Organocatalytic Michael Addition of Naphthoquinone with α,β‐Unsaturated Ketones: Primary Amine Catalyzed Asymmetric Synthesis of Lapachol Analogues

Abstract

A highly efficient organocatalytic synthesis of lapachol analogues from the Michael addition of naphthoquinone to various α,β‐unsaturated ketones catalyzed by primary amines is presented. Good to high yields (up to 93 %) and high to excellent enantioselectivities (up to 98 % ee) were obtained for the target compounds. MS (ESI) provided evidence for the key intermediates in the proposed mechanism.

Catalytic asymmetric reactions and synthesis of quinones

“…cinchonidine amine C21 in combination with TFA as a co-catalyst (Scheme 27). 62 α,β-Unsaturated ketone 112 with various substitutions at the phenyl group reacted well with 2-hydroxy-1,4-naphthoquinone 12 to afford the corresponding products 114 in good to excellent yields and enantioselectivities. Cycloalkenones 113 were also investigated and found to give the corresponding products 115 in high yields and enantioselectivities.…”

Advanced Routes in Synthesis and Reactions of Lawsone Molecules (2‐Hydroxynaphthalene‐1,4‐dione)

“…Stirring 1 with cyclopent‐2‐en‐1‐one or cyclohex‐2‐en‐1‐one in THF in the presence of trifloroacetic acid afforded (R)‐2‐hydroxy‐3‐(3‐oxocyclopentyl)naphthalen‐1,4‐dione ( 118a ) or (R)‐2‐hydroxy‐3‐(3‐oxocyclohexyl)naphthalen‐1,4‐dione ( 118b ), respectively (Scheme ).…”

Enantioselective Michael Addition of Cyclic β-Diones to α,β-Unsaturated Enones Catalyzed by Quinine-Based Organocatalysts

“…Therefore, a broad range of conjugate additions of α,β-unsaturated enones with various different nucleophiles have been successfully established with constantly high enantiocontrol [ 15 , 16 , 17 , 18 , 19 ]. However, the asymmetric Michael addition of cyclic 1,3-dicarbonyl compounds [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ], except for 4-hydroxycoumarin and its analogues [ 7 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ], to α,β-unsaturated enones, especially chalcones, generally draws less attention in comparison with other type of donors [ 37 , 38 , 39 ], albeit the adducts of such a conjugate addition reaction are versatile precursors to construct several classes of compounds possessing enormous bioactivities [ 40 , 41 ]. Liu and Feng have successfully developed an efficient Michael addition between dimedone and cinnamones employing the unmodified chiral diphenylethylenediamine (DPEN) [ 37 ].…”

“…Based on our continuous interest in asymmetric Michael reactions involving α,β-unsaturated enones [ 42 , 43 , 44 , 45 ], herein we would like to further extend the scope of donor to cyclic β-diones [ 20 , 21 , 22 , 23 , 46 , 47 , 48 , 49 ]. Dimedone and its analogues smoothly react with a variety of α,β-unsaturated enones, furnishing the corresponding adducts in good yields and high levels of optical purities.…”