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

Abstract

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.

Desymmetric Partial Reduction of Malonic Esters

“…The capability of the desymmetrization to access aldehydes directly, together with the versatile reactivity of the carbonyl, provided a convenient entry point to a variety of natural products and bioactive molecules containing a quaternary stereocenter. For example, the Horner–Wadsworth–Emmons (HWE) olefination of aldehyde 46-al , followed by hydrogenation and imide ring closure, expeditiously gave glutethimide ( 60 ), a hypnotic sedative, in its enantioenriched form (Figure A) . Aldol reactions are also applicable to the chiral aldehydes ( 35 and 37 ), and naturally occurring yezo’otogirin G and H ( 63 and 64 ) were obtained in excellent enantioselectivity after a facile oxidation of the adducts 61 and 62 (Figure B).…”

Chemistry of Ketene Transformation to Gasoline Catalyzed by H-SAPO-11

“…Ketene (CH 2 CO) is an important intermediate in organic synthesis. − Recently, it was identified as the intermediate in a number of reactions, such as syngas conversion to hydrocarbons over bifunctional metal oxide and zeolite composite catalysts (OXZEO), − methanol to hydrocarbons (MTH), − dimethyl ether (DME) carbonylation to methyl acetate, − and CO 2 hydrogenation to hydrocarbons. , In syngas conversion, CH 2 CO could be a carrier for the CH 2 intermediate, which is produced from the hydrogenation of the surface carbon species following the reaction with CO . It has been successfully detected by highly sensitive synchrotron-based vacuum ultraviolet photoionization mass spectrometry over ZnCrO x under syngas conversion conditions, although it is known to be very active and difficult to detect experimentally .…”

Chiral Cyclopropenimine‐catalyzed Asymmetric Michael Addition of Bulky Glycine Imine to α,β‐Unsaturated Isoxazoles

“…The asymmetric Michael additions can be realized by various chiral metal-or organo-catalysts to provide Michael adducts in high yields and enantioselectivities. [1][2][3] With the Renaissance of organocatalysis, [4][5][6][7] many chiral organocatalysts have been discovered to inspire different activation modes in organic synthesis. Among them, chiral Brønsted acids, chiral hydrogenbonding catalysts, and chiral bifunctional amines are very attractive for their structural diversity and high efficiency in catalytic asymmetric synthesis.…”

“…The asymmetric Michael addition is regarded as a very important reaction for chiral C−C and C−X (X is heteroatom) bond formations in modern organic synthesis. The asymmetric Michael additions can be realized by various chiral metal‐ or organo‐ catalysts to provide Michael adducts in high yields and enantioselectivities [1–3] . With the Renaissance of organocatalysis, [4–7] many chiral organocatalysts have been discovered to inspire different activation modes in organic synthesis.…”