One catalyst for two distinct reactions: sequential asymmetric hetero Diels-Alder reaction and diethylzinc addition

This paper describes the successful development of a series of chiral zinc catalysts containing (R)-3,3′-Br₂-BINOL ligand and various diimine activators for enantioselective HDA reaction of Danishefsky's diene with aldehydes through a combinatorial approach, affording the corresponding 2,3-dihydro-4H-pyran-4-one derivatives in excellent yields and enantioselectivities. The application of this type of catalysts was also extended to the diethylzinc addition to the benzaldehyde, affording the corresponding secondary alcohol with up to 94.5% ee under optimized conditions. On the basis of these facts, the integration of two distinct enantioselective reactions, HDA and diethylzinc addition reactions, has been realized in one-pot with the promotion of a single chiral zinc catalyst in a sequential manner. The impact of diimine additive on the catalytic system of HDA reaction was also investigated by probing the nonlinear effect of reaction system. The positive nonlinear effect exhibited in the catalytic system could be attributed to the poor solubility of the heterochiral zinc species. On the basis of various experimental findings disclosed in this research, a possible mechanism for the asymmetric induction in the 3,3′-Br₂-BINOL/Zn/diimine catalyzed enantioselective HDA reaction of Danishefsky's diene with aldehydes was outlined.     

Storable, powdered chiral zirconium complex for asymmetric aldol and hetero Diels-Alder reactions

A storable, powdered chiral zirconium catalyst for asymmetric aldol and hetero Diels-Alder reactions has been developed. The catalyst has the same activity as that prepared in situ even after being stored for 3 months. Moreover, this chiral Zr catalyst worked efficiently not only for asymmetric aldol reactions but also for asymmetric hetero Diels-Alder reactions affording the corresponding addition products with high enantioselectivities.     

A new cationic,chiral catalyst for highly enantioselective Diels-Alder reactions

[reaction: see text] The Diels-Alder reaction of cyclopentadiene and 2-methacrolein is catalyzed by a chiral Lewis acid to form the exo adduct in 96% yield and 96% ee.     

A completely selective and strongly accelerated Diels-Alder reaction mediated by hydrogen bonding

A Diels-Alder cycloaddition between a furan and a maleimide is presented in which the presence of complementary hydrogen bonding sites dramatically accelerate the reaction and, additionally, ensure that only one of two possible diastereoisomers is formed.     

A new class of C1-symmetric monosulfoximine ligands for enantioselective hetero Diels-Alder reactions

Quinoline-based C1-symmetric sulfoximines have been used as chiral ligands in copper-catalyzed asymmetric hetero Diels-Alder reactions leading to cycloadducts with up to 96% ee.     

A practical new chiral controller for asymmetric Diels-Alder and alkylation reactions

[formula: see text] The enantiomerically pure hydroxy sulfones (+)- and (-)-2 have been prepared from 1,2-epoxycyclohexane by a simple and practical procedure. The acrylate esters of these alcohols undergo BCl3-catalyzed Diels-Alder reactions with a variety of dienes at -78 to -55 degrees C in CH2Cl2 or C7H8 with high dienophile face selectivity (Table 1). The chiral esters so formed are readily cleaved with recovery of the controllers (+)- or (-)-2. Esters of (+)- and (-)-2 can be converted to Z-potassium enolates and alkylated with high face selectivity.     

Syntheses,structures and catalytic activity for Friedel-Crafts reactions of substituted indenyl rhenium carbonyl complexes

The complexes [(η⁵-C₉H₆R)Re(CO)₃] [R = ⁿBu (8), ^tBu (9), CH(CH₂)₄ (10), Ph (11), Bz (12), 4-methoxyphenyl (13), 4-chlorophenyl (14)] were synthesized by refluxing substituted indenyl ligands [C₉H₇R] [R = ⁿBu (1), ^tBu (2), CH(CH₂)₄ (3), Ph (4), Bz (5), 4-methoxyphenyl (6), 4-chlorophenyl (7)], and Re₂(CO)₁₀ in decalin. The molecular structures of 9, 10, 12, and 13 were determined by X-ray diffraction analysis. These four crystals have similar molecular structures of the mononuclear carbonyl complex. In each of these molecules, Re is η⁵-coordinated to the five-membered ring of the indenyl group. Complexes 8–14 have catalytic activity for Friedel-Crafts reactions of aromatic compounds with a variety of alkylation and acylation reagents. Compared with traditional catalysts, these mononuclear metal carbonyl complexes have obvious advantages such as high activities, mild reaction conditions, high selectivity, and environmentally friendly chemistry.     

LCAO–MO studies on hydrogen bonding: The interaction between carbonyl and hydroxyl groups

Potential curves that show the energy dependence of hydrogen bonds between carbonyl and hydroxyl groups on the O? H bond length, on the distance between the molecules, and on the angle between the functional groups have been calculated with the CNDO /2 method. The results are presented for a small model system–formaldehyde/water—and for the dimer of formic acid. Good agreement is obtained with the available experimental data. The influence of the molecular geometry on the calculated results is discussed.     

Asymmetric Diels-Alder reactions with hydrogen bonding heterogeneous catalysts and mechanistic studies on the reversal of enantioselectivity

Chiral bis(oxazoline) complexes of Cu(II), Zn(II) and Mg(II) have been immobilized on silica support via hydrogen-bonding interactions. Up to 93% ee is obtained in the Diels-Alder reaction between 3-((E)-2-butenoyl)-1,3-oxazolin-2-one and cyclopentadiene at room temperature with the heterogeneous bis(oxazoline) complexes, and the catalysts can be recycled without losing enantioselectivity. Experimental and theoretical studies show that the reversal of the absolute product configuration upon immobilization of the PhBOX-Cu(II) catalyst is triggered by the anion dissociation from Cu(II) onto the surface of the support.     

A highly effective cobalt catalyst for olefin aziridination with azides: hydrogen bonding guided catalyst design

[Co(P1)], which was designed on the basis of potential hydrogen-bonding interactions in the metal-nitrene intermediate, is a highly active aziridination catalyst with azides. [Co(P1)] can effectively aziridinate various aromatic olefins with arylsulfonyl azides under mild conditions, forming sulfonylated aziridines in excellent yields. The Co-based system enjoys several attributes associated with the relatively low cost of cobalt and the wide accessibility of arylsulfonyl azides. Furthermore, it generates stable dinitrogen as the only byproduct.     

A versatile Ru catalyst for the asymmetric transfer hydrogenation of both aromatic and aliphatic sulfinylimines

A highly efficient Ru catalyst based on an achiral, very simple, and inexpensive amino alcohol ligand (2‐amino‐2‐methylpropan‐1‐ol) has been developed for the asymmetric transfer hydrogenation (ATH) of chiral N‐(tert‐butylsulfinyl)imines. This complex is able to catalyze the ATH of both aromatic and the most challenging aliphatic sulfinylimines by using isopropyl alcohol as the hydrogen source. The diastereoselective reduction of aromatic, heteroaromatic, and aliphatic sulfinylketimines, including sterically congested cases, over short reaction times (1–4 h), followed by desulfinylation of the nitrogen atom, affords the corresponding highly enantiomerically enriched (ee up to >99 %) α‐branched primary amines in excellent yields. The same ligand was equally effective for the synthesis of both (R)‐ and (S)‐amines by using the appropriate absolute configuration in the iminic substrate. DFT mechanistic studies show that the hydrogen‐transfer process is stepwise. Moreover, the origin of the diastereoselectivity has been rationalized.     

A mechanistic probe for asymmetric reactions: deuterium isotope effects at enantiotopic groups

The development of a mechanistic probe that is especially suitable for the study of asymmetric reactions is presented. Chemically innocuous enantiotopic methyl groups are utilized as probes for the distinct environments that develop at the transition state for the (-)-B-chlorodiisopinocampheylborane reduction of 4'-methylisobutyrophenone. 2H kinetic isotope effects (KIEs) are determined for both enantiotopic methyl groups using two types of competition reactions. One competition is that between the d3-methyl enantiomeric isotopomers. The other competition reaction is that between the d6-dimethyl and perprotiated isotopologues. The rate constant ratios can be converted into kinetic isotope effects upon each of the individual enantiotopic methyl groups by invoking the rule of the geometric mean. The resulting isotope effect measurements yield highly precise values and contribute further understanding to the transition structure for this stereoselective reduction. The results are discussed in the context of steric isotope effects and the origins of these effects, which arise from the impact of steric crowding upon the anharmonicity of C-H bonds in the transition structure relative to the reactant state.     

