Hetero-Substituted Unsaturated Systems

This chapter deals with the generation of polar organometallic intermediates 

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Hetero-Diels-Alder reactions performed with trifluoromethyl-substituled heterodienes or with trifluoromcthyl-substituted heterodienophiles have resulted in the synthesis of a large number of fluoro-heterocyclic compounds. Ketones, thioketones, imincs, nitriles, and their parent a,/3-unsaturated systems have been studied in cycloaddition reactions. Cycloadditions are regioselec-tive. An interesting aspect is the competition with ene-type reactions, aldol reactions and, depending on the partners, with [2 + 2]-cycloaddition reactions. 

Mechanistically, the one-pot transformation can be rationalized by a sequence of chemoselective coupling of ort/to-halogenated (hetero)aromatic acid chlorides 81 and electron rich terminal alkynes 4, followed by nucleophilic addition of the sulfide ion to the a,p-unsaturated system 86 to furnish the anionic Michael adduct 87, and finally an intramolecular nucleophilic aromatic substitution in the sense of an addition-elimination process concludes the sequence (Scheme 46). 

Examples of the completely unsaturated 10 -electron hetero-aromatic ring system are known for all the above heterocycles. The chemical reactivity of these heterocyclic systems can be viewed as a microcosm of heterocyclic chemistry. Although little explored, the literature on these compounds is already replete with examples of imaginative synthetic entry, nucleophilic and electrophilic substitution reactions, mechanistically intriguing molecular rearrangements and compilations of spectral data, which now allow structure assignment to new reaction products with relative certainty. 

Aiming at the pyranose form of sugars, normal type hetero-Diels-Alder reactions were extensively used for the synthesis of functionally substituted dihydropyran and tetrahydropyran systems (5-10) (see routes A - D in the general Scheme 1) which are also important targets in the "Chiron approach" to natural product syntheses (2.) Hetero-Diels-Alder reactions with inverse electron demand such as a, p-unsaturated carbonyl compounds (l-oxa-1,3-dienes) as heterodienes and enol ethers as hetero-dienophiles, are an attractive route for the synthesis of 3,4-dihydro-2H-pyrans (11). 

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