Mechanistic Study of Intramolecular Aldol Reactions of Dialdehydes

Duarte, Filipe J. S.; Cabrita, Eurico J.; Frenking, Gernot; Santos, A. Gil

doi:10.1002/ejoc.200800222

Cited by 17 publications

(24 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The transition‐state structures shown in Figure 3 for the proline‐catalyzed cyclization of hept‐2‐enedial ( 1 ) are, in many aspects, similar to the model recently proposed by us22b and List and co‐workers4d for the cyclization of heptanedial. The differences arise from the γ,δ‐double bond, which was absent in the aldol cyclization of List and co‐workers.…”

Section: Resultssupporting

confidence: 76%

See 1 more Smart Citation

α‐Ketoheterocycles as Inhibitors of Leishmania mexicana Cysteine Protease CPB

et al. 2010

View full text Add to dashboard Cite

Cysteine proteases of the papain superfamily are present in nearly all eukaryotes and also play pivotal roles in the biology of parasites. Inhibition of cysteine proteases is emerging as an important strategy to combat parasitic diseases such as sleeping sickness, Chagas disease, and leishmaniasis. Inspired by the in vivo antiparasitic activity of the vinylsulfone-based cysteine protease inhibitors, a series of α-ketoheterocycles were developed as reversible inhibitors of a recombinant L. mexicana cysteine protease, CPB2.8. Three isoxazoles and especially one oxadiazole compound are potent reversible inhibitors of CPB2.8; however, in vitro whole-organism screening against a panel of protozoan parasites did not fully correlate with the observed inhibition of the cysteine protease.

show abstract

Section: Resultssupporting

confidence: 76%

“…It is known that the main driving force for the cyclization step is the stabilization of the negative charge on the forming alkoxide group 22b. 24 This means that any attractive electrostatic contact with the O1 atom will contribute to the stabilization of the transition state.…”

Section: Resultsmentioning

confidence: 99%

α‐Ketoheterocycles as Inhibitors of Leishmania mexicana Cysteine Protease CPB

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Two mechanistic proposals can be found in the literature. Although many theoretical studies of aldol reactions have been reported in the literature, [55][56][57][58][59][60][61][62][63][64][65][66] only few studies are focused on the Lewis-acid catalyzed Mukaiyama aldol reactions. The first step is the carbon-carbon bond formation.…”

Section: Introductionmentioning

confidence: 99%

The Mechanism of Iron(II)-Catalyzed Asymmetric Mukaiyama Aldol Reaction in Aqueous Media: Density Functional Theory and Artificial Force-Induced Reaction Study

et al. 2015

View full text Add to dashboard Cite

Density functional theory (DFT), combined with the artificial force-induced reaction (AFIR) method, is used to establish the mechanism of the aqueous Mukaiyama aldol reactions catalyzed by a chiral Fe(II) complex. On the bases of the calculations, we identified several thermodynamically stable six- or seven-coordinate complexes in the solution, where the high-spin quintet state is the ground state. Among them, the active intermediates for the selectivity-determining outer-sphere carbon-carbon bond formation are proposed. The multicomponent artificial force-induced reaction (MC-AFIR) method found key transition states for the carbon-carbon bond formation, and explained the enantioselectivity and diastereoselectivity. The overall mechanism consists of the coordination of the aldehyde, carbon-carbon bond formation, the rate-determining proton transfer from water to aldehyde, and dissociation of trimethylsilyl group. The calculated full catalytic cycle is consistent with the experiments. This study provides important mechanistic insights for the transition metal catalyzed Mukaiyama aldol reaction in aqueous media.

show abstract

“…The mechanism of the proline catalyzed aldol reaction has been studied by Boyd,2 Houk,3 and other groups 4. The reaction takes place through an enamine intermediate.…”

Section: Introductionmentioning

confidence: 99%

“…In that model, hydrogen bonding and the geometry for proton transfer play important roles and determine the stereoselectivity of the reaction. Catalysis of the aldol reaction by proline analogs, including bicyclic prolines,5 heteroatom-substituted prolines,4c prolinamides,6 prolinol ethers7, and amine-, ammonium-, and tetrazole-functionalized pyrrolidines8 (Figure 1), have also been studied computationally. Computational investigations of the Mannich,9 Michael addition,6e, 7b, 10 and Morita-Baylis Hillman11 reactions by proline catalysts have also been reported.…”

Section: Introductionmentioning

confidence: 99%

Computational investigations of the stereoselectivities of proline-related catalysts for aldol reactions☆

Allemann

Houk

2010

Journal of Molecular Catalysis A: Chemical

View full text Add to dashboard Cite

Computational investigation of the aldol reaction of benzaldehyde with acetone catalyzed by various proline derivatives and 2-azetidine carboxylic acid reveal the origins of stereoselectivities of these reactions. Structural differences between catalysts and transition states were analyzed with density functional theory geometries in order to establish the key factors that will help in the design of new catalysts.

show abstract

Mechanistic Study of Intramolecular Aldol Reactions of Dialdehydes

Cited by 17 publications

References 50 publications

α‐Ketoheterocycles as Inhibitors of Leishmania mexicana Cysteine Protease CPB

α‐Ketoheterocycles as Inhibitors of Leishmania mexicana Cysteine Protease CPB

The Mechanism of Iron(II)-Catalyzed Asymmetric Mukaiyama Aldol Reaction in Aqueous Media: Density Functional Theory and Artificial Force-Induced Reaction Study

Computational investigations of the stereoselectivities of proline-related catalysts for aldol reactions☆

Contact Info

Product

Resources

About