Diastereoselective Synthesis of Highly Substituted Five-Membered-Ring Oxygen Heterocycles by Zirconocene-Mediated C-C Coupling Reactions

Abstract

As homoenolate equivalents, zirconocene-1-aza-1,3-diene complexes were used for the first time in stereoselective synthesis. By insertion of an unsymmetrical ketone in the Zr-C σ bond, sterically demanding trisubstituted dihydro- and tetrahydrofuran derivatives were prepared in good overall yields and with high diastereoselectivities (see below).

Rearrangements and Stereomutations of Metallacycles Derived from Allenes and Imidozirconium Complexes

“…The MAD moiety is strongly bent with respect to the Zr−N−C plane, but Zr−C11 and Zr−C12 bond distances of 2.65 and 2.54 Å, respectively, reveal that 18 is best described as a metallacyclopentene, rather than as an η 4 -MAD complex. This observation has been made in other reports from the literature. − The strain of the bridgehead double bond is evident in the reduced torsion angle about that bond (157°). When crystals of 18a were redissolved in C 6 D 6 , the same 3:1 mixture of 18a and 18b was observed by 1 H NMR spectroscopy.…”

Ancillary Ligand and Ketone Substituent Effects on the Rate of Ketone Insertion into Zr−C Bonds of Zirconocene−1-Aza-1,3-diene Complexes

“…Evidently, the electropositive zirconium outweighs the influence of nitrogen, and the zirconocene−1-aza-1,3-diene complexes (or azazirconacyclopentenes) can be viewed as homoenolate equivalents. Such an umpolung strategy has been successfully used in the synthesis of various N-substituted pyrroles and oxygen-containing heterocycles . However, broader applications of this synthetic methodology are hampered by the limited electrophiles that are available for insertion into Zr−C bonds of the zirconacycles; only isocyanides and ketones , have been identified as viable substrates for insertion.…”

“…Such an umpolung strategy has been successfully used in the synthesis of various N-substituted pyrroles and oxygen-containing heterocycles . However, broader applications of this synthetic methodology are hampered by the limited electrophiles that are available for insertion into Zr−C bonds of the zirconacycles; only isocyanides and ketones , have been identified as viable substrates for insertion.…”