Chapter 8. Prolinol Silyl Ethers as Asymmetric Organocatalysts

Šebesta, Radovan; Sorádová, Zuzana

doi:10.1039/9781782622093-00166

Cited by 3 publications

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“…It is well known that many aminocatalytic reactions 1 do not progress at all or require several days for completion—we will call this the first general issue—while others afford random stereoselectivities, depending strongly on features of the substrate and catalyst—the second general issue. Long series of trials are very often carried out to find appropriate catalysts and conditions.…”

Section: Introductionmentioning

confidence: 99%

“…The starting enamine is formed by the reaction of the aldehyde with a secondary amine (such as the Jørgensen–Hayashi catalyst, henceforward JH), 1 as in Figure 2. The first reaction intermediate, the hemiaminal ( N , O -acetal), which in polar solvents may be in equilibrium with its ionic counterpart, an iminium hydroxide, is rarely depicted.…”

Section: Introductionmentioning

confidence: 99%

“…We wish to account for the cases in which the stoichiometric reactions are feasible but do not work under catalytic conditions, as well as for the differences in the stereochemical outcome using aldehydes and ketones as Michael donors. Thus, we aim to answer question (a) and to find an explanation for points (b)–(d):Can cyclobutanes be formed in all reactions between enamines and polarized C–C double bonds?When reacting with β-nitrostyrene in the presence of appropriate secondary amines, aldehydes afford syn adducts (usually 2R,3S) in excellent yields and stereoselectivities, whereas ketones afford the other syn adducts (usually 2S,3R), 1,7−10 with exceptions in special cases; 11 this is known since the pioneering works on this Michael reaction. 8 However, poor results are obtained with ( S )-proline, often with disappointing enantiomeric ratios (er’s), as shown in Figure 3, eqs 1 and 2.…”

Section: Introductionmentioning

confidence: 99%

“…8 However, poor results are obtained with ( S )-proline, often with disappointing enantiomeric ratios (er’s), as shown in Figure 3, eqs 1 and 2. The possible stereodirecting role of the COOH in these nitro-Michael reactions has therefore been questioned; 9 nevertheless, the corresponding nitronate ions and nitronate-containing intermediates may strongly interact with acidic protons (of thioureas, for example) or with Lewis acids.α-Branched aldehydes such as isobutyraldehyde, plus β-nitrostyrene, give poor yields (in relation to non-α-branched aldehydes) 1 with the JH catalyst. 3c , 3f Recourse to special catalysts is necessary for partial improvement (Figure 3, eq 3).…”

Section: Introductionmentioning

confidence: 99%

“…12h−12k The non-α-branched aliphatic nitroalkenes investigated to date afford lower stereoselectivities than aromatic nitroalkenes (β-nitrostyrene and congeners) and α-branched nitroalkenes. 1 We too, several years ago, were faced with the two above-mentioned general issues when attempting to develop new prolinol derivatives 13 related to that of Peng et al (catalyst A ). 14 We hoped that some of the catalysts ( B – I , Figure 4) might be applied to both aldehydes and ketones, as well as to aliphatic nitroalkenes (not only to β-nitrostyrene and its derivatives), and would therefore enjoy a wider use in total synthesis.…”

Section: Introductionmentioning

confidence: 99%

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NMR and Computational Studies on the Reactions of Enamines with Nitroalkenes That May Pass through Cyclobutanes

