Atroposelective Access to Oxindole-Based Axially Chiral Styrenes via the Strategy of Catalytic Kinetic Resolution

Abstract

Atroposelective synthesis of axially chiral molecules has attracted substantial attention from chemists because of the importance of such molecules. However, catalytic asymmetric synthesis of axially chiral styrenes or vinyl arenes is underdeveloped and challenging due to the low rotational barrier and weak configurational stability of such molecules. Therefore, the development of powerful strategies for the catalytic atroposelective synthesis of axially chiral styrenes or vinyl arenes is of great importance. In this work, we have accomplished the first atroposelective access to oxindole-based axially chiral styrenes by the strategy of catalytic kinetic resolution, and this strategy offered two kinds of oxindole-based axially chiral styrene derivatives in good diastereoselectivities (up to 94:6 dr) and excellent enantioselectivities (up to 98% ee) with high selectivity factors (S up to 106). This strategy not only provides easy access to oxindole-based axially chiral styrenes but also offers a robust method for synthesizing bisamide derivatives bearing both axial and central chirality. More importantly, this strategy has added a new class of members to the atropisomeric family, especially to the family of axially chiral styrenes.

Atropisomerism in Styrene: Synthesis, Stability, and Applications

“…Later, the same group 36 reported a kinetic resolution of indole-based vinyl aniline 128 (Scheme 25). The resolution, featuring a high selectivity factor (S), allowed efficient control of conversion and enantioselectivity and offered an approach to a new class of atropisomeric styrenes.…”

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

“…In the presence of CPA 20 , racemic oxindole-based styrenes reacted with azalactones via hydrogen bonding, and the azalactones underwent asymmetric ring opening to form axially chiral oxindole-based styrenes 85 in up to 53% yield with good diastereoselectivities (up to 94:6 dr) and enatioselectivities (up to 95% ee) . Moreover, the racemic oxindole-based styrenes underwent kinetic resolution to afford other axially chiral styrenes 86 in moderate yields (up to 54%) with excellent enantioselectivities (up to 96% ee) and high selectivity factors (SF up to 106) [ 92 ]. This strategy is critical for accessing axially chiral the oxindole-based styrenes and provides a robust method for the synthesis of bisamide derivatives that are both axially and centrally chiral ( Scheme 28 ).…”

Stereoselective Organocatalytic Construction of Spiro Oxindole Pyrrolidines Using Unsaturated α‐Ketoesters and α‐Ketoamides

“…Other, somewhat less reactive dipolarophiles, such as activated alkynes, allenes, methyleneindolinones, or imines, required stronger Brønsted acid for activation [12] . Oxindol‐core was recently incorporated into axially‐chiral compounds via atroposelective kinetic resolution mediated by Brønsted acids [13] …”