A large set of tetrahydro-2-benzazepines with an α-hydroxy or α-(aryl)alkoxy substituted benzyl moiety in the 5-position was prepared according to the recently reported C6C1 + C3N synthetic strategy. The Heck reaction of 2-iodobenzaldehyde acetal 4 and the subsequent Stetter reaction led to the ketone 7, which was reduced diastereoselectively to form the like-configured alcohol 8. The diastereomeric unlike-configured alcohol 9 was obtained by a Mitsunobu inversion of 8. Alkylation and reductive cyclization of the diastereomeric alcohols 8 and 9 provided like- and unlike-configured 2-benzazepines 13 and 23, which allowed the introduction of various substituents at the N-atom. Analysis of the relationship between the structure and the σ1 affinity revealed that large substituents such as the butyl, benzyl or 4-phenylbutyl moiety at the benzazepine N-atom resulted in high affinity ligands. A p-methoxybenzyl ether is less tolerated by the σ1 receptor than a methyl ether or an alcohol. The unlike-configured alcohols 25d and 27d show slightly higher σ1 affinity than their like-configured diastereomers 15d and 17d. With respect to the σ1 affinity, σ1/σ2 selectivity and lipophilic ligand efficiency, like- and unlike-configured alcohols 15d and 25d represent the most promising σ1 ligands of this series. Interactions of the novel 2-benzazepines with various binding sites of the NMDA receptor were not observed.