Spirocycles play an important role in drug discovery and development. The direct, catalytic, and enantioselective synthesis of spirocycles from readily available starting materials and in an atom economic manner remains a highly sought-after task in organic synthesis. Herein, an enantioselective Pd-hydride-catalyzed cycloaddition method for the synthesis of spirocyclic compounds directly from two classes of commonly available starting materials, 1,3-enynes and cyclic carbon−hydrogen (C−H) bonds, is reported. The reactions employ a chiral Pd/WingPhos catalyst to both suppress the formation of bis-allenyl by-products and control the stereoselectivity. 1,3-Enynes are used as dielectrophilic four-carbon units in the cycloaddition reactions, which also enables an enyne substrate-directed enantioselectivity switch with good levels of stereocontrol. The present spirocycle synthesis tolerates a broad range of functional groups of 1,3-enyne substrates, including alcohols, esters, nitriles, halides, and olefins. A variety of diverse cyclic nucleophiles, including pharmaceutically important heterocycles and carbocycles, can be flexibly incorporated with spiro scaffolds.

Scheme 4. Pd-catalyzed enantioselective decarboxylative allylic alkylation. [a] [Pd 2 (dba) 3 ] (3.5 mol %), L2 (8.75 mol %). [b] At 55 8C.Scheme 5. Catalytic enantioselective total synthesis of (À)-aspidospermidine. Reaction conditions: a) HCO 2 H, RT; b) LiAlH 4 , THF, À20 8C, then HCl (2 m); c) K 2 OsO 4 ·2 H 2 O, NMO, THF/H 2 O (1:1), then NaIO 4 ; d) 1,2-ethanedithiol, BF 3 ·Et 2 O, CH 2 Cl 2 ; e) Raney nickel, H 2 , EtOH, 60 8C; f) LiAlH 4 , Et 2 O, reflux; g) Na/NH 3 , THF, À78 8C. NMO = Nmethylmorpholine-N-oxide.

The first catalytic asymmetric [2 + 2] cycloaddition of oxabicyclic alkenes and terminal alkynes has been developed. This iridium-catalyzed enantioselective [2 + 2] cycloaddition allows the formation of four stereocenters in a single step with excellent enantioselectivity (94-->99% ee).

We report the first catalytic asymmetric approach to octahydroindolones and a divergent enantioselective synthesis of perhydroindole alkaloids, as exemplified by lycorine-type Amaryllidaceae alkaloids (+)-α-lycorane and (+)-lycorine, from a common intermediate by using a highly concise route. The assembly of octahydroindolones employs a catalytic enantioselective 1,4-conjugate addition of nitro dienynes, followed by a TsOH-catalyzed cascade synthesis of highly functionalized enones, and a diastereoselective intramolecular Michael addition.