Copper-catalyzed asymmetric tandem double Michael reactions of diethylzinc to α,β-unsaturated ketones followed by trapping with nitroolefins

Recent Developments in Enantioselective Domino Reactions. Part B: First Row Metal Catalysts

“…Earlier in 2019, Hu and Hou reported an enantioselective three-component copper-catalyzed domino double Michael reaction of α,β-unsaturated ketones 112 with nitroolefins 113 and ZnEt 2 using chiral P,Nligands. [36] The optimal catalyst was in situ generated from only 2 mol% of CuCl and 2.5 mol% of chiral ligand 114. Performed at 0 °C in toluene as solvent, the reaction afforded a wide range of functionalized chiral products 115 exhibiting three contiguous stereocenters as single diastereomers with good yields (65-88%) and uniformly excellent enantioselectivities (90-97% ee), as illustrated in Scheme 29.…”

“…Earlier in 2019, Hu and Hou reported an enantioselective three‐component copper‐catalyzed domino double Michael reaction of α,β‐unsaturated ketones 112 with nitroolefins 113 and ZnEt 2 using chiral P,N‐ligands [36] . The optimal catalyst was in situ generated from only 2 mol% of CuCl and 2.5 mol% of chiral ligand 114 .…”

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

“…In contrast to conjugate additions to nitroolefins, these activated alkenes can also be utilized in the enolate trapping step. In the last decade, several highly stereoselective methodologies have been published that demonstrate the Cu- or Ni-catalyzed conjugate addition of organozincs to α,β-unsaturated ketones 14 followed by the reaction of the metal enolate with a nitroolefin ( 20 ) ( Table 1 ) [ 30 – 33 ]. These reactions were facilitated by different ligand families (phosphite/phosphine-pyridine amide, phosphine-sulfoxide, phosphoramidite, MINBOL, see Figure 1 ) and they usually showed excellent diastereoselectivity (dr >20:1).…”

Recent Advances in Selected Asymmetric Reactions Promoted by Chiral Catalysts: Cyclopropanations, Friedel–Crafts, Mannich, Michael and Other Zinc-Mediated Processes—An Update

“…The appropriate β-difluoromethylated carbonyl compounds 84 were formed with enantioselectivities around 80% of ee in high to excellent chemical yields [79]. Chiral P,N-ligands 88 were also used in copper-mediated tandem double Michael reactions of diethylzinc to α,β-unsaturated ketones 86 followed by trapping with nitroalkenes 87 (Scheme 32) [80]. The corresponding tandem products were in high yields and with excellent enantioselectivities [80].…”

“…Chiral P,N-ligands 88 were also used in copper-mediated tandem double Michael reactions of diethylzinc to α,β-unsaturated ketones 86 followed by trapping with nitroalkenes 87 (Scheme 32) [80]. The corresponding tandem products were in high yields and with excellent enantioselectivities [80]. Silyl ethers of diarylprolinol were also used in the highly stereoselective synthesis of spiro pyrazolones via Michael/Conia-ene cascade reaction [82] and in the synthesis of biaryl atropoisomers via domino Michael-Henry reaction affording the substituted nitrocyclohexanecarbaldehydes [83].…”