Coupling in Heteroaromatic Systems

Heteroaromatic systems (furans, pyrroles, pyridines, thiophenes, etc.) show couplings analogous to those in benzenoid systems. In furan, for instance, couplings occur between all of the ring protons. Typical values of coupling constants for furanoid rings are as follows. 

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FIGURE 7.71 Expansions of the ring proton resonances from the 300-MHz H NMR spectrum of furfuryl alcohol. The resonances from the hydroxymethyl side chain are not shown. 

Heteronuclear coupling of to and to was discussed in Chapter 6, Sections 6.15 and 6.16. Fluorine-19 is the only natural isotope for this element, and while phosphorus has more than one isotope, phosphorus-31 is the most abundant. This section will cover couplings to F and Since F and P each have a nuclear spin of 1/2, the principles discussed earlier in this chapter apply directly to interpreting resonances coupled to these elements. 

FIGURE 5.64 Expansions of the aromatic ring proton multiplets from the 300-MHz H NMR spectrum of 2-nitrophenol. The hydroxyl resonance is not shown. 

Nuclear Magnetic Resonance Spectroscopy Part Three Spin-Spin Coupling 

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There are also some couplings in which hydrazones are formed but for which the azo tautomer is not detectable and probably does not exist. This is the case in some coupling reactions involving methyl groups of aromatic heterocycles (see, for example, 12.48 and 12.49 in Sec. 12.5). Replacement of a methyl proton by an arylazo group (Scheme 12-3) would result in an azo compound containing an sp3-hybridized — CH2 — group (12.1). The latter is less stable than the tautomeric hydrazone (12.2), in which there is a n-n orbital overlap from the heteroaromatic to the aromatic system. 

Lastly, reference will be made to the investigation of Elguero and Wolf G967,ii9) concerning phosphorus attached heteroaromatic systems by the heteroatom, in which couplings such as P-H5 in pyrazoles (123) and P-H3 in indazoles (124) are found. 

As mentioned previously, the partially reduced forms of five membered heteroaromatic systems might act as olefins in insertion reactions. This behaviour is characteristic particularly of dihydrofuranes. The olefin insertion and the following / hydride elimination should in principle lead to a trisubstituted olefin, which is rarely observed, however. Typical products of this reaction are 2-aryl-2,3-dihydrofuranes. A characteristic example of such a reaction is presented in 6.54. The coupling of 4-iodoanisole and dihydrofurane led to the formation of the chiral 2-anisyl-2,3-dihydrofurane in excellent yield.83 The shift of the double bond, which leads to the creation of a new centre of chirality in the molecule, opens up the way for enantioselective transformations. Both intermolecular and intramolecular variants of the asymmetric Heck reaction have been studied extensively.84... 

The heteroaryl Heck reaction is an efficient tool for the introduction of other five membered heteroaromatic systems too (for more details see Chapter 6.4.). Chloropyrazines reacted readily with oxazole to give the coupled product (7.57.), consisting solely of the 5-oxazolyl isomer.77 Extension of the reaction to imidazole led to a similar observation,78 and the expected 5-pyrazyl-imidazole derivative was isolated in acceptable yield. Reactions using thiophene as the masked olefin gave similar results. Under forcing conditions the 2,5-diarylation of fiiran was also observed.77... 

Radical anions derived from 2,5-diformylthieno[3,2-6]thiophene (39) as well as (40) were studied in connection with the conformational analysis of heteroaromatic carbonyl compounds. Different ESR signals were given by distinct rotational isomers. Information on interconversion of the rotamers could not be obtained since the radicals were unstable at the temperatures necessary for interconversion. On the other hand, ketyl radicals derived from ketones (41) and (42) are relatively more stable at the temperatures needed for the study of the conformational mobility in these systems. The ESR spectra of the bis-thienothienyl ketyls from (41) and (42) at room temperature show that the unpaired electron is coupled to three pairs of equivalent protons. Both spectra exhibited a certain amount of asymmetry, which was enhanced by lowering the temperature. At -10°C the highfield part of the spectra split into new lines arising from two species which have similar hyperfine splitting, but different g factors. These have been identified as the rotational isomers of the radicals. The two preferred conformations are cis-trans and trans-trans. An examination... 

Although single bond carbon-13 proton coupling constants (Vch) show a dependency on the geometry of the ring, a value of 200 Hz is considered typical for a carbon attached to oxygen in a heteroaromatic system (B-72MI22203). Values for 2- and 4-pyranone and furan are presented in Table 11. 

Heteroaromatic sulfoxides and sulfones ligand exchange and coupling in sulfuranes and //Avo-substitutions, 49, 1 Heteroaromatic systems, Claisen rearrangements in, 42, 203 Heteroaromatics, quantitative analysis of steric effects in, 43, 173 Heterocycles aromaticity of, 17, 255 chiral induction using, 45, 1 containing the sulfamide moiety,... 

Diaryl ketones can also be prepared by coupling aryl iodides with phenylboronic acid (12-28), in the presence of CO and a palladium catalyst.This reaction has been extended to heteroaromatic systems, with the preparation of phenyl 4-pyridyl ketone from phenylboronic acid and 4-iodopyridine. 2-Bromopyridine as coupled with phenylboronic acid, CO and a palladium catalyst to give phenyl... 

The major reaction pathway in all cases consists of reduction to the neutral radical followed by coupling, primarily or exclusively in the 4-position with respect to the ring nitrogen. Like the dimeric dianions formed by dimerization of, for example 91 , the neutral dimeric products obtained from positively charged A-heteroaromatic systems are in many cases difficult to isolate since they are easily reoxidized back to the substrate cations. 

In order to obtain analogs of 1,2-dihydroisoquinolines in which the aromatic carbocycle is replaced by various heteroaromatic systems, the furopyridines (19), the thieno[3,2-c]pyridines (20), and the thieno[2,3-c]-pyridines (21) were synthesized (70BSB301 71JHC57). By Grignard coupling of 4-chloro-19 with allylmagnesium chloride in the presence of catalytic... 

In a study of the relative ligand coupling efficiencies between oxygen, sulfur and nitrogen containing heteroaromatic systems, the correlation between the ligand coupling abilities and the C-NMR values of the ipso carbon atoms (6 in ppm are reported in Scheme 3.15) was not clearly... 

The direct synthesis of arylzinc halides from the halide and activated zinc <90TL4413,9lJOCl445> can also be applied to heteroaromatic systems, (e.g. bromo- and iodopyridines). In the electrophilic pyrimidine 2-position zincation and coupling of the iodo derivative took place to the extent of 26%... 

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