Electron-withdrawing groups dehydrogenation

Reports of [4 + 2] cycloadditions of cyclobutenes bearing electron-withdrawing groups on the double bond have appeared. Predominantly exo products are formed from (709 X = CN, CO2R, or COCl) and cyclopentadiene, whereas (709 X = COjH) gives mainly (88%) the cndo-isomer. This reversal of stereochemical course is rationalized by the existence of an intramolecular H-bond and its influence on the non-bonded interactions in the transition state. A new synthesis of benzo-cyclobutenes employs the condensation of (709 X = COjMe) with butadiene and subsequent oxidative decarboxylation and dehydrogenation. This sequence has also been applied to the synthesis of the annelated benzocyclobutene (710). " ... 

In 2013, Hong and coworkers reported a one-pot protocol to achieve similar structures by a sequential Pd(II)-catalyzed dehydrogenation-oxidative Heck-cyclization process [23]. Using 20 mol% Pd(TFA)2, 1.0 equiv. of Cu(OAc)2, the cyclohexanones could easily react with electron-deficient olefins to afford coumarins in PivOH under an O2 atmosphere with modest to high yields (Scheme 3.8). It is noted that the product scope is somewhat extended to the coumarins with electron-withdrawing groups on the aromatic rings. In addition, the obtained coumarin products could be further alkenylated to provide an extended it-system. 

Firstly, (benzylidenamino)acetaldehyde acetals 58 are formed they are cyclized to give 4-alkoxy>3,4-dihydroisoquinolines 59, which are converted into isoquinolines by loss of ROH. The electrophilic cyclization is favoured by meta- and or /zo-electron-releasing substituents in the arylaldehyde. Electron-withdrawing substituents (especially NO2 groups) favour an alternative ring closure leading to oxazoles 61 with dehydrogenation. 

Other substrates for flavo-dehydrogenases include structures with electron-withdrawing (activating) groups next to the position of dehydrogenation. Such reactions appear to be initiated by abstraction of the relatively acidic a-hydrogen atom by a basic residue (e.g. His), thus involving a carbanion of the substrate as an intermediate or a transition state. 

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