By using a novel, simple, and convenient synthetic route, enantiopure 6-ethynyl-BINOL (BINOL=1,1-binaphthol) was synthesized and anchored to an azidomethylpolystyrene resin through a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The polystyrene (PS)-supported BINOL ligand was converted into its diisopropoxytitanium derivative in situ and used as a heterogeneous catalyst in the asymmetric allylation of ketones. The catalyst showed good activity and excellent enantioselectivity, typically matching the results obtained in the corresponding homogeneous reaction. The allylation reaction mixture could be submitted to epoxidation by simple treatment with tert-butyl hydroperoxide (TBHP), and the tandem asymmetric allylation epoxidation process led to a highly enantioenriched epoxy alcohol with two adjacent quaternary centers as a single diastereomer. A tandem asymmetric allylation/Pauson-Khand reaction was also performed, involving simple treatment of the allylation reaction mixture with Co2(CO)8/N-methyl morpholine N-oxide. This cascade process resulted in the formation of two diastereomeric tricyclic enones in high yields and enantioselectivities.

Shibasaki's REMB catalysts (REMB; RE = Sc, Y, La-Lu; M = Li, Na, K; B = 1,1'-bi-2-naphtholate; RE/M/B = 1/3/3) are among the most enantioselective asymmetric catalysts across a broad range of mechanistically diverse reactions. However, their widespread use has been hampered by the challenges associated with their synthesis and manipulation. We report here the self-assembly of novel hydrogen-bonded rare earth metal BINOLate complexes that serve as bench-stable precatalysts for Shibasaki's REMB catalysts. Incorporation of hydrogen-bonded guanidinium cations in the secondary coordination sphere leads to unique properties, most notably, improved stability toward moisture in solution and in the solid state. We have exploited these properties to develop straightforward, high-yielding, and scalable open-air syntheses that provide rapid access to crystalline, nonhygroscopic complexes from inexpensive hydrated RE starting materials. These compounds can be used as precatalysts for Shibasaki's REMB frameworks, where we have demonstrated that our system performs with comparable or improved levels of stereoselectivity in several mechanistically diverse reactions including Michael additions, aza-Michael additions, and direct Aldol reactions.

Abstract Polystyrene-supported (PS) diarylprolinol catalysts 1?a (Ar=phenyl) and 1?b (Ar=3,5-bis(trifluoromethyl)phenyl) have been developed. Operating under site-isolation conditions, PS-1?a/1?b worked compatibly with PS-bound sulfonic acid catalyst 2 to promote deoligomerization of paraldehyde and subsequent cross-aldol reactions of the resulting acetaldehyde in one pot, affording aldol products in high yields with excellent enantioselectivities. The effect of water on the performance of the catalytic system has been studied and its optimal amount (0.5?equiv) has been determined. The dual catalytic system (1/2) allows repeated recycling and reuse (10 cycles). The potential of this methodology is demonstrated by a two-step synthesis of a phenoperidine analogue (68?% overall yield; 98?%?ee) and by the preparation of highly enantioenriched 1,3-diols 4 and 3-methylamino-1-arylpropanols 5, key intermediates in the synthesis of a variety of druglike structures.

Heterobimetallic Lewis acid catalysts are broadly useful and methods to recycle them have immediate applications. However, their immobilization through covalent binding can be challenging. Non-covalent immobilization of supported asymmetric catalysts is attractive due to ease of preparation and potential for reversible binding. We report a novel non-covalent binding strategy for Shibasaki's REMB framework {RE=rare earth metal; M=Li, Na, K; B=BINOL; RE:M:B=1:3:3, [M-3(sol)(n)][(BINOLate)(3)RE]} and explore the reactivity of the supported catalyst.