2-Azabicyclo[2.1.1]hexanes. 2. Substituent Effects on the Bromine-Mediated Rearrangement of 2-Azabicyclo[2.2.0]hex-5-enes (original) (raw)
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5 (6)-anti-Substituted-2-azabicyclo [2.1. 1] hexanes: A Nucleophilic Displacement Route
Journal of Organic Chemistry, 2009
Nucleophilic displacements of 5(6)-anti-bromo substituents in 2-azabicyclo[2.1.1]hexanes (methanopyrrolidines) have been accomplished. These displacements have produced 5-anti-X-6-anti-Y-difunctionalized-2-azabicyclo[2.1.1]hexanes containing bromo, fluoro, acetoxy, hydroxy, azido, imidazole, thiophenyl, and iodo substituents. Such displacements of anti-bromide ions require an amine nitrogen and are a function of the solvent and the choice of metal salt. Reaction rates were faster and product yields were higher in DMSO when compared to DMF and with CsOAc compared to NaOAc. Sodium or lithium salts gave products, except with NaF, where silver fluoride in nitromethane was best for substitution by fluoride. The presence of electron-withdrawing F, OAc, N 3 , Br, or SPh substituents in the 6-anti-position slows bromide displacements at the 5-anti-position.
2-Azabicyclo[2.2.0]hex-5-enes and 2-Azabicyclo[2.2.0]hexanes. A Review
HETEROCYCLES, 2004
The synthesis and reactions of 2-azabicyclo[2.2.0]hex-5-enes and 2-azabicyclo[2.2.0]hexanes are reviewed. CONTENTS INTRODUCTION I. SYNTHESIS OF 2-AZABICYCLO[2.2.0]HEX-5-ENES A. Synthesis of 2-azabicyclo[2.2.0]hex-5-enes via electrocyclic ring closure. B. Synthesis of 2-azabicyclo[2.2.0]hex-5-enes via thermal [4+2] cycloadditions. II. SYNTHESIS OF 2-AZABICYCLO[2.2.0]HEXANES A. Synthesis of 2-azabicyclo[2.2.0]hexanes via photochemical [2+2] cycloaddition. B. Synthesis of 2-azabicyclo[2.2.0]hexanes via additions to the 5,6-alkene of 2-azabicyclo-[2.2.0]hex-5-enes. 1. Hydrogenation. 2. Reductive arylation. 3. Cycloaddition reactions. a. [4+2] Cycloaddition reactions. b. [2+1] Cycloaddition reactions. 4. Oxidative hydroboration. 5. Halogen and pseudohalogen additions.
Synthesis of new 7-azabicyclo[2.2.1]heptane derivatives
Arkivoc, 2009
The synthesis of new 7-azabicyclo[2.2.1]heptane derivatives has been achieved in a four-step synthetic sequence, starting from readily available cyclohex-3-enecarboxylic acid, Curtius reaction, stereoselective bromination leading to major benzyl(cis-3,trans-4-dibromocyclohex-1yl)carbamates (amides or sulfonamides), followed by NaH-mediated intramolecular cyclization. The synthesis and free radical cyclization of precursors 4-7, as well as the synthesis of a conformationally constrained epibatidine analogue 3 exploiting the reactivity of the 7azabicyclo[2.2.1]hept-2-yl radical in intramolecular reactions, are described. The N-sulfonyl functional motif is the only one to afford a cyclized product when incorporated in the radical precursor.
2-AZABICYCLO[2.2.2]OCT-7-ENES. 1. Synthesis from Polysubstituted 1,2-DIHYDROPYRIDINES
Heterocyclic Communications, 2002
Polysubstituted 1,2-dihydropyridines are found to undergo [4+2] cycloaddition as reactive dienes with maleic anhydride, dimethyl fumarate and methyl acrylate. Thermal reverse Diels-Alder reaction of azabicyclooctenes 2a and 2 's demonstrated. Isomerization of 6-ero-methoxycarbonyl-2-azabicyclooctene 4 to 6-€«<fo-diastereomer 5 upon treatment with /-BuOK is also shown. Although 1,2-dihydropyridine (1,2-DHP) derivatives regarded as endocyclic 1-aminodienes undergo cycloaddition reactions offering a convenient access to functionalized 2-azabicyclo[2.2.2]oct-7-enes, the reactivity of 1,2-DHP containing electron-withdrawing groups (EWG) has been investigated only to a small extent. Herein we disclose our results of experiments intended to explore the utility of EWG substituted 1,2-DHP in Diels-Alder cycloaddition with some dienophiles. Cycloaddition of 1,2-DHP i with maleic anhydride in benzene at 65 °C or under reflux afforded adducts 2. Dihydropyridine la and maleic anhydride gave azabicyclooctene 2a in 39% yield under reflux, whereas the yield was 60% by performing the cycloaddition at 65 °C. A moderate yield of azabicyclooctenes is a consequence of the reverse [4+2] cycloaddition process. Facilitated by higher temperature (65-75 °C) decomposition of azabicyclooctene 2a was also demonstrated (Fig. 1). rJ The outcome of cycloadducts 2 depends upon the nature of 1,2-DHP substituents. The yields are decreased by EWG at 3-C of 1,2-DHP i (Table 1) whereas the formation of corresponding cycloadducts from 1,2-DHP lb and lc (R'= R 2 = COCH 3 , CN) did not proceed at all. The cycloaddition of 3-unsubstitutcd 1,2-DHP lj-n was not affected significantly by 4-aryl substituent (R 3 = H, OCH 3 , CH 3 , Br, NO:) whereas the reaction of dienes la,d-f, h, containing EWG at 3-C was facilitated by electron-donating groups in the aryl moiety. This result is quite unexpected because the 4-aryl substituent and diene plane of 1,2-DHP molecule are almost perpendicular to one another [1], i.e. the 4-aryl substituent is out of conjugation. la-n
