Silicon‐based Bulky Group−Tuned Parallel Kinetic Resolution in Copper‐Catalyzed 1,3‐Dipolar Additions

Abstract

The development of new strategies or reaction processes that tease new reactivity of functional groups continues to spur synthetic chemists toward innovative solutions that access new compounds. Herein, we find that the silicon‐based bulky group enables a 1,3‐dipolar addition−initiated parallel kinetic resolution (PKR) to occur unexpectedly, leading to the highly enantioselective synthesis of two structurally different types of amino acid derivatives via chemodivergent [3+2] cycloaddition reactions and tandem conjugate addition‐elimination reaction respectively. The resulting and structurally divergent enantioenriched amino acid derivatives that contain four contiguous stereogenic centers and an all‐carbon quaternary center were obtained with up to 99% ee with >95:1 dr and good yields.magnified image

Mechanistic Details of Asymmetric Bromocyclization with BINAP Monoxide: Identification of Chiral Proton-Bridged Bisphosphine Oxide Complex and Its Application to Parallel Kinetic Resolution

“…Finally, we sought to develop a chemodivergent PKR of racemic ene-yne 17 (Table ). As shown in Table , the cyclization products were formed at essentially equal reaction rates, regardless of the electronic difference between terminal alkene and internal alkene.…”

Current applications of kinetic resolution in the asymmetric synthesis of substituted pyrrolidines

“…In 2018, Xu and co-workers developed a parallel kinetic resolution involving a copper catalysed 1,3-dipolar cycloaddition between racemic Morita-Baylis-Hillman (MBH) adducts rac-146 and glycine aldimino esters (Scheme 43). 107 Pyrrolidines containing four stereogenic centres including one all-carbon quaternary were obtained in excellent diastereoselectivities and enantioselectivities. Glutamic acid derivatives were also produced during the reaction and were obtained in similarly excellent enantioselectivities.…”

The Discovery of Multifunctional Chiral P Ligands for the Catalytic Construction of Quaternary Carbon/Silicon and Multiple Stereogenic Centers

“…Having demonstrated the 1,3-dipolar addition of glycine aldimino esters with activated alkenes, we were interested in investigating more novel diastereo- and enantioselective homo-1,3-dipolar [3 + 2] cycloadditions of glycine aldimino esters 58 with various electrophilic reagents, such as Morita–Baylis–Hillman (MBH)-type acetates and silyl ethers, 1,1-disubstituted cyclopropenes, and aromatic imines (Scheme ). With Ag/Xing-Phos as the catalyst, a variety of chiral imidazolidines 76 bearing three stereocenters were obtained with high ee values (16 examples, up to 99% ee) and diastereoselectivities (up to 96:4 dr) . In addition, the polymerization of glycine aldimino esters provided chiral polyimidazolidines in high yields (91–96%).…”