69052-92-2Relevant academic research and scientific papers
Iterative synthesis of alkenes by insertion of lithiated epoxides into boronic esters
Bojaryn, Kevin,Fritsch, Stefan,Hirschhaüser, Christoph
supporting information, p. 2218 - 2222 (2019/04/10)
The insertion of lithiated epoxides into boronic esters followed by thermal syn-elimination provides a stereospecific entry to alkenes. This process avoids transition metals and is amenable to iteration to provide higher substitution patterns.
Tetrasubstituted olefin synthesis via Pd-catalyzed addition of arylboronic acids to internal alkynes using O2 as an oxidant
Zhou, Chengxiang,Larock, Richard C.
, p. 3184 - 3191 (2007/10/03)
The Pd(II)-catalyzed reaction of arylboronic acids and internal alkynes provides a convenient route to a wide variety of tetrasubstituted olefins. The reaction is conducted in DMSO using molecular O2 as an oxidant in the absence of any base. The reaction involves the cis addition of two aryl groups from the arylboronic acid to opposite ends of the triple bond of the internal alkyne. The synthesis tolerates a wide variety of functional groups, including alcohol, aldehyde, ester, TMS, and acetal groups. Electron-rich dialkylacetylenes, such as 4-octyne, provide highly substituted 1,3-dienes in moderate yields. The very mild O2/DMSO conditions also afford good to excellent yields of biaryls by the homocoupling of arylboronic acids.
Regio- and stereoselective route to tetrasubstituted olefins by the palladium-catalyzed three-component coupling of aryl iodides, internal alkynes, and arylboronic acids
Zhou, Chengxiang,Larock, Richard C.
, p. 3765 - 3777 (2007/10/03)
The Pd-catalyzed three-component coupling of readily available aryl iodides, internal alkynes, and arylboronic acids provides a convenient, one-step, regio- and stereoselective route to tetrasubstituted olefins in good to excellent yields, although electron-poor aryl iodides and dialkylalkynes normally afford only low yields under our standard reaction conditions. The proper combination of substrates and reaction conditions is important for high yields. The presence of water generally substantially increases the yields of the desired tetrasubstituted olefins. The reaction involves cis-addition of the aryl group from the aryl iodide to the less hindered or more electron-rich end of the alkyne, while the aryl group from the arylboronic acid adds to the other end. A modified, room-temperature procedure has also been successfully developed, which works very well for some substrates. Tamoxifen and its derivatives are synthesized in a concise, regio- and stereoselective manner by applying our synthetic protocol.
Design and synthesis of acyclic triaryl (Z)-olefins: A novel class of cyclooxygenase-2 (COX-2) inhibitors
Uddin, Md. Jashim,Rao, P.N. Praveen,Knaus, Edward E.
, p. 5929 - 5940 (2007/10/03)
A group of acyclic 2-alkyl-1,1-diphenyl-2-(4-methylsulfonylphenyl)ethenes was designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1 and COX-2 isozyme inhibition structure-activity studies identified 1,1-diphenyl-2-(4-methylsulfonylphenyl)hex-1-ene as a highly potent (IC 50 = 0.014 μM), and an extremely selective [COX-2 selectivity index (SI) > 7142], COX-2 inhibitor that showed superior anti-inflammatory (AI) activity (ID50 = 2.5 mg/kg) relative to celecoxib (ID 50 = 10.8 mg/kg). This initial study was extended to include the design of a structurally related group of acyclic triaryl (Z)-olefins possessing an acetoxy (OAc) substituent at the para-position of the C-1 phenyl ring that is cis to a C-2 4-methylsulfonylphenyl substituent. COX-1 and COX-2 inhibition studies showed that (Z)-1-(4-acetoxyphenyl)-1-phenyl-2-(4-methylsulfonylphenyl) but-1-ene [(Z)-13b] is a potent (COX-1 IC50 = 2.4 μM; COX-2 IC50 = 0.03 μM), and selective (COX-2 SI = 81), COX-2 inhibitor which is a potent AI agent (ID50 = 4.1 mg/kg) with equipotent analgesic activity to celecoxib. A molecular modeling (docking) study showed that the SO2Me substituent of (Z)-13b inserts deep inside the 2°-pocket of the COX-2 active site, where one of the O-atoms of SO 2 group undergoes a H-bonding interaction with Phe518. The p-OAc substituent on the C-1 phenyl ring is oriented in a hydrophobic pocket comprised of Met522, Gly526, Trp387, Tyr 348, and Tyr385, and the C-2 ethyl substituent is oriented towards the mouth of the COX-2 channel in the vicinity of amino acid residues Arg120, Leu531, and Val349. Structure-activity data acquired indicate that a (Z)-olefin having cis C-1 4-acetoxyphenyl (phenyl) and C-2 4-methylsulfonylphenyl substituents, and a C-1 phenyl substituent in conjunction with either a C-2 hydrogen or short alkyl substituent provides a novel template to design acyclic olefinic COX-2 inhibitors that, like aspirin, have the potential to acetylate COX-2.
