Tethered Carbonyl Group Research Articles

Rhodium-catalyzed synthesis of multi-substituted furans from N-sulfonyl-1,2,3-triazoles bearing a tethered carbonyl group

The efficient synthesis of highly functionalized furan derivatives from 1-sulfonyl-1,2,3-triazoles with a pendent carbonyl group is reported. The process involves an intramolecular trapping of α-imino carbene and subsequent aromatization.

ChemInform Abstract: Rhodium(I)‐Catalyzed Cyclization of Allenynes with a Carbonyl Group Through Unusual Insertion of a C=O Bond into a Rhodacycle Intermediate.

AbstractNovel Rh‐catalyzed cyclizations of allenynes with a tethered carbonyl group are presented.

Rhodium(I)‐Catalyzed Cyclization of Allenynes with a Carbonyl Group through Unusual Insertion of a CO Bond into a Rhodacycle Intermediate

Rhodium(I)-catalyzed cyclization of allenynes with a tethered carbonyl group was investigated. An unusual insertion of a CO bond into the C(sp(2) )-rhodium bond of a rhodacycle intermediate occurs via a highly strained transition state. Direct reductive elimination from the obtained rhodacyle intermediate proceeds to give a tricyclic product containing an 8-oxabicyclo[3.2.1]octane skeleton, while β-hydride elimination from the same intermediate gives products that contain fused five- and seven-membered rings in high yields.

Development of a Practical Synthesis of Toll-like Receptor Agonist PF-4171455: 4-Amino-1-benzyl-6-trifluoromethyl-1,3-dihydroimidazo [4,5-c] pyridin-2-one

The development and implementation of a scalable process for the manufacture of the Toll-like receptor (TLR7) agonist PF-4171455 (1) is described. Initial routes used to synthesise 1 in milligram quantities were unsuitable for large-scale synthesis to provide bulk material. As part of the transfer between Medicinal Chemistry and Research-API, collaboration provided a fit for purpose route for the kilo-scale synthesis of 1. Key aspects of the synthesis included (i) a safe and practical synthesis of a key nitropyridone intermediate 7 over four steps, (ii) a sequential regioselective chlorination to selectively functionalise 7 and (iii) use of a carbamate as a tethered carbonyl group, allowing an efficient regiospecific synthesis of 1.

Ru3(CO)12‐Catalyzed Intramolecular Allylic Transfer Reaction of Tethered Carbonyl Group and Allylic Acetate Moiety.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Ru 3(CO) 12-catalyzed intramolecular allylic transfer reaction of tethered carbonyl group and allylic acetate moiety

A ruthenium catalyzed intramolecular allylic transfer reaction of allylic acetates containing aldehydes or ketones to form cis-homoallylic cyclopentanols and cyclohexanols as a major component is described. The use of Ru 3(CO) 12 (1 mol %) to promote reaction results in a convenient procedure for intramolecular allylation of carbonyl functionalities.

Further studies on Ni(0)-catalyzed cyclization of a branched 1,3-diene and tethered aldehyde via oxa-nickelacycle intermediate

The reactivity of oxa-nickelacycles 7, generated by the reaction of a branched 1,3-diene and tethered carbonyl group with a Ni(0) complex, was investigated in detail. It was found that oxa-nickelacycles 7 are relatively stable and that β-hydride elimination from 7 occurred at a high temperature, producing the cyclized dienes 51 and/or 52 in good yields. This Ni(0)-catalyzed cyclization via β-hydride elimination from oxa-nickelacycles tolerated various substituents on the diene moiety and could be applied to a five- to seven-membered ring construction. Next, transmetalation of oxa-nickelacycle 7 with various organometallic reagents was investigated. It was found that the tandem reaction, i.e. cyclization of 6 followed by transmetalation of the resulting oxa-nickelacycle 7, proceeded smoothly, giving 53 and/or 54 in good yields. In addition, the catalytic cycle in this transmetalation reaction was also established.

A New Method for the Preparation of 2‐Thio Substituted Furans by Methylsulfanylation of γ‐Dithiane Carbonyl Compounds.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A new method for the preparation of 2-thio substituted furans by methylsulfanylation of gamma-dithiane carbonyl compounds.

