Heterocycle-fused -catalyzed synthesis

An efficient paUadium(II)-catalyzed synthesis of heterocycle-fused P-naphthylamines was accomplished via nucleophilic addition of a carbon-palladium bond to the intramolecular cyano group initiated by nucleopal-ladation (oxypalladation or aminopalladation) ofalkynes (140L6184). 

The synthesis of functionalized 1,2-dioxane derivatives was developed using the tris(2,4-pentanedionato)manganese(lll)-alkene system and the man-ganese(III) acetate-1,3-dicarbonyl compoimd-alkene system. The endoper-oxidation catalytically proceeded in air imder very mild reaction conditions and the excellent yield of the endoperoxides was achieved, hi addition, heterocycle-fused or -substituted dioxanes could be synthesized according to the manganese(III)-catalyzed endoperoxidation. The hydroperoxidation also occurred in the reaction of the cyclic 1,3-diamides with alkenes. Furthermore, the direct hydroperoxidation of the cyclic 1,3-diamides was effective in the absence of alkenes. 

Transition Metal-Catalyzed Synthesis of Fused Five-Membered Aromatic Heterocycles... 

Scheme 12.68 Pt-catalyzed synthesis of fused polycyclic heterocycles. 12.7...

A palladium-catalyzed one-step synthesis of dihydrobenzo[fc]furan-based fused aromatic heterocycles from bifunctional bromoenoates or bromoalkyl indoles and iodoarenes was reported, and an example is provided in the scheme below <060L3601>. 2-Alkyl- or 2-aryl-substituted benzo[ >]furans were synthesized by a copper-TMEDA catalyzed intramolecular annulation from the corresponding ketones <06OL1467>. 

One of the earliest uses for rhodium(II)-catalyzed dipoles was demonstrated in Davies furan synthesis [22]. Isomiinchnones were also shown to produce substituted furans [115]. Additional furan syntheses have been described using silylacetates [116], unsaturated esters [117], and fluoroalkyl diazo acetates [118]. The synthesis of furofuranones and indenofuranones 35 from a-diazo ketones having pendant alkynes has also been reported (Eq. 6) [119]. Other fused heterocyclic systems include furo[3,4-c]furans [120, 121] furo[2,3-b]furans [122] as well as thiobenzofurans [123], and benzoxazoles[124] have also been synthesized with this methodology. 

Dieckmann cyclizations of diesters of type (210) are catalyzed by potassium f-butoxide in toluene, sodium in xylene, or sodium hydride in DMF, and produce 1-benzazepinones in good yields. The method is also applicable to the synthesis of azepines fused to other heterocycles, e.g. pyrrolo[2,3-6]azepin-4-ones (211) (81H(16)399). 

Appropriately substituted hydroxy amides and ureas can be used instead of diamines. Thus, acid-catalyzed cyclocondensation of iV-carbamoyl prolinols 137 (R1 = H, (CH2)3) (Scheme 27) with aldehydes RCHO (R = Ph, 2-MeOC6H4, 2-naphthyl, etc.) stereoselectively afforded a series of pyrroldine-fused oxadiazepinones 46 (Scheme 5) <1990CPB2627, 1990H(30)287, 1996LA927>. Similar heterocyclization of 4-(2-hydroxyethylthio)-2-azetidinone with acetone dimethyl acetal was used in the synthesis of azetidinone-fused oxathiazepanes of type 33 (X = S) (Figure 4) <1980JA2039>. 

A domino total synthesis of spirotryprostatin B (2) and three of its isomers has been published by Overman and Rosen, who apply two sequential palladium-catalyzed reactions (one-pot) to assemble the two spiro-fused rings [10] (Scheme 3). This work again makes it clear that complex heterocyclic systems may represent a harder challenge to synthetic... 

The acid-catalyzed cyclization of appropriate aryloxyketones formed benzo[l,2-6 5,4-6 ]difuran and benzo[ 1,2-6 4,5-6 ]difuran (63BSF1003). Another variation involved the cyclization of an aryl thioacetal to a benzo[l,2-6 4,5-6 ]dithiophene <86CB3198>. In investigations of the synthesis of a unit of the CC-1065 skeleton (see Section 7.21.12), a carbene derived from the azo-compound (59) constructed the cyclopropano-fused benzodipyrrole (60) by simultaneous formation of the heterocyclic ring and the cyclopropane ring <83TL4773>. 

Palladiumcopper-catalyzed heterocyclization provides a useful approach to thiazolo-fused systems as illustrated by the synthesis of substituted thiazolo[3,2- ]benzimidazoles 57 from 2-propargylmer-capto benzimidazole 56 via a tandem Sonogashira cross-coupling with iodoaryls and a subsequent exocyclic heterocyclization (Scheme 35) <2004TL5747>. 

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