Induction of Planar Chirality Using Asymmetric Click Chemistry by a Novel Desymmetrisation of 1,3‐Bisalkynyl Ferrocenes

Abstract

The Front Cover shows the first use of the new asymmetric CuAAC click reaction to induce planar stereogenicity. Stereodifferentiation in asymmetric induction (in the first CuAAC) and kinetic resolution (in the second CuAAC) are both influenced by (R,R)‐Ph‐Pybox ligands on copper and so both contribute to the observed ees of the chiral monotriazole products. We acknowledge Daniel Starling for graphic design and QuteMol for images of space filling models of Ph‐Pybox which were generated from xyz data obtained by DFT calculations by the authors using Gaussian. More information can be found in the Full Paper by G. R. Stephenson et al.

Planar Chiral Pseudo‐Isocoumarins by Copper Catalysed Desymmetrisation

“…Although both of these ligands successfully generated an ee , we were disappointed that neither could improve on the original result. We found it particularly surprising that no ee was generated when using bisoxazoline ligand ( S,S )‐Ph‐box, although this could indicate that kinetic resolution played a major role in the ee generated in an analogous asymmetric copper catalysed azide‐alkyne cycloaddition reaction [30] . This copper‐ligand catalyst system cannot discriminate between the two enantiotopic alkynes in this process, so it is unlikely that ee is generated in an asymmetric induction process with an analogous compound in an asymmetric click reaction.…”

Catalytic Enantioselective Construction of Chiroptical Boron-Stereogenic Compounds

“…In the presence of Cu­(CH 3 CN) 4 PF 6 (10 mol %) as the catalyst, BOX L1 – L3 (12 mol %) as the chiral ligands, and DABCO (1,4-diazabicyclo[2.2.2]­octane, 2.0 equiv) as the base in CHCl 3 at room temperature, the reaction between 1a with benzyl azide 2a successfully delivered the desired monocycloaddition product 3a , albeit in low yields with poor selectivities (Table , entries 1–3). In fact, the sense of the remote stereochemical information on the catalyst’s ligand environment and the overreaction toward undesired ditriazole are two severe problems in desymmetric CuAAC reactions. − To address these issues, bulky indane-fused BOX ligands L4 – L6 were tested in the transformation. The corresponding product 3a could be obtained in 24–64% yields with 41–54% ee (entries 4–6).…”

“…Herein, we report the exploration and realization of the first catalytic enantioselective construction of boron-stereogenic compounds via an asymmetric copper-catalyzed azide–alkyne cycloaddition reaction (CuAAC) (Scheme c). Despite that the CuAAC reaction has been intensively studied and has found numerous applications in many areas of research, − asymmetric CuAAC is largely unexplored until recently. − In 2005, Fokin, Finn, and co-workers pioneered the study, proving the feasibility of enantioselective CuAAC via desymmetrization or kinetic resolution . In 2013, Zhou and co-workers developed a highly enantioselective CuAAC by desymmetrizing oxindolediynes, which allowed the successful construction of carbon stereogenic centers .…”

“…In 2013, Zhou and co-workers developed a highly enantioselective CuAAC by desymmetrizing oxindolediynes, which allowed the successful construction of carbon stereogenic centers . Later, a handful of desymmetric CuAAC reactions of prochiral dialkynes were also reported. ,,− ,, Here, assisted by an indane-fused bisoxazoline (BOX) ligand with two large bulky side arms, , this enantioselective CuAAC reaction not only gives access to a wide range of novel highly functionalized boron-stereogenic heterocycles in high yields with good to excellent enantioselectivities but also produces optically active terminal alkyne and triazole moieties with various potential application prospects. Further transformation of the chiral tetracoordinate boron compounds delivers several complex heterocyclic entities bearing boron-stereogenic centers without the loss of enantiopurity.…”

Highly Enantioselective CuAAC of Functional Tertiary Alcohols Featuring an Ethynyl Group and Their Kinetic Resolution

“…This is because asymmetric CuAAC is very challenging and successful methods are limited, [17] despite the wide application of CuAAC since its discovery by the groups of Meldal [18a] and Sharpless [18b] . Apart from some desymmetrization protocols that reported by our group [19] and Uozumi, [20a,b] Xu, [20c–e] Stephenson, [20f] the use of CuAAC for KR has met with only limited success [21] . Early attempts at KR of α‐benzylic azides [21a] and 3‐propargyl oxindole [21b] afforded moderate selectivity, and while a highly enantioselective synthesis of α‐triazoles from racemic azides was achieved by Topczewski recently, the corresponding KR gave unsatisfactory results [22] .…”