Synthesis of and base-induced rearrangements in the 1,4-diazabicyclo[4.1.0]hept-4-ene system
The Journal of Organic Chemistry, 1975
The synthesis and base-induced reactions of 2,3,5,7-tetraphenyl-1,4-diazabicyclo[4.1.O]hept-4-enes are described. These compounds are prepared from the reaction of meso-and rac-stilbenediamine with 1,3-diphenyl-2,3-dibromo-l-propanone. The assignment of stereochemistry about the ring system was made on the basis of the NMR spectra of the various structural isomers. The 1,4-diazabicyclo[4.1.0]hept-4-ene ring system was found to undergo an interesting set of reactions on treatment with base. The particular product formed was found to depend on both the initial stereochemistry of the ring system as well as on the experimental conditions used. The exo,exo isomer 4 gave l-benzyl-2,3,5-triphenyldihydropyrazine (10) on treatment with potassium tert-butoxide. The other possible isomeric diazabicycloheptenes gave triphenylpyrazine when benzene was used as a solvent. When the reaction was carried out in tert-butyl alcohol, 2-benzyl-3,5,6-triphenylpyrazine (7), 2,3,5,7-tetraphenyl-1,4-diazacyclohepta-1,3,5-triene (13), and 2,4,5,7-tetrapheny1-3,6-diazabicyclo[3.2.0] hepta-3,g-diene were isolated as the major products. The mechanistic pathways involved in the base-induced reactions are discussed.
The Journal of Organic Chemistry, 1996
The photochemistry of 11,12-dibenzoyl-9,10-dihydro-9-(hydroxymethyl)-10-methoxy-9,10-ethenoanthracene (7a) and 11,12-dibenzoyl-9,10-dihydro-9-(1-hydroxyethyl)-10-methoxy-9,10-ethenoanthracene (7b) has been studied through steady-state photolysis, product analysis, and laser flash photolysis. Irradiation of 7a in benzene, methanol, or acetone gave 69-72% yields of a dibenzopentalene ketone 11a, arising through a dibenzosemibullvalene precursor. Irradiation of 7b, which exists in equilibrium with its cyclic form 7b′, gave a mixture of the dibenzopentalene ketone 11b (41%) and the dibenzopentalenopyran derivative, 16b′ (26%). The photochemistry of 11,12-dibenzoyl-9,10-dihydro-9,10-dimethoxy-9,10-ethenoanthracene (17) has been reinvestigated. Irradiation of 17 in benzene and methanol gives a 90% yield of an isomeric pentacyclic product 24, formed through the rearrangement of a dibenzosemibullvalene precursor. Irradiation of 17 in aqueous methanol gives a mixture of the dibenzopentalene ketone 22 (40%) and a pentacyclic methanol adduct 21 (34%). The structures of 7b′, 11a,b, 16b′, 21, and 24 were confirmed through X-ray crystallographic analysis. The 308 nm laser flash photolysis of 7a,b in benzene results in the formation of their triplets (φ T ) 0.55-0.76). These triplets possess short lifetimes (0.45-0.75 µs) and are quenched by oxygen, 2,2,6,6-tetramethylpiperidinyl-1-oxy (TEMPO), 4-hydroxy-2,2,6,6tetramethylpiperidinyl-1-oxy (HTEMPO), ferrocene, and -carotene at rates in the range (0.26-4.7) × 10 9 M -1 s -1 .
Journal of Organic Chemistry, 1996
The photochemistry of 11,12-dibenzoyl-9,10-dihydro-9-(hydroxymethyl)-10-methoxy-9,10-ethenoanthracene (7a) and 11,12-dibenzoyl-9,10-dihydro-9-(1-hydroxyethyl)-10-methoxy-9,10-ethenoanthracene (7b) has been studied through steady-state photolysis, product analysis, and laser flash photolysis. Irradiation of 7a in benzene, methanol, or acetone gave 69-72% yields of a dibenzopentalene ketone 11a, arising through a dibenzosemibullvalene precursor. Irradiation of 7b, which exists in equilibrium with its cyclic form 7b′, gave a mixture of the dibenzopentalene ketone 11b (41%) and the dibenzopentalenopyran derivative, 16b′ (26%). The photochemistry of 11,12-dibenzoyl-9,10-dihydro-9,10-dimethoxy-9,10-ethenoanthracene (17) has been reinvestigated. Irradiation of 17 in benzene and methanol gives a 90% yield of an isomeric pentacyclic product 24, formed through the rearrangement of a dibenzosemibullvalene precursor. Irradiation of 17 in aqueous methanol gives a mixture of the dibenzopentalene ketone 22 (40%) and a pentacyclic methanol adduct 21 (34%). The structures of 7b′, 11a,b, 16b′, 21, and 24 were confirmed through X-ray crystallographic analysis. The 308 nm laser flash photolysis of 7a,b in benzene results in the formation of their triplets (φ T ) 0.55-0.76). These triplets possess short lifetimes (0.45-0.75 µs) and are quenched by oxygen, 2,2,6,6-tetramethylpiperidinyl-1-oxy (TEMPO), 4-hydroxy-2,2,6,6tetramethylpiperidinyl-1-oxy (HTEMPO), ferrocene, and -carotene at rates in the range (0.26-4.7) × 10 9 M -1 s -1 .