ABSTRACT
The symmetry breaking of meso primary diols bearing a tetrahydropyran ring was employed, using catalytic asymmetric acyl transfer, to control all-carbon quaternary stereocenters. The planar chiral Fu DMAP catalyst was used in this reaction to reach a high degree of enantioselectivity (up to 97:3 e.r.) through a synergic effect combining a desymmetrization step and a kinetic resolution. Moreover, a beneficial effect was exhibited by C6F6 solvent, yielding the first example of an organocatalyzed asymmetric acyl transfer. The desymmetrized monoesters were then used to obtain, after a straightforward ring opening sequence, complex polyketide building blocks bearing all-carbon quaternary stereocenters.
ABSTRACT
The key is symmetry! A convergent synthetic approach of the highly cytotoxic natural product (-)-callystatinâ A was developed assembling three fragments through Julia-Kocienski olefination and Stille cross-coupling. The new strategy relies on a pivotal local symmetry of the target molecule. In this preliminary study, particular attention was devoted to facilitate the catalytic enantiocontrol of strategic stereogenic centers present in each of the fragments (see scheme).
Subject(s)
Fatty Acids, Unsaturated/chemistry , Alkenes/chemistry , Animals , Callyspongia/chemistry , Fatty Acids, Unsaturated/chemical synthesis , StereoisomerismABSTRACT
An unprecedented strategy to access highly enantioenriched dihydropyrazoles is described. It involves formal [4+1] cycloadditions of in situ-derived azoalkenes and sulfur ylides catalyzed by a chiral copper/Tol-BINAP complex. A variety of synthetically and biologically important dihydropyrazoles have been obtained with high enantioselectivities (up to 97:3 er) in good yields (83-97%).
Subject(s)
Alkenes/chemistry , Azo Compounds/chemistry , Pyrazoles/chemical synthesis , Sulfur/chemistry , Catalysis , Crystallography, X-Ray , Cyclization , Models, Molecular , Molecular Structure , Organometallic Compounds/chemistry , Pyrazoles/chemistry , StereoisomerismABSTRACT
A highly convergent and protecting-group-free synthesis of (+)-crocacin C, featuring an enzymatic enantioselective desymmetrization of a meso-diol, a base-induced ring opening of a THP ring, and a one-pot hydrostannylation/Stille coupling as the key steps, is reported. The natural product was obtained in 11 steps and 22.3% overall yield starting from readily available oxabicycle 1. Finally, a unique enantioselective step, an enzymatic desymmetrization, revealed four stereogenic centers and created one in C4 of the THP furnishing the dense building block 4 with high enantioselectivity (ee >98%).
Subject(s)
Alkenes/chemical synthesis , Amides/chemical synthesis , Alkenes/chemistry , Amides/chemistry , Catalysis , Cyclization , Models, Molecular , Molecular Structure , Stereoisomerism , Structure-Activity RelationshipABSTRACT
The enantioselective enzymatic desymmetrization of several highly substituted meso-tetrahydropyranyl diols is described. This transformation leads to valuable building blocks containing up to five stereogenic centers, which are revealed in a single step with both high yields and excellent enantiomeric excesses. Moreover, it was shown that this kind of building blocks could provide an easy access to both enantiomers of highly functionalized stereotetrads.
