Direct synthesis of previously inaccessible bridgehead azabicyclics by intramolecular cyclization of alpha-sulfonamido and alpha-sulfonimido radicals

Syntheses of the first bridgehead sultams and the only known bridgehead disulfonimide are described. Both approaches capitalize on the electrophilicity of alpha-sulfonyl radicals and their propensity to undergo intramolecular ring closure. Where double bonds are concerned, 5-exo and 6-exo pathways operate preferentially as long as structural strain is not excessive. When the reaction center is a carbon-carbon triple bond, the first cyclization gives rise to vinyl radicals that hold sufficient reactivity to capture solvent benzene. In the case of 45, this sequential reaction leads importantly to the introduction of a styrene functionality sufficiently activated to allow a second ring closure to be kinetically feasible. The solid-state structural features of 12 and 17 have been elucidated by X-ray crystallographic methods. Despite key differences from the norm in the alignment of the nitrogen lone pair relative to the adjacent sulfonyl groups, these compounds exhibit good hydrolytic stability. For 13, generation of the alpha-sulfonamide carbanion is possible and regiospecific oxidation with chromyl acetate has been achieved.     

Solvolysis of bridgehead chlorides with strained bridgehead double bond.

Product study and kinetic data of the solvolysis of the bridgehead chlorides (

) and (

indicate the neighboring group participation of the strained bridgehead double bonds.     

Synthesis of bridgehead nitrogen heterocycles

Reductive cyclizations of N-[2-(2-pyridyl)ethyl]imides were accomplished by employing a palladium on carbon catalyst in ethanolic acetic acid as the hydrogenation medium. Reduction of the corresponding N-[2-(2-quinolyl)ethyl]imides ceased at the 1,2,3,4-tetrahydroquinolyl stage. Controlled reduction of the tetrahydroquinolyl imides with sodium borohydride gave amido alcohols which afforded bridgehead nitrogen heterocycles upon cyclodehydration.     

Double bridgehead olefins via pyrolysis

Pyrolysis of diacetate $\text{5}$ produced 3 major products, $\text{6}$–$\text{8}$. The most reasonable pathway to these products, supported by deuterium labelling studies, is via double bridgehead olefins

and

.     

Microwave assisted synthesis of bridgehead alkenes

A new, concise method to synthesize triene precursors for the type 2 intramolecular Diels-Alder reaction has been developed. Microwave irradiation of the trienes provides a convenient method for the synthesis of bridgehead alkenes. Higher yields, shorter reaction times, and lower reaction temperatures provide a general and efficient route to this interesting class of molecules.     

Diazabicycloalkanes with bridgehead nitrogen atoms

By heating 1-(2-hydroxyethyl)benzo[b]-1-azonium-4-azabicyclo-[2.2.2]octene halides in anhydrous solvents or via thermolysis, opening of the bicycle occurs with formation of the corresponding N-(2-hydroxyethyl)-N-(2-haloethyl)-1, 2,3,4-tetrahydroquinoxalines. In the presence of base, fission of the hydroxyethyl group principally occurs.For Communication 25, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1091–1094, August, 1992.     

Bredt规则和双环桥烯化合物

本文评述了Bredt规则和双烯化合物特征及合成发展。     

Heterocycles with the bridgehead N atom

2,3,5,7-Tetramethyloxazolo[3,2-a]pyrimidinium perchlorate in reactions with sodium hydroxide, sodium ethoxide, and pyrrolidine undergoes earlier unknown recyclization into 1-substituted pyrrolo[1,2-c]pyrimidines. Recyclization of the same salt under the action of ammonia gives 2,3,5,7-tetramethylimidazo[1,2-a]pyrimidine. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1611–1614, August, 2007.     

19F chemical shifts of bridgehead fluorides

The ¹⁹F chemical shifts of a series of bridgehead fluorides are reported. It is found that, contrary to earlier conclusions based on a limited number of substrates, the fluorine shifts occur randomly.     

Synthesis of phosphoric esters of bridgehead alcohols

Dibenzylphosphates of 1-adamantanol and kemantane, 1-adamantyl phosphate, and a series of diphenyl phosphates of bridgehead alcohols have been prepared.     

Hydroxypropyl substituted nitrogen bridgehead fused cyanopyridines

The reaction of 2-hetaryl-2-(tetrahydro-2-furanyliden)acetonitriles with substituted acetonitriles as C-nucleophiles has been investigated and the mechanism of the reaction has been suggested. A base promoted Michael addition of the substituted acetonitriles to 2-hetaryl-2-(tetrahydro-2-furanyliden)acetonitriles followed by ring transformations has provided novel convenient synthetic methods to nitrogen bridgehead fused cyanopyridines bearing hydroxypropyl side chain. The structures of obtained compounds have been established based on NMR spectroscopy investigation and X-ray diffraction data.     

Synthesis of enantiomeric bridgehead substituted bisnoradamantane derivatives

The preparation of (+)- and (−)-12 by resolution of (±)-12 with (R)-N-phenylpantolactam, (R)-13, is described. From (+)- and (−)-12 a series of chiral bisnoradamantane derivatives, whose chirality stems from substitution at the bridgehead positions, have been obtained in both enantiomeric forms.     

Bicyclo[5.3.1]undec-1(10)-ene bridgehead olefin stability and the taxane bridgehead olefin

MM2 calculations have shown how substituent and conformational effects play a role in the stabilities of systems containing the bicyclo[5.3.1]undec-I(10)-ene moiety and that the taxane diterpene skeleton which possesses this structural feature is surprisingly stable.     

Bicyclic oxonium ions with an oxygen bridgehead

Electron impact induced fragmentation of 4-(ω-phenoxymethyl and -ethyl)tetrahydn pyranes results in abundant [M ? 93] + ions through loss of a phenoxy radical. These ions are all produced in high yields by isobutane chemical ionization through loss of phenol from the quai molecular ions. Labelling data (²H, ¹³C) provide evidence for the l-oxoniabicyclo[2.2.1]heptane ai l-oxoniabicyclo[2.2.2]octane structures of the electron impact produced decomposing (ion sour and first field free region) ions [M ? 93]L in the case of the methyl and ethyl compounds, respective.     

Synthesis of bicyclo[6.2.2] bridgehead dienes

Bicyclo[6.2.2]dodecadienes ($\text{2}$), ($\text{3a}$), and ($\text{3b}$) having two bridgehead double bonds were synthesized by the pyrolysis of the acetate ($\text{1}$).     

Synthesis and biological activity of bridgehead nitrogen heterocycles

The reaction of 3-(2,4-dichlorophenyl)-5-mercapto 1,2,4–1H-triazole with α-haloketones and with 1,2-dibromoethane leading to the formation of fused heterocycles were carried out and the orientation of cyclization was studied. The reaction of 3-(2,4-dichlorophenyl)-5-mercapto-4-amino-1,2,4-s-triazole with α-haloketones     

Sterically congested macrobicycles with heteroatomic bridgehead functionality

A series of cyclophanes composed of two triarylelement caps linked by two-atom bridges has been synthesized. The bridgehead functional groups include phosphines in combination with amines, hydrosilanes, methylsilanes, and ethoxysilanes. Computational studies accurately predicted that when the bridgehead substituents are small (lone pairs or protons), an in_,in bridgehead stereochemistry is strongly favored, but larger bridgehead substituents favor the formations of in_,out stereoisomers. The X-ray structures, spectra, and reactivity of these compounds are discussed, as well as the resolution of one of the cyclophanes into pure enantiomers.