E- and Z-, di- and tri-substituted alkenyl nitriles through catalytic cross-metathesis

Abstract

Nitriles are found in many bioactive compounds, and are among the most versatile functional groups in organic chemistry. Despite many notable recent advances, however, there are no approaches that may be used for preparation of di- or trisubstituted alkenyl nitriles. Related approaches which are broad in scope and can deliver the desired products in high stereoisomeric purity are especially scarce. Here, we describe the development of several efficient catalytic cross-metathesis strategies, which provide direct access to a considerable range of Z - or E -disubstituted cyano-substituted alkenes or their corresponding trisubstituted variants. Depending on the reaction type, a molybdenum-based monoaryloxide pyrrolide (MAP) or chloride (MAC) complex may be the optimal choice. The utility of the approach, enhanced by an easy-to-apply protocol for utilization of substrates bearing an alcohol or a carboxylic acid moiety, is highlighted in the context of applications to synthesis of biologically active compounds.

Pushing the Bounds of Olefin Metathesis with Vanadium

“…Additionally, significant advances in Z-selective metathesis were reported with ruthenium by the groups of Jensen, [34][35][36] Grubbs, [37][38][39][40] and Hoveyda, [41] while Schrock and Hoveyda demonstrated success with molybdenum and tungsten. [28][29][30][31][32][33][42][43][44][45] While advancements in new catalysts based on group 6 metals and ruthenium should and will continue apace, it is worthwhile to investigate other metals to meet challenges in the field as well. For instance, despite many impressive accomplishments, some ruthenium-based catalysts generate minor amounts of decomposition products which catalyze olefin isomerization, leading to the production of undesired isomers which are challenging to remove through common purification techniques.…”

Olefin metathesis: what have we learned about homogeneous and heterogeneous catalysts from surface organometallic chemistry?

“…However, recent advances have shown the d 0 Schrock-type catalysts are particularly efficient for the metathesis of functionalized olens, even allowing the formation of uoroand chloro-alkenes in a stereoselective way. 77,78,80,[131][132][133] To probe the applicability of SOMC catalysts towards this type of olens, ethyl (or methyl) oleate was typically used as a test substrate in some of the studies cited above. While it is very early to draw any structure-activity relationships in this area, these results have generally proven that well-dened silicasupported catalysts based on Re, 134 Mo, 59,60,63,64,108,135 and W 101,106,107,122,123,135 alkylidenes are sufficiently functional group tolerant and can easily reach TONs of 500-1000, with the best record so far being the cationic W oxo NHC complex on silica reaching TON of ca.…”

Impact of Ethylene on Efficiency and Stereocontrol in Olefin Metathesis: When to Add It, When to Remove It, and When to Avoid It

“…There was no conversion when the corresponding monosubstituted aryl olefin was used (owing to unstable methylidene formation). In another example, subjection of a 1:5 mixture of E ‐aryl alkene 79 and fumaronitrile to 5.0 mol % Mo‐8 b and 6.0 mol % B(C 6 F 5 ) 3 (to dissociate the pyridyl ligand) afforded E ‐alkenyl nitrile 80 in 87 % yield and with 96:4 E : Z selectivity; as before, none of the desired olefin was detected when a monosubstituted alkene was used [65] …”