Paraldehyde as an Acetaldehyde Precursor in Asymmetric Michael Reactions Promoted by Site‐Isolated Incompatible Catalysts

Fan, Xinyuan; Rodríguez‐Escrich, Carles; Sayalero, Sonia; Pericàs, Miquel À.

doi:10.1002/chem.201302087

Cited by 45 publications

(33 citation statements)

References 64 publications

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“…After the successful employment of vinyl acetate as an indirect source of acetaldehyde, Pericas et al 67 recently showed the use of cyclic trimer paraldehyde (110), as a precursor for acetaldehyde.…”

Section: Paraldehyde In Asymmetric Micheal Reactionmentioning

confidence: 99%

Acetaldehyde in asymmetric organocatalytic transformations

Kumar

Rizvi

et al. 2015

RSC Adv.

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The role of acetaldehyde as a nucleophile in various asymmetric C-C bond forming transformations is 5 presented, with consideration not only to the optimizations of reaction parameters relevant to product formation, polymerization, by-products, purifications, chirality and instability of final products, but also the application of final products in the synthesis of bioactive molecules. The review is organized according to the use of acetaldehyde in different organocatalytic reactions covering the most recent reports. In the last section indirect sources of acetaldehyde are discussed from the perspective of difficult 10 handling and its requirement of slow addition as well as freshly distilled in some of the transformations, which is one of the most critical issues in the late exploitation of acetaldehyde as a nucleophile in synthetic chemistry.

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Section: Paraldehyde In Asymmetric Micheal Reactionmentioning

confidence: 99%

Acetaldehyde in asymmetric organocatalytic transformations

Kumar

Rizvi

et al. 2015

RSC Adv.

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“…In order to overcome the problems of low boiling point and high reactivity of acetaldehyde, several groups attempted the use of acetaldehyde surrogates, such as paraldehyde and vinyl acetate, in asymmetric organocatalytic cross‐aldol reactions. In particular, vinyl acetate is typically used as an acyl donor in enzyme‐catalyzed transesterification reactions.…”

Section: Enantioselective Reactions Using Simple Acetaldehydementioning

confidence: 99%

“…Similarly to the aldol reaction, three molecules of acetaldehyde are generated by the reaction of paraldehyde with polymer‐bounded p ‐toluenesulfonic acid ( 12 ) which then undergo Michael addition with β‐nitroolefin through enamine catalysis. The best result (91 % ee ) was obtained when the two incompatible solid‐supported (co)‐catalysts were confined into a teabag, in CH 2 Cl 2 (Scheme ) …”

Section: Enantioselective Reactions Using Simple Acetaldehydementioning

confidence: 99%

Acetaldehyde: A Small Organic Molecule with Big Impact on Organocatalytic Reactions

Kim

et al. 2015

Chemistry A European J

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Stereocontrolled formation of carbon-carbon and carbon-heteroatom bonds through asymmetric organocatalysis is a formidable challenge for modern synthetic chemistry. Among the most significant contributions to this field are the transformations involving the use of acetaldehyde or α-heteroatom-substituted acetaldehydes for constructing valuable synthons (e.g., amino acid derivatives and hydroxycarbonyl). In this Minireview, versatile (enantioselective) organocatalytic transformations are discussed.

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“…In our approach, [11] cheap and easy-to-handle paraldehyde (3.7 € per mol; b.p. 123 O C) is employed as a convenient source of acetaldehyde, which is slowly generated by acid-catalyzed deoligomerization (polystyrene-bound sulfonic acid).…”

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confidence: 99%

“…Noteworthy, the combined use of 1 b/2 under these conditions does not require the physical separation of the two resins, as was the case for the combined use of the silyl ether of 1 a and 2 in Michael additions of acetaldehyde. [11] The scope of the cross-aldol reaction was studied next under the optimized reaction conditions, and the results are listed in Table 2. It was established that benzaldehydes with either ortho, meta, or para electron-withdrawing substituents afforded the desired cross-aldol products with generally good yields and excellent enantioselectivities ( Table 2, entries 1-9).…”

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confidence: 99%

Highly Enantioselective Cross‐Aldol Reactions of Acetaldehyde Mediated by a Dual Catalytic System Operating under Site Isolation

Fan

Rodríguez‐Escrich

Wang

et al. 2014

Chemistry A European J

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: Polystyrene-supported (PS) diarylprolinol catalysts 1 a (Ar = phenyl) and 1 b (Ar = 3,5-bis(trifluoromethyl)-phenyl) have been developed. Operating under site-isolation conditions, PS-1 a/1 b worked compatibly with PS-bound sulfonic acid catalyst 2 to promote deoligomerization of paraldehyde and subsequent cross-aldol reactions of the resulting acetaldehyde in one pot, affording aldol products in high yields with excellent enantioselectivities. The effect of water on the performance of the catalytic system has been studied and its optimal amount (0.5 equiv) has been determined. The dual catalytic system (1/2) allows repeated recycling and reuse (10 cycles). The potential of this methodology is demonstrated by a two-step synthesis of a phenoperidine analogue (68 % overall yield ; 98 % ee) and by the preparation of highly enantioenriched 1,3-diols 4 and 3-methylamino-1-arylpropanols 5, key intermediates in the synthesis of a variety of druglike structures.The aldol reaction has attracted plenty of interest due to its pivotal role in organic synthesis. [1] Among the various methods available to carry out this reaction enantioselectively, the organocatalytic methods stand out for several reasons: 1) under extremely mild reaction conditions excellent stereocontrol can be achieved in up to two newly formed stereocenters, 2) no prefunctionalization of any of the reactants is required, and 3) the reactions take place in a metal-free environment, which avoids product contamination with toxic metal derivatives. [2] Therefore, important developments have been achieved since the first report on the direct asymmetric intermolecular aldol reaction catalyzed by proline in 2000. [3] The use of acetaldehyde (the simplest enolizable aldehyde), however, has been a great challenge due to its high reactivity and its inherent tendency to oligomerize. [4] In 2008, Hayashi and co-workers reported the first asymmetric aldol reaction of acetaldehyde with good yields and excellent enantioselectivities by using diaryprolinol as the catalyst. [5] Shortly after, the same reaction was tested with a diamine catalyst to afford aldol products with varying yields (34-99 %) and enantioselectivities (69-92 %). [6] Recently, a water compatible diarylprolinol derivative has been reported to promote this reaction in brine, affording aldol products in good yields and ee's. [7] Despite the excellent results in these reports, some problems remain unsolved in this reaction, especially from the practical point of view. For instance, the low boiling point of acetaldehyde (21 O C) seriously hampers its transportation, storage, and handling, therefore increasing cost and energy consumption. From the reaction perspective, the tendency to oligomerization and high reactivity of acetaldehyde is detrimental, since side reactions are common. To overcome these drawbacks, an interesting example was reported recently using vinyl acetate as acetaldehyde precursor in cross-aldol reactions. The recorded enantioselectivities, however, were very low (10-20 %...

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Paraldehyde as an Acetaldehyde Precursor in Asymmetric Michael Reactions Promoted by Site‐Isolated Incompatible Catalysts

Cited by 45 publications

References 64 publications

Acetaldehyde in asymmetric organocatalytic transformations

Acetaldehyde in asymmetric organocatalytic transformations

Acetaldehyde: A Small Organic Molecule with Big Impact on Organocatalytic Reactions

Highly Enantioselective Cross‐Aldol Reactions of Acetaldehyde Mediated by a Dual Catalytic System Operating under Site Isolation

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