A Simple and Effective Co‐Catalyst for Ring‐Closing Enyne Metathesis Using Grubbs I type Catalysts: A Practical Alternative to “Mori’s Conditions”

Abstract

In 1998 Mori reported [1] that ethylene improved turnover in the ring-closing metathesis (RCM) of enynes (1!2), [2] employing Grubbs generation I catalyst (3 a); for example, low yields of 2 a-c under 1 atm argon, became near-quantitative (99 %) under 1 atm. ethylene.[1] Subsequent kinetic analysis [3] revealed that ethylene not only increases the turnover frequency, but also reduces the impact of catalyst deactivation processes. The beneficial effect of ethylene is observed with many enyne substrates, particularly those with terminal alkyne moieties, and unsurprisingly, "Moris conditions" have been widely adopted (Scheme 1). [4] Two basic mechanisms have been proposed for the RCM of enynes involving intermolecular [5] metal-alkylidene propagation. These mechanisms are often referred to as the "yne-then-ene" and "ene-then-yne" pathways.[2] Evidence for both pathways has been presented, and phosphine catalysts, for example, 3 a, [6] appear to favour the "ene-then-yne" pathway (cycle A, Scheme 2). [7] For RCM involving phosphine catalysts, for example, 3 a, and terminal enynes, computational investigations [7,8] and isotopic labelling experiments [3] support earlier proposals [5b, 9] that ethylene acts as an alkene surrogate for the enyne (1) in the release of product (2) through alkene-alkylidene exchange with intermediate 5.[10] A second alkene-alkylidene exchange of 6 (R = H) with 1, to generate 4, connects the secondary cycle B with primary cycle A, [11] liberating the ethylene (R = H), which thus acts as a co-catalyst.During our earlier study of "Moris conditions" [3] we noted that co-reaction of the about threefold-faster-reacting substrate 1 c with 1 a resulted in a small but noticeable decrease in the rate of RCM of 1 a. This suggested to us that an appropriately "tuned" alk-1-ene might be able to act as an efficient co-catalyst, in a manner analogous to ethylene. Herein we report on a kinetic and isotopic labelling investigation into this concept, and the development of a simple alkene co-catalyst that provides practical advantage to "Moris conditions" for the RCM of terminal enynes using Grubbs I catalyst (3 a). Scheme 2. The "ene-then-yne" cycle (A) for RCM of enynes 1!2 and secondary cycle B to account for acceleration under "Moris conditions" in which R = H.