Abstract
Benzofused seven-membered heterocycles such as 1,4-benzo[e]diazepines (1,4-BZDs) and 1,4-benzo[e]oxazepines (1,4-BZOs) were efficiently synthesized by Rh-catalyzed hydrofunctionalization of internal alkynes and allenes in good to excellent yields. The asymmetric hydroamination of (aminomethyl)anilines gave rise to 3-vinyl-1,4-BZDs with excellent enantioselectivities. Orthogonal N-deprotection of 1,4-BZDs allowed an easy entry to an advanced pyrrolobenzodiazepine metabolite of the V2-receptor antagonist Lixivaptan.
Highlights
Benzofused seven-membered heterocycles such as 1,4benzo[e]diazepines (1,4-BZDs) and 1,4-benzo[e]oxazepines (1,4-BZOs) were efficiently synthesized by Rh-catalyzed hydrofunctionalization of internal alkynes and allenes in good to excellent yields
1,4-benzo[e]oxazepines (1,4-BZOs) possess recognized pharmacological activity in the treatment of Alzheimer disease8 and as tranquilizers.9. These highly relevant biological activities of 1,4-BZDs have inspired chemists over the years to develop a variety of synthetic approaches based on Friedel−Crafts reactions,10 ring expansions,11 aza-Michael cyclizations,12 click chemistry,13 heteroannulations,14 Ugi condensations,15 or 1,5-hydride transfer cyclization reactions
Transition metal-catalyzed asymmetric hydrofunctionalization/cyclization of allenes/internal alkynes has been used as an eco-friendly strategy to afford enantioenriched five- and six-membered heterocycles from achiral starting materials
Summary
Rh-Catalyzed Hydrofunctionalizations of Alkynes and Allenes to α-Vinylated Heterocycles pubs.acs.org/joc. To accomplish our synthetic goal, we proceeded to evaluate the Rh-catalyzed asymmetric hydroamination of 1d (Table 1), with a slight modification of our previous conditions regarding reactants loadings and temperature. We began our study exploring the virtually unknown intramolecular Rh-catalyzed hydrofunctionalizations of internal alkynes to seven-membered heterocycles (Scheme 2). Gratifychiral ligand Brønsted 1,4-BDZ 2 entrya alkyne 1
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