Titanocene(III)-Catalyzed Formation of Indolines and Azaindolines

Abstract

Reductive cyclization of epoxides tethered to substituted anilines and aminopyridines in the presence of 3 mol % of titanocene(III) chloride and stoichiometric manganese metal promotes a radical annulation to form 3,3-disubstituted indolines and azaindolines.

Palladium‐Catalyzed Carbonylation of Amines: Switchable Approaches to Carbamates and N,N′‐Disubstituted Ureas

“…Next, the carbonylation reactions of p-toluidine 1e with other alcohols were also examined. Although tert-butyl alcohol appeared to be unsuitable in this process (3t), the desired carbamates 3p-3s were obtained in moderate yields when ethanol, 2-propanol, benzyl alcohol, or allyl alcohol were employed ( Table 2, entries [16][17][18][19][20].…”

Azetidinones as Zinc‐Binding Groups to Design Selective HDAC8 Inhibitors

“…Product 18 is known. [36] Compound 23 is known, [37] but was prepared following the procedure reported in Reference [38]. Further details on the preparation of compounds 11, 14, and 15 can be found in the Supporting Information, as can full spectral data on intermediate compounds.…”

Titanocene(III)-catalyzed conversion of N-(epoxyalkyl)anilines into indolines

“…We recently developed a synthesis of 3,3-disubstituted indolines that uses in situ generated titanocene(III) chloride 4,5 to promote a new epoxide-opening rearrangement, transforming N-(epoxyalkyl)anilines into indolines. 6 Although most one-step protocols to prepare indolines through carbon-carbon bond formation involve an activation of an aryl halide using either a transition metal 7 or a radical initiator, 8 we envisioned exploring a complementary approach toward indoline preparation that uses the reductive opening of an epoxide derived from an allyl When lowering the reaction concentration to 0.03 M and using 10 mol% of precatalyst in the presence of 80 mol% of manganese powder under sonication, a 3:1 ratio of indoline 2a to tetrahydroquinoline 3a was observed by GC analysis of the crude reaction mixture (Table 1, entry 1). Next, we tested if a methyl substituted alkene substrate would react more selectively and avoid the formation of the undesired mixtures of 2a and 3a.…”

“…10 The use of aminopyridine substrates offered the possibility of applying our methodology toward the preparation of azaindolines. 6,11 Although the chemoselective epoxidation of alkenes in the presence of the pyridine moiety was precedented, attempts to efficiently prepare the epoxide on an unsubstituted aminopyridine substrate were unsuccessful. This negative result was primarily due to the reactivity of the pyridine nitrogen toward either m-CPBA or DMDO, i.e.…”