Organocatalytic Conjugate Addition of Formaldehyde <i>N,N</i>-Dialkylhydrazones to β<i>,</i>γ-Unsaturated α-Keto Esters

Herrera, Raquel P.; Monge, David; Martı́n-Zamora, Eloı́sa; Fernández, Rosario; Lassaletta, José M.

doi:10.1021/ol071292c

Cited by 105 publications

(63 citation statements)

References 22 publications

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“…[6] Another relevant example involves oxazol-5A C H T U N G T R E N N U N G (2 H)-ones as aryloyl anion equivalents in the conjugate addition to enoylphosphonates, [7] which also relies on Brønsted-acid catalysis. In addition, one report by Enders uses a-aminonitriles as Michael donors in the enan- tioselective b-glyoxylation of a,b-unsaturated aldehydes under iminium catalysis, which proceeded with enantioselectivities of about 85 % ee, to give the final 1,4-dicarbonyl compounds in moderate overall yield.…”

Section: In Memory Of Our Colleague and Friend Rafael Suaumentioning

confidence: 99%

Organocatalytic Enantioselective Formal Conjugate Addition of a Hydroxymoyl Anion to α,β‐Unsaturated Aldehydes

Alonso

Reyes

Carrillo

et al. 2011

Chemistry A European J

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In memory of our colleague and friend Rafael SuauThe conjugate addition reaction is a fundamental transformation in organic chemistry. The wide variety of reagents amenable to participate as Michael donors or acceptors makes this reaction extremely versatile, allowing the preparation of many different classes of highly functionalized compounds in a very easy and reliable way. Moreover, the conjugate addition reaction also occurs very often with the concomitant generation of one or more stereocenters and, in this context, intense research has focused on the development of catalytic enantioselective approaches for carrying out this important reaction in a stereocontrolled way.[1] Although most of the methodologies reported to date involve the use of transition-metal catalysts, several organocatalytic enantioselective variants of the conjugate addition reaction have been developed in the last few years;[2] many of which have performed excellently with regard to chemical efficiency and stereocontrol. On the other hand, many research groups have also directed their attention to finding novel reactivity patterns applied to the conjugate addition reaction by using umpoled reagents, [3] which have expanded the array of compounds which can be used as Michael donors or acceptors, to further increase the scope of this methodology. In particular, the enantioselective conjugate addition of acyl or formyl anions to a,b-unsaturated carbonyl compounds or related derivatives entails a particular interest because this transformation allows the preparation of 1,4-dicarbonyl compounds, which are classically much more difficult to access by standard C À C bond forming reactions than the corresponding 1,3-or 1,5-dicarbonyl compounds.[4] However, despite the enormous potential of the oxime moiety and the key role played by this functional group in plenty of organic reactions, the development of umpoled reagents that behave as hydroxymoyl anion equivalents remains unexploited.In fact, even for the related case of the conjugate addition of acyl/formyl anion equivalents, enantioselective versions for this particular transformation under metal-free conditions are very scarce (see Scheme 1). For example, the Stetter reaction using N-heterocyclic carbenes (NHC) as catalysts can be an extremely effective approach for the formal enantioselective conjugate addition of acyl anions, [5] but it is ineffective when trying to use formaldehyde as the Michael donor.For the particular case of the conjugate addition of a formyl anion equivalent, there is only one single example related to an enantioselective organocatalytic version; this involves the use of N,N-dialkylhydrazones as Michael donors, which undergo conjugate addition to b,g-unsaturated a-ketoesters under chiral Brønsted-acid catalysis to give moderate levels of enantioselection.[6] Another relevant example involves oxazol-5A C H T U N G T R E N N U N G (2 H)-ones as aryloyl anion equivalents in the conjugate addition to enoylphosphonates, [7] which also relies on Brønsted-acid catalysis. In...

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Section: In Memory Of Our Colleague and Friend Rafael Suaumentioning

confidence: 99%

Organocatalytic Enantioselective Formal Conjugate Addition of a Hydroxymoyl Anion to α,β‐Unsaturated Aldehydes

Alonso

Reyes

Carrillo

et al. 2011

Chemistry A European J

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“…By using in this case β,γ-unsaturated α-keto esters 297 as enoate surrogates, it was found that the addition of 51k was strongly accelerated by catalytic amounts of thioureas. The best results in terms of selectivity were achieved by employing (1S,2R)-aminoindan-2-ol-derived thiourea 298, [136] which led to adducts 299 in good yields and enantioselectivities (Scheme 54). [137] These compounds are versatile 1,4-dicarbonyl compounds that can be transformed into nitriles 300 by MMPP·6H 2 O. Additionally, ozonolytic cleavage of 299 (R = Me) afforded an unstable intermediate that was further oxidized by a HCO 2 H/H 2 O 2 mixture and treated with SOCl 2 /MeOH to obtain succinate 301 resulting from deoxidative decarboxylation.…”

