Dataset Information

Efficient Synthesis of ?-CF3/SCF3-Substituted Carbonyls via Copper-Catalyzed Electrophilic Ring-Opening Cross-Coupling of Cyclopropanols.

ABSTRACT: The first copper-catalyzed ring-opening electrophilic trifluoromethylation and trifluoromethylthiolation of cyclopropanols to form Csp3-CF3 and Csp3-SCF3 bonds have been realized. These transformations are efficient for the synthesis of ?-CF3- and ?-SCF3-substituted carbonyl compounds that are otherwise challenging to access. The reaction conditions are mild and tolerate a wide range of functional groups. Application to a concise synthesis of LY2409021, a glucagon receptor antagonist that is used in clinical trials for type 2 diabetes mellitus, is reported as well.

SUBMITTER: Li Y

PROVIDER: S-EPMC4690544 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Efficient Synthesis of β-CF3/SCF3-Substituted Carbonyls via Copper-Catalyzed Electrophilic Ring-Opening Cross-Coupling of Cyclopropanols.

Li Yong Y Ye Zhishi Z Bellman Tabitha M TM Chi Teng T Dai Mingji M

Organic letters 20150417 9

The first copper-catalyzed ring-opening electrophilic trifluoromethylation and trifluoromethylthiolation of cyclopropanols to form Csp3-CF3 and Csp3-SCF3 bonds have been realized. These transformations are efficient for the synthesis of β-CF3- and β-SCF3-substituted carbonyl compounds that are otherwise challenging to access. The reaction conditions are mild and tolerate a wide range of functional groups. Application to a concise synthesis of LY2409021, a glucagon receptor antagonist that is use ...[more]

PMID: 25885795

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Project description:Investigation of complex molecular systems depends on our ability to correlate physical measurements with molecular structure. Interpretation of studies that rely on synthetic polymers is generally limited by their heterogeneity; i.e., there is variation in the number and arrangement of the monomeric building blocks that have been incorporated. Superior physics and biology can be performed with materials and tools that exert precise control over the sequence and spacing of functional groups. An interest in functional ligands combined with a desire to control the orientation and stereochemistry of monomer incorporation led to the design of new substrates for ruthenium-catalyzed ring-opening metathesis polymerization (ROMP). We discovered that ROMP of cyclobutene-1-carboxamides provides uniform and translationally invariant polymers. In contrast, cyclobutene-1-carboxylate esters ring open upon treatment with ruthenium catalyst, but they are stable to homopolymerization. However, in the presence of cyclohexene monomers, they undergo alternating ROMP (AROMP or alt-ROMP) to give copolymers with a precisely controlled sequence. The alternating cyclobutene ester/cyclohexene pair provides access to functional group spacing larger than is possible with homopolymers. This can be desirable; for example, polymers with a regular 8-10 Å backbone spacing of cationic charge and with between four and eight cationic groups were the most effective antibacterial agents and had low cytotoxicity. Moreover, the AROMP chemistry allows alternation of two functional moieties: one associated with the cyclohexene and one attached to the cyclobutene. In the case of antibacterial copolymers, the alternating chemistry allowed variation of hydrophobicity via the cyclohexene while maintaining a constant cation spacing through the cyclobutene. In the case of copolymers that bear donor and acceptor groups, strict alternation of the groups increased intrachain charge transfer. Like cyclobutene-1-carboxylate esters, bicyclo[4.2.0]oct-7-ene-7-carboxylate esters ring open upon treatment with ruthenium catalyst and undergo ring opening cross-metathesis with cyclohexene to form alternating copolymers. The corresponding bicyclo[4.2.0]oct-7-ene-7-carboxyamides isomerize to the bicyclo[4.2.0]oct-1(8)-ene-8-carboxamides before they can ring open. However, the isomerized amides undergo ruthenium-catalyzed ring opening metathesis and rapidly AROMP with cyclohexene. Our alternating copolymer systems allow functionality to be placed along a polymer chain with larger than typical spacing. We have used both homopolymers and alternating copolymers for defining the functional group density required for targeting a cell surface and for the exploration of functional group positioning within a polymer chain. These polymer systems provide access to new materials with previously inaccessible types of nanoscale structures.

Dataset Information

Efficient Synthesis of ?-CF3/SCF3-Substituted Carbonyls via Copper-Catalyzed Electrophilic Ring-Opening Cross-Coupling of Cyclopropanols.

Publications

Efficient Synthesis of β-CF3/SCF3-Substituted Carbonyls via Copper-Catalyzed Electrophilic Ring-Opening Cross-Coupling of Cyclopropanols.

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