Thiourea-catalyzed asymmetric michael addition of activated methylene compounds to alpha,beta-unsaturated imides: dual activation of imide by intra- and intermolecular hydrogen bonding

A thiourea-catalyzed asymmetric Michael addition of activated methylene compounds to alpha,beta-unsaturated imides derived from 2-pyrrolidinone and 2-methoxybenzamide has been developed. In the case of 2-pyrrolidinone derivatives, the reaction with malononitrile proceeded in toluene with high enantioselectivity, providing the Michael adducts in good yields. However, the nucleophiles that could be used for this reaction were limited to malononitrile due to poor reactivity of the substrate. Further examination revealed that N-alkenoyl-2-methoxybenzamide was the best substrate among the corresponding benzamide derivatives bearing different substituents on the aromatic ring. Indeed, several activated methylene compounds such as malononitrile, methyl alpha-cyanoacetate, and nitromethane could be employed as a nucleophile to give the Michael adducts in good to excellent yields with up to 93% ee. The results of spectroscopic experiments clarified that this enhanced reactivity can be attributed to the intramolecular hydrogen-bonding interaction between the N-H of the imide and the methoxy group of the benzamide moiety. Thus, the key to the success of the catalytic enantioselective Michael addition is dual activation of the substrate by both intramolecular hydrogen bonding in the imide and intermolecular hydrogen bonding with thiourea 1a, as well as the activation of a nucleophile by the tertiary amine of the bifunctional thiourea.     

Origins of the diastereoselectivity in hydrogen bonding directed Diels-Alder reactions of chiral dienes with achiral dienophiles: a computational study

In this study, the origins of diastereoselectivity in the hydrogen bonding assisted Diels-Alder reactions of chiral dienes with achiral dienophiles have been investigated with density functional methods. The distortion/interaction model has been applied to shed light on the origins of selectivity. C9-Substituted chiral anthracene templates (R = (CH(3))(OCH(3))(H), R = (CH(3))(OH)(H), R = (CH(3))(CH(2)CH(3))(H) and R = (-CH(2)-C(CH(3))(OCH(3))(H)) are used to rationalize the role of a stereogenic center and H-bonding on the product distribution ratio. Even though hydrogen bonding increases the reactivity of the diene, the stereoselectivity is reduced because of the hydrogen bonding capacity of both diastereomeric transition states. The interaction energies of the studied anthracene templates with N-methyl maleimide at the transition state correlate linearly with an increase in reactivity. The selectivity is determined by both favorable distortion and interaction energies. The π-facial selectivity induced by the presence of a chiral auxiliary in 1-substituted 1,3-pentadienes (R1 = (CH(3))(OCH(3))(H) and R1 = (CH(3))(OH)(H)) has also been modeled in order to rationalize the role of the stereogenic center and H-bonding on the stereoselectivity of an aliphatic diene. In both parts, the product distribution ratios calculated from Boltzmann distributions based on Gibbs free energies are in reasonable agreement with the experimental results. Finally the role of OH-substituted five-membered pyrrolidine on C9 of anthracene is investigated since the successful usage of the conformationally rigid pyrrolidines in asymmetric synthesis is well known. Overall, both in the acyclic system and in anthracene, the facilitation due to H-bonding is reflected in the interaction energies: the higher the difference in interaction energies in the transition structures of the two diastereomers, the more selective the H-bonding assisted Diels-Alder reaction is.     

