Z- isomers were previously achieved via ring-closing alkyne metathesis. However, in 2013 Grubbs reported the use of a chelating ruthenium catalyst to afford Z macrocycles in high selectivity. The selectivity is attributed to the increased steric clash between the catalyst ligands and the metallacyclobutane intermediate that is formed. The increased steric interactions in the transition state lead to the Z olefin rather than the E olefin, because the transition state required to form the E- isomer is highly disfavored. Cocatalyst Additives are also used to overturn conformational preferences, increase reaction concentration, and chelate highly polar groups, such as esters or amides, which can bind to the catalyst. Titanium isopropoxide (Ti(OiPr)4) is commonly used to chelate polar groups to prevent catalyst poisoning and in the case of an ester, the titanium Lewis acid binds the carbonyl oxygen. Once the oxygen is chelated with the titanium it can no longer bind to the ruthenium metal of the catalyst, which would result in catalyst deactivation. This also allows the reaction to be run at a higher effective concentration without dimerization of starting material. Another classic example is the use of a bulky Lewis acid to form the E-isomer of an ester over the preferred Z-isomer for cyclolactonization of medium rings. In one study, the addition of aluminum tris(2,6-diphenylphenoxide) (ATPH) was added to form a 7-membered lactone. The aluminum metal binds with the carbonyl oxygen forcing the bulky diphenylphenoxide groups in close proximity to the ester compound. As a result, the ester adopts the E-isomer to minimize penalizing steric interactions. Without the Lewis acid, only the 14-membered dimer ring was observed. By orienting the molecule in such a way that the two reactive alkenes are in close proximity, the risk of intermolecular cross-metathesis is minimized. Limitations Many metathesis reactions with ruthenium catalysts are hampered by unwanted isomerization of the newly formed double bond, and it is believed that ruthenium hydrides that form as a side reaction are responsible. In one study it was found that isomerization is suppressed in the RCM reaction of diallyl ether with specific additives capable of removing these hydrides. Without an additive, the reaction product is 2,3-dihydrofuran and not the expected 2,5-dihydrofuran (together with the formation of ethylene gas). Radical scavengers, such as TEMPO or phenol, do not suppress isomerization; however, additives such as 1,4-benzoquinone or acetic acid successfully prevent unwanted isomerization. Both additives are able to oxidize the ruthenium