Regioselectivity heterocyclic synthesis

Microwave-promoted reactions continue to extend their reach in heterocyclic synthesis. Regioselective N4-aminoethylation of the l,4-benzodiazepin-2-one 94 was observed under microwave conditions in DMF/K2C03 to afford, for example, 96a and 96b in 64% and 67% yield respectively (Table 4). In contrast, the thermal reaction at 80 °C in DMF with K.2CC)3 as base gave the Nl-aminoethylation products (95a, 65%) and (95b, 76%). These results were... 

Azine oxides are versatile starting materials for heterocyclic synthesis and are frequently used for regioselective ring substitution reactions, most of which proceed with loss of the oxide substituent. Occasionally some unusual selectivities are observed. For example, treatment of 3-methoxypyrazine A-oxide with equimolar amounts of diethylcarbamoyl chloride and 4-methoxytoluene-a-thiol in refluxing acetonitrile gave 2-methoxy-6-(4-methoxybenzylthio)-pyrazine as the sole product in 60% yield. 

An interesting new approach to l,3-diazepin-2-ones 61 via a palladium-catalysed highly regioselective, cyclisation of 2-vinylpyrrolidines 59 with aryl isocyanates 60 has been developed by Zhou and Alper <03JOC3439>. This reaction has considerable potential for further applications in heterocyclic synthesis. 

P. Wessig, Regioselective photochemical synthesis of carbo- and heterocyclic compounds the Norrish/Yang reaction. Chapter 57 in ref. 22. 

More impressively, azadienes, such as 59, that could tautomerise to enamines 58 also give good yields of adducts 60 with high regioselectivity and endo stereoselectivity. 1-Azadienes are still not easy to use but enough methods are now available to make heterocycle synthesis by this route a practical proposition. 

Using electrophilic and nucleophilic aromatic substitution in five- and six-membered heterocycles. Chemo- and regioselectivity The synthesis of pyridazines... 

Wessig, P., Regioselective Photochemical Synthesis of Carbo and Heterocyclic Compounds the Norrish/Yang Reaction. In Horspool, W. M., Lenci, F. (eds), CRC Handbook of Organic Photochemistry and Photobiology, 2nd edn, CRC Press LLC, Boca Raton, FL, 2004, Chapter 57, pp. 1 20. 

Attanasi OA, FUippone P, Guidi B, Mantellini F, Santeusanio S (2001) Regioselective synthesis of stable 2-(trifluoromethyl)-2,3-dihydro-lH-pyrrol-2-ols and derived fluorinated heterocycles. Synthesis 1837-1845... 

An "early" example of alternative heterocyclic synthesis was reported by Endo [96], who prepared a cyclic dithio-urethane (a l,3-thioxazolidine-2-thione) by coupling of an aziridine and CS2. Under optimized conditions (-40 °C, 1 equivalent of CS2,5mol% LiBr as catalyst, tetrahydrofuran 30 min), the desired product was produced in quantitative conversion and regioselectivity. These conditions reflect a rather green approach toward these S-containing heterocycles though only one example was reported. The coupling reaction between CS2 and epoxides represents a... 

Regioselective Photochemical Synthesis of Carbo- and Heterocyclic Compounds... 

Regioselective and stereoselective template synthesis in chemistry of fullerenes annelated with heterocycles or linked with heterocyclic fragments 99ACR537. 

Dipolar addition to nitroalkenes provides a useful strategy for synthesis of various heterocycles. The [3+2] reaction of azomethine ylides and alkenes is one of the most useful methods for the preparation of pyrolines. Stereocontrolled synthesis of highly substituted proline esters via [3+2] cycloaddition between IV-methylated azomethine ylides and nitroalkenes has been reported.147 The stereochemistry of 1,3-dipolar cycloaddition of azomethine ylides derived from aromatic aldehydes and L-proline alkyl esters with various nitroalkenes has been reported. Cyclic and acyclic nitroalkenes add to the anti form of the ylide in a highly regioselective manner to give pyrrolizidine derivatives.148... 

Heterocycles can be employed as precursors for the synthesis of pyrazoles. Pyrazoles can be synthesized by three-membered ring substrates. For example, allyl amines 12 and pyrazoles 13 could be obtained by hydrazinolysis of 2-ketoaziridines 11 <06TL255>. Regioselective ring opening of 3-aryl-2-benzoyl-l,l-cyclopropanedicarbonitriles 14 with hydrazine provided a new process for the synthesis of 5-aryl-3-phenylpyrazoles 15 <06JHC495>. 

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