Section: Activation By Brønsted Acids or H-bonding Organocatalystsmentioning

confidence: 99%

Aldehyde N,N‐Dialkylhydrazones as Neutral Acyl Anion Equivalents: Umpolung of the Imine Reactivity

et al. 2007

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The isoelectronic replacement of the α‐carbon of enamines by nitrogen leads to the corresponding hydrazones, and thus, they can be termed “aza‐enamines”. Hence, aldehyde N,N‐dialkylhydrazones enable analogous electrophilic substitutions at the imine carbon that corresponds to the β‐carbon of enamines. In addition, after hydrolysis of the product hydrazones to the parent ketones or aldehydes, these reactions constitute an umpolung of the classical carbonyl reactivity and overall a nucleophilic acylation or formylation. This review covers the aza‐enamine chemistry from its very beginning in the late 1960s up to this year. In the first part, reactions of aromatic, aliphatic, and heterocyclic aldehyde N,N‐dialkylhydrazones with highly reactive substrates such as the Vilsmeier and Mannich reagents, sulfonyl isocyanates, perfluoroacetic anhydride, and inorganic electrophiles such as halogens and phosphorus tribromide are described. The hydrazones of α,β‐unsaturated aldehydes react as vinylogous aza‐enamines at the terminal carbon providing unsaturated aldehydes. As electron‐rich dienes and dienophiles, they also form Diels–Alder adducts and thus interesting N‐heterocycles. The second part covers carbon–carbon bond formations of the sterically less‐demanding formaldehyde N,N‐dialkylhydrazones with synthetically very useful electrophiles such as various Michael acceptors and carbonyl compounds. Formaldehyde SAMP‐hydrazone and related derivatives generally give excellent asymmetric inductions. Finally, first organocatalytic versions of the aza‐enamine chemistry are presented. In summary, the rich chemistry of aldehyde N,N‐dialkylhydrazones as neutral acyl anion, formyl anion, and cyanide equivalents is demonstrated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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“…However,c ompared with a,b-unsaturated ketones and nitroalkene, b,g-unsaturated a-keto esters as Michael acceptors are limited. [11] The asymmetric addition of 1,3-difunctionald onors to b,g-unsaturated-a-ketoesters catalyzed by organocatalysts [11b-p] and chiralm etal catalysts basedo nc opper, [11r] nickel, [11s] yttrium, [11t] and zinc [11u] has received intense attention,b ecause the reaction can follow ad omino acetalization to construct ac hiral six-membered oxygenated heterocycle. Retrosynthetically,achiral five-membered oxygen heterocycle can be formed throught he reaction of b,g-unsaturateda-ketoester with 1,2-difunctional compound such as a-hydroxyacetophenone, which has acted as donor in the Michael addition of a,b-unsaturated ketones or nitroalkenes.…”

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“…After 30 min, the reaction afforded the anti-product in 63 %i solated yield ( 13 CNMR spectrar evealed that major product anti-3a was obtained as an equilibrating mixture of anomers (about 2:1) caused by 2-OH and 2-COOCH 3 .T hese anomers equilibrated slowly enough so as to appear as separatec ompounds in 1 Ha nd 13 CNMR spectra but quickly enough that they did not resolve by chromatography.T he trace of the racemic anti-3a on ac hiral HPLC column showed only one pair of peaks for the two enantiomers. [11,14] However,t he minor synproduct was ar apid equilibrium between the cyclic hemiketal syn-3a and the Michael-typeproduct syn-3a'. [15] As eries of ligandsw ere then examined and the results are summarized in Ta ble 1.…”

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A New Strategy for Enantioselective Construction of Multisubstituted Five‐Membered Oxygen Heterocycles via a Domino Michael/Hemiketalization Reaction

Hua

Liu

Huang

et al. 2015

Chemistry A European J

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A new highly enantioselective domino Michael/hemiketalization reaction of α-hydroxyacetophenone with β,γ-unsaturated α-keto esters for the synthesis of 2,2,4,5-tetrasubstituted chiral tetrahydrofurans is reported. With 2 mol % intramolecular dinuclear zinc-AzePhenol complex prepared in situ from the reaction of multidentate semi-azacrown ether ligand with ZnEt2 , the corresponding anti-multisubstituted tetrahydrofuran products were obtained in up to 90 % yields, and 98 % enantiomeric excess (ee) at 0 °C for 45 min. Moreover, the products were easily converted to 2,3,5-trisubstituted 2,3-dihydrofurans without any loss in optical activity.

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Organocatalytic Conjugate Addition of Formaldehyde N,N-Dialkylhydrazones to β,γ-Unsaturated α-Keto Esters

Cited by 105 publications

References 22 publications

Organocatalytic Enantioselective Formal Conjugate Addition of a Hydroxymoyl Anion to α,β‐Unsaturated Aldehydes

Organocatalytic Enantioselective Formal Conjugate Addition of a Hydroxymoyl Anion to α,β‐Unsaturated Aldehydes

Aldehyde N,N‐Dialkylhydrazones as Neutral Acyl Anion Equivalents: Umpolung of the Imine Reactivity

A New Strategy for Enantioselective Construction of Multisubstituted Five‐Membered Oxygen Heterocycles via a Domino Michael/Hemiketalization Reaction

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