Copper-Promoted Coupling Research Articles

Asymmetric Synthesis of Methoxylated Ether Lipids: Total Synthesis of n-3 Polyunsaturated Docosahexaenoic Acid-Like Methoxylated Ether Lipid.

The first total synthesis of a docosahexaenoic acid (DHA)-like methoxylated ether lipid (MEL) is reported. This compound constitutes an all-cis methylene skipped hexaene framework identical to that present in DHA, the well-known omega-3 polyunsaturated fatty acid. The polyene C22 hydrocarbon chain, bearing a methoxyl group in the 2-position and R-configuration at the resulting chiral center, is attached by an ether linkage to the pro-S hydroxymethyl group (sn-1 position) of a glycerol backbone. The asymmetric synthesis is highly convergent and based on the polyacetylene approach involving iterative copper-promoted coupling reactions of propargyl bromides with terminal alkynes and semihydrogenation of the resulting hexayne. Starting from enantiopure R-solketal and racemic epichlorohydrin, the targeted MEL was accomplished in an 8.2% yield over eight steps (longest linear sequence) involving an enantio- and diastereopure glyceryl glycidyl ether key C6-building blocks from which the polyynes were constructed.

Copper-Promoted Coupling of Propiophenones and Arylhydrazines for the Synthesis of 1,3-Diarylpyrazoles

Synthesis of 1,3-diarylpyrazoles from commercial substrates and/or simple transformations is still underrated. In this report, we have developed a method for copper-promoted coupling of propiophenones and arylhydrazines. The reactions afforded substituted pyrazoles in the presence of TEMPO oxidant, acetic acid additive, and DMF solvent. A number of functionalities were compatible with reaction conditions, including halogens, methoxy, trifluoromethyl, and nitro groups. An indazole could be obtained if an electron-poor propiophenone was used.

ChemInform Abstract: Alkoxydienes via Copper‐Promoted Couplings: Utilizing an Alkyne Effect.

AbstractBy screening of a variety of phosphines, alkenes, and alkynes as ligands for the copper‐promoted coupling of boronate (Ib) with alcohol (II), 3‐hexyne (HXY) is found to be the best ligand.

Allyl Vinyl Ethers by Copper-Promoted Coupling of Vinyl Boronates to Alcohols

A cross-coupling methodology for the synthesis of allyl vinyl ethers from vinyl boronates and allylic alcohols mediated by Cu(OAc)2 is reported and a plausible reaction mechanism is presented. A variety of functional groups is tolerated, such as acetals, esters or sulfides.

Copper-Promoted Coupling of Vinyl Boronates and Alcohols: A Mild Synthesis of Allyl Vinyl Ethers

A copper-promoted coupling of vinyl pinacol boronate esters and alcohols for the synthesis of enol ethers is reported. The reaction occurs in 50-99% yield and is compatible with a variety of functional groups. Cupric acetate is the copper source, and triethylamine buffer is used to prevent protodeboration; the reaction occurs at room temperature. In addition to excellent chemoselectivity, the reaction is stereospecific.

Synthesis of 2,2′,6-Trisubstituted and 2,2′,6,6′-Tetrasubstituted Diaryl Sulfides and Diaryl Sulfones by Copper-Promoted Coupling and/or Ortholithiation

Stoichiometric copper(I) iodide, in the presence of potassium carbonate and ethylene glycol, promotes the coupling of even highly sterically encumbered 2,6-disubstituted thiophenols and aryl iodides to form hindered diarylsulfides. Hindered diarylsulfones may be made in a complementary fashion by ortholithiation of the sulfone oxidation products of less hindered diarylsulfides.

Operationally Simple Copper-Promoted Coupling of Terminal Alkynes with Benzyl Halides

Benzyl chlorides and bromides are shown to undergo copper-promoted coupling with a variety of terminal alkynes including, for the first time, electron-poor acetylenes such as methyl propiolate. The reaction permits easy access to a wide range of (functionalized) benzyl-substituted propiolates (as well as several related alkynes) from commercially available benzyl halides. These products should in turn function as useful building blocks for the synthesis of previously inaccessible (functionalized) benzyl-substituted heterocycles.