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A simple two catalyst component system consisting of primary β-amino alcohols as a catalyst and amino acids as a co-catalyst put together works as an efficient organocatalyst system in the hetero Diels-Alder reaction of isatins with enones to afford the chiral spirooxindole-tetrahydropyranones in good chemical yields and stereoselectivities (up to 86%, up to 85 : 15 dr., up to 95% ee).

Asymmetric Michael addition of β-keto esters with trans-β-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).

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).

The new hybrid-type squaramide-fused amino alcohol containing both a Bronsted 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.

The hybrid type squaramide fused amino alcohol (SFAA) containing both Bronsted basic site and hydrogen bonding site in the molecule showed highly catalytic activity as an organocatalyst in the enantioselective Diels-Alder reaction (DA) of 3-hydroxy-2-pyridones with maleimides to afford the chiral endo-4-hydroxy-2-azabicyclo[2.2.2]octanes (4-hydroxy-isoquinuclidines) with excellent chemical yields and enantioselectivities (up to 95%, up to 98% ee). Particularly, the use of 4-brominated 2-pyridones afforded the corresponding chiral 4-hydroxyisoquinuclidines in both excellent chemical yield and enantioselectivity (95%, 98% ee) having an opposite absolute stereochemistry in comparison with the chiral endo-DA adduct from the reactions using common 3-hydroxy-2-pyridones. The obtained DA adducts could be used as synthetic precursors for the 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.

A series of hybrid-type squaramide-fused amino alcohol (SFAA) catalysts were synthesized, and their catalytic efficiency in the enantioselective nitro-aldol reaction of various isatins with nitromethane has been described. This transformation afforded chiral 3-substituted 3-hydroxyoxindoles in excellent chemical yields (up to 99 %) with high enantioselectivities (up to 95 % ee). The resulting chiral 3-hydroxyoxindoles can be further used as synthetic precursors for the synthesis of several natural products that have a broad spectrum of fascinating biological activities.

Chiral primary β-amino alcohols, constuting adjacently positioned Bronsted base and Bronsted acid sites, are emerging as very valuable bifunctional organocatalysts in a wide array of asymmetric organic transformations. Primary β-amino alcohols represent inexpensive alternatives to other primary amino organocatalysts such as chiral diamines and cinchona-alkaloid-derived primary amines, being easy to synthesize and air-stable and offering the potential for introduction of different functional groups and also for alteration of steric sites. Here we reveal the catalytic use of simple primary β-amino alcohols and their derivatives as organocatalysts in Diels–Alder cycloaddition, aldol condensation, Michael addition, 1,3-dipolar cycloaddition, the Morita–Baylis–Hillman reaction, cascade cyclization, allylation of isatins, Friedel–Crafts alkylation and epoxidation of olefins.

A number of 3-hydroxy-6-(hydroxymethyl)-2-(2-phenyl-4H-chromen-4-yl)-4H-pyran-4-ones (3) have been synthesized in a one pot catalyst free reaction of 2-hydroxy chalcone (1) with kojic acid (2) in toluene at reflux temperature and evaluated for antimicrobial and anti-biofilm activities. Compounds 3a, 3e, 3f, 3l showed potent antimicrobial activity against Staphylococcus aureus MLS-16 MTCC 2940, Bacillus subtilis MTCC 121 and Escherichia coli MTCC 739, whereas 3b and 3k exhibited excellent activity against Bacillus subtilis MTCC 121 and Escherichia coli MTCC 739, while 3g showed promising activity against Bacillus subtilis MTCC 121 and Escherichia coli MTCC 739. On the other hand, compounds 3a, 3b and 3l showed very good anti-biofilm activity and 3g showed moderate activity against Bacillus subtilis MTCC 121. Whereas, compounds 3a and 3f showed moderate activity against Escherichia coli MTCC 739, while compounds 3a, 3b, 3k and 3l displayed similar activity against Staphylococcus aureus MLS-16 MTCC 2940.

A simple, highly efficient and selective oxidative cross coupling of imidazo[1,2-a]pyridine (IP) compounds (1) and methylketones (2), promoted by molecular iodine in DMSO in the presence of a catalytic amount of PTSA has been realized in a one pot reaction. This strategy has provided a general route for the synthesis of 1-aryl-2-(2-phenylimidazo[1,2-a]pyridin-3-yl)ethane-1,2-diones (3) with a new C–C bond formation through Kornblum oxidation followed by nucleophilic attack of IP compounds (1) on the in situ formed phenylglyoxal. Simple reaction conditions, no metal catalysts and selective product formation are the advantages of this protocol.

Synthesis of a series of novel aryl and heteroaryl fused 2,8-dioxabicyclo[3.3.1]nonanes (3) was accomplished by one pot, catalyst free reaction of 2-hydroxy chalcone (1) with 3-trifluoromethyl substituted pyrazolone (2) in xylene at reflux temperature. The role of the trifluoromethyl functional group in formation of 3 was confirmed by comparative studies with 3-methyl substituted pyrazolones (2c,d) and the outcome is presented.

