22516-18-3Relevant academic research and scientific papers
Pyrrolidines and Piperidines by Ligand-Enabled Aza-Heck Cyclizations and Cascades of N-(Pentafluorobenzoyloxy)carbamates
Hazelden, Ian R.,Carmona, Rafaela C.,Langer, Thomas,Pringle, Paul G.,Bower, John F.
supporting information, p. 5124 - 5128 (2018/03/26)
Ligand-enabled aza-Heck cyclizations and cascades of N-(pentafluorobenzoyloxy)carbamates are described. These studies encompass the first examples of efficient non-biased 6-exo aza-Heck cyclizations. The methodology provides direct and flexible access to carbamate protected pyrrolidines and piperidines.
Enantioselective Hydroazidation of Trisubstituted Non-Activated Alkenes
Meyer, Daniel,Renaud, Philippe
supporting information, p. 10858 - 10861 (2017/08/30)
A one-pot procedure for the enantioselective hydroazidation of non-activated trisubstituted alkenes is described. Hydroboration with monoisopinocampheylborane (IpcBH2) provides dialkylboranes that are in situ selectively converted into monoalkyl-substituted catecholboranes; these undergo radical azidation upon treatment with benzenesulfonyl azide and a radical initiator. Enantiomerically enriched azides were thus obtained in yields of 59–81 % and enantioselectivities of up to 94:6 e.r. (98:2 e.r. if the intermediate dialkylborane is purified by crystallization). A rapid access to enantiomerically pure (+)-rodocaine is also described. The use of other arenesulfonyl radical traps enables enantioselective hydroallylation, hydrosulfanylation, and hydrobromination reactions with yields of 71–86 %.
Diverse N-Heterocyclic Ring Systems via Aza-Heck Cyclizations of N-(Pentafluorobenzoyloxy)sulfonamides
Hazelden, Ian R.,Ma, Xiaofeng,Langer, Thomas,Bower, John F.
supporting information, p. 11198 - 11202 (2016/10/13)
Aza-Heck cyclizations initiated by oxidative addition of Pd0-catalysts into the N?O bond of N-(pentafluoro-benzoyloxy)sulfonamides are described. These studies, which encompass only the second class of aza-Heck reaction developed to date, provide direct access to diverse N-heterocyclic ring systems.
Conformation-based restrictions and scaffold replacements in the design of hepatitis C virus polymerase inhibitors: Discovery of deleobuvir (BI 207127)
LaPlante, Steven R.,B?s, Michael,Brochu, Christian,Chabot, Catherine,Coulombe, René,Gillard, James R.,Jakalian, Araz,Poirier, Martin,Rancourt, Jean,Stammers, Timothy,Thavonekham, Bounkham,Beaulieu, Pierre L.,Kukolj, George,Tsantrizos, Youla S.
supporting information, p. 1845 - 1854 (2014/04/03)
Conformational restrictions of flexible torsion angles were used to guide the identification of new chemotypes of HCV NS5B inhibitors. Sites for rigidification were based on an acquired conformational understanding of compound binding requirements and the roles of substituents in the free and bound states. Chemical bioisosteres of amide bonds were explored to improve cell-based potency. Examples are shown, including the design concept that led to the discovery of the phase III clinical candidate deleobuvir (BI 207127). The structure-based strategies employed have general utility in drug design.
Palladium-catalyzed carbonylative heck-type reactions of alkyl iodides
Bloome, Kayla S.,Alexanian, Erik J.
supporting information; experimental part, p. 12823 - 12825 (2010/11/03)
A palladium-catalyzed carbonylative Heck-type cyclization of alkyl halides is described. Treatment of a range of primary and secondary alkyl iodides with catalytic palladium(0) under CO pressure forms a variety of synthetically versatile enone products. The reactivity described represents a rare example of a palladium-catalyzed Heck-type cyclization involving unactivated alkyl halides with β-hydrogens. Alkene substitution is well tolerated, and mono-and bicyclic carbocycles may be easily accessed.
