98585-81-0Relevant academic research and scientific papers
Bicyclo[1.1.1]pentyl Sulfoximines: Synthesis and Functionalizations
B?r, Robin M.,Br?se, Stefan,Langer, Lukas,Nieger, Martin
, (2020/02/20)
Herein we present the first synthesis of bicyclo[1.1.1]pentyl (BCP) sulfoximines from the corresponding sulfides. Both BCPs and sulfoximines are bioisosteres used in medicinal chemistry and therefore desirable motifs. The access to BCP sulfides was enabled by the thiol addition to [1.1.1]propellane as published before. A broad scope with specific limitations was discovered for the sulfoximination. To diversify the sulfoximines, N-acylations and N-arylations were performed. As the N-arylation was low yielding we optimized the copper(I) catalyzed reaction. A wide range of aryl iodides could be deployed and competitive reactions showed that aryl bromides react equally fast. In a scale-up we prepared a suitable precursor for a BCP drug analogue. In this work several molecular structures could be determined by single-crystal X-ray diffraction. (Figure presented.).
Insertion of [1.1.1]propellane into aromatic disulfides
B?r, Robin M.,Heinrich, Gregor,Nieger, Martin,Fuhr, Olaf,Br?se, Stefan
supporting information, p. 1172 - 1180 (2019/06/08)
Herein we present the synthesis of symmetrically and unsymmetrically substituted 1,3-bissulfanylbicyclo[1.1.1]pentanes from disulfides and [1.1.1]propellane. Bicyclo[1.1.1]pentanes (BCPs) recently gained interest as rigid linkers and as bioisosters of parasubstituted benzene and alkyne moieties. The most promising precursor for BCPs is [1.1.1]propellane (1). The available methods to synthesize BCPs are quite limited and many groups contribute to the development of novel methods. The insertion of 1 into disulfide bonds is known, but has never been thoroughly investigated. In this study, we show that an UV initiated radical reaction can be used to synthesize symmetrically and unsymmetrically substituted BCP sulfides by reaction of [1.1.1]propellane (1) with disulfides. Depending on the ratio of 1 to the disulfide, only the BCP product (with up to 98% yield) or a mixture of BCP and [2]staffane can be obtained. The reaction tolerates functional groups such as halogens, alkyl and methoxy groups. The separation of the corresponding BCP and [2]staffane products is challenging but possible by column chromatography and preparative TLC in most cases. Single crystal X-ray diffraction analysis confirms the rod-like structure of the [2]staffanes that is often required in material applications.
Alkyl and Aryl Thiol Addition to [1.1.1]Propellane: Scope and Limitations of a Fast Conjugation Reaction
B?r, Robin M.,Kirschner, Stefan,Nieger, Martin,Br?se, Stefan
, p. 1373 - 1382 (2017/12/26)
Herein the addition of different thiols to the strained carbon–carbon bond of [1.1.1]propellane (1) is reported. The reaction pathway was investigated, addition reactions with substituted thiols, hydrogen sulfide and protected cysteine were performed, and
Synthesis of bisbicyclo[1.1.1]pentyldiazene. The smallest bridgehead diazene
Hossain,Timberlake
, p. 6282 - 6285 (2007/10/03)
Bisbicyclo[1.1.1]pentyldiazene, the smallest bicyclic azo compound, has been synthesized from the precursor [1.1.1]propellane via synthesis of N,N′-bis(bicyclo[1.1.1]pentyl)sulfamide and azoxybicyclo[1.1.1]pentane. The UV absorption of this diazene at 382 nm indicates that the compound is the trans isomer. Conversion to the cis isomer by irradiation was not possible because of attainment of a photostationary state. However, on the basis of the photochemical studies, the absorption of the cis-[1.1.1] isomer is estimated to be 384 nm.
Reactions of [1.1.1]propellane
Wiberg, Kenneth B.,Waddell, Sherman T.
, p. 2194 - 2216 (2007/10/02)
The free radical addition reactions of [1.1.1]propellane (1) are described in some detail and allowed the preparation of a wide variety of 1,3-disubstituted bicyclo[1.1.1]pentanes. The reaction of 1 with free radicals was more rapid than that of bicyclo[1.1.0]butane (2), whereas bicyclo[2.1.0]pentane (3) was relatively inert. In some cases the free-radical additions led to oligomers, and in the case of tetrahydrofuran addition the chain-transfer constant was measured. The addition of thiophenol to 1 followed by reduction with the lithium radical anion from 4,4′-di-tert-butylbiphenyl gave 1-lithiobicyclo[1.1.1]petane, from which a variety of 1-substituted bicyclo[1.1.1]pentanes may be prepared. In the Baeyer-Villiger oxidation of 1-benzoylbicyclo[1.1.1]pentane, the terf-butyl group migrated in preference to the bicyclopentyl group. Conversion of the ketone to the tosylhydrazone followed by base treatment gave products of the type expected from the corresponding carbene. The reaction of 1 with NO in carbon disulfide gave a unique reaction in which nitro and thiocyano groups were introduced. The reactions of 1, 2, and 3 with NO2 also were examined. Whereas 1 gave 1,3-dinitrobicyclo[1.1.1]pentane, the other hydrocarbons followed different reaction paths. The reaction of 1 with electron-deficient alkenes and alkynes are described in some detail and are compared with the corresponding reactions of 2 and 3. Here, the relative reactivities of 1 and 2 were often comparable but varied considerably with the reagent used. Again, 3 was relatively unreactive. The reaction of 1 with Rh(I) gave a dimer, and evidence is presented for a metallocarbene intermediate.
Formation and Reactions of 1-Lithiobicyclopentane
Wiberg, Kenneth B.,Waddell, Sherman T.
, p. 289 - 292 (2007/10/02)
Bicyclopentyllithium was prepared in two steps from the readily available propellane and proved to be a versatile intermediate in the preparation of a wide variety of 1-substituted bicyclopentanes.