Several related methods for the preparation of differentially substituted 2-thiofurans are described. The general procedure involves the formation of a thionium ion from a gamma-dithianyl substituted carbonyl compound followed by cyclization of this reactive intermediate onto the tethered carbonyl group. Two methods for thionium ion generation were explored. One of these involved an acid-catalyzed reaction of beta-ketenedithioacetals, prepared from the condensation of 2,2-bis(methylsulfanyl)acetaldehyde with a variety of ketones. Cyclization followed by loss of methane thiol gave 2-thiofurans 17, 18 and 23, 24 in 70-90% yield. Attempts to prepare 5-heteroatom substituted 2-thiofurans from the corresponding beta-ketenedithioacetal amides or esters were unsuccessful, leading to 1,2-thio rearranged products. A more successful route involved the reaction of beta-acetoxy-gamma-thianyl carbonyl compounds with dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF). Treatment of the dithiane with this reagent resulted in the smooth generation of a thionium ion. Cyclization followed by loss of acetic acid afforded thiofurans 17, 18, 23, 47-49, 51, and 61-64 in 40-100% yield. The N-butenyl substituted thioamido furan furnished a rearranged hexahydropyrroloquinolin-2-one in high yield when heated at 110 degrees C.

ChemInform Abstract: Nickel‐Catalyzed Cyclization of 1,3‐Diene with a Tethered Carbonyl Group and Its Application to Synthesis of Natural Products

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ニッケル触媒を用いる１，３‐ジエンとカルボニル基との立体選択的環化反応の開発と有機合成への応用

A nickel-promoted intramolecular cyclization of 1, 3-diene with the tethered carbonyl group was developed using the catalyst generated by reduction of Ni(acac)2 with DIBAL-H in the presence of PPh3. The reaction course of this cyclization can be accounted for by two possible mechanisms. In one mechanism, a nickel hydride complex plays a key role and the cyclization proceeds via πallylnickel intermediate. In the other mechanism, a zerovalent nickel complex is the active species and the cyclization proceeds via the nickelacycle intermediate. These mechanistic considerations led to find two nickel (0) -catalyzed cyclizations of 1, 3-diene and the tethered aldehyde, in which the five- to seven-membered ring products were produced in a regio- and stereoselective manner via, π-allylnickel intermediate (Type I cyclization) or via transmetalation process of nickelacycle intermediate with iBu2Al-acac (Type II cyclization). We also succeeded in applying these cyclizations to the syntheses of (-) -elaeokanine C and (+)-prostaglandin F2α, and in demonstrating the catalytic asymmetric cyclization using Type I cyclization.

Carbohydrate to Carbocycle Conversions via Intramolecular Propargylation with Et2Zn/Pd(0)/Yb(OTf)3

Carbohydrate-derived propargylic esters react with Et2Zn and catalytic Pd(0), in the presence of a Lewis acid, to generate nucleophilic allenyl metal species capable of intramolecular addition to a tethered carbonyl group. This results in the formation of enantiomerically pure functionalized cyclopentanes with high stereoselectivity and in preparatively useful yields. A high preference is observed for a trans relationship between the alkynyl and OH groups in the cyclopentane products, implying that the cyclization proceeds through open transition states.

ChemInform Abstract: Further Studies on Nickel‐Promoted or ‐Catalyzed Cyclization of 1,3‐Diene and a Tethered Carbonyl Group.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Further Studies on Nickel-Promoted or -Catalyzed Cyclization of 1,3-Diene and a Tethered Carbonyl Group

A nickel-promoted intramolecular cyclization of 1,3-diene with the tethered carbonyl group was developed using the catalyst generated by reduction of Ni(acac)2 with DIBAL-H in the presence of PPh3. It was found that the addition of 1,3-CHD to the reaction mixture affected the regiochemistry of olefin on the side chain of the cyclized product. The reaction course of this cyclization can be accounted for by two possible mechanisms. In one mechanism, a nickel hydride complex plays a key role and the cyclization proceeds via π-allylnickel intermediate. In the other mechanism, a zero-valent nickel complex is the active species and the cyclization proceeds via nickelacycle intermediates. These mechanistic considerations led to finding two nickel(0)-catalyzed cyclizations of 1,3-diene and the tethered aldehyde, in which the five- to seven-membered ring products were produced in a regio- and stereoselective manner via π-allylnickel intermediate or via a transmetalation process of nickelacycle intermediates with iBu2-ALAC.