Bimetallic tandem catalysis-enabled enantioselective cycloisomerization/carbonyl-ene reaction for construction of 5-oxazoylmethyl α-silyl alcohol.

A bimetallic tandem catalysis-enabled enantioselective cycloisomerization/carbonyl-ene reaction was developed. The reaction proceeded well with a broad range of N-propargylamides and acylsilanes, affording the target chiral 5-oxazoylmethyl α-silyl alcohols in up to 95% yield and 99% ee under mild conditions. Importantly, this facile protocol was available for the late-stage modification of several bioactive molecules. Based on the mechanistic study and control experiments, a possible catalytic cycle and transition state are proposed to elucidate the reaction process and enantioinduction.

Enantioselective Synthesis of Azetidines through [3 + 1]-Cycloaddition of Donor-Acceptor Aziridines with Isocyanides.

The enantioselective [3 + 1]-cycloaddition of racemic donor-acceptor (D-A) aziridines with isocyanides was first realized under mild reaction conditions using a chiral N,N'-dioxide/MgII complex as catalyst, providing a facile route to enantioenriched exo-imido azetidines with good to excellent yield (up to 99%) and enantioselectivity (up to 94% ee). An obvious chiral amplification effect was observed in this system, and an explanation was elucidated based on the experimental investigation and X-ray crystal structure of the enantiomerically pure catalyst.

Asymmetric Catalytic (2+1) Cycloaddition of Thioketones to Synthesize Tetrasubstituted Thiiranes.

Herein, we report the first example of enantioselective (2+1) cycloaddition of thioketones with α-diazo pyrazoleamides for the direct synthesis of tetrasubstituted thiiranes. In the presence of chiral N,N'-dioxide/cobalt(ΙΙ) complexes (2-5 mol%), excellent efficiency (up to 99 % yield within 15 mins) and high stereoselectivity (up to >19 : 1 dr and 97 % ee) are available. Elaborations of thiiranes via desulfuration have also been conducted to deliver tetrasubstituted olefins. Density functional theory calculations reveal that the reaction initiates from a doublet state cobalt(ΙΙ) carbenoid, which is followed by a quartet cobalt(ΙΙ)-bound thiocarbonyl ylide pathway. This work provides a route for the selective construction of tetrasubstituted thiiranes and olefins that are otherwise difficult to access.

Enantioselective Synthesis of Nitriles Containing a Quaternary Carbon Center by Michael Reactions of Silyl Ketene Imines with 1-Acrylpyrazoles.

The enantioselective construction of quaternary carbon centers is a marked challenge in asymmetric catalysis research. It is extremely difficult when a chiral catalyst can not distinguish the facial selectivity of the substrate through bond interactions. Here we realized an enantioselective Michael reaction of silyl ketene imines to 1-acrylpyrazoles using a chiral N,N'-dioxide-Co(II) complex. The protocol is highly efficient for the construction of nitrile-, aryl-, and dialkyl-bearing carbon centers and has been successful applied in the divergent synthesis of pharmaceuticals and natural products. The through-space dispersion interactions between unbound silyl ketene imines and the 1-acrylpyrazole-bonded catalyst play a key role in facilitating the reactivity and the enantioselectivity of this process.