105542-98-1Relevant articles and documents
Scalable synthesis of 1-bicyclo[1.1.1]pentylamine via a hydrohydrazination reaction
Bunker, Kevin D.,Sach, Neal W.,Huang, Qinhua,Richardson, Paul F.
, p. 4746 - 4748 (2011)
The reaction of [1.1.1]propellane with di-tert-butyl azodicarboxylate and phenylsilane in the presence of Mn(dpm)3 to give di-tert-butyl 1-(bicyclo[1.1.1]pentan-1-yl)hydrazine-1,2-dicarboxylate is described. Subsequent deprotection gives 1-bicyclo[1.1.1]pentylhydrazine followed by reduction to give 1-bicyclo[1.1.1]pentylamine. The reported route marks a significant improvement over the previous syntheses of 1-bicyclo[1.1.1] pentylamine in terms of scalability, yield, safety, and cost.
α-Cyclodextrin Encapsulation of Bicyclo[1.1.1]pentane Derivatives: A Storable Feedstock for Preparation of [1.1.1]Propellane
Matsunaga, Tadafumi,Kanazawa, Junichiro,Ichikawa, Tomohiro,Harada, Mei,Nishiyama, Yusuke,Duong, Nghia Tuan,Matsumoto, Takashi,Miyamoto, Kazunori,Uchiyama, Masanobu
, p. 2578 - 2582 (2021)
The bicyclo[1.1.1]pentane (BCP) scaffold is useful in medicinal chemistry, and many protocols are available for synthesizing BCP derivatives from [1.1.1]propellane. Here, we report (1) the α-cyclodextrin (α-CD) encapsulation of BCP derivatives, affording a stable, readily storable material from which BCPs can be easily and quantitatively recovered and (2) new and simple protocols for deiodination reaction of 1,3-diiodo BCP to afford [1.1.1]propellane in protic/aprotic/polar/non-polar solvents. The combination of these methodologies enables simple, on-demand preparation of [1.1.1]propellane in various solvents under mild conditions from α-CD capsules containing 1,3-diiodo BCP.
Cubane, Bicyclo[1.1.1]pentane and Bicyclo[2.2.2]octane: Impact and Thermal Sensitiveness of Carboxyl-, Hydroxymethyl- and Iodo-substituents
Dallaston, Madeleine A.,Houston, Sevan D.,Williams, Craig M.
, p. 11966 - 11970 (2020)
With the burgeoning interest in cage motifs for bioactive molecule discovery, and the recent disclosure of 1,4-cubane-dicarboxylic acid impact sensitivity, more research into the safety profiles of cage scaffolds is required. Therefore, the impact sensitivity and thermal decomposition behavior of judiciously selected starting materials and synthetic intermediates of cubane, bicyclo[1.1.1]pentane (BCP), and bicyclo[2.2.2]octane (BCO) were evaluated via hammer test and sealed cell differential scanning calorimetry, respectively. Iodo-substituted systems were found to be more impact sensitive, whereas hydroxymethyl substitution led to more rapid thermodecomposition. Cubane was more likely to be impact sensitive with these substituents, followed by BCP, whereas all BCOs were unresponsive. The majority of derivatives were placed substantially above Yoshida thresholds—a computational indicator of sensitivity.
Spectroscopic and computational studies on the rearrangement of ionized [1.1.1]propellane and some of its valence isomers: The key role of vibronic coupling
Mueller, Beat,Bally, Thomas,Pappas, Robert,Williams, Ffrancon
, p. 14649 - 14660 (2010)
The [1.1.1]propellane radical cation 1?+, generated by radiolytic oxidation of the parent compound in argon and Freon matrices at low temperatures, undergoes a spontaneous rearrangement to form the distonic 1,1-dimethyleneallene (or 2-vinylideneallyl) radical cation 3?+ consisting of an allyl radical substituted at the 2-position by a vinyl cation. In similar matrix studies, it is found that the isomeric dimethylenecyclopropane radical cation 2?+ also rearranges to 3?+. The unusual molecular and electronic structure of 3?+ has been established by the results of ESR, UV-vis, and IR spectroscopic measurements in conjunction with detailed theoretical calculations. Also of particular interest is an NIR photoinduced reaction by which 3?+ is cleanly converted to the vinylidenecyclopropane radical cation 4?+, a process that can be represented in terms of a single electron transfer from the allyl radical to the vinyl cation followed by allyl cation cyclization. The specificity of this photochemical reaction provides additional strong chemical evidence for the structure of 3?+. Theoretical calculations reveal the decisive role of vibronic coupling in shaping the potential energy surfaces on which the observed ring-opening reactions take place. Thus vibronic interaction in 1?+ mixes the 2A1′ ground state, characterized by its "non-bonding" 3a1′ SOMO, with the 2E″ first excited state resulting in the destabilization of a lateral C-C bond and the initial formation of the methylenebicyclobutyl radical cation 5?+. The further rearrangement of 5?+ to 3?+ occurs via 2 ?+ and proceeds through two additional lateral C-C bond cleavages characterized by transition states of extremely low energy, thereby explaining the absence of identifiable intermediates along the reaction pathway. In these consecutive ring-opening rearrangements, the "non-bonding" bridgehead C-C bond in 1?+ is conserved and ultimately transformed into a normal bond characterized by a shorter C-C bond length. This work provides strong support for the Heilbronner-Wiberg interpretation of the vibrational structure in the photoelectron spectrum of 1 in terms of vibronic coupling.
