Tandem Long Distance Chain-Walking/Cyclization via RuH₂(CO)(PPh₃)₃/Brønsted Acid Catalysis: Entry to Aromatic Oxazaheterocycles

Abstract

A novel route to 1,3-oxazaheterocycles based on cooperative Ru-H/Brønsted acid catalysis is reported. The use of the commercially available RuH2(CO)(PPh3)3 complex allows for an efficient long distance chain-walking process while the Brønsted acid is responsible for generation of an electrophilic iminium ion which is trapped intramolecularly by an alcohol moiety. The alcohol, besides its nucleophilic function, also plays an important role in the stabilization of the Ru catalyst.

A General Strategy for Open‐Flask Alkene Isomerization by Ruthenium Hydride Complexes with Non‐Redox Metal Salts

“…This process is normally catalyzed by transition metals such as Fe, Pd, Rh, Ni, Ir, Cr, and Ru, among which ruthenium hydride complexes have been demonstrated with a strong affinity to facilitate the hydrometallation of versatile olefins and are applied widely in C=C bond migration reactions, for instance, the isomerization of S ‐, O ‐, and N ‐allyl compounds by air‐sensitive [RuClH (CO)(PPh 3 ) 3 ], allylic alcohols to saturated ketones by ruthenium cyclopentadienyl complexes, and of terminal alkenes by the cationic version of [RuCl(PPh 3 ) 2 (3‐phenylindenyl)], (C 5 Me 5 )Ru complexes, and the classical Grubbs metathesis catalysts . Moreover, double bond migration catalyzed by Ru−H catalysts is an important pathway in the methodology of organic synthesis by tandem processes, such as the synthesis of 1,2‐annulated trans ‐tetrahyrdofurans with Chaudret's catalyst ([RuH(η 5 ‐C 8 H 11 ) 2 ][BF 4 ]), heterocycles by isomerization and cycloisomerization, C−C bond formation using a RuHCl (CO)(PPh 3 ) 3 /Brønsted acid binary catalytic system, and aromatic oxazaheterocycles …”

“…1) the isomerization was catalyzed by RuH 2 (CO)(PPh 3 ) 3 /Mg 2+ , but the reaction was unfeasible for Ru(CO) 3 (PPh 3 ) 2 (Table S3); 2) cis ‐stilbene could be isomerized (Table , entry 14) in which no allyl H atom beside the C=C bond could migrate; 3) alcohols as hydrogen‐donor solvents were beneficial (Table S1) because of their ability to stabilize the catalytically active Ru−H species; 4) 1 H NMR spectra displayed the disappearance of the Ru−H signal immediately after the addition of alkene (vide infra). In the metal hydride addition–elimination mechanism, free alkene coordinates to Ru−H species, then insertion into the Ru−H bond yields a secondary metal−alkyl, subsequent β‐hydride elimination yields the isomerized product and regenerates the initial Ru−H catalyst (Scheme ) –. Thus, in this process the cis and trans isomers should be both generated.…”

“…The concentration of extra PPh 3 had a negative influence on the rate of the isomerization reaction (Table S11), and a linear dependence between the reciprocal of the rate constant and the concentration of added PPh 3 was obtained (Figure ), which was in good agreement with that of other reports . The results of our 31 P NMR spectroscopy, GC–MS, and kinetic studies indicate clearly that the dissociation of a PPh 3 ligand from RuH 2 (CO)(PPh 3 ) 3 was an important step in the isomerization similar to previous studies . The dissociation of PPh 3 formed an unoccupied coordination site for alkene, which thus benefitted the catalytic isomerization.…”

Palladium-Catalyzed Long-Range Deconjugative Isomerization of Highly Substituted α,β-Unsaturated Carbonyl Compounds

“…A longer distance may also influence site selectivity of the triggering event with a gradual decay of the directing electronic and steric effects . In Figure A are displayed some of the most notable and successful examples of recently developed long-range alkene isomerization with substrates possessing a refunctionalizable terminus. , In 2000, Mori and co-workers disclosed the thermodynamically counterintuitive long-range deconjugative isomerization of α,β-unsaturated amides and esters using a well-defined [Ru–H] precatalyst (Figure , A.1) . Although several terminal functions were demonstrated to be compatible (−OBn, −CCSiR 3 , −HCCH–Ph, −OSiR 3 , −CH­(SnR 3 ) 2 ), only disubstituted olefins were employed and the products were obtained as statistical E / Z mixtures.…”

Cooperative Use of Brønsted Acids and Metal Catalysts in Tandem Isomerization Reactions of Olefins

“…In principle any ‘pendant’ nucleophile that does not hinder the process of isomerization can be used for attack on the carbenium species. Sa and co‐workers extended the scope of the isomerizing cyclizations that typically relied on the C−C bond formation to the use of attached alcohols as nucleophiles (Scheme ) . They employed a range of hydroxy‐substituted anilines or benzylamines 64 to access 1,3‐oxazaheterocycles 65 .…”