Chiral Cyclohexyl-Fused Spirobiindanes: Practical Synthesis, Ligand Development, and Asymmetric Catalysis

1,1′-Spirobiindane
has been one type of privileged skeleton for chiral ligand design,
and 1,1′-spirobiindane-based chiral ligands have demonstrated
outstanding performance in various asymmetric catalysis. However,
the access to enantiopure spirobiindane is quite tedious, which obstructs
its practical application. In the present article, a facile enantioselective
synthesis of cyclohexyl-fused chiral spirobiindanes has been accomplished,
in high yields and excellent stereoselectivities (up to >99% ee), via a sequence of Ir-catalyzed asymmetric hydrogenation
of α,α′-bis­(arylidene)­ketones and TiCl4 promoted asymmetric spiroannulation of the hydrogenated chiral ketones.
The protocol can be performed in one pot and is readily scalable,
and has been utilized in a 25 g scale asymmetric synthesis of cyclohexyl-fused
spirobiindanediol (1S,2S,2′S)-5, in >99% ee and 67%
overall yield for four steps without chromatographic purification.
Facile derivations of (1S,2S,2′S)-5 provided straightforward access to chiral
monodentate phosphoramidites 6a–c and a tridentate phosphorus-amidopyridine 11, which
were evaluated as chiral ligands in several benchmark enantioselective
reactions (hydrogenation, hydroacylation, and [2 + 2] reaction) catalyzed
by transition metal (Rh, Au, or Ir). Preliminary results from comparative
studies showcased the excellent catalytic performances of these ligands,
with a competency essentially equal to the corresponding well-established
privileged ligands bearing a regular spirobiindane backbone. X-ray
crystallography revealed a close resemblance between the structures
of the precatalysts 20 and 21 and their
analogues, which ultimately help to rationalize the almost identical
stereochemical outcomes of reactions catalyzed by metal complexes
of spirobiindane-derived ligands with or without a fused cyclohexyl
ring on the backbone. This work is expected to stimulate further applications
of this type of readily accessible skeletons in development of chiral
ligands and functional molecules.