Metin Balci

Synthesis of conduritols and related compounds

New and stereospecific syntheses for all conduritol isomers have been developed starting from appropriate 1.3-cyclohexadiene derivatives. Oxygen functionalities were introduced by photooxygenation. Application of the ene-reaction of singlet oxygen to 1.4-cyclohexadiene and its derivatives afforded diene system which can be easily trapped by second mol of singlet oxygen to give 49 and 50. Thiourea reduction of the peroxide linkages followed by oxidation gave the corresponding pent01 derivatives. Furthermore, reaction of unsaturated endoperoxides with 1.2.4.5- temine derivatives 59-63 afforded new bicyclic endoperoxides with unusual structures.

Design and synthesis of pyrrolotriazepine derivatives: an experimental and computational study.

The pyrrole derivatives having carbonyl groups at the C-2 position were converted to N-propargyl pyrroles. The reaction of those compounds with hydrazine monohydrate resulted in the formation of 5H-pyrrolo[2,1-d][1,2,5]triazepine derivatives. The synthesis of these compounds was accomplished in three steps starting from pyrrole. On the other hand, attempted cyclization of a pyrrole ester substituted with a propargyl group at the nitrogen atom gave, unexpectedly, the six-membered cyclization product, 2-amino-3-methylpyrrolo[1,2-a]pyrazin-1(2H)-one as the major product. The expected cyclization product with a seven-membered ring, 4-methyl-2,3-dihydro-1H-pyrrolo[2,1-d][1,2,5]triazepin-1-one was formed as the minor product and was converted quantitatively to the major product. The formation mechanism of the products was investigated, and the results obtained were also supported by theoretical calculations.

High temperature bromination VI: Bromination of benzobarrelene

Abstract The electrophilic addition of bromine to benzobarrelene in chloroform at 10° C followed by repeated chromatography combined with fractional crystallization allowed us to isolate ten products 12–21 Structural determination of these compounds revealed that the barrelene skeleton was rearranged completely. 18–21 are alcohol compounds which arise from hydrolysis of 12, 13, 14, and 15, respectively. High temperature bromination of benzobarrelene in decalin at 150 °C followed by repeated chromatography combined with fractional crystallization gave us 18 products. Nonrearranged products 24, 25, and 26 have been isolated in 50% yield. All compounds have been characterized properly, especially by 200 MHz 1H NMR and 50 MHz 13C NMR spectra. Furthermore, it has been concluded that high temperature bromination of bicyclic systems gives more non-rearranged products. If the molecule is more strained, the tendency to rearrange decreases as in the case of benzonorbornadiene.

A new and stereospecific synthesis of conduritol-F and conduritol-Bs

Abstract A new and stereospecific synthesis for conduritol-F has been developed starting from transbenzenediacetate 5 and oxepine-benzeneoxide 8 where the oxygen functionalities were introduced in both cases by photooxygenation; suitable ring opening reactions gave the desired conduritol-F. Acid-catalyzed ring opening reaction of 11 in aceticanhydride gave conduritol-F and conduritol-B in a ratio of 2:1.

Stereoselective synthesis of bishomo-inositols as glycosidase inhibitors.

For the synthesis of various bishomo-inositol derivatives, 1,3,3a,7a-tetrahydro-2-benzofuran was used as the key compound. For further functionalization of the diene unit, the diene was subjected to photooxygenation, epoxidation, and cis-hydroxylation reactions. The endoperoxide linkage was cleaved by thiourea. The remaining double bond was subjected to epoxidation and cis-hydroxylation reactions. The epoxide rings and tetrahydrofuran rings formed were opened by acid-catalyzed reaction with sulfamic acid. The combination of these reactions resulted in the formation of various new inositol derivatives such as bishomo-chiro-inositol, bishomo-myo-inositol, and two isomeric bishomo-allo-inositols.

A new and stereospecific synthesis of an inositol analogue: bis-homoinositol

Abstract The photooxygenation of trans -8-(acetyloxy)bicyclo[4.2.0]octa-2,4-dien-7-yl acetate afforded the bicyclic endoperoxide. Reduction of the endoperoxide with thiourea followed by acetylation gave the corresponding tetraacetate. The KMnO 4 oxidation of the tetraacetate followed by acetylation gave dihydroxytetraacetate Ammonolysis of tetraacetate afforded the bis-homoinositol, bicyclo[4.2.0]octane-2,3,4,5,7,8-hexol.

High Temperature Bromination. Part 12: Bromination of 7-Oxabenzonorbornadiene: Synthesis of 2,3-Dibromo-7-oxabenzonorbornadiene

Abstract The electrophilic addition of bromine to 7-oxabenzonorbornadiene ( 8 ) at 0°C led in high yield to the formation of dibromoaldehyde 10 . However, high-temperature bromination of 8 in carbon tetrachloride at 77°C gave non-rearranged products 17 and 18 . From the elimination of non-rearranged products, 2-bromo-7-oxabenzonorbornadiene ( 12 ) was obtained. Similarly, bromination of monobromide 12 at 77°C yielded the non-rearranged tribromides 19 and 20 while bromination of 12 at 0°C gave the rearranged product 11 . The dehydrobromination of tribromides ( 19 , 20 ) provided the 2,3-dibromo-7-oxabenzonorbornadiene ( 21 ), which is a synthon for the trimerization, in high yield

Synthesis of new conduritol analogues derived from bicyclooctatriene: Bis-homo-conduritol-D and bis-homoconduritol-F

Abstract The first synthesis of conduritol analogues 2 and 3 is reported. The key compound 7 reacted with KMnO 4 and m-chloroperbenzoic acid in a stereospecific manner to give syn -addition products 9 and 10 , respectively. Zinc-dust elimination of 10 followed by epoxide opening resulted in the formation of 3b . The free tetrol 3 was obtained by ammonolysis. The other tetrol isomer 2 was obtained by similar synthetic steps.

CoTPP-catalyzed rearrangement of 1.4-endoperoxides

Abstract Bicyclic endoperoxides with strained and perturbed diene moiety have been submitted to CoTPP-catalyzed rearrangement. Side reaction, like formation of epoxyenone, has been suppressed and yield of the formation of bisepoxides highly increased.

Intramolecular Heterocyclization of O-Propargylated Aromatic Hydroxyaldehydes as an Expedient Route to Substituted Chromenopyridines under Metal-Free Conditions

A concise and regioselective approach to the synthesis of chromenopyridine and chromenopyridinone derivatives was developed. The synthetic strategy relies on the O-propargylation of aromatic hydroxyaldehydes followed by reaction with propargylamine. The intramolecular cycloaddition reaction between the alkyne and azadiene, which is formed as an intermediate, furnished the desired skeletons.