Ruthenium-catalyzed two-component addition to form 1,3-dienes: optimization, scope, applications, and mechanism.
A two component coupling of an allene and an activated olefin to form 1,3-dienes has been developed. The requisite allenes are synthesized either from terminal alkynes by a one carbon homologation using copper(I) iodide, paraformaldehyde, and diisopropylamine, via an ortho ester-Claisen rearrangement from a propargylic alcohol, or via a Wittig type reaction on a ketene generated in situ from an acid chloride. Mono- through tetrasubstituted allenes could be synthesized by these methods. Either cyclopentadienylruthenium(II) cyclooctadiene chloride or cyclopentadienylruthenium(II) trisacetonitrile hexafluorophosphate catalyze the addition reaction. When the former catalyst is employed, an alkyne activator is added to help generate the active catalyst. Through systematic optimization studies, a range of conditions was examined. The optimal conditions consisted of the use of cerium(III) trichloride heptahydrate as a cocatalyst in dimethylformamide as a solvent at 60 degrees C. The reaction was found to be chemoselective, and a wide range of functionality was tolerated, including esters, alcohols, nitriles, and amides. When substituted allenes are used, good selectivity can be obtained with proper substitution. A mechanism involving a ruthenacycle is proposed to account for the selectivity or lack thereof in product formation. With disubstituted allenes, selectivity is obtained when beta-hydrogen elimination is favored from a specific site. In tri- and tetrasubstituted allenes, steric issues concerning the C-C bond forming event appear to be the dominant factor in determining product formation. This process represents a highly atom-economical synthesis of 1,3-dienes in a controlled fashion. The utility of the 1,3-diene products was demonstrated by their use in Diels-Alder reactions to form a variety of cyclic systems including polycyclic structures. This sequence represents a convergent atom economic method for ring formation by a series of simple additions.
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BM
Department of Chemistry, Stanford University, Stanford, California 94305, USA.
Pinkerton
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AB
Seidel
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M
D000466:Alkadienes / Q000138:chemical synthesis* / Q000737:chemistry; D000475:Alkenes / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D009942:Organometallic Compounds / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*
D000466:Alkadienes; D000475:Alkenes; D009942:Organometallic Compounds; C025947:propadiene; D012428:Ruthenium