Z Selectivity: Recent Advances in one of the Current Major Challenges of Olefin Metathesis

Abstract

The stereoselective formation of carbon–carbon double bonds is a longstanding topic in organic chemistry. Since the early 90s, catalytic olefin metathesis has emerged as a synthetic tool of choice for the creation of carbon–carbon double bonds, and its use is now widespread. However, except for the synthesis of small cycles, the reversible character of olefin metathesis usually results in the formation of the thermodynamic E product, and more generally in mixtures of E and Z products. This issue has been addressed in different ways; these are reviewed herein. Synthetic protocols, which aim at the selective synthesis of Z olefins, for example, sequential alkyne metathesis/cis‐hydrogenation, and the use of removable silyl groups, are summarized. Tailor‐made molybdenum, tungsten and ruthenium catalysts, which allow for very high stereoselectivity, are also reviewed. The advances achieved with these methods and catalysts are illustrated by the synthesis of various natural products or their precursors.

Recent Advancements in Stereoselective Olefin Metathesis Using Ruthenium Catalysts

“…As understanding for the stereochemical arrangement stereoselective OM research focused on the desymmetrization of achiral olefins to provide chiral molecules through the alteration of the ligand scaffold [11,16,17]. As understanding for the stereochemical arrangement of the metallacycle intermediate progressed, further variations were made in continual pursuit of one of the unmet challenges in OM: kinetic Z-selectivity [18][19][20]. An incredible amount of effort has been devoted to these quests, which have opened the door to numerous discoveries.…”

Stereoretentive Olefin Metathesis: An Avenue to Kinetic Selectivity

“…Later, Grubbs and coworkers introduced a highly efficient, Z-selective olefin metathesis catalyst that utilized a cyclometalated rutheniumcarbene species. [27][28][29][30][31][32][33][34][35][36] The aryl group on the N-heterocyclic carbene (NHC) forces all the substituents on the ruthenacycle syn ( Figure 1 (b)). Subsequent reports by the Jensen [37][38][39] and Hoveyda [40][41][42][43] groups also described Z-selective ruthenium catalysts.…”

NHC Backbone Configuration in Ruthenium-Catalyzed Olefin Metathesis

“…The use of N-heterocyclic carbenes (NHCs) as ancillary ligands [9,10] for ruthenium olefin metathesis complexes (second generation catalysts) has led to tremendous advances in the design of robust and effective catalysts for various metathesis applications, including some challenging and difficult transformations [11][12][13][14][15].…”

“…Modifications of the NHC ligand include the nature of the ring backbone (saturated or unsaturated), substitution at the nitrogen atoms and at the carbon atoms of the backbone, ring-size variation, introduction of heteroatoms in the skeleton, and introduction of chirality [11][12][13][14][15]. Among these, modifications of the steric and electronic properties of substituents on the backbone and/or the nitrogen atoms have had a significant impact on catalyst activity, stability and selectivity in several metathesis applications [16][17][18][19][20][21][22][23][24][25][26][27][28][29].…”