Second-generation oxidative aminations

Second-Generation Oxidative Aminations Regioseiectivity as a Function of Mechanism... 

An enyne metathesis approach to pyrrole-2-phosphonates was reported <07CEJ203>. Treatment of enyne amine 10 with a second-generation Grubbs ruthenium catalyst in the presence of the oxidant tetrachloroquinone (TCQ) gave pyrrole-2-phosphonate 11. 

Synthesis of oxazabicycloalkanes and related products was achieved by a one pot electron-proton-electron (EPE) transfer mediated reactions of the amine moiety [317]. Here the iminium cation is formed from the second electron oxidation of the a-aminoalkyl radical, generated via the a-deprotonation of the planar aminium radical owing to their low ionization potential. The iminium cation thus formed can... 

Yes 10 the first question A benzylie curbon is oxidized. No to tlie. second, for two rciisons. First, the amine is a reactive and oxidizable functional group and would have to be protected. Second, generation of a new stereocenter in exclusively the proper configuration would be diflicult, although resolution of a racemic product mixture into its enantiomers would be straightforward. 

A second-generation process ronte was developed that improves upon the initial process route (Scheme 6). - - In this simplified process approach, the molecular symmetry of the starting caronic anhydride was maintained to the latest stage possible. Caronic anhydride (30) was initially converted directly to imide 40 by heating with either ammonium hydroxide or formamide with DMAP under Dean-Stark conditions. In an alternative two-step protocol, heating of 30 with benzyl amine produced an intermediate benzyl imide, which was deprotected to 40 under catalytic hydrogenation conditions. Reduction of imide 40 with lithium aluminum hydride afforded 41, which was desymmetrized under oxidative conditions to produce racemic imine 42. Diastereoselective cyanation favored trans-43, which underwent methanolysis under Pinner conditions. Finally, classical resolution by crystallization with D-DTTA afforded 24 as the D-DTTA salt with >95% ee. 

Improved efficiency in the synthesis of 24 was ultimately achieved via an enzymatic desymmetrization approach (Scheme 7). In the key step of this route, an asymmetric oxidation of achiral amine 41 promoted by monoamine oxidase (MAON) under an oxygen atmosphere afforded intermediate 42. In this streamlined process, sodium bisulfite was included in the enzymatic oxidation mixture to effect direct conversion to sulfonate 44. Treatment of 44 with sodium cyanide provided the trans-nitrile 43 as a single diastereomer in approximately 90% yield from pyrrolidine 41. As in the second-generation synthesis, the nitrile is hydrolyzed to the methyl ester under Pinner conditions (HCI, methanol). In the manufacturing process, the product was converted to its free base using NaOH, then crystallized as the HCI salt from i-propanol and methyl t-... 

These are the most common diazeniumdiolates, formed by the reaction of secondary amines and polyamines with nitric oxide in basic media [214, 215]. They are stable solids, capable of regenerating two equivalents of nitric oxide along with the starting amine in neutral or acidic buffers. The half-life of NO generation varies from a few seconds to many hours, depending on the amine. The decomposition to NO is a spontaneous, first-order reaction at constant pH. 

FMO also oxidizes primary and secondary amines. For example, it N-hydroxylates both amphetamine and methamphetamine to generate the corresponding hydroxylamines (Fig. 4.27) (70). It then catalyzes a second N-hydroxylation of both metabolites. The two A, A -dihydroxy intermediates eliminate water to generate the oxime in the case of amphetamine and the nitrone in the case of methamphetamine. 

The catalytic activity of MAO can be simply characterized as two half-reactions (Fig. 4.33). In the first half-reaction, the amine substrate is oxidized and the FAD cofactor is reduced. In the second half-reaction, the imine product is released and the FAD cofactor reoxidized generating peroxide. The released imine chemically hydrolyzes to the corresponding aldehyde. 

In a second step, the gel is fimctionahzed for NA attachment. Common methods for polyacrylamide gel fimctionahzation are based on the treatment of the polymerized support with reagents such as hydrazine or ethylenedi-amine. These treatments generate amine groups in the gel that can react with amine-modified ONDs via glutaraldehyde coupling, or directly with oxidized DNA probes (Fig. 15). Alternatively, the fimctional groups may be introduced by copolymerization reactions (e.g. co-polymerization with N-hydroxysuccinimide acryhc or oxirane acryhc derivatives) [59]. 

There are demethylases which act like amine oxidases that are dependent in their mechanism on their cosubstrate flavine adenine dinucleotide (FAD). So far, lysine-specific demethylase 1 (LSDl) is the only representative of this class [62]. LSDl, as an amine oxidase leads to oxidation of the methylated lysine residue, generating an imine intermediate, while the protein-bound cosubstrate FAD is reduced to FAD H2. In a second step, the imine intermediate is hydrolyzed to produce the demethylated histone lysine residue and formaldehyde. Importantly the reduced cosubstrate is regenerated to its oxidized form by molecular oxygen, producing hydrogen peroxide (Figure 5.7) [62, 63]. 

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