3897-04-9Relevant academic research and scientific papers
Sequential enolboration/hydroformylation/aldol addition: A new one-pot cascade reaction for the regio- and diastereoselective formation of carbocyclic quaternary centres from acyclic olefins
Keraenen, Mark D.,Eilbracht, Peter
, p. 1688 - 1690 (2004)
Starting from unsaturated carbonyl compounds a mild new cascade reaction involving enolboration, rhodium-catalysed hydroformylation and intramolecular aldol addition in a regio- and diastereoselective fashion leads to cyclic compounds containing highly-functionalised quaternary carbon centres.
Syntheses of cyclohexenone derivatives by the ruthenium complex-catalysed reactions of allylic compounds with β-keto esters
Zhang, Shi-Wei,Mitsudo, Take-aki,Kondo, Teruyuki,Watanabe, Yoshihisa
, p. 55 - 62 (1995)
Allylic compounds such as allyl alcohols and allylamines react with two equivalent moles of acetoacetates in the presence of a catalytic amount of Ru(cod)(cot) (cod = cycloocta-1,5-diene; cot = cycloocta-1,3,5-triene) at 100 deg C for 5 h to give cyclohexenone derivatives in high yields.Keywords: Ruthenium; Allyl; Cyclohexane; Catalyst; Alcohol; Amine
Development of Pyrazolopyrimidine Anti- Wolbachia Agents for the Treatment of Filariasis
Berry, Neil G.,Cassidy, Andrew,Clare, Rachel H.,Cook, Darren A.,Ford, Louise,Hong, W. David,Johnston, Kelly L.,Kavanagh, Stefan,Leung, Suet C.,McGillan, Paul,Nixon, Gemma L.,O'Neill, Paul M.,Taylor, Mark J.,Ward, Stephen A.,Webborn, Peter J. H.,Wenlock, Mark C.
, p. 1421 - 1426 (2021)
Anti-Wolbachia therapy has been identified as a viable treatment for combating filarial diseases. Phenotypic screening revealed a series of pyrazolopyrimidine hits with potent anti-Wolbachia activity. This paper focuses on the exploration of the SAR for this chemotype, with improvement of metabolic stability and solubility profiles using medicinal chemistry approaches. Organic synthesis has enabled functionalization of the pyrazolopyrimidine core at multiple positions, generating a library of compounds of which many analogues possess nanomolar activity against Wolbachia in vitro with improved DMPK parameters. A lead compound, 15f, was selected for in vivo pharmacokinetics (PK) profiling in mice. The combination of potent anti-Wolbachia activity in two in vitro assessments plus the exceptional oral PK profiles in mice puts this lead compound in a strong position for in vivo proof-of-concept pharmacodynamics studies and demonstrates the strong potential for further optimization and development of this series for treatment of filariasis in the future.
THE DIANION CLAISEN REARRANGEMENT OF β-HYDROXY ESTERS
Kurth, Mark J.,Yu, Chan-Mo
, p. 5003 - 5006 (1984)
Claisen rearrangement of β-hydroxy allylic ester dianions provides stereocontrolled access to three contiguous chiral centers on an acyclic framework; an unambiguous method has been developed for assessing diastereoselectivity.
Synthesis of 3-Carbonyl Trisubstituted Furans via Pd-Catalyzed Aerobic Cycloisomerization Reaction: Development and Mechanistic Studies
Barboza, Amanda A.,Neto, Attilio Chiavegatti,Rosset, Isac G.,Jardim, Guilherme A. M.,Ferreira, Marco A. B.
, p. 3923 - 3942 (2021/04/02)
Herein, we report the synthesis of 3-carbonyl-trisubstituted furans via Pd-catalyzed oxidative cycloisomerization reactions of 2-alkenyl-1,3-dicarbonyl scaffolds, using molecular oxygen as the sole oxidant to regenerate active palladium catalytic species, featuring good functional tolerance and mild reaction conditions. Deep investigation of intermediates and transition states of the reaction mechanism were conducted via experimental and DFT studies, providing a detailed mechanistical profile. The new developed methodology presents a greener alternative to Wacker-type cycloisomerizations and avoids the use of stoichiometric amounts of oxidants and strong acid additives.
