Wacker Oxidation of Methylenecyclobutanes: Scope and Selectivity in an Unusual Setting

Methylenecyclobutanes are found to undergo Wacker oxidation via a semi-pinacol-type rearrangement. Key to a successful process is the use of tert-butyl nitrite as oxidant, which not only enables efficient catalyst turn-over but also ensures high Markovnikov-selectivity under mild conditions. Thus, cyclopentanones (26 examples) can be accessed in an overall good yield and excellent selectivity (up to 97 % yield, generally >99 : 1 ketone:aldehyde ratio). Stereochemical analysis of the reaction sequence reveals migration aptitudes in line with related 1,2-shifts. By introducing a pyox ligand to palladium, prochiral methylenecyclobutanes can be desymmetrized, thus realizing the first enantioselective Wacker oxidation.     

Asymmetric synthesis of novel spirocycles via a chiral phosphoric acid catalyzed desymmetrization

A straightforward method for the asymmetric preparation of novel lactone and lactam spirocycles is described. An initial desymmetrization via a chiral Brønsted acid yields enantioenriched lactones which readily undergo a second cyclization to give the desired spirocycle.     

Desymmetric hydrogenation of a meso-cyclic acid anhydride toward biotin synthesis

Catalytic reactivity in the hydrogenation of a cyclic anhydride to a biotin synthetic intermediate has been investigated on the basis of Lyons’ original method using Wilkinson Ru complex, revealing the high performance of DPPF and XANTPHOS diphosphines possessing wide bite angles. The results have shown a new trail for design of the corresponding asymmetric catalysts, and the potential utility of (S,S)-Et-FerroTANE and (S,S)-(R,R)-Ph-TRAP has been demonstrated.     

Application of oxetane ring opening toward stereoselective synthesis of zincophorin fragment

A stereoselective synthesis of the C1–C11 fragment of zincophorin was achieved by using an intramolecular oxetane ring opening reaction as the key step. The oxetane moiety was synthesized by employing a desymmetrization protocol developed at our group and a non-Evans syn aldol as the key steps toward the synthesis.     

Recent advances of desymmetrization protocol applied in natural product total synthesis

Desymmetrization synthesis strategy has simplified and improved the efficiency of synthesis, which attracted great attention in the past few decades. Since the strategy has been developed rapidly and got a wide range of applications in natural product total synthesis, the rules are urgent to be summarized. In this Letter, the recent developments of desymmetrization protocol in natural product total synthesis were summarized.     

Studies towards the total synthesis of (−)-callystatin A

The synthesis of C₁-C₁₂ and C₁₃-C₂₂ fragments of (−)-callystatin A is accomplished employing desymmetrization strategy for the creation of five chiral centres of the polypropionate fragment and application of cross-metathesis (CM) reaction for the first time for this molecule.     

Highly efficient selective monohydrolysis of dialkyl malonates and their derivatives

The highly efficient selective monohydrolysis of symmetric diesters has been applied to monohydrolysis of several dialkyl malonates and their derivatives. The best conditions apply 0.8-1.2 equiv of aqueous KOH with a co-solvent, THF or acetonitrile, at 0 °C. The procedure is highly practical, yielding the corresponding half-esters in high yields in a straightforward manner, without inducing decarboxylation. It was found that the selectivity tends to become higher with increased hydrophobicity.     

Desymmetrization by direct cross-metathesis producing hitherto unreachable P-stereogenic phosphine oxides

Desymmetrization of prochiral di- and trialkenyl phosphine oxides by cross-metathesis with various olefinic partners allowed direct access to novel racemic P-stereogenic products featuring two or three different alkenyl groups. The excellent control of product selectivity and E/Z selectivity allowed the preparation of desymmetrized products in good yields from readily available precursors. These are the first examples of desymmetrization of prochiral substrates by direct cross-metathesis.     

Recent examples of the use of biocatalysts with high accessibility and availability in natural product synthesis

Utilization of biocatalysts with high accessibility and availability, which have recently been applied in the preparation of enantiomerically enriched starting materials and synthetic intermediates for natural product syntheses (mainly 2013–2017) are summarized in this review. The main contents are as follows: 1) recruitment of biocatalysts for the transformation of organic compounds; 2) special precautions for preparative-scale biocatalytic synthetic experiments; 3) asymmetric reduction of carbonyl substrates; 4) kinetic resolution of alcohol and carboxylate enantiomers; 5) desymmetrization of multifunctional alcohol and carboxylate substrates; and 6) recognition of remote and non-central chirality.