Newly designed optically active cage type 2-azanorbornane-based amino amide organocatalysts were developed and employed in the asymmetric Michael addition of β-keto esters with nitroolefins to afford the chiral Michael adducts with good chemical yields (up to 99%) and stereoselectivities (up to diastereomeric ratio (dr) = 97 : 3, up to 96% enantiomeric excess (ee)).

Over recent decades, enantioselective organocatalysis has garnered significant attention within the dominion of organic chemistry. This field offers the potential for intricate organic transformations with high stereoselectivity, employing small-molecule organic compounds as catalysts. Chiral primary beta-amino alcohols and primary alpha-amino amides, which feature adjacent enamine (Br & oslash;nsted base site) and hydrogen-bonding sites (Br & oslash;nsted acid site), along with flexible bulky substituents to modulate steric factors, are highly valuable multifunctional organocatalysts. Their characteristics make them cost-effective alternatives, as they are easily synthesized, airstable, and adaptable for introducing various functional groups and adjusting steric environments. Isatin derivatives, particularly 3-substituted-3-hydroxyindolin-2-ones, have garnered significant interest from both organic and medicinal chemists due to their presence in several natural products and drug candidates. Acknowledging the significance of straightforward organocatalysts and 3-substituted-3-hydroxyindolin-2-ones, this study reveals the catalytic efficiency of primary beta-amino alcohols and primary alpha-amino amides in enantioselective reactions involving isatins to produce 3-substituted-3-hydroxyindolin-2-ones.

Distinct types of new boron fused primary amino amide organocatalysts were designed and synthesized from commercially available amino acids. Their catalytic activities were investigated in asymmetric crossed aldol reaction of ketones with aromatic aldehydes to afford the corresponding chiral anti-aldol adducts with good chemical yields, moderate diastereoselectivity and good to excellent enantioselectivities (up to 94% yields, up to 90 : 10 dr, up to 94% ee).

Catalytic functionality of new optically active thiourea fused γ-amino alcohols was examined in the asymmetric Mannich reaction of β-keto active methylene compounds with imines to afford chiral Mannich products, β-amino keto compounds, with continuous chiral centers, that are versatile synthetic intermediates for deriving various biologically active compounds. In particular, the thiourea fused γ-amino alcohols showed satisfactory catalytic activity in this reaction and afforded chiral Mannich products in excellent chemical yield (up to 88%) and stereoselectivities (up to syn : anti/93 : 7 dr, up to 99% ee).

Chiral primary α-amino amides, consisting of an adjacent enamine bonding site (Bronsted base site), a hydrogen bonding site (Bronsted acid site), and flexible bulky substituent groups to modify the steric factor, are proving to be extremely valuable bifunctional organocatalysts for a wide range of asymmetric organic transformations. Primary α-amino amides are less expensive alternatives to other primary amino organocatalysts, such as chiral diamines and cinchona-alkaloid-derived primary amines, as they are easy to synthesize, air-stable, and allow for the incorporation of a variety of functional groups. In recent years, we have demonstrated the catalytic use of simple primary α-amino amides and their derivatives as organocatalysts for the aldol reaction, Strecker reaction, Michael tandem reaction, allylation of aldehydes, reduction of N-Aryl mines, opening of epoxides, hydrosilylation, asymmetric hydrogen transfer, and N-specific nitrosobenzene reaction with aldehydes.

-New sugar based ??-amino silyl ether organocatalysts were synthesized and their catalytic ability was examined in asymmetric Michael addition of ??-keto esters with nitroolefins affording chiral Michael adducts with quaternary carbon stereocenter in good to excellent chemical yields, diastereoselectivities and moderate enantioselectivities (up to 97%, up to dr. 85:15, up to 56% ee).

New small γ-turn type N-primary amino terminal tripeptides were synthesized and their functionality as an organocatalyst was examined in the asymmetric aldol reaction of various ketones with different aromatic aldehydes under solvent-free neat conditions to afford the desired chiral anti-aldol products in good to excellent chemical yields, diastereoselectivities and enantioselectivities (up to 99%, up to syn : anti/13 : 87 dr, up to 99% ee).

New two catalysts component system comprising of a primary β-amino silyl ethers as an organocatalyst and N-protected amino acids as a co-catalyst put together worked as an efficient organocatalyst system in the hetero Diels-Alder reaction of isatins with enones affording the chiral spirooxindole-tetrahydropyranones in good chemical yields and stereoselectivities (up to 94%, up to dr 78:22., up to 85% ee).

Simple primary β-amino alcohols act as an efficient organocatalysts in the asymmetric Michael addition of β-keto esters with nitroalkenes affording highly pure chiral Michael adducts. Also, both enantiomers of the adducts were obtained, depending on the specific catalyst used and reaction temperature.