et al. 2019

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The addition of aldehyde enamines to nitroalkenes affords cyclobutanes in all solvents, with all of the pyrrolidine and proline derivatives tested by us and with all of the substrates we have examined. Depending on the temperature, concentration of water, solvent polarity, and other factors, the opening and hydrolysis of such a four-membered ring may take place rapidly or last for several days, producing the final Michael-like adducts (4-nitrobutanals). Thirteen new cyclobutanes have now been characterized by NMR spectroscopy. As could be expected, s-trans-enamine conformers give rise to all-trans-(4S)-4-nitrocyclobutylpyrrolidines, while s-cis-enamine conformers afford all-trans-(4R)-4-nitrocyclobutylpyrrolidines. These four-membered rings can isomerize to adduct enamines, which should be hydrolyzed via their iminium ions. MP2 and M06-2X calculations predict that one iminium ion is more stable than the other iminium species, so that protonation of the adduct enamines can be quite stereoselective; in the presence of water, the so-called syn adducts (e.g., OCH–*CHR–*CHPh–CH2NO2, with R and Ph syn) eventually become the major products. Why one syn adduct is obtained with aldehydes, whereas cyclic ketones (the predicted ring-fused cyclobutanes of which isomerize to their enamines more easily) produce the other syn adduct, is also explained by means of molecular orbital calculations. Nitro-Michael reactions of aldehyde enamines that “stop” at the nitrocyclobutane stage and final enamine stage do not work catalytically, as known, but those of cyclic ketone enamines that do not work stop at the final enamine stage (if their hydrolysis to the corresponding nitroethylketones is less favorable than expected). These and other facts are accounted for, and the proposals of the groups led by Seebach and Hayashi, Blackmond, and Pihko and Papai are reconciled.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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NMR and Computational Studies on the Reactions of Enamines with Nitroalkenes That May Pass through Cyclobutanes

et al. 2019

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Synthesis of Highly Functionalized Hydrindanes via Sequential Organocatalytic Michael/Mukaiyama Aldol Addition and Telescoped Hydrozirconation/Cross-Coupling as Key Steps: En Route to the AB System of Clifednamides

et al. 2021

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The AB ring systems of the clifednamide family, polycyclic tetramate macrolactames (PoTeMs), were prepared by a new, convergent approach employing an intramolecular Diels−Alder (IMDA) reaction. Key steps comprise an organocatalytic Michael addition (>90% enantiomeric excess (ee)), a Mukaiyama aldol reaction for the convergent installation of a diene moiety, and a telescoped hydrozirconation/cross-coupling grafting an enone. The following IMDA furnished a highly functionalized hydrindane (diastereomeric ratio (dr) = 91:1) with the same configuration as the clifednamide scaffold. Advantages of this route are only one required protecting group, 13% overall yield over 9 steps (reduced from previously 17 steps/1.3% overall), and the potential access to the key intermediates in the clifednamide biosynthesis.

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Amino-Catalyzed Reactions of Aldehydes with Chiral Nitroalkenes

et al. 2021

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Chiral nitroalkenes are used for the first time in Michael additions of aldehydes, catalyzed by pyrrolidine derivatives. They yield the same major stereoisomer with either (S)-proline or (R)-proline, but this asymmetric induction does not overcome the effect of sterically more congested catalysts. Nitrocyclobutane intermediates are often formed, which are more stable than those from (E)-1-nitro-2-phenylethene. The cyclobutanes and final products were characterized by 2D NMR and chemical correlations.A SciFinder-n search indicates that over 1,000 articles contain additions of carbonyl/carboxyl compounds to (E)-1-nitro-2-phenylethene (-nitrostyrene), although the number is reduced to ca. 670 or 170 if the words "asymmetric" or "organocatalytic", respectively, are entered. In fact, to check the performance of chiral catalysts, the reaction of cyclohexanone with -nitrostyrene has been used as a paradigmatic example. 1 The nitro-Michael reactions of aldehydes and nitroalkenes, as Seebach, Hayashi et al. 2 and Burés, Amstrong, and Blackmond demonstrated, 3 are (2+2)-cycloadditions (formal or stepwise). 4 Depending on the temperature, solvent polarity, and concentration of H2O and organic acid in the medium, these cyclobutanes undergo quick or slow ring opening and hydrolysis to 4nitrobutanals, as summarized in Scheme 1.

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Chapter 8. Prolinol Silyl Ethers as Asymmetric Organocatalysts

Cited by 3 publications

References 0 publications

NMR and Computational Studies on the Reactions of Enamines with Nitroalkenes That May Pass through Cyclobutanes

NMR and Computational Studies on the Reactions of Enamines with Nitroalkenes That May Pass through Cyclobutanes

Synthesis of Highly Functionalized Hydrindanes via Sequential Organocatalytic Michael/Mukaiyama Aldol Addition and Telescoped Hydrozirconation/Cross-Coupling as Key Steps: En Route to the AB System of Clifednamides

Amino-Catalyzed Reactions of Aldehydes with Chiral Nitroalkenes

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