Although significant progress has been made in constructing three-dimensional, C(sp³)-rich bioisosteres for pyridines, the development of catalytic enantioselective approaches to access chiral nitrogen-containing bridged scaffolds remains limited and challenging. Herein, we report a chiral Brønsted acid-catalyzed enantioselective reduction of imines harnessing Hantzsch ester as the hydrogen source under mild conditions, delivering structurally diverse chiral 3-azabicyclo[3.1.1]heptanes (27 examples) in generally good yields with high enantiocontrol (up to 93% yield, 97% ee). The reaction can be scaled up to 2 mmol with full preservation of the excellent outcomes. These saturated heterocycles serve as versatile precursors, as demonstrated by conversion to bicyclo[2.1.1]hexanes via a facile nitrogen-deletion strategy with complete retention of enantiopurity. Notably, the enantioenriched 3-aza-BCHep can serve as a secondary amine organocatalyst, promoting the asymmetric Friedel–Crafts alkylation of indole with an α,β-unsaturated aldehyde in excellent yield and promising stereoinduction. This work establishes a practical route to access enantiopure saturated heterocyclic scaffolds, offering new three-dimensional candidates as potential pyridine isosteres in drug discovery and asymmetric catalysis.

The CuH-catalyzed regio-, diastereo-, and enantioselective reduction of vinyl-substituted 1,2-diketones has been achieved, efficiently affording a range of vinyl-substituted syn-1,2-diols, motifs that are ubiquitous in bioactive molecules and serve as valuable building blocks in organic synthesis. Totally 24 diol products were obtained smoothly (up to 91% yield) with a high level of stereoselectivity control (up to 99% ee and > 20:1 dr). The protocol tolerates both aryl and alkyl substrates, and the products facilitate a range of further transformations. The work represents a new choice that addresses the limitations of known methods.