Bimolecular Cross‐Metathesis of a Tetrasubstituted Alkene with Allylic Sulfones

Abstract

Exquisite control of catalytic metathesis reactivity is possible through ligand‐based variation of ruthenium carbene complexes. Sterically hindered alkenes, however, remain a generally recalcitrant class of substrates for intermolecular cross‐metathesis. Allylic chalcogenides (sulfides and selenides) have emerged as “privileged” substrates that exhibit enhanced turnover rates with the commercially available second‐generation ruthenium catalyst. Increased turnover rates are advantageous when competing catalyst degradation is limiting, although specific mechanisms have not been defined. Herein, we describe facile cross‐metathesis of allylic sulfone reagents with sterically hindered isoprenoid alkene substrates. Furthermore, we demonstrate the first example of intermolecular cross‐metathesis of ruthenium carbenes with a tetrasubstituted alkene. Computational analysis by combined coupled cluster/DFT calculations exposes a favorable energetic profile for metallacyclobutane formation from chelating ruthenium β‐chalcogenide carbene intermediates. These results establish allylic sulfones as privileged reagents for a substrate‐based strategy of cross‐metathesis derivatization.

Relay Cross Metathesis for the Iterative Construction of Terpenoids and Synthesis of a Diterpene-Benzoate Macrolide of Biogenetic Relevance to the Bromophycolides

“…To commence our investigations enantiopure epoxide 2 , as a relay-actuated Δ 6,7 -functionalized monoterpenoid derivative, was prepared from diol 1 using the method of Corey et al (Scheme ). Using our previously identified conditions (10 mol % ruthenium benzylidene precatalyst 5 , alkene [5 equiv], 50 °C, 1 h), attempted relay cross metathesis reaction between epoxide 2 and citral ( 3 ) , to give C 15 -sesquiterpenoid 4 using 5 was unsuccessful (Table , entry 1). Further attempts with 10 equiv of 3 (entry 2) or at room temperature (entry 3) or with 2 mol % catalyst loading (entry 4) also failed.…”

“…3:1 at the newly formed olefin (Δ 6,7 ) and as ca. 2−3:1 at the α,βunsaturated aldehyde by 1 H NMR and assigned on the basis of characteristic 13 C NMR shielded methyl resonances for E-isomers (see the Supporting Information). c Purification not attempted due to complex mixtures of products.…”

“…The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.0c00935. General experimental section; experimental details and characterizing data for compounds; comparison of 1 H and 13 C NMR shifts of E,E,E-19 (P = Et) vs E,E,E-19 (P = MOM); copies of 1 H and 13 C spectra for all compounds (PDF)…”

Cross metathesis of (-)-β-pinene, (-)-limonene and terpenoids derived from limonene with internal olefins

“…ene revealed that both regioselectivities could be obtained depending on the nature of the catalyst [30]. The cross-metathesis of a sterically hindered vinylheterocyclic substrate with 2-methylbut-2-ene in the presence of the catalyst Ru2 yielded a mixture of the two regioisomers in a disubstituted/trisubstituted double bond ratio of 2.4/1.0 [31]. The regioselectivity leading to the formation of a 1,2-disubstituted double bond is also exemplified by the cross metathesis of 2-methylbut-2-ene with n-butyl acrylate in which the trans-n-butyl crotonate was formed in 83% yield [26] due to the higher reactivity of the alkene than the acrylate to generate a ruthenium ethylidene species, as also observed under stoichiometric conditions from the first generation cyclohexyl ester ruthenium carbene RuCl2(PCy3)2(=CHCO2Cy) and 2-methyl-1pentene [32].…”

Alkene Cross‐Metathesis with 2,5‐Dimethyl‐2,4‐Hexadiene Enables Isobutylenyl/Prenyl Functionalizations and Rubber Valorization

“…[31][32][33] An alternative compound for introducing prenyl groups by alkene cross-metathesis reactions without low temperature or pressure regulation requirements would be the highly symmetric alkene 2,3-dimethyl-2-butene (Figure 1, top middle) which, however, it is difficult to find as a reactant in any reported metathesis reaction. [34,35] This can be due to its fully tetrasubstituted alkene structure, which severely hampers the initial formation of the intermediate metal carbene complex. [36] We will confirm in this work the unreactivity of this alkene under standard alkene metathesis conditions (see ahead).…”