Enamines transfer hydrogenation intermediate

An intermediate at the same oxidation level can be produced in a totally different manner via the ready condensation of an rr/i >-nitrobenzaldehyde with nitromethane reduction to an anilino-enamine has been achieved traditionally with metal/acid combinations, and more recently by catalytic transfer hydrogenation. 

Mechanistically, the Brpnsted acid-catalyzed cascade hydrogenation of quinolines presumably proceeds via the formation of quinolinium ion 56 and subsequent 1,4-hydride addition (step 1) to afford enamine 57. Protonation (step 2) of the latter (57) followed by 1,2-hydride addition (step 3) to the intermediate iminium ion 58 yields tetrahydroquinolines 59 (Scheme 21). In the case of 2-substituted precursors enantioselectivity is induced by an asymmetric hydride transfer (step 3), whereas for 3-substituted ones asymmetric induction is achieved by an enantioselective proton transfer (step 2). 

Scheme 6.104 Key intermediates of the proposed catalytic cycle for the 100-catalyzed Michael addition of a,a-disubstituted aldehydes to aliphatic and aromatic nitroalkenes Formation of imine (A) and F-enamine (B), double hydrogen-bonding activation of the nitroalkene and nucleophilic enamine attack (C), zwitterionic structure (D), product-forming proton transfer, and hydrolysis.

The scope and mechanism of ionic hydrogenation of iminium cations have been investigated for a CpRuH catalyst bearing a chelating diphosphine.64 The mechanism involves three steps hydride transfer (from the catalyst) to form an amine, coordination of H2 to the resulting ruthenium cation, followed by proton transfer from the dicoordinated H2 to the amine. The cationic intermediate [e.g. CpRu(dppm)( 72-H2)+] can be used to hydrogenate enamines provided that the latter are more basic than the product amine. The relative reactivity of C=C and C=N bonds in a, ft -unsaturated iminium cations has also been investigated. 

Rivire and Lattes used LiNH2 and NaNHj in liquid ammonia at — 70°C, in hexamethylphosphortriamide at room temperature or t-BuOK/HMPA at room temperature for allylamine enamine isomerizations. An anion formed by deprotonation of the allylamine at C was considered to be the intermediate species in the isomerization. Intramolecular transfer of hydrogen in the transition state of the isomerization was suggested to explain both the kinetic formation of the Z-enamine and the absence of exchange with deuteriated base during the isomerization. Quantum chemical calculations showed that the Z-carbanion (61) is actually more stable than the -carbanion (62). 

Ab initio calculations performed by Bigot and Roux have led to an alternative mechanism involving two photochemical steps and the intermediacy of an azirine, as shown in Scheme 40 . Hydrogen atom transfer from the enamine nitrogen to the nitrile carbon of 173 would generate diradical intermediate 177, which would then collapse to the postulated azirine 178. In a second photochemical step, the azirine would then undergo carbon-carbon bond homolysis to 179 followed by reclosure to the imidazole 176. In support of this proposed second photochemical step, structurally similar azirines have been shown to undergo facile carbon-carbon bond photolysis . This mechanism does not, however, explain the initial formation of a thermally unstable intermediate with the observed IR stretch, since azirines of this type are thermally stable at room temperature . ... 

The mechanism of the Hajos-Wiechert reaction has not been without controversy. The original paper by Hajos and Parrish proposed two possible mechanisms. The first, via the carbinolamine 7, proposed addition of proline to a ketone, followed by a nucleophilic attack of the pendant, remote enol [transition state 8]. Calculations by Houk and Clemente show that this is one of the higher energy pathways. The second proposed mechanistic pathway proceeded via an enamine intermediate, followed by carbon-carbon bond formation via transition state 9 and a hydrogen transfer between nitrogen and... 

As shown in Scheme 6.54, the mechanism of this process starts with the formation of imine 371, from compounds 368 and 369. Then, imine 371 is attacked by enamine 367. After proton transfer and cyclization, product 370 is obtained. The pure jyn-stereoselectivity is assumed over the hydrogen bond of intermediate 373. 

Only the electron pushing for formation of an enamine is shown here (Scheme 10.19), because the formation of an imine follows the same pathway except for the last step. After combination of the electrophile and nucleophile (step 1), two proton transfers are required (steps 2 and 3). Such transfers do not typically occur as one intramolecular step, but instead involve two steps. The result is a tetrahedral intermediate, called a carbinolamine. The car-binolamines are sometimes stable enough to be isolated, thereby confirming their viability as intermediates in the formation of imines and enamines. A 1,2-elimination leads to hydroxide plus an iminium ion (step 4). To quench the positive charge on the nitrogen of the iminium, the hydroxide deprotonates an a-hydrogen (step 5). These reactions are often performed in benzene or a similar nonpolar solvent, so the proton transfers involve the added amine, as shown in the mechanism. The reaction can be driven to completion by the removal of water from the flask, often using a Dean-Stark apparatus. 

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