Substituted cyclopentanes or tetrahydrofurans bearing two vinyl groups have been investigated in cross‐metathesis reactions to explore chemodiscrimination of the two olefin bonds. The syntheses consisted of ring opening of constrained unsaturated β‐lactams or bicyclic β‐amino acids, followed by cross‐metathesis to test the chemodifferentiation of the divinyl‐substituted azetidinones or β‐amino esters in the presence of various ruthenium‐based catalysts.

A stereocontrolled approach to highly functionalized 3,4‐disubstituted azetidin‐2‐ones and β2, 3‐amino acid derivatives from readily available cycloalkadienes was achieved. The syntheses involved 1,3‐dipolar cycloaddition of chlorosulfonyl isocyanate, followed by ring‐opening metathesis of the unsaturated bi‐ or tricyclic β‐lactams, and cross‐metathesis of the resulting divinyl‐substituted azetidinones. The substituted lactams were subsequently transformed by heteroring‐opening into the corresponding functionalized acyclic β2, 3‐amino acid derivatives.

Through the ring‐opening metathesis of norbornene or oxanorbornene β‐amino acids with ethylene in the presence of certain Ru catalysts, a facile and convenient stereocontrolled one‐step method was devised for the preparation of divinylated cispentacins and oxacyclic cispentacin stereoisomers with four chiral centres. The products are interesting scaffolds for peptide chemistry and for the synthesis of novel functionalised materials through olefinic bond transformations. The ring‐opening metathesis proceeds without affecting the chiral centres of the starting molecules, so that their stereochemistry was conserved and determines the configuration of the chiral centres in the products.

Ring-opening metathesis (ROM) of various unsaturated, constrained bicyclic ring systems has been investigated with the use of commercial ruthenium-based catalysts. Starting from various cyclodienes, the corresponding derived bicyclic lactone, lactam, and isoxazoline derivatives were submitted to ROM under ethenolysis. These functionalized, strained bicyclic systems afforded novel highly-functionalized diolefinated heterocyclic scaffolds in ROM reactions with stereocontrol, through the conservation of the configuration of the stereogenic centers of the starting compounds.

Because of their biological relevance, cyclic β-amino acids have generated increasing interest and had significant impact in drug research over the past two decades. Their preparation and further functionalization towards new types of molecular entities have received large interest in synthetic and medicinal chemistry. Various types of metathesis reactions, such as ring-opening (ROM), ring-closing (RCM), or cross metathesis (CM) are used widely for access to either alicyclic β-amino acids or other densely functionalized derivatives of this group of compounds. This account intends to provide an insight into the most relevant synthetic routes to this class of derivatives with the application of metathesis reactions. The review focuses on the presentation of selective and stereocontrolled methodologies in view of versatility, robustness, limitations and efficiency.1 Introduction2 Synthesis and Transformation of Cyclic β-Amino Acids through Metathesis Reactions2.1 Synthesis of Five- and Six-Membered Cyclic β-Amino Acids by Ring-Closing Metathesis2.2 Synthesis of Five- and Six-Membered Cyclic β-Amino Acids by Cross Metathesis2.3 Synthesis of β-Amino Acids with Larger Ring Systems by Ring- Closing Metathesis2.4 Synthesis of β-Amino Acids with Condensed Ring Systems by Ring-Rearrangement Metathesis2.5 Stereocontrolled One-Step Synthesis of Functionalized Cispentacin and Transpentacin Derivatives2.5.1 Stereocontrolled Synthesis of Functionalized Cispentacin and Transpentacin Derivatives through Ring-Opening Metathesis of Norbornene β-Amino Acid Derivatives2.5.2 Stereocontrolled Synthesis of Functionalized Azetidinones and β-Amino Acid Derivatives from Condensed Ring β-Lactams by Ring-Opening Metathesis2.5.3 Carbon–Carbon Double Bond Functionalization of β-Amino Acid Derivatives and β-Lactams with α,β-Unsaturated Carbonyl Compounds through Cross Metathesis2.5.4 Synthesis of Functionalized β-Amino Acid Derivatives and β-Lactams through Chemoselective Cross Metathesis3 Conclusions and Outlook