Enantioselective
desymmetrization by direct monofunctionalization
of prochiral diols is a powerful strategy to prepare valuable synthetic
intermediates in high optical purity. Boron acids can activate diols
toward nucleophilic additions; however, the design of stable chiral
catalysts remains a challenge and highlights the need to identify
new chemotypes for this purpose. Herein, the discovery and optimization
of a bench-stable chiral 9-hydroxy-9,10-boroxarophenanthrene
catalyst is described and applied in the highly enantioselective desymmetrization
of 2-aryl-1,3-diols using benzylic electrophiles under operationally
simple, ambient conditions. Nucleophilic activation and discrimination
of the enantiotopic hydroxy groups on the diol substrate occurs via
a defined chairlike six-membered anionic complex with the hemiboronic
heterocycle. The optimal binaphthyl-based catalyst 1g features a large aryloxytrityl group to effectively shield one of
the two prochiral hydroxy groups on the diol complex, whereas a strategically
placed “methyl blocker” on the boroxarophenanthrene
unit mitigates the deleterious effect of a competing conformation
of the complexed diol that compromised the overall efficiency of the
desymmetrization process. This methodology affords monoalkylated products
in enantiomeric ratios equal or over 95:5 for a wide range of 1,3-propanediols
with various 2-aryl/heteroaryl groups.
A rapid, mild and metal-free intermolecular cyclopropanation between iodonium ylides and alkene-containing substrates mediated by PhI(OAc)·BuNI is reported. Iodonium ylides of cyclic and acyclic 1,3-dicarbonyls were reacted with a variety of mono-, di-, tri- and tetra-substituted alkenes of various structural types to give 29 cyclopropanes in up to 97% yield.
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