Generation of Diverse Molecular Complexity from Simple Hydrocarbons

In an effort to make diverse molecular complexity from simple hydrocarbons, tricarbonyl(cyclohexadienyl)iron(+1) cation was prepared in two steps from 1, 3-cycloxehadiene. Reactivity of the symmetric iron cation with heteroatom nucleophiles and stabilized carbon nucleophiles was studied. Nucleophilic attack of potassium phthalimide at the dienyl terminus of the cation followed by oxidative decomplexation with Ce4+ provided the ligand N-(2,4-cyclohexadiene-1-yl)phthalimide. A series of stereochemically diverse polyhydroxyl aminocyclohexane aminocyclitols derivatives and a number of racemic and optically active hydroxy-and polyhydroxy 1,3-diaminocyclohexane derivatives have been synthesized from N-(2,4-cyclohexadiene-1-yl)phthalimide. The relative stereochemistries of the compounds ware assigned on the basis of the 1H NMR data as well as X-ray single crystal diffraction analysis. In a similar attempt tricabonyl(η5-6-styrylcyclohepta-2,4-diene-1-yl)iron(+1) cation was synthesized in three steps from 1, 3, 5, 7-cyclooctatetraene. Reactivity with various nucleophiles was studied. Nucleophilic attack of lithium dimethylallyl malonate at the less hindered pentadienyl terminus of the cation, decomplexation by Ce4+ followed by rearranged ring closing metathesis using 1st generation Grubbs catalyst gave skeletally unusual (5E, 7Z, 9Z)-dimethylbicyclo[4.4.1]undeca-5,7,9-triene-2,2-dicarboxylate. Reaction of potassium phthalimide with tricabonyl(η5-6-styrylcyclohepta-2,4-diene-1-yl)iron(+1) cation in a similar fashion, followed by decomplexation with Ce4+ gave racemic 2-(1S, 6R)-6-((E)-styryl)cyclohepta-2, 4-diene-1-yl)isoindoline-1, 3-dione. Asymmetric dihydroxylation of the iron free ligand with ADmix-β followed by cycloaddition with singlet oxygen generated two optically active separable diastereomeric endoperoxides, which led to the synthesis of a number of racemic and optically active functionalized endoperoxides

Generation of Molecular Complexity from Cyclooctatetraene: Preparation of Optically Active Protected Aminocycloheptitols and Bicyclo[4.4.1]undecatriene

The racemic (6-cyclo-heptadienyl)Fe(CO)3+ cation ((±)-7), prepared from cyclooctatetraene, was treated with a variety of carbon and heteroatom nucleophiles. Attack took place at the less hindered C1 dienyl carbon and decomplexation of the (cycloheptadiene)Fe(CO)3 complexes gave products rich in functionality for further synthetic manipulation. In particular, a seven-step route was developed from racemic (6-styryl-2,4-cycloheptadien-1-yl)phthalimide ((±)-9 d) to afford the optically active aminocycloheptitols (−)-20 and (+)-20

De novo synthesis of polyhydroxyl aminocyclohexanes

The syntheses of 12 stereochemically diverse polyhydroxyl aminocyclohexane (“aminocyclitols”) derivatives are described. These short syntheses require 2–5 steps from N-(2,4-cyclohexadien-1-yl)phthalimide, which is prepared in two steps from tricarbonyl(cyclohexadienyl)iron(1+). The relative stereochemistries of the aminocyclitols were assigned by 1H NMR spectroscopy as well as X-ray diffraction analysis

Synthesis of Hydroxy- and Polyhydroxy-Substituted 1,3-Diaminocyclohexanes

The synthesis of hydroxy-trans-1,3-diaminocyclo­hexanes based on nitroso-Diels-Alder cycloaddition of (cyclohexadienyl)phthalimide is reported

Spectral Data for Generation of Molecular Complexity from Cyclooctatetraene: Preparation of Optically Active Protected Aminocycloheptitols and Bicyclo[4.4.1]undecatriene

Spectral data created in the course of the research project. Supports specific findings in Generation of Molecular Complexity from Cyclooctatetraene: Preparation of Optically Active Protected Aminocycloheptitols and Bicyclo[4.4.1]undecatriene . The racemic (6-cyclo-heptadienyl)Fe(CO)3+ cation ((±)-7), prepared from cyclooctatetraene, was treated with a variety of carbon and heteroatom nucleophiles. Attack took place at the less hindered C1 dienyl carbon and decomplexation of the (cycloheptadiene)Fe(CO)3 complexes gave products rich in functionality for further synthetic manipulation. In particular, a seven-step route was developed from racemic (6-styryl-2,4-cycloheptadien-1-yl)phthalimide ((±)-9 d) to afford the optically active aminocycloheptitols (−)-20 and (+)-20

Sprectral data for Generation of Molecular Complexity from Cyclooctatetraene Using Dienyliron and Olefin Metathesis

Spectral data used in the course of researching Generation of molecular complexity from cyclooctatetraene using dienyliron and olefin metathesis methodology . Transformation of the simple hydrocarbon cyclooctatetraene into a variety of polycyclic skeletons was achieved by sequential coordination to iron, reaction with electrophiles followed by allylated nucleophiles, decomplexation and olefin metathesis

Generation of Molecular Complexity from Cyclooctatetraene: Preparation of Optically Active Protected Aminocycloheptitols and Bicyclo[4.4.1]undecatriene

The racemic (6-cyclo-heptadienyl)Fe(CO)3+ cation ((±)-7), prepared from cyclooctatetraene, was treated with a variety of carbon and heteroatom nucleophiles. Attack took place at the less hindered C1 dienyl carbon and decomplexation of the (cycloheptadiene)Fe(CO)3 complexes gave products rich in functionality for further synthetic manipulation. In particular, a seven-step route was developed from racemic (6-styryl-2,4-cycloheptadien-1-yl)phthalimide ((±)-9 d) to afford the optically active aminocycloheptitols (−)-20 and (+)-20

Generation of Molecular Complexity from Cyclooctatetraene Using Dienyliron and Olefin Metathesis Methodology

Transformation of the simple hydrocarbon cyclooctatetraene into a variety of polycyclic skeletons was achieved by sequential coordination to iron, reaction with electrophiles followed by allylated nucleophiles, decomplexation and olefin metathesis

Reactivity of (1-methoxycarbonylpentadienyl)iron(1+) cations with hydride, methyl, and nitrogen nucleophiles

The reaction of tricarbonyl and (dicarbonyl)triphenylphosphine (1-methoxycarbonyl-pentadientyl)iron(1+) cations 7 and 8 with methyl lithium, NaBH3CN, or potassium phthalimide affords (pentenediyl)iron complexes 9a-c and 11a-b, while reaction with dimethylcuprate, gave (E,Z-diene)iron complexes 10 and 12. Oxidatively induced-reductive elimination of 9a-c gave vinylcyclopropanecarboxylates 17a-c. The optically active vinylcyclopropane (+)-17a, prepared from (1S)-7, undergoes olefin cross-metathesis with excess (+)-18 to yield (+)-19, a C9C16 synthon for the antifungal agent ambruticin. Alternatively reaction of 7 with methanesulfonamide or trimethylsilylazide gave (E,E-diene)iron complexes 14d and e. Huisgen [3 + 2] cyclization of the (azidodienyl)iron complex 14e with alkynes afforded triazoles 25a-e