Studies concerning the electrophilic amino-alkene cyclisation for the synthesis of bicyclic amines
Klein, Johannes E. M. N.,Mueller-Bunz, Helge,Evans, Paul
supporting information; experimental part, p. 986 - 995 (2009/05/30)
The bromination of a series of cyclohexenyl substituted secondary amines 1a-i has been investigated using Br2, PHT and NBS. In the case of Br2 and NBS the secondary amines preferentially undergo N-bromination. In contrast, PHT cleanly affords the products of alkene dibromination. In the case of Br2 the N-bromo species then give the products of alkene dibromination, albeit less efficiently. On subsequent treatment with K2CO3 these dibromides form the corresponding hexahydroindoles 2a-h and octahydroquinoline 2i. The presence of an N-substituent bearing a stereogenic centre (1h and 1i) was studied and the products 2h and 2i were isolated with no diastereoselectivity. When NBS was used a novel cyclisation, forming bromo-substituted octahydroindoles 9a,b and d, was observed. In relation to this sequence it was shown that these products were not intermediates in the former Br2/PHT processes and that the reaction only proceeded in the presence of the succinimide by-product of N-bromination.
An advanced intermediate for the synthesis of (±)-pumiliotoxin C and its analogues
Shao, Zhi-Hui,Peng, Fang-Zhi,Chen, Jing-Bo,Wang, Chen-Ying,Huang, Rong,Tu, Yong-Qiang,Li, Liang,Zhang, Hong-Bin
, p. 2031 - 2038 (2007/10/03)
Compound 1 as a versatile intermediate for the synthesis of (±)-pumiliotoxin C and its analogues was prepared from commercially available cyclohexanone. The key step in the synthesis was the construction of octahydroquinoline ring by a stereoselective ami
Stereo- and regioselectivity of cyclization reactions in conformationally restricted epoxy ketones: Evaluation of C- versus O-alkylation process
Crotti, Paolo,Badalassi, Fabrizio,Di Bussolo, Valeria,Favero, Lucilla,Pineschi, Mauro
, p. 8559 - 8572 (2007/10/03)
The intramolecular addition reaction of metal enolates of ketones to oxiranes has been applied to a series of epoxy ketones derived from cyclohexene oxide. γ-Hydroxy ketones (γ-HKs, C-alkylation products) or hydroxy enol ethers (HEEs, O-alkylation products) are obtained, depending on the nature of the cyclic transition state in each case involved and the application of the Fu?rst-Plattner rule. The formation of HEEs by reaction of the same epoxy ketones under acid conditions is also described. In some cases, regioconvergent or chemoselective processes are conveniently obtained.
Consecutive 6-endo trigonal cyclisations from polyene acyl radical intermediates leading to decalone and perhydrophenanthrone ring constructions
Chen, Ligong,Gill, G. Bryon,Pattenden, Gerald,Simonian, Houri
, p. 31 - 44 (2007/10/03)
A range of substituted Se-phenyl 5,9-dieneselenoates, viz. 15a, 25, 26, 27, 42 and 52, have been synthesised and their reactions with Bu3SnH-AIBN investigated.The diene esters 15a, 42 and 52 are shown to lead to decalone and to perhydrophenanthrone derivatives, viz. 19, 43 and 53, respectively, via consecutive 6-endo trig modes of cyclisations starting from the corresponding 5,9-diene acyl radical intermediates.By contrast, the 5,9-dienoates 25 and 27 lacking alkyl substitution at C-9 instead underwent cyclisation to the indanones 36 and 37, respectively, and the 6-methyl substituted analogue 26 produced only the cyclopentanone 38 on treatment with Bu3SnH-AIBN.
A Stereoselective Synthesis of (+/-)-trans-Cycloalkanopiperidines and Cycloalkanopyrrolidines via Hydroboration
Brown, Herbert C.,Salunkhe, Ashok M.
, p. 1265 - 1268 (2007/10/02)
A highly stereoselective synthesis of trans-cycloalkanopiperidines and cycloalkanopyrrolidines has been achieved via hydroboration of bromocycloalkenes with dichloroboranes.The intermediate bromocycloalkylboronic acids were converted into azidocycloalkylboronates.Addition of two equivalents of boron trichloride in dichloromethane generated dichloroboranes which, by an intramolecular cyclisation gave intermediates 11.These can be readily hydrolyzed to get the corresponding important nitrogen heterocycles in good yields and excellent stereochemical purities.
