Heteroaromatic systems, coupling

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... 

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%... 

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. 

In the case of some heteroaromatic systems such as furan, pyrimidine, and others, the one-bond heteronuclear coupling constants can exceed 200 Hz. For example, the Jch coupling of the 2-position of furan is 210Hz the 2-position of pyrimidine is also about 208Hz. When molecules containing such structural moieties are studied by direct heteronuclear shift correlation methods using the normal 140 Hz compromise optimization, respon.ses for positions in the molecule such as the 2-position of a furanyl substituent may be either very weak or even completely absent. 

Benzo- as well as heteroaromatic systems were obtained allowing for a variable substitution pattern in the benzoazepine frameworks. To access the dibenzo-diazepine or dibenzoxazepinone frameworks according to C-N cross-coupling methodology, a different strategy had to be pursued. The introduction of the nitrogen atom or the amide functionaHty was accompHshed by the condensation of ammonia with keto- or ester-carbonyl frmctionaHties (Scheme 13.96 and Scheme 13.97) [142],... 

In contrast to traditional metal-catalyzed cross-coupling reactions of organome-tallic nucleophiles with organic electrophiles, C—H activation methods avoid the need for the pre-activation of one or both coupling components not only does this minimize the amount of wasteful by-products generated, but it also dramatically simplifies a synthetic route. In addition, C—H activation methods are often milder than conventional methods, and can overcome the inherent reactivity patterns of the heteroaromatic system and allow access to products that could not otherwise be obtained. 

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