Synthesis of [5,6]‐Bicyclic Heterocycles with a Ring‐Junction Nitrogen Atom: Rhodium(III)‐Catalyzed C−H Functionalization of Alkenyl Azoles

Abstract

The first syntheses of privileged [5,6]-bicyclic heterocycles,w ith ring-junction nitrogen atoms,b yt ransition metal catalyzedC ÀHf unctionalization of C-alkenyl azoles is disclosed. Several reactions are applied to alkenyl imidazoles, pyrazoles,a nd triazoles to providep roducts with nitrogen incorporated at different sites.A lkyne and diazoketone coupling partners give azolopyridines with various substitution patterns.Inaddition, 1,4,2-dioxazolone coupling partners yield azolopyrimidines.F urthermore,t he mechanisms for the reactions are discussed and the utility of the developed approach is demonstrated by iterative application of CÀHf unctionalization for the rapid synthesis of apatented drug candidate.

Catalytic Transformations of Functionalized Cyclic Organic Carbonates

“…[58,59] With the introduction of ad irecting group possessing nucleophilic or electrophilic character,s ubsequent intramolecular cyclization after initial CÀHa midation is feasible giving rise to bicyclicc ompounds (Scheme 20). Thus,t he synthesis of quinazolines [60] and their N-oxides, [61] benzimidazoles, [62] azolopyrimidines [63] and thiadiazine-1-oxides [64] was achieved in as ingle step.T he use of an electrophilic enaminone directing group gave rise to 4-quinolone product. [65] Thea midation of more challenging C(sp 2 ) À Ha nd C(sp 3 ) À Hb onds can be also achieved though the scope is limited to the use of specially designed substrates such as oxime ethers,s ubstituted 8-methylquinolines and thioamides.…”

Katalytische Umwandlung von funktionalisierten cyclischen organischen Carbonaten

“…Transformation von 1,4,2-Dioxazol-5-onen 1,4,2-Dioxazol-5-one (Dioxazolone,c yclische Nitrilcarbonate) sind aufgrund ihrer schwachen N-O-Bindung bei milden Bedingungen leicht zu aktivieren. Aufd iese Weise konnten Chinazoline [60] und ihre N-Oxide, [61] Benzimidazolene, [62] Azolopyrimidine [63] und Thiadiazin-1-oxide [64] in einem Syntheseschritt hergestellt werden. Als besonders geeignet zeigten sich diese Substrate bei Reaktionen, die die C-H-Amidierung von (Hetero)Arenen beinhalten (Schema 19).…”

“…[58,59] Durch die Einführung einer dirigierenden Gruppe mit einem nukleophilen oder elektrophilen Charakter wird nach einer vorausgehenden C-H-Amidierung eine anschließende intramolekulare Cyclisierung ermçglicht, die die Bildung von bicyclischen Verbindungen fçrdert (Schema 20). Aufd iese Weise konnten Chinazoline [60] und ihre N-Oxide, [61] Benzimidazolene, [62] Azolopyrimidine [63] und Thiadiazin-1-oxide [64] in einem Syntheseschritt hergestellt werden. Ausd er Verwendung einer elektrophilen dirigierenden Enaminon-Gruppe ergibt sich die Mçglichkeit der Synthese von 4-Chinolonen.…”

Rhodium(III)‐Catalyzed Regioselective C−H Activation/Annulation for the Diverse Pyrazole‐Core Substituted Furans

“…Recently, several synthetic approaches have been demonstrated for C−H bond functionalization of pyrazoles . The typical and representative methods include Pd‐ or Rh‐catalyzed directed sp 3 C−H bond arylation of 1‐ethylpyrazole with aryliodide or triarylboroxine (Scheme a), Rh(III)‐catalyzed C−H functionalization of alkenyl pyrazoles with diazo compounds (Scheme b), and Rh(III)‐catalyzed C−H allylation of 1‐phenylpyrazole with allyl carbonates (Scheme c) . Despite several reports of sp 2 or sp 3 C−H bond arylation and annulation, there is no example of pyrazole‐directed C−H functionalization for the construction of biologically interesting heterocycles such as furans.…”