Catalytic Palladium-Mediated Bisdiene Carbocyclizations:  Bisdiene to Enediene Cycloisomerizations

Abstract

The palladium-catalyzed cycloisomerization of acyclic bisdienes to cyclized enedienes defines a novel strategy for the stereoselective cyclization of certain unsymmetric bisdiene substrates to form functionalized five- and six-membered rings. The full details of our investigation into this novel cycloisomerization, including our observations on substrate requirements, stereoselectivity, the influence of the catalyst precursor, and some mechanistic insights drawn from deuterium labeling studies, are discussed.

On the Nature of the Catalytic Palladium-Mediated Elimination of Allylic Carbonates and Acetates To Form 1,3-Dienes

“…We became interested in the details of this reaction as a result of other studies in our labs and prepared allylic carbonate 1a and two isotopically labeled derivatives (i.e., 1b and 1c ). Palladium-catalyzed elimination of 1a under the Tsuji conditions (0.10 equiv of [Pd(OAc) 2 /PBu 3 ], THF, 25 °C, 12 h) affords 4-methyl-2,4-heptadiene ( 2 ) as a 1.3:1 mixture of isomers about the trisubstituted double bond.…”

Regio- and Stereoselective Monoepoxidation of Dienes using Methyltrioxorhenium: Synthesis of Allylic Epoxides

“…Following the acylation procedure above, ( E )-5-methylhexa-2,4-dien-1-ol 49 (180 mg, 1.6 mmol) was treated with acetic anhydride (0.18 mL, 1.9 mmol) and pyridine (0.22 mL, 2.4 mmol) in CH 2 Cl 2 (10 mL) at rt for 12 h. Chromatographic purification of the crude product using 10–20% EtOAc/hexanes as eluent afforded 31 ( 50 ) (210 mg, 85%) as a clear oil. TLC: R f ≈ 0.6 (10% EtOAc/hexanes).…”

Controlling Mode Selectivity in Palladium-Catalyzed Bisdiene Carbocyclizations: Optimizing for Cyclization-Trapping over Cycloisomerization

“…The proton is presumably supplied by the trapping reagent to generate intermediates such as 6 and/or 7 . The two differ in that 6 is cationic and complexed with ligand (L), whereas 7 is neutral and associated with counterion X, not L. We reported that cycloisomerization products likely arise via deprotonation of 6 or 7 , , and thus, the tendencies of 6 and 7 to preferentially add nucleophile or deprotonate is potentially a key to controlling the cyclization mode.

1 A mechanistic model, showing potential roles for the counterion (X, catalyst precursor), ligand (L), and trapping agent (R 2 OH).

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“…We are interested in palladium-catalyzed reactions of 1,3-dienes, , specifically, the intramolecular reactions of acyclic substrates containing two 1,3-diene moieties within their structure (i.e., bisdienes). Two of the reaction modes exhibited by such substrates, (i) cyclization with trapping by a pronucleophile and (ii) cycloisomerization to a cyclized enediene, are particularly relevant to the present study.…”