Asymmetric Intramolecular Desymmetrization of meso-α,α′-Diazido Alcohols with Aryldiazoacetates: Assembly of Chiral C₃ Fragments with Three Continuous Stereocenters

Abstract

The chiral Cu-complex-catalyzed intramolecular interception of meso-α,α'-diazido alcohols with aryldiazoacetates is explored. Most of the enantioenriched α-imino esters with three continuous stereocenters are produced with good to excellent yield and enantioselectivity, and a chiral pocket model is proposed for rationalization of the asymmetric desymmetrization.

Synthesis of Isoindoles from Intramolecular Condensation of Benzyl Azides with α-Aryldiazoesters

“…The rhodium­(II)-catalyzed interception of the diazo compounds with organic azides was initially reported by Wee and co-workers, and two unexpected imines were observed during their exploration of the C–H insertion with indoline diazoamides . Then the conversion was confirmed by Lecourt and Micouin and further explored in our group and the Doyle group, demonstrating its excellent efficiency in the synthesis of α-imine esters. We envisioned that the isoindole 2a could be accessed with the interception reaction of 1a , featuring an azidomethyl moiety attached on the ortho -position of the α-aryldiazoester (Scheme ).…”

“…The isoindole 4a had been previously prepared by Mathias’s group . Azides 4b – 4m were prepared according to our previously reported procedure, and isochromanones 3a was purchased from Accela. The lactones 3b , 3c , 3e , 3f , 3g , 3h , 3i , 3k , 3l were prepared from the known dicarboxylic acids.…”

Enantioselective Cu(I)-Catalyzed Cycloaddition of Prochiral Diazides with Terminal or 1-Iodoalkynes

“…The desymmetrization of prochiral azides is a potentially useful strategy to access multifunctional chiral azides, as shown by intramolecular desymmetric cyclization of diazides to chiral 5,6-dihydro-1,4-oxazin-2-ones developed by Gu et al However, exploiting intermolecular desymmetrization of diazides is very challenging because it is difficult to achieve excellent enantiotopic group discrimination while suppressing side difunctionalization, due to the linear shape of azide group without bulky shielding group. This is clearly demonstrated by the only precedent shown in eq 1. , To examine whether our recently developed PYBOX ligands bearing a bulky shielding group offer a flexible solution to develop asymmetric CuAAC, , we first designed a prochiral diazido alcohol 1 for reaction development.…”

Enantioselective Construction of Cyclobutanes: A New and Concise Approach to the Total Synthesis of (+)-Piperarborenine B

“…We began our study by using side-arm-modified BOX (SaBOX) ligand L1 with two pendant benzyl groups as side arms − and copper perchlorate as the catalyst and 4-methoxystyrene ( 2a ) as a model substrate (Table ). When performed at room temperature or 0 °C, the reaction proceeded very fast and was complete within a few minutes but without any chiral induction (entries 1 and 2).…”