Sequential Staudinger Ketene−Imine Cycloaddition, RCM Approach to Highly Rigid Macrocrocyclic Bisazetidinones

Abstract

An efficient approach to highly rigid macrocyclic bisazetidinones with interesting structural feature was achieved via sequential Staudinger ketene-imine cycloaddition of o-allyloxyphenoxyketene and bis-arylidenediamines followed by RCM. The ketene-imine cycloaddition afforded the corresponding bis-o-allyloxyphenoxyazetidinones as the cis-cis diastereomers, exclusively obtained as a mixture of cis-syn-cis and cis-anti-cis. RCM of the latter using Grubbs' catalysts afforded good yields of the corresponding novel macrocyclic bisazetidinones. The cis-anti-cis bisazetidinones are readily identified by (1)H NMR using Eu(hfc)(3) chiral shift reagent. (1)H NMR indicated the high shielding effect of the aryl substituents on one of the ortho-H's of the condensed phenylene ring, and VT (1)H NMR indicates the highly restricted rotation of the aryl groups, thus offering a highly rigid system.

Variable-Sized bis(4-spiro-fused-β-lactam)-Based Unsaturated Macrocycles: Synthesis and Characterization

“…During our recent interest in the construction of new types of azacrown ethers, − a wide spectrum of macrocycles composed of two β-lactam sites, which are covalently linked with various organic and organometallic linkers through their 1,3-,1,4-, 3,4-, and 1,3,4-positions, have been achieved and reported in literature . However, examples of macrocycles incorporating bis-4-spiro-β-lactams moieties in their backbone core structures are still limited.…”

Sequential Diimination, Staudinger [2 + 2] Ketene–Imine Cycloaddition, and Ring-Closing Metathesis (RCM) Reactions: In Route to Bis(4-spiro-fused-β-lactams)-Based Macrocycles

“…In recent years, our research group and others have emerged this synthetic strategy in the synthesis of a collection of unsaturated azacrown ethers (Figure ). − The target macrocycles consist of two β-lactams units that are covalently linked through their 1,3-, 1,4-, 3,4-, and 1,3,4-positions with different organic/organometallic bridges such as alkyl, ferrocene, or variable length ethyelene glycolyl linkers. , All reported structures are composed of four diasteriomeric hydrogens, that is, two diastereomeric hydrogens per each β-Lactam unit, and to the best of our knowledge, there have been no reports describing the synthesis of bis-spiro-fused β-lactams-based azacrown ethers.…”

“…Yield and H a Chemical Shifts of syn/anti Azetadinone Rings ofDienes 4,5, and 6 and Macrocycles 7,8,and 9 …”

Sequential Staudinger ketene–imine cycloaddition, RCM approach to polycyclic macrocyclic bisazetidinones

“…1). 2,3 Subsequently the same procedure has then been applied for the synthesis of macrocyclic bisazetidinone polyethers 3 incorporating ferrocene moiety inside the macrocycles. 4 Moreover, bis-b-lactams 4, 5 were macrocyclized via M-C or M-N (M = Pd or Pt) 5 bonds.…”