First Asymmetric Synthesis of (Un)saturated 1‐Alkylbenzo[c]azepin‐3‐ones: Extension to the Corresponding Benzazepines

Abstract

A flexible route for the stereoselective synthesis of a variety of structurally diverse (1R)‐1‐alkyldihydro and tetrahydrobenzazepin(ones) has been developed. The key step is a highly diastereoselective 1,2‐addition process applied to a stereopure aromatic hydrazone combined with a ring‐closing metathesis reaction to secure the formation of the seven‐membered azaheterocycle ring system.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

N,N-Dialkylhydrazones in Organic Synthesis. From Simple N,N-Dimethylhydrazones to Supported Chiral Auxiliaries

“…The addition proceeded on the Re face of the chelated hydroxyhydrazone, providing, after hydrogenolysis, the (R)-Rtrifluoromethylated amines 202. 186 An ingenious approach to the construction of chiral benzazepine derivatives 187 and cyclic alkaloid skeletons 188 was realized by the combination of a diastereoselective 1,2-addition and the ring-closing metathesis reaction. For example, the highly stereoselective 1,2-addition to benzylprotected 4-hydroxybutyraldehyde or 5-hydroxypentanal SAMP-hydrazones (Scheme 37), combined in a one-pot reaction of the directly resulting lithium hydrazide with acryloyl chloride, gave hydrazine derivatives 204.…”

Anionic [4+3] heteroannulation of 2-azidoacrylates: a modular synthesis of 2-benzazepin-1-ones

“…4 Consequently, the development of practical and flexible synthetic methods for benzazepines in general is in growing demand. The literature methods for 2-benzazepines include intramolecular Mitsunobu amination, 5 ring closing metathesis, 6 Friedel-Crafts reaction, 7 Pictet-Spengler reaction, 8 Bischler-Napieralski reaction, 9 Pummerer cyclization, 10 7-endo-trig radical cyclization, 11 reductive amination, 12 ring expansion, 13 1,7-electrocyclization 14 and Heck reaction. 15 In conjunction with our interest in anionic [4+2] benzannulations, 16 we encountered an unprecedented result in the reaction of azidoacrylate 1a with phthalide 2a, which resulted in the formation of benzazepinone 3a (Table 1).…”