An Efficient Synthesis of Chiral Diamines with Rigid Backbones: Application in Enantioselective Michael Addition of Malonates to Nitroalkenes

Abstract

A new and efficient route for synthesis of enantiomerically pure biisoindoline and its isomer based on the diaza-Cope rearrangement reaction with chiral 1,2-bis(2-hydroxylphenyl)-1,2-diaminoethane as starting material has been developed. The newly prepared biisoindoline was employed as a chiral ligand in the Ni(II)-catalyzed enantioselective Michael addition of malonates to conjugated nitroalkenes, and good to excellent enantioselectivities were obtained.

Recent Developments in Enantioselective Nickel(II)‐Catalyzed Conjugate Additions

“…In situ generated chiral nickel(II) catalysts have also been applied to induce chirality in these reactions. As a recent example, Huang and Xia have designed new chiral diamines, such as bisisoindolines with a rigid backbone, which were prepared through a rapid and reliable procedure based on a diaza‐Cope rearrangement reaction with chiral 1,2‐bis(2‐hydroxyphenyl)‐1,2‐diaminoethane as starting material for the first time 30. Among them, chiral bisisoindoline 5 was found as optimal ligand of NiBr 2 to promote the nickel(II)‐catalyzed conjugate addition of malonates to nitroalkenes, providing high yields and good enantioselectivities of up to 90% ee , as shown in Scheme ( second part ).…”

Chiral 1,1′‐Bi(tetrahydroisoquinoline)‐Type Diamines as Efficient Ligands for Nickel‐Catalysed Enantioselective Michael Addition to Nitroalkenes

“…Most systems that are used in this respect employ readily available trans ‐1,2‐diaminocyclohexane (DACH; 1 ) or 1,2‐diphenylethane‐1,2‐diamine (DPEN; 2 ) derivatives (Figure 1). A further increase of rigidity of DPEN‐derived ligands was exemplified by the incorporation of two phenyl groups into a 1,1′‐bi(isoindoline) moiety, such as in ligand 4 7. However, despite straightforward synthetic access to structurally related, chiral 1,1′‐bi(tetrahydroisoquinolines),8 such diamines have rarely been utilised as chiral ligands 8c.…”

Cyclization vs. Cyclization/Dimerization in o-Amidostilbene Radical Cation Cascade Reactions: The Amide Question

“…Creative bisindoline construction is also increasing in importance as recent developments clearly indicate. For example, the highly efficient successive amide transfer approach leading to C2 symmetric bisindolines [ 7 ]; diaza-Cope rearrangement resulting in C3-C3’ bisisoindolines [ 8 ] and the [CoCl(PPh 3 ) 3 ] mediated indolyl bromide homolyisis/dimerisation [ 9 ].…”