Chiral primary β-amino alcohols, constuting adjacently positioned Bronsted base and Bronsted acid sites, are emerging as very valuable bifunctional organocatalysts in a wide array of asymmetric organic transformations. Primary β-amino alcohols represent inexpensive alternatives to other primary amino organocatalysts such as chiral diamines and cinchona-alkaloid-derived primary amines, being easy to synthesize and air-stable and offering the potential for introduction of different functional groups and also for alteration of steric sites. Here we reveal the catalytic use of simple primary β-amino alcohols and their derivatives as organocatalysts in Diels–Alder cycloaddition, aldol condensation, Michael addition, 1,3-dipolar cycloaddition, the Morita–Baylis–Hillman reaction, cascade cyclization, allylation of isatins, Friedel–Crafts alkylation and epoxidation of olefins.

The simple, efficient and one-pot, catalyst-free protocol leads to the synthesis of new 2-sulfenylimine chromene compounds.

The synthesis of 2-sulfenylimine chromene compounds (8) is accomplished by reacting benzaldehyde (1), malanonitrile (2) and dimedone (3) followed by sequential addition of N-chlorosuccinimide and thiophenols to the in situ formed 2-amino-4(H) chromenes (4) in a one pot, catalyst free, five component reaction in toluene medium. When aniline was employed as the nucleophile in place of thiophenol, the formation of hexahydrobenzofuran-2-N-phenyl carboxamide derivatives (5) was observed. Excellent yields, simple reaction conditions and high compatibility are the advantages of this protocol.

Various of the novel title compounds (III) (16 examples) display potent antimicrobial activities, e.g. (IIIa-c), (IIIg), (IIIi), as well as very good anti-biofilm activity.

Various aryl(phenylimidazo[1,2-a]pyridinyl)ethanediones are selectively obtained with a new C—C bond formation via Kornblum oxidation followed by nucleophilic attack of a imidazo[1,2-a]pyridine on the in situ generated phenylglyoxal.

For the first time, a simple, efficient, and catalyst free protocol to synthesize a series of novel 3-trifluoromethyl substituted title compounds is developed.

A mild and efficient method for the functionalization of chromen-2-ones with amidoalkyl derivatives have been developed starting from 4-trifluoromethyl substituted chromen-2-ones, aromatic aldehydes and acetamide promoted by stannous chloride dihydrate in a one pot three component reaction under solvent free condition. Simple reaction conditions, high yields and environmentally benign procedure are the advantage of this protocol.

The reaction of chromene derivatives (I) with NCS affords dihydrofurans (III) after an unusual rearrangement in good yields.

A simple, catalyst free, water mediated, one pot four component, green protocol was developed for title compounds 7 starting from aromatic aldehydes (1), malononitrile (2), 1,3-diones (3) and N-chlorosuccinimide (NCS) in a sequential addition reaction at ambient temperature. The approach presented herein, for the first time, is through an unusual rearrangement where NCS was reacted with 2-amino-7,7-dimethyl-5-oxo-4-aryl-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4), which was formed by the Knoevenagel condensation of aldehyde and malononitrile followed by the Michael addition of 3. In addition, this novel protocol is compatible with various aldehydes and active C–H functional derivatives, accomplishes high yields and follows the GAP chemistry principle. Interestingly, compound 4 when reacted with NCS in alcohol medium gave 2-cyano-6,6-dimethyl-4-oxo-3-aryl-2,3,4,5,6,7-hexahydrobenzofuran-2-carboxylate (5).

A mild and efficient method for the functionalization of chromen-2-ones with amidoalkyl derivatives have been developed starting from 4-trifluoromethyl substituted chromen-2-ones, aromatic aldehydes and acetamide promoted by stannous chloride dihydrate in a one pot three component reaction under solvent free condition. Simple reaction conditions, high yields and environmentally benign procedure are the advantage of this protocol.

