Gold(I)‐Catalyzed Highly Diastereo‐ and Enantioselective Cyclization–[4+3] Annulation Cascades between 2‐(1‐Alkynyl)‐2‐alken‐1‐ones and Anthranils

Abstract

This work reports gold‐catalyzed [4+3]‐annulations of 2‐(1‐alkynyl)‐2‐alken‐1‐ones with anthranils to yield epoxybenzoazepine products with excellent exo‐diastereoselectivity (dr>25:1). The utility of this new gold catalysis is manifested by applicable substrates over a broad scope. More importantly, the enantioselective versions of these [4+3]‐cycloadditions have been developed satisfactorily with chiral gold catalysts under ambient conditions (DCM, 0 °C); the ee levels range from 88.0–99.9 %. With DFT calculations, we postulate a stepwise pathway to rationalize the preferable exo‐stereoselection.

Gold(I)‐Catalyzed Highly Diastereo‐ and Enantioselective Cyclization–[4+3] Annulation Cascades between 2‐(1‐Alkynyl)‐2‐alken‐1‐ones and Anthranils

“…Compound 5 was subjected to m-CPBA-oxidation (1.1 equiv) in DCM to yield a N-hydroxyamine derivative 6 that was characterized by X-ray diffraction. [10] Alternatively, alkylation of compound 5 with MeI/K 2 CO 3 in DMF [11b] furnished N-methylated benzoazepine derivative 7 in excellent yield (95 %). Hydrolytic opening of the furan ring of compound 5 with H 2 SO 4 in HOAc:H 2 O [11c] (3:1) at 50 8C afforded 3,4-diketodehydrobenzoazepine derivative 8 in 47 % yield.…”

“…The performance of L 3 AuCl/AgNTf 2 in different solvents (entries 7-8) at 0 8C were also very effective: DCE (80 % yield, 99.4 % ee) and toluene (83 % yield, 91.1 % ee). The absolute configuration of compound (+)-3 a was inferred from the X-ray diffraction of its bromo relative (+)-3 d. [10] The generality of these enantioselective annulations was further assessed with various 2-(1-alkynyl)-2-alken-1-ones 1 and anthranils 2 with variations of the R 1 -R 6 substituents ( Table 5). In nearly all cases, the use of L 3 AuCl/AgNTf 2 enabled high enantioselectivity with ee > 90 %, whereas compound (+)-4 i was obtained in 88 % ee using L 4 ligand (entry 12).…”

“…The molecular structure of compound (+)-3 d was confirmed with X-ray diffraction. [10] For meta-chlorophenyl substrate 1 e (R 2 = 3-ClC 6 H 4 ) , its resulting compound (+)-3 e was produced in 74 % yield and 95.6 % ee (entry 3). A 3-thiophene-containing 2-(1-alkynyl)-2-alken-1-one 1 f delivered the desired product (+)-3 f with 92.4 % ee (entry 4).…”

“…AgNTf 2 alone in DCM was completely inactive (entry 10). The molecular structure of compound 3 a was confirmed by its X-ray diffraction [10] to reveal an exo-configuration.…”

“…We next varied the alkenyl substituents (R 1 ) of enynones 1 i-1 j with R 2 = 4-XC 6 H 4 (X = Me and Cl) and their resulting products 3 i and 3 j were obtained in 75-79 % yields (entries 8-9). For methyl-and 3thienyl-substituted alkene derivatives 1 k and 1 l, these reactions furnished compounds 3 k and 3 l in 71 % and 77 % yields (entries [10][11]. Variations of the ketone substituents were also suitable to this gold catalysis.…”