Sugar based gamma-amino alcohol was used in asymmetric Michael addition of beta-keto esters with nitroolefins for the first time affording the corresponding several chiral Michael adducts bearing quaternary chiral carbon center in moderate to good chemical yields and stereoselectivities (up to 98%, up to dr. 95:5, up to 84% ee).

Asymmetric Michael addition of beta-keto esters with trans-beta-nitroolefins using chiral amino amide organocatalyst was tried and afforded synthetically useful chiral Michael adducts in both excellent chemical yields (up to 99%) and stereoselectivities (up to dr. 99:1, up to 98% ee).

New optically active 2‐azanorbornane‐based amino alcohol organocatalysts were designed and synthesized, and these catalysts were successfully employed in the asymmetric Michael reaction of β‐keto esters with nitroolefins to obtain the corresponding chiral Michael adducts with both high chemical yields (up to 99 %) and high stereoselectivities (up to dr = 91:9, up to 91 % ee ).

The new hybrid-type squaramide-fused amino alcohol containing both a Brønsted basic site and hydrogen-bonding sites in the molecule showed a high catalytic activity as an organocatalyst in the enantioselective domino Michael addition/cyclization reaction of oxoindolines with cyclic 1,3-diketones to afford the chiral spiro-conjugated oxindoles featuring 2-aminopyrans fusing with carbo-heterocyclic ring systems with excellent chemical yields (up to 98%) and enantioselectivities (up to 95% ee). The obtained chiral spiro-conjugated 2-aminopyrans bearing quaternary stereogenic carbon center could be used as synthetic precursors for several natural products that have a broad spectrum of fascinating biological activities.

A new type of amino amide organocatalysts was designed and synthesized from commercially available amino acids in easy steps. Their catalytic activities were examined in enantioselective crossed aldol reaction of various acyclic and cyclic ketones with aromatic aldehydes to afford the corresponding chiral anti-aldol adducts with good to excellent chemical yields, diastereoselectivities and enantioselectivities (up to 99%, up to syn:anti = 1:99, up to 97% ee). (C) 2018 Elsevier Ltd. All rights reserved.

A design of a chiral organocatalyst is very important for obtaining of a chiral product with a high optical purity in a catalytic asymmetric reaction. Recently, we developed a series of chiral beta-amino alcohol organocatalysts A that showed high level of catalytic activity in some asymmetric reactions. These beta-amino alcohols are stable in air, and have two advantageous features, easy preparation and exhibiting high stereoselectivity in an enantioselective reaction. This review summarizes our recent works involving the Diels-Alder (DA) reactions of 1,2-dihydropyridines, anthrones or 3-hydroxy-2-pyridones as dienes with dienophiles, the asymmetric 1,3-dipolar cycloaddition of nitrones with alpha,beta-unsaturated aldehydes and the crossed aldol reaction of isatins with acetaldehyde, by the use of the simple primary beta-amino alcohols as efficient chiral organocatalysts for the asymmetric reactions.

The hybrid‐type squaramide‐fused amino alcohol (SFAA) containing both a Brønsted basic site and a hydrogen‐bonding site in the molecule showed high catalytic activity as an organocatalyst in the enantioselective Diels–Alder (DA) reactions of 3‐hydroxy‐2‐pyridones with maleimides to afford chiral endo‐4‐hydroxy‐2‐azabicyclo[2.2.2]octanes (4‐hydroxyisoquinuclidines) with excellent chemical yields and enantioselectivities (up to 95 % yield and 98 % ee). In particular, the use of 4‐brominated 2‐pyridones afforded the corresponding chiral 4‐hydroxyisoquinuclidines with both excellent chemical yields and enantioselectivities (95 %, 98 % ee) with an opposite absolute stereochemistry in comparison with the chiral endo‐DA adducts obtained from the reactions performed with common 3‐hydroxy‐2‐pyridones. The DA adducts obtained could be used as synthetic precursors for several natural products that have a broad spectrum of fascinating biologically activities.

Enantioselective crossed aldol reactions of isatin derivatives and acetaldehyde have been developed with a series of simple diamino alcohol catalysts to afford 3-substituted 3-hydroxyindolin-2-ones in high chemical yields (up to 95 %) and optical purities (up to 92 %  ee ). The synthetic potential of the present protocol has been demonstrated by concise, enantioselective, protecting-group-free, and transition metal-free total syntheses of antitumor and antiviral agents with the tryptanthrin architecture, that is, phaitanthrin B and cephalanthrin A, along with the biologically active indolidine alkaloids chimonamidine and donaxaridine as well as the formal synthesis of CPC-1. The highly enantioselective outcome of this catalytic crossed aldol reaction was evaluated by calculating the Gibbs free energies of the possible transition states.