The advent of well-defined catalysts for olefin metathesis which combine high activity, durability, and excellent tolerance towards polar functional groups has revolutionized the field. The past decade has seen the rapid embrace of these reagents as tools for advanced organic and polymer chemistry and the success of this development is witnessed by a plethora of elegant applications to the synthesis of natural and nonnatural products. This review article provides an overview of these developments and intends to familiarize the reader with some very recent advances which hold the promise to expand the scope of the reaction even further. Moreover, the positive impact of metathesis on the fundamental logic of retrosynthetic planning is demonstrated by means of typical examples. Finally, it will be shown that metathesis is by no means restricted to alkenes as substrates, and some comments on metathesis reactions following unconventional mechanistic pathways will also be presented.

Olefin Metathesis and Beyond

http://aether.cmi.ua.ac.be/artikels/Artikels%20Gitte/Artikels/Reviews/Trans.%20Metal.%20catal.%20reactions%20Chem.%20rev.%20042127.pdf

Transition-Metal-Catalyzed Reactions in Heterocyclic Synthesis

Synthesis of oxygen- and nitrogen-containing heterocycles by ring-closing metathesis.

Ruthenium-Catalyzed Reactions for Organic Synthesis.

Metal-Mediated Synthesis of Medium-Sized Rings

A strategy is described for the enantioselective construction of medium-ring cyclic ethers by merging the asymmetric aldol addition of glycolates with a ring-closing metathesis reaction. Cyclic ethers of seven-, eight-, and nine-membered rings are readily available through a ring-closing metathesis without cyclic conformational constraints, by exploiting the acyclic conformational bias of the gauche effect. A short formal synthesis of the eight-membered ether (+)-laurencin, a red algae metabolite, has been accomplished utilizing the aldol−metathesis combination.

An Asymmetric Aldol−Ring-Closing Metathesis Strategy for the Enantioselective Construction of Oxygen Heterocycles: An Efficient Approach to the Enantioselective Synthesis of (+)-Laurencin

The ring closing metathesis reaction has rapidly become an important transformation in organic synthesis.1 Examples of many ring sizes with a variety of functional appendages2 have been constructed by this powerful method, largely because of the advent of the functionally tolerant ruthenium3 and molybdenum4 carbene complexes. Even kinetically and thermodynamically disfavored eight-membered rings have been prepared by ringclosing metathesis. However, virtually all5 successful eight-membered ring closures have required the incorporation of cyclic conformational constraints6 or rigid acyclic conformational control elements to avoid formation of dimers or oligomers.7 It is noteworthy that cyclic constrained dienes underwent more efficient ringclosing metathesis to form eight-membered rings when the two olefinic chains were positioned trans on the cyclic constraint than when they were cis.7 Grubbs6a has attributed this effect to a greater difference in energy between the diene and the cyclic olefin in the cissubstituted substrate. We reasoned that dienes with an appropriate acyclic conformational bias might allow eight (or nine)-membered ring formation and avoid the additional strain imposed by a fused ring attached to the newly formed cyclic olefin. We recently reported an asymmetric aldol-ring-closing metathesis strategy for the enantioselective synthesis of the carbocyclic fragment of the nucleoside analogue 1592U89.8 In view of the importance of enantioselective approaches to cyclic ethers of all sizes, particularly eightand nine-membered ring metabolites that are abundant in marine algae,9 an extension of the aldol-metathesis strategy to oxygen heterocycles seemed in order. We report here an efficient, general strategy for the asymmetric synthesis of sixto nine-membered cyclic ethers.10

Asymmetric Aldol−Ring-Closing Metathesis Strategy for the Enantioselective Construction of Six- to Nine-Membered Oxygen Heterocycles

A general and efficient synthesis of carbocyclic and hexenopyranosyl nucleosides has been developed. The strategy combines three key transformations: an asymmetric aldol addition to establish the relative and absolute configuration of the pseudosugar, a ring-closing metathesis to construct the pseudosugar ring, and a Trost-type palladium(0)-mediated substitution to assemble the pseudosugar and the aromatic base. Carbovir, abacavir, and their 2'-methyl derivatives as well as hexenopyranosyl nucleoside analogues have been prepared by this sequence.

Allison L. Choy

Papers

An Asymmetric Aldol−Ring-Closing Metathesis Strategy for the Enantioselective Construction of Oxygen Heterocycles: An Efficient Approach to the Enantioselective Synthesis of (+)-Laurencin

Asymmetric Aldol−Ring-Closing Metathesis Strategy for the Enantioselective Construction of Six- to Nine-Membered Oxygen Heterocycles

An efficient, general asymmetric synthesis of carbocyclic nucleosides: Application of an asymmetric aldol/ring-closing metathesis strategy

Ring closing metathesis for the formation of medium ring ethers: the total synthesis of (−)-isolaurallene

An Improved Synthetic Preparation of 3-Butenal