Synthesis of Six-Membered Heterocycles

As with five-membered heterocycles, phosphorus pentasulfide may replace a ring oxygen atom by sulfur, or it may effect replacement in an acyclic precursor and then bring about cyclization. Thus isochroman-l-one (99) is converted into thioisochroman-l-thione (100) under the same conditions a 3-arylisocoumarin( 101) produces a 3-ary 1-1-thioisocoumarin (102) only, with no replacement of the ring oxygen atom.122 A typical example of thiation, followed by cyclization, is the formation of 2-alkyl- or 2-aryl-3,l-benzo-thiazine-4-thiones (103) from /V-acylanthranilic acid esters (104) by treatment with phosphorus pentasulfide in boiling xylene.122 

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The Diels-Alder reaction is of wide scope. Not all the atoms involved in ring formation have to be carbon atoms the hetero-Diels-Alder reaction involving one or more heteroatom centers can be used for the synthesis of six-membered heterocycles. The reverse of the Diels-Alder reaction—the retro-Diels-Alder reaction —also is of interest as a synthetic method. Moreover and most importantly the usefulness of the Diels-Alder reaction is based on its 5y -stereospecifi-city, with respect to the dienophile as well as the diene, and its predictable regio-and c ifo-selectivities. °... 

The transition metal catalyzed synthesis of six membered heterocycles attracted less attention than the preparation of five membered rings. The majority of examples discussed in this chapter achieves the formation of the ring through the combination of two fragments, forming a carbon-carbon and a carbon-heteroatom bond. 

Table V. Synthesis of Six-Membered Heterocycles Containing Perfluoro-alkyl Groups...

The synthesis of six-membered heterocyclic ketones by intramolecular Claisen condensation was described in the chapter and we pointed out that it doesn t matter which way round the cycHzation happens as the product is the same. For example ... 

The hetero-Diels-Alder reaction is amongst the most efficient processes for the synthesis of six-membered heterocyclic ring systems. Solvent-free conditions have been used to improve reactions of heterodienophiles and heterodynes with low reactivities. Cado et al. (1997) have described the hetero-Diels-Alder reaction of ethyl lH-perimidine-2-acetate as heterocyclic ketene aminal with ethyl propiolate nnder solvent-free conditions with focused microwave irradiation. The new fused perimi-dines (23) were obtained in good yields (67-98%). 

Carbene reactions have not been widely utilized for the synthesis of six-membered heterocycles containing two nitrogen atoms. 

Hetero Diels-Alder cycloaddition reactions are of great importance in organic chemistry for the synthesis of six-membered heterocyclic ring systems. " In the past heterodienophiles and -dienes with one or more oxygen, nitrogen or sulfur atoms have been examined in thermal and Lewis acid-catalyzed reactions. " ... 

Catalytic asymmetric formal [4-1-2] cycloaddition reactions offer a versatile and elegant approach to the asymmetric synthesis of six-membered heterocycles. In 2006, Bode and coworkers demonstrated NHC-catalysed generation of enolate equivalents from enals for enantioselective Diels-Alder reactions. Reaction with a,p-unsaturated imine 100 provided the dihy-dropyridinones 101 in good yield and with remarkable enantioselectivities (Scheme 20.44). 

Properties of ILs 439 4.2.1 Synthesis of Six-Membered Heterocycles with One Heteroatom 459... 

Recent Developments in Ionic Liquids Research 440 4.2.2 Synthesis of Six-Membered Heterocycles ... 

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