Catalytic Asymmetric Homologation of Ketones with α-Alkyl α-Diazo Esters
Tan, Fei,Pu, Maoping,He, Jun,Li, Jinzhao,Yang, Jian,Dong, Shunxi,Liu, Xiaohua,Wu, Yun-Dong,Feng, Xiaoming
supporting information, p. 2394 - 2402 (2021/02/16)
The homologation of ketones with diazo compounds is a useful strategy to synthesize one-carbon chain-extended acyclic ketones or ring-expanded cyclic ketones. However, the asymmetric homologation of acyclic ketones with α-diazo esters remains a challenge due to the lower reactivity and complicated selectivity. Herein, we report the enantioselective catalytic homologation of acetophenone and related derivatives with α-alkyl α-diazo esters utilizing a chiral scandium(III) N,N′-dioxide as the Lewis acid catalyst. This reaction supplies a highly chemo-, regio-, and enantioselective pathway for the synthesis of optically active β-keto esters with an all-carbon quaternary center through highly selective alkyl-group migration of the ketones. Moreover, the ring expansion of cyclic ketones was accomplished under slightly modified conditions, affording a series of enantioenriched cyclic β-keto esters. Density functional theory calculations have been carried out to elucidate the reaction pathway and possible working models that can explain the observed regio- and enantioselectivity.
Nickel-Catalyzed Alkyl-Alkyl Cross-Electrophile Coupling Reaction of 1,3-Dimesylates for the Synthesis of Alkylcyclopropanes
Chen, Pan-Pan,Hong, Xin,Jarvo, Elizabeth R.,McGinnis, Tristan M.,Sanford, Amberly B.,Thane, Taylor A.
supporting information, (2020/03/23)
Cross-electrophile coupling reactions of two Csp3-X bonds remain challenging. Herein we report an intramolecular nickel-catalyzed cross-electrophile coupling reaction of 1,3-diol derivatives. Notably, this transformation is utilized to synthesize a range of mono- and 1,2-disubstituted alkylcyclopropanes, including those derived from terpenes, steroids, and aldol products. Additionally, enantioenriched cyclopropanes are synthesized from the products of proline-catalyzed and Evans aldol reactions. A procedure for direct transformation of 1,3-diols to cyclopropanes is also described. Calculations and experimental data are consistent with a nickel-catalyzed mechanism that begins with stereoablative oxidative addition at the secondary center.
Atroposelective Synthesis of Axially Chiral N-Arylpyrroles by Chiral-at-Rhodium Catalysis
Chen, Shuming,Han, Feng,Houk, K. N.,Ivlev, Sergei,Meggers, Eric,Xie, Xiulan,Ye, Chen-Xi
supporting information, p. 13552 - 13556 (2020/06/05)
A transformation of fluxional into configurationally stable axially chiral N-arylpyrroles was achieved with a highly atroposelective electrophilic aromatic substitution catalyzed by a chiral-at-metal rhodium Lewis acid. Specifically, N-arylpyrroles were alkylated with N-acryloyl-1H-pyrazole electrophiles in up to 93 percent yield and with up to >99.5 percent ee, and follow-up conversions reveal the synthetic utility of this new method. DFT calculations elucidate the origins of the observed excellent atroposelectivity.
Electrochemical oxidative cyclization of olefinic carbonyls with diselenides
Guan, Zhipeng,Wang, Yunkun,Wang, Huamin,Huang, Yange,Wang, Siyuan,Tang, Hongding,Zhang, Heng,Lei, Aiwen
supporting information, p. 4976 - 4980 (2019/09/30)
The tandem cyclization of olefinic carbonyls with easily accessible diselenides facilitated by electrochemical oxidation has been successfully developed, which provides an environmentally friendly method for the construction of C-Se and C-O bonds simultaneously. A series of seleno dihydrofurans and seleno oxazolines, bearing fragile heterocycles, subtle C-I bonds and supernumerary vinyl groups, were forged using this elegant chelation strategy. Neither metal catalysts nor external chemical oxidants are required to promote this transformation.
Catalytic C?C Bond Formation Using a Simple Nickel Precatalyst System: Base- and Activator-Free Direct C-Allylation by Alcohols and Amines
Sweeney, Joseph B.,Ball, Anthony K.,Smith, Luke J.
supporting information, p. 7354 - 7357 (2018/05/03)
A “totally catalytic” nickel(0)-mediated method for base-free direct alkylation of allyl alcohols and allyl amines is reported. The reaction is selective for monoallylation, uses an inexpensive NiII precatalyst system, and requires no activating reagents to be present.