Many biologically active compounds, including pharmaceuticals, are optically active. Often, only one of the enantiomers is required because the enantiomers display different in vivo activities. In pharmaceuticals in particular, differences in the absolute configuration can affect not only the pharmacological activity but also the toxicity. Catalytic asymmetric synthesis, in which a low amount of a chiral molecular catalyst theoretically enables infinite production of an optically active compounds, is among the most important current challenges in organic synthetic chemistry; it is also important in terms of energy saving and environmental friendliness. Environmental effects now have to be considered in chemical syntheses, and environmentally benign organic syntheses have been receiving attention. The chiral catalysts used in catalytic asymmetric syntheses can be divided into two categories: organometallic catalysts and metal-free chiral organocatalysts. Particularly, organocatalysts are stable in air, easy to handle, and inexpensive, so they are being focused on as next-generation, environmentally friendly catalysts. On these backgrounds, author aimed to develop the new hybrid type squaramide fused amino alcohol (SFAA) organocatalysts. This SFAA organocatalyst was successfully prepared from commercially available amino esters by using simple organic transformations and the catalytic activity were demonstrated in the enantioselective (1) nitroaldol, (2) Diels-Alder and (3) domino Michael addition cyclization reactions. (1) The enantioselective nitroaldol reaction was established with various isatins and nitromethanes using SFAA organocatalysts. This protocol provides chiral 3-substituted 3-hydroxyoxindoles in excellent chemical yields and high enantioselectivities. The obtained 3-substituted 3-hydroxyoxindoles are important synthetic precursors for many biological active and natural compounds such as donaxaridine (anti-cancer drug). (2) The enantioselective Diels-Alder reaction was established with 3-hydroxy-2-pyridones and maleimides using SFAA organocatalysts. This protocol provides the chiral 4-hydroxyisoquinnuclidines in both excellent chemical yields and enantioselectivities. The obtained chiral 4-hydroxyisoquinnuclidines are synthetic intermediates for many biological active compounds such as oseltamivir phosphate (anti-influenza drug). (3) The enantioselective domino Michael addition cyclization reaction was established with 3-dicyano-2- indanones and 1,3-cyclic carbonyl compounds using SFAA organocatalysts. This protocol provides the chiral spiro-conjugated 2-aminopyrans in both excellent chemical yields and enantioselectivities. The obtained chiral spiro-conjugated 2-aminopyrans are significant synthetic intermediates for many biological compounds such as 2-amino-tetrahydrochromene (anti-leishmaniasis). In this study, author revealed that the new explored new hybrid type squaramide fused amino alcohol (SFAA) organocatalyst having both three hydro-bonding sites and a basic site in the compound with a substrate shows satisfactory catalytic activity in the enantioselective (1) nitroaldol, (2) Diels-Alder and (3) domino Michael addition cyclization reactions. It is expected that this result might be able to greatly contribute the development of new drug and its related compounds., 医薬品を含む多くの生物活性化合物は光学活性物質であり, その鏡像異性体は異なる生体内活性を示すことが多いため, 有効な一方の鏡像異性体を高選択的に合成するための不斉合成反応の開発が重要である. ごく少量の不斉分子によって触媒化される触媒的不斉合成反応の開発は省エネルギーや環境調和の観点から有機合成化学領域の最も重要な研究課題の一つであり, 金属を含有しない有機分子触媒は空気中で安定であり取り扱いやすく安価であるという利点なども有するため, 次世代の環境調和型触媒として現在活発に研究開発が行なわれている.著者は, 新規多点認識型有機分子触媒としてアミノアルコールとスクアラミドが融合したハイブリッド型触媒（SFAA 触媒）を設計し, それを, エナンチオ選択的 (1) イサチン類とニトロアルケン類との不斉ニトロアルドール反応，(2) 3-ヒドロキシ-2-ピリドン類とマレイミド類との塩基触媒不斉ディールス・アルダー (DA) 付加環化反応, さらに (3) インダノン類と1,3-ジカルボニル類とのドミノマイケル付加環化反応にそれぞれ適用し，その有機分子触媒としての機能性を検討した.(1) SFAA 有機分子触媒 A を合成し, 触媒 A を用いるイサチン類とニトロアルカン類との不斉ニトロアルドール反応を検討した．その結果, 触媒 A が不斉触媒活性を示し, 本反応によって優れた化学収率と良好な光学収率で光学活性オキシインドール誘導体を与えることを見出した. 得られるオキシインドール誘導体は，抗癌作用を持つドナキサリジン誘導体などの有用な合成中間体である．(2) SFAA 有機分子触媒 A を用いる3-ヒドロキシ-2-ピリドン類とマレイミド類との不斉ディールス・アルダー反応を検討した．その結果，触媒 A が不斉触媒活性を示し, 本反応によってほぼ完全な化学収率と優れた光学収率で光学活性イソキヌクリジン誘導体が得られることを見出した。得られるイソキヌクリジン誘導体は，タミフルなどの抗ウイルス活性化合物の有用な合成中間体である．(3) SFAA 有機分子触媒 A を用いるインダノン類と1,3-ジカルボニル類との不斉ドミノマイケル付加環化反応を検討した．その結果，触媒 A が不斉触媒活性を示し, 本反応によってほぼ完全な化学収率と優れた光学収率で光学活性スピロ-2-アミノピラン類が得られることを見出した。得られるスピロ-2-アミノピラン誘導体は，寄生原虫病であるリーシュマニア症に有効な化合物を合成するための有用な合成中間体である．本研究において著者は, その分子中に「基質との 3 点の水素結合部位と１点の塩基性部位を併せ持つ多点認識機能を持つアミノアルコール-スクアラミドハイブリッド型触媒 (SFAA触媒)」を開発することに成功し, それらが創薬に有効な不斉ニトロアルドール反応，不斉ディールス・アルダー付加環化反応および不斉ドミノマイケル付加環化反応においてそれぞれ良好な不斉触媒活性を示すことを明らかにした. また，本反応によって得られる化合物は様々な医薬品をはじめとする生物活性化合物の合成中間体として有用であることから，本研究の成果は, 新薬創製の合成開発研究に大きく貢献できると期待される.