Protonated heteroaromatic nucleus

Radical-based carbon-carbon bond formation with electron-deficient heteroaromatics. The reaction entails an intermolecular addition of a nucleophilic radical to protonated heteroaromatic nucleus. 

The (Z)- and ( )-styrylpyrazine structures 20j and 20k were assigned on the base of the mass, NMR, and UV spectral data. The mass spectrum of Z isomer (20j) shows a base peak (the molecular ion) at m/z 210 with a peak at m/z 133 formed by the loss of a phenyl group firom 20j. The H-NMR spectrum shows the presence of five aromatic and two olefinic protons in addition to one heteroaromatic proton and two methyl groups attached to the heteroaromatic nucleus. Ozonolysis of the Z isomer (20j) yields 3-formyl-2,5-dimethylpyrazine (487) and benzaldehyde, confirming the styryl moiety in 20j. The ( )-styryl derivative (20k) is readily isomerized to the Z isomer (20j) on exposure to sunlight (Scheme 60). Extraction of the pyrazines from I. humillis in the dark indicates that E isomer 20k is the naturally occurring product 144,145). 

Nucleophiles can be introduced at C4 of 1,2-type 64 (Scheme 15) and at C4 or C5 of 1,3-type N-alkoxyazolium salts 67 (Scheme 16) by an allylic displacement of ROH and loss of a proton. This reaction mode competes with the nucleophilic addition followed by elimination of ROH described in Section 1.5.1.3. Consequently all ring protons in 1,2-type and 1,3-type azoles become activated but predictions of product distribution turn difficult. In all cases the net result is replacement of hydrogen at the heteroaromatic nucleus with a nucleophile. The sequence can be performed in one pot. 

In Ref [6] the macroscopic proton association constants (PAC) of many of these compounds have been determined in solution. Kj and K2 are the PAC of the side chain and heteroaromatic nucleus, respectively. Our PA s are calculated in the gas phase, however, as both PA and PAC values are for a series of molecules, their relative values should correlate. Therefore, we have related PA s of l-A, and 9-12, calculated with the PAC s depending on the protonated centres and the type of T/C s (for instance, 1A+ with logK2, or iB with logKi). The best correlation has been found for iA+ and logK2 (Fig. 6), with the PA values obtained from the 6-31G //6-31G wave functions and the direct reactions (I) with a good linear relationship ... 

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