Synthesis of novel cage quaternary salts via nucleophilic substitution of 1,3-diiodobicyclo[1.1.1 ]pentane. Further evidence for a stable 3-iodo-1-bicyclo[1.1.1]pentyl cation
Adcock, James L.,Gakh, Andrei A.
, p. 4875 - 4878 (1992)
Nucleophilic substitution of 1,3-diiodobicyclo[1.1.1]pentane by tertiary amines and pyridines was investigated. The structure of cage quaternary salts obtained together with the observation of the competitive addition of pyridine in the reaction of [1.1.1]propellane with iodine indicate the existence of a relatively stable "hot intermediate" very close in its structure to a stabilized 3-iodo-1-bicyclo[1.1.1]pentyl cation.
Electrophilic Activation of [1.1.1]Propellane for the Synthesis of Nitrogen-Substituted Bicyclo[1.1.1]pentanes
A?ssa, Christophe,Duarte, Fernanda,Goundry, William R. F.,Livesley, Sarah,Morris, James A.,Robertson, Craig M.,Sterling, Alistair J.
supporting information, (2021/11/30)
Strategies commonly used for the synthesis of functionalised bicyclo[1.1.1]pentanes (BCP) rely on the reaction of [1.1.1]propellane with anionic or radical intermediates. In contrast, electrophilic activation has remained a considerable challenge due to t
Visible-Light-Induced 1,3-Aminopyridylation of [1.1.1]Propellane with N-Aminopyridinium Salts
Shin, Sanghoon,Lee, Seojin,Choi, Wonjun,Kim, Namhoon,Hong, Sungwoo
supporting information, p. 7873 - 7879 (2021/03/08)
Through the formation of an electron donor–acceptor (EDA) complex, strain-release aminopyridylation of [1.1.1]propellane with N-aminopyridinium salts as bifunctional reagents enabled the direct installation of amino and pyridyl groups onto bicyclo[1.1.1]pentane (BCP) frameworks in the absence of an external photocatalyst. The robustness of this method to synthesize 1,3-aminopyridylated BCPs under mild and metal-free conditions is highlighted by the late-stage modification of structurally complex biorelevant molecules. Moreover, the strategy was extended to P-centered and CF3 radicals for the unprecedented incorporation of such functional groups with pyridine across the BCP core in a three-component coupling. This practical method lays the foundation for the straightforward construction of new valuable C4-pyridine-functionalized BCP chemical entities, thus significantly expanding the range of accessibility of BCP-type bioisosteres for applications in drug discovery.
A continuous flow synthesis of [1.1.1]propellane and bicyclo[1.1.1]pentane derivatives
Donnelly, Kian,Baumann, Marcus
supporting information, p. 2871 - 2874 (2021/03/23)
A continuous flow process to generate [1.1.1]propellane on demand is presented rendering solutions of [1.1.1]propellane that can directly be derivatised into various bicyclo[1.1.1]pentane (BCP) species. This was realised in throughputs up to 8.5 mmol h-1providing an attractive and straightforward access to gram quantities of selected BCP building blocks. Lastly, a continuous photochemical transformation of [1.1.1]propellane into valuable BCPs bearing mixed ester/acyl chloride moieties was developed.
Divergent Strain-Release Amino-Functionalization of [1.1.1]Propellane with Electrophilic Nitrogen-Radicals
Kim, Ji Hye,Ruffoni, Alessandro,Al-Faiyz, Yasair S. S.,Sheikh, Nadeem S.,Leonori, Daniele
supporting information, p. 8225 - 8231 (2020/03/04)
Herein we report the development of a photocatalytic strategy for the divergent preparation of functionalized bicyclo[1.1.1]pentylamines. This approach exploits, for the first time, the ability of nitrogen-radicals to undergo strain-release reaction with [1.1.1]propellane. This reactivity is facilitated by the electrophilic nature of these open-shell intermediates and the presence of strong polar effects in the transition-state for C?N bond formation/ring-opening. With the aid of a simple reductive quenching photoredox cycle, we have successfully harnessed this novel radical strain-release amination as part of a multicomponent cascade compatible with several external trapping agents. Overall, this radical strategy enables the rapid construction of novel amino-functionalized building blocks with potential application in medicinal chemistry programs as p-substituted aniline bioisosteres.
Bicyclo[1.1.1]pentane-Derived Building Blocks for Click Chemistry
Kokhan, Serhii O.,Valter, Yevheniia B.,Tymtsunik, Andriy V.,Komarov, Igor V.,Grygorenko, Oleksandr O.
, p. 6450 - 6456 (2017/12/01)
Syntheses of bicyclo[1.1.1]pentane-derived azides and terminal alkynes – interesting substrates for click reactions – are described. With a few exceptions, these compounds were prepared in two or three steps starting from common synthetic intermediates – the corresponding carboxylic acids. The key step in the synthesis of 1-azidobicyclo[1.1.1]pentanes is a copper-catalysed diazo-transfer reaction with imidazole-1-sulfonyl azide. The preparation of bicyclo[1.1.1]pentyl-substituted alkynes relies on a Seyferth–Gilbert homologation with dimethyl 1-diazo-2-oxopropylphosphonate (Ohira–Bestmann reagent). Both types of target compounds were found to be suitable substrates for click reactions, and thus they are promising building blocks for medicinal, combinatorial and bioconjugate chemistry. A practically important side result of this study was a multigram preparation of Boc-monoprotected 1,3-diaminobicyclo[1.1.1]pentane – a representative bicyclic conformationally restricted diamine derivative.
