The Vinylogous Aldol and Related Addition Reactions: Ten Years of Progress

Casiraghi, Giovanni; Battistini, Lucia; Curti, Claudio; Rassu, Gloria; Zanardi, Franca

doi:10.1021/cr100304n

Cited by 496 publications

(171 citation statements)

References 386 publications

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“…14 Isolation of the aldehyde 11 afforded the opportunity to assay the vinylogous Mukaiyama aldol reaction using the 2-silyloxyfuran 12a (TMSOF) in the presence of Lewis acids such as TiCl 4 or SnCl 4 .…”

Section: Resultsmentioning

confidence: 99%

Oxidative cyclization of γ-alkylidene butenolides. Stereoselective preparation of spirolactones

Fernández¹,

Clemente-Tejeda

Bermejo

2012

Arkivoc

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Section: Resultsmentioning

confidence: 99%

Oxidative cyclization of γ-alkylidene butenolides. Stereoselective preparation of spirolactones

Fernández¹,

Clemente-Tejeda

Bermejo

2012

Arkivoc

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“…[6] In most studies as ingle vinylogous substrate,e ither the electrophilic or nucleophilic partner,w as used. [1,[3][4][5][6][7] In 2013 Jørgensen and co-workers reported the first organocatalytic doubly vinylogous Michael-type reaction, namely the 1,6-addition of alkylidene lactones to 2,4-dienals with the formation of an ew stereocenter (Scheme 1a).[8] It is significantly difficult to simultaneously activate the two vinylogous partners at their remote reactive sites whilst achieving high regio-, diastereo-, and enantiocontrol. Indeed, to the best of our knowledge there are no precedents for the catalytic, asymmetric doubly vinylogous Michael addition (DVMA) to 2,4-dienones,the much less reactive analogues of 2,4-dienals.…”

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confidence: 99%

Direct Catalytic Asymmetric Doubly Vinylogous Michael Addition of α,β‐Unsaturated γ‐Butyrolactams to Dienones

Guo

Dai

et al. 2015

Angewandte Chemie

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An asymmetric doubly vinylogous Michael addition (DVMA) of a,b-unsaturated g-butyrolactams to sterically congested b-substituted cyclic dienones with high site-, diastereo-, and enantioselectivity has been achieved. An unprecedented DVMA/vinylogous Michael addition/isomerization cascade reaction affords chiral fused tricyclic g-lactams with four newly formed stereocenters.Remote stereocontrol in catalytic asymmetric reactions is am ajor challenge in modern organic synthesis. [1,2] Recently,a symmetric organocatalysis has been successfully applied to the functionalization of unsaturated carbonyl compounds at their g-, d-, and e-positions with high stereo-and site-selectivity.[1] Thet wo basic activation strategies exploit LUMO-lowering and HOMO-raising effects,whereby iminium ions and either di-or trienamines are formed by condensation of the carbonyl substrates with the amine function of chiral organocatalysts. [1,3] Melchiorre and coworkers achieved the d-functionalization of enones by using ac inchona-based primary amine,w hich forms an iminium ion with the polyunsaturated carbonyl substrate,t hus delivering the LUMO-lowering effect through the conjugated p system.[4] Enamine catalysis [5] was also successfully applied to vinylogous systems.D i-and trienamine catalysis, [5b,c] usually employing chiral secondary amines to activate the g and e sites of unsaturated aldehydes,has led for instance to aseries of Diels-Alder cycloadditions [5e] and other remote functionalization reactions. [6] In most studies as ingle vinylogous substrate,e ither the electrophilic or nucleophilic partner,w as used. [1,[3][4][5][6][7] In 2013 Jørgensen and co-workers reported the first organocatalytic doubly vinylogous Michael-type reaction, namely the 1,6-addition of alkylidene lactones to 2,4-dienals with the formation of an ew stereocenter (Scheme 1a).[8] It is significantly difficult to simultaneously activate the two vinylogous partners at their remote reactive sites whilst achieving high regio-, diastereo-, and enantiocontrol. Indeed, to the best of our knowledge there are no precedents for the catalytic, asymmetric doubly vinylogous Michael addition (DVMA) to 2,4-dienones,the much less reactive analogues of 2,4-dienals. Ther ealization of such ar eaction would prove the broad applicability of the organocatalytic vinylogous activation patterns,t hus representing as ignificant advance in the field. Moreover,asymmetric doubly vinylogous reactions naturally leave two unsaturated CÀCbonds in the product and provide

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“…[5] However, to the best of our knowledge, there are not examples available concerning the development of catalyst-free, aqueous or neat Mukaiyama-type vinylogous Mannich addition methodology, [8,9] in spite of the distinct advantage of being atom conservative and more eco-friendly as compared to the conventional organic-phase, catalyzed counterparts. To address this issue, in connection with our ongoing studies focused on the exploitation of heterocyclic silyl dienolates in the vinylogous addition to C=X bonds, [8d,10] we herein present the first uncatalyzed aqueous and solvent-free three-component vinylogous Mukaiyama-Mannich reaction (VMMnR) employing a pyrrole ketene silyl-N,O-acetal, an aromatic amine, and diverse classes of aldehydes.…”

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confidence: 99%

Aqueous and Solvent‐Free Uncatalyzed Three‐Component Vinylogous Mukaiyama–Mannich Reactions of Pyrrole‐Based Silyl Dienolates

et al. 2011

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A catalyst-free, environmentally benign three-component vinylogous Mukaiyama-Mannich reaction of pyrrole-based silyl dienolates is presented, which works effectively in both aqueous and solvent-free environments. Both lipophilic and hydrophilic aldehyde candidates are suitable substrates, allowing access to a rich repertoire of unsaturated vicinal aminolactam structures with virtually complete g-site selectivity and moderate to good anti-diastereoselectivity. The utility of this technology is highlighted by protecting group-free synthesis of densely hydroxylated, sugar-related lactam frameworks. The role of water as an indispensable H-bonding reaction propeller is demonstrated.Keywords: catalyst-free conditions; green chemistry; Mukaiyama-Mannich reaction; synthetic methods; vinylogy; water The development of enabling chemical methodologies that fulfil such emblematic keywords as water, solvent-free, environment awareness, atom economy, and practicality is one of the greatest challenges of contemporary organic synthesis.[1] To this goal, several aqueous and solvent-free versions of leading carboncarbon bond-forming reactions have been successfully explored, [2] including the venerable Diels-Alder cycloaddition, [3] the aldol addition reaction, [4] the Mannich [5] and Michael couplings, [6] the Claisen rearrangement, [3b,7] to mention only a few.As for the Mannich reaction in particular, significant progress has been made for direct and indirect, two-component and three-component executions, few of which adopting neutral water as the reaction medium or even under solvent-free conditions. [5] However, to the best of our knowledge, there are not examples available concerning the development of catalyst-free, aqueous or neat Mukaiyama-type vinylogous Mannich addition methodology, [8,9] in spite of the distinct advantage of being atom conservative and more eco-friendly as compared to the conventional organic-phase, catalyzed counterparts. To address this issue, in connection with our ongoing studies focused on the exploitation of heterocyclic silyl dienolates in the vinylogous addition to C=X bonds, [8d,10] we herein present the first uncatalyzed aqueous and solvent-free three-component vinylogous Mukaiyama-Mannich reaction (VMMnR) employing a pyrrole ketene silyl-N,O-acetal, an aromatic amine, and diverse classes of aldehydes. Two complementary protocols are established, with which both hydrophobic aldehydes (aqueous and solvent-free conditions) and hydrophilic aldehydes (aqueous conditions) operate, furnishing g-substituted d-aminopyrrolinone units in high isolated yields, with excellent levels of g-site selectivity and chemoselectivity, and moderate to high diastereoselectivity in favour of anti-configured adducts.We initiated our journey by evaluating the one-pot three-component VMMnR between N-Boc-protected trimethylsilyloxypyrrole (1a), 3-methylbutanal (2a), and aniline (3a) in pure neutral water under vigorous stirring at room temperature (Table 1, entry 1). Very poor amounts of the Mannich product ...

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The Vinylogous Aldol and Related Addition Reactions: Ten Years of Progress

Cited by 496 publications

References 386 publications

Oxidative cyclization of γ-alkylidene butenolides. Stereoselective preparation of spirolactones

Oxidative cyclization of γ-alkylidene butenolides. Stereoselective preparation of spirolactones

Direct Catalytic Asymmetric Doubly Vinylogous Michael Addition of α,β‐Unsaturated γ‐Butyrolactams to Dienones

Aqueous and Solvent‐Free Uncatalyzed Three‐Component Vinylogous Mukaiyama–Mannich Reactions of Pyrrole‐Based Silyl Dienolates

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