Chiral bicyclic guanidine-catalyzed enantioselective reactions of anthrones

Chiral bicyclic guanidine 1 was found to be an excellent catalyst for reactions between anthrones and various dienophiles. The catalyst can tolerate a range of substituents and substitution patterns, making several anthrone derivatives suitable for this reaction. Both Diels-Alder and Michael adducts were obtained in excellent yields, high regioselectivities, and high enantioselectivities. This is the first case of a highly enantioselective base-catalyzed anthrone Diels-Alder reaction.     

Enantioselective Michael addition of anthrone to nitroalkenes catalyzed by bifunctional thiourea-tertiary amines

A highly bifunctional thiourea-tertiary amine-catalyzed enantioselective Michael addition reaction of anthrone to a wide variety of nitroalkenes has been developed, and the corresponding adducts were obtained smoothly in high yields (up to 97%) and good enantioselectivities (up to 94% ee).     

Enantioselective synthesis of nitrocyclopropanes via conjugate addition of bromomalonate to nitroalkenes catalyzed by Ni(II) complexes

A novel one-pot methodology for the catalytic enantioselective synthesis of highly functionalized nitrocyclopropanes promoted by chiral nickel complexes is developed. The treatment of bromomalonates with nitroalkenes under the mild reaction conditions afforded the corresponding Michael adducts which cyclizes to controlled reaction conditions with excellent diasteroselectivities (>99 de) and enantioselectivities (up to 99% ee).     

Enantioselective 1,6-Michael addition of anthrone to 3-methyl-4-nitro-5-alkenyl-isoxazoles catalyzed by bifunctional thiourea-tertiary amines

A simple and efficient method for the enantioselective 1,6-Michael addition reaction of anthrone to a series of 3-methyl-4-nitro-5-alkenyl-isoxazoles with a bifunctional thiourea-tertiary amine as catalyst is described. This transformation proceeds smoothly with 10 mol % catalyst and provides a series of Michael adducts bearing 3-methyl-4-nitro-isoxazole and anthrone units with good to high enantioselectivities (up to 96% ee) and in very high yields (up to 99%).     

Chiral primary amine thiourea promoted highly enantioselective Michael reactions of isobutylaldehyde with maleimides

Chiral primary amine thiourea catalysts were first successfully applied to promote Michael addition of isobutyraldehyde to maleimides. A variety of N-aryl and N-aliphatic maleimides provided Michael adducts in excellent yields (up to 98%) and enantioselectivities (up to 99% ee) with 5 mol % catalyst.     

Organocatalyzed asymmetric Michael reaction of β-aryl-α-ketophosphonates and nitroalkenes

The first enantioselective Michael reaction of β-aryl-α-ketophosphonates and nitroalkenes has been realized by using a new bifunctional Takemoto-type thiourea catalyst. The primary Michael adducts obtained were converted in situ to the corresponding amides through the aminolysis. High yields, excellent diastereoselectivities (>95:5 dr), and good enantioselectivities (up to 81% ee) have been achieved for the corresponding α,β-disubstituted γ-nitroamides. This reaction again demonstrated that α-ketophosphonates are interesting pronucleophiles that can be used as amide surrogates in organocatalyzed reactions.     

Enantioselective Michael addition of isobutyraldehyde to nitroalkenes organocatalyzed by chiral primary amine-guanidines

Primary amine-guanidines derived from trans-cyclohexane-1,2-diamines are used as organocatalysts for the enantioselective conjugate addition of isobutyraldehyde to arylated and heteroarylated nitroalkenes. The reaction was performed in the presence of imidazole as the additive in aqueous DMF as the solvent at 0 °C. The corresponding Michael adducts bearing a new stereocenter were obtained in high yields and with enantioselectivities of up to 80%. Theoretical calculations are used to justify the observed sense of the stereoinduction.     

Asymmetric carbon-carbon bond formations by conjugate additions of lithiated N-boc allylic amines to nitroalkenes: enantioselective synthesis of functionalized cyclopentanoids

[reaction: see text] Allylic organolithiums generated by enantioselective deprotonation of N-Boc-N-(p-methoxyphenyl) allylic amines undergo conjugate additions with nitroalkenes to provide enecarbamates containing two contiguous stereogenic centers in good yields with high diastereoselectivities and enantioselectivities. Further elaboration of these adducts to enantioenriched substituted cyclopentanones and aminocyclopentanes is reported.     

Pyrrolidine-thiourea as a bifunctional organocatalyst: highly enantioselective Michael addition of cyclohexanone to nitroolefins

[reaction: see text] Asymmetric Michael additions of cyclohexanone to both aryl and alkyl nitroolefins in the presence of 20 mol % of organocatalyst 2b and 10 mol % of n-butyric acid afford adducts 5 with high diastereoselectivities and enantioselectivities.     

Conjugate addition of 1,3-dicarbonyl compounds to maleimides using a chiral C2-symmetric bis(2-aminobenzimidazole) as recyclable organocatalyst

The recyclable chiral 2-aminobenzimidazole-derived organocatalyst 1f efficiently promotes the room temperature asymmetric conjugate addition of 1,3-diketones, β-ketoesters, and malonates to maleimide and N-substituted maleimides, affording the corresponding Michael adducts in excellent yields and enantioselectivities even at gram scale.     

Aromatic l-prolinamide-catalyzed asymmetric Michael addition of aldehydes to nitroalkenes

Two chiral aromatic l-prolinamides were synthesized in high overall yield (95%) from N-Boc-l-proline and served as organocatalysts in asymmetric Michael reactions of aldehydes to nitroalkenes. Under the optimized reaction conditions, (S)-N-tritylpyrrolidine-2-carboxamide 4 was found to be a highly efficient organocatalyst for the Michael addition, and the corresponding Michael adducts were obtained in good yields (up to 94%), with excellent enantioselectivities (up to 99% ee) and diastereoselectivities (up to 99:1 dr).     

Chiral amine thiourea-promoted enantioselective Michael addition reactions of 3-substituted benzofuran-2(3H)-ones to maleimides

A highly diastereo- and enantioselective Michael addition reaction with respect to prochiral 3-substituted benzofuran-2(3H)-ones and maleimides by a chiral bifunctional thiourea-tertiary amine catalyst was investigated. The corresponding adducts, containing a quaternary center at the C3-position of the benzofuran-2(3H)-one as well as a vicinal tertiary center, were generally obtained in high yields (up to 99%) with very good diastereo- (up to >20:1 dr) and enantioselectivities (up to 97% ee).     

Organocatalytic synthesis of quaternary stereocenter bearing a fluorine atom: enantioselective conjugate addition of α-fluoro-β-ketoesters to nitroalkenes

The catalytic enantioselective conjugate addition reaction of α-fluoro-β-ketoesters to nitroalkenes promoted by chiral bifunctional organocatalysts is described. The treatment of α-fluoro-β-ketoesters with nitroalkenes under mild reaction conditions afforded the corresponding Michael adducts containing a fluorinated quaternary stereogenic center with excellent enantioselectivity (up to >99% ee).     

Chiral squaramides catalyzed diastereo- and enantioselective Michael addition of α-substituted isocyanoacetates to N-aryl maleimides

An efficient diastereo- and enantioselective Michael addition of α-substituted isocyanoacetates to N-aryl maleimides catalyzed by quinine or cyclohexane-1,2-diamine derived squaramide catalysts has been disclosed, affording the corresponding adducts in good yields (up to 99%), high diastereoselectivities (up to >20:1 dr) and good to excellent enantioselectivities (up to 94% ee) under mild conditions.     

Diastereodivergent Asymmetric Michael Addition of Cyclic Azomethine Ylides to Nitroalkenes: Direct Approach for the Synthesis of 1,7‐Diazaspiro[4.4]nonane Diastereoisomers

The first highly diastereoselective and enantioselective catalytic asymmetric Michael addition of cyclic azomethine ylides with nitroalkenes have been developed to diastereodivergently generate either the syn or anti adducts by employing N,O‐ligand/Cu(OAc)₂ and N,P‐ligand/Cu(OAc)₂ catalytic systems. Both catalytic systems exhibit broad substrate applicability to afford the corresponding Michael adducts in good to excellent yields, with excellent levels of diastereo‐ (up to 99:1 diastereomeric ratio) and enantioselectivities (up to >99 % enantiomeric excess). Importantly, the chiral 1,7‐diazaspiro[4.4]nonane diastereomer derivatives can be easily obtained in good yields through facile NaBH₄ reduction of the Michael adducts.     

Asymmetric Michael Additions of α-Nitrocyclohexanone to Aryl Nitroalkenes Catalyzed by Natural Amino Acid-Derived Bifunctional Thioureas

A series of new thiourea catalysts prepared from natural amino acids have been applied in organocatalytic asymmetric Michael additions of α-nitrocyclohexanone to nitroalkenes. The resulting addition products are formed with excellent enantioselectivities (up to an er of 98:2) in good yields (up to 90%).     

Catalytic asymmetric Michael addition with curcumin derivative

Catalytic asymmetric Michael additions with curcumin derivatives were achieved by a new series of tertiary amine-thiourea organocatalysts to afford the Michael adducts in high yields and excellent enantioselectivities.     

Asymmetric Michael reactions of α,α-disubstituted aldehydes with maleimides using a primary amine thiourea organocatalyst

Primary amine thiourea organocatalyst 8 was used to promote Michael additions of bulky α,α-disubstituted aldehydes, such as isobutyraldehyde with maleimides to afford the corresponding adducts in high to excellent yields and with up to 91% ee.     

Enantioselective Michael additions of aldehydes to nitroalkenes catalyzed with ionically tagged organocatalyst

Enantioselective organocatalytic Michael additions affords useful building blocks for many biologically and medicinally relevant compounds. Ionically-tagged diphenylprolinol silyl ether efficiently catalyzes several Michael additions of aldehydes to nitroalkenes in ionic liquids. The Michael additions work well in ionic liquids; yields up to 95% and enantioselectivities up to 95% ee were achieved. Furthermore, in some cases, the catalytic system was reusable.      

Silver-catalyzed diastereo- and enantioselective Michael additions of 2-oxazoline- and 2-thiazoline-4-carboxylate to nitroalkenes

The silver/ThioClickFerrophos (a chiral ferrocenyl P,S-ligand)-catalyzed Michael additions of 2-oxazoline- and thiazoline-4-carboxylate to nitroalkenes were highly anti-selective and enantioselective and produced the corresponding adducts in high yields.