nucleophilic addition of the negatively polarized ylide carbon center (see the resonance structure 1 above) to the carbonyl carbon center of an aldehyde or ketone. A betain 8 is thus formed, which can cyclize to give the oxaphosphetane 9 as an intermediate. The latter decomposes to yield a trisubstituted phosphine oxide 4—e.g. triphenylphosphine oxide (with R = Ph) and an alkene 3. The driving force for that reaction is the formation of the strong double bond between phosphorus and oxygen ... 

Aldehyde oxidations occur through intermediate l/l-diols, or hydrates, which are formed by a reversible nucleophilic addition of water to the carbonyl group. Even though formed to only a small extent at equilibrium, the hydrate reacts like any typical primary or secondary alcohol and is oxidized to a carbonyl compound (Section 17.7). 

The Cannizzaro reaction takes place by nucleophilic addition of OH- to an aldehyde to give a tetrahedral intermediate, which expels hydride ion as a leaving group and is thereby oxidized. A second aldehyde molecule accepts the hydride ion in another nucleophilic addition step and is thereby reduced. Benzaldehyde, for instance, yields benzyl alcohol plus benzoic acid when heated with aqueous NaOH. 

The retro-Claisen reaction occurs by initial nucleophilic addition of a cysteine -SH group on the enzyme to the keto group of the /3-ketoacyl CoA to yield an alkoxide ion intermediate. Cleavage of the C2-C3 bond then follows, with expulsion of an acetyl CoA enolate ion. Protonation of the enolate ion gives acetyl CoA, and the enzyme-bound acyl group undergoes nucleophilic acyl substitution by reaction with a molecule of coenzyme A. The chain-shortened acyl CoA that results then enters another round of tire /3-oxidation pathway for further degradation. 

Step 4 of Figure 29.12 Oxidative Decarboxylation The transformation of cr-ketoglutarate to succinyl CoA in step 4 is a multistep process just like the transformation of pyruvate to acetyl CoA that we saw in Figure 29.11. In both cases, an -keto acid loses C02 and is oxidized to a thioester in a series of steps catalyzed by a multienzynie dehydrogenase complex. As in the conversion of pyruvate to acetyl CoA, the reaction involves an initial nucleophilic addition reaction to a-ketoglutarate by thiamin diphosphate vlide, followed by decarboxylation, reaction with lipoamide, elimination of TPP vlide, and finally a transesterification of the dihydrolipoamide thioester with coenzyme A. 

Steps 7-8 of Figure 29.12 Hydration and Oxidation The final two steps in the citric acid cycle are the conjugate nucleophilic addition of water to fumarate to yield (S)-malate (L-malate) and the oxidation of (S)-malate by NAD+ to give oxaloacetate. The addition is cataiyzed by fumarase and is mechanistically similar to the addition of water to ris-aconitate in step 2. The reaction occurs through an enolate-ion intermediate, which is protonated on the side opposite the OH, leading to a net anti addition. 

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