Arene-ruthenium complexes with salicyloxazolines: diastereoselective synthesis, configurational stability and applications as asymmetric catalysts for Diels-Alder reactions

Reaction of the dimers [RuCl2(eta6-arene)]2 (arene = benzene, p-cymene, mesitylene) with salicyloxazolines in the presence of NaOMe gives complexes [RuCl(R-saloxaz)(arene)] (1-5) which have been fully characterised. Complexes [RuL(iPr-saloxaz)(mes)]Y (L = py, 2-Mepy, 4-Mepy; PPh3; Y- = SbF6 or BPh4) 6-9 were prepared by treating the chloride 2a with ligand L and NaY (Y- = SbF6 or BPh4) in methanol at reflux. Halide complexes [RuX(iPr-saloxaz)(mes)](X = Br, 10; X = I, 11) were synthesised by treating 2a with AgSbF6 then with 1.2 equivalents of KBr or NaI, the methyl complex [RuMe(iPr-saloxaz)(mes)] 12 was synthesised from 2a by reaction with MeLi. Five complexes, [RuCl(iPr-saloxaz)(mes)] 2a, [RuCl(tBu-saloxaz)(p-cymene)] 3b, [RuCl(Ph-saloxaz)(mes)] 5a, [Ru(4-Mepy)(iPr-saloxaz)(mes)][SbF6] 7, and [Ru(PPh3)(iPr-saloxaz)(mes)][SbF6] 9, have been characterised by X-ray crystallography. Treatment of complexes 1-5 with AgSbF6 gives cationic species which are enantioselective catalysts for the Diels-Alder reaction of acroleins with cyclopentadiene, the effect of substituents on enantioselectivity has been examined.     

Cp*Rh complexes with pyridyloxazolines: synthesis, fluxionality and applications as asymmetric catalysts for Diels-Alder reactions

Half-sandwich complexes [RhCl(pymox)Cp*][SbF(6)](1-7)(pymox = pyridyloxazoline) have been synthesised as single diastereomers. Treatment of these with AgSbF(6) generates dications [Rh(OH(2))(pymox)Cp*](2+) which are fluxional at room temperature and which are enantioselective catalysts for the Diels-Alder reaction of methacrolein and cyclopentadiene. Treatment of the dication [Rh(OH(2))((i)Pr-pymox)Cp*](2+) with [X](-) gives [RhX((i)Pr-pymox)Cp*][SbF(6)](X = Br, I) as single diastereomers whilst reaction with 4-Mepy (4-methylpyridine) gives [Rh(4-Mepy)((i)Pr-pymox)Cp*][SbF(6)] as a mixture of diastereomers. Two complexes, [RhCl((i)Pr-pymox)Cp*][SbF(6)](3) and [RhCl(Bz-pymox)Cp*][SbF(6)](6) have been characterised by X-ray crystallography.     

Tetraethylammonium hydrogen carbonate: A cheap,efficient, and recyclable catalyst for transesterification reactions under solvent-free conditions

Tetraethylammonium hydrogen carbonate (TEAHC) was proven to be an efficient catalyst for transesterification reactions in the absence of solvent. The reaction between isopropenyl or ethyl acetate and an alcohol (not efficient in the absence of catalyst) was induced by the presence of TEAHC, which seems to assist the proton transfer from the alcohol to the ester, yielding the corresponding acetate in very good yields in the absence of any solvent. Moreover, the TEAHC can be recycled several times without significant loss in activity.     

Intramolecular [4 + 2] cycloadditions of iminoacetonitriles: a new class of azadienophiles for hetero Diels-Alder reactions

Iminoacetonitriles participate as reactive dienophiles in stereoselective intramolecular hetero Diels-Alder reactions which afford substituted quinolizidines. The cycloadduct with exo-oriented cyano group is obtained as the major or exclusive product of the reaction as a consequence of the alpha-amino nitrile anomeric effect The alpha-amino nitrile moieties incorporated in the cycloadducts constitute latent iminium ions, which upon exposure to mild protic or Lewis acids are unmasked, setting the stage for further useful synthetic transformations. For example, reductive decyanation with NaBH3CN excises the cyano group, while Bruylants reaction with Grignard reagents and acetylides lead to alpha-substituted amines. The substrates for these [4 + 2] cycloadditions are prepared from readily available alcohols via a Mitsunobu coupling reaction with the previously unknown, easily prepared reagent HN(Tf)CH2CN followed by cesium carbonate promoted elimination of trifluoromethanesulfinate.