Iminium Activation in Catalytic Enantioselective Conjugate Additions

Vicário, José L.; Reyes, Efraím; Badı́a, Dolores; Carrillo, Luisa

doi:10.1002/9783527630578.ch6

Cited by 15 publications

(10 citation statements)

References 235 publications

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“…Iminium species are able to be attacked by nucleophiles at C-1 and C-3 whereas dienamines react with electrophiles at C-2 and C-4 (Scheme ). As the result of this dual reactivity and the ambivalent character of the formed species, it has been possible to get the α-, β-, and γ-functionalization of the enals, as well as the attack to their carbonyl carbons (C-1) . The regioselectivity control difficulties derived from the ambivalent character of the iminium species have been overcome by the well-defined tendencies of the nucleophiles to attack on C-3 or C-1, , whereas for dienamines this problem was solved modulating the steric hindrance at C-2 and C-4 .…”

Section: Introductionmentioning

confidence: 99%

“…As the result of this dual reactivity and the ambivalent character of the formed species, it has been possible to get the α-, β-, and γ-functionalization of the enals, as well as the attack to their carbonyl carbons (C-1) . The regioselectivity control difficulties derived from the ambivalent character of the iminium species have been overcome by the well-defined tendencies of the nucleophiles to attack on C-3 or C-1, , whereas for dienamines this problem was solved modulating the steric hindrance at C-2 and C-4 . On the other hand, chemoselectivity control difficulties derived from the dual reactivity (iminium vs dienamine) were obviated by using reagents without dual reactivity (nucleophiles or electrophiles).…”

Section: Introductionmentioning

confidence: 99%

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Control of the Dual Reactivity (Iminium-Dienamine) of β-Arylmethyl α,β-Unsaturated Aldehydes in Organocatalytic 1,3-Dipolar Cycloadditions with N-Benzoyl C,N-Cyclic Azomethine Imines

et al. 2014

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1,3-Dipolar cycloadditions of C,N-cyclic azomethine imines with α,β-unsaturated aldehydes can be performed with complete control of the regio-, exo-, and enantioselectivity under aminocatalytic conditions. The so far never studied competence of the iminium-dienamine reactivity inherent to β-alkyl α,β-unsaturated aldehydes was studied, which was possible by allowing achievement of complete control of the chemoselectivity in reactions of the β-arylmethyl derivatives with azomethine imines by using different additives and organocatalysts, whose role has been rationalized by DFT calculations and chemical proofs. Thus, it has been possible to selectively obtain the pyrazolidines resulting from both the attack to the C2-C3 (via iminium) and the C3-C4 (via dienamine) bonds at the starting enals, which can be used as precursors of interesting tetrahydroisoquinolinic compounds.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Control of the Dual Reactivity (Iminium-Dienamine) of β-Arylmethyl α,β-Unsaturated Aldehydes in Organocatalytic 1,3-Dipolar Cycloadditions with N-Benzoyl C,N-Cyclic Azomethine Imines

et al. 2014

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“…Enantioselective Michael addition is one of the most powerful reactions in organic synthesis that forms a carbon–carbon bond, thereby affording synthetically valuable chiral building blocks . One of the most common strategies to enable such reactions includes the organocatalytic activation of electrophiles via iminium catalysis .…”

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confidence: 99%

Stereodivergent Carbon–Carbon Bond Formation between Iminium and Enolate Intermediates by Synergistic Organocatalysis

2020

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We report here a stereodivergent method for the Michael addition of aryl acetic acid esters to α,β-unsaturated aldehydes catalyzed by a combination of a chiral pyrrolidine and a chiral Lewis base. This reaction proceeds through a synergistic catalytic cycle which consists of one cycle leading to a chiral iminium electrophile and a second cycle generating a nucleophilic chiral enolate for the construction of a carbon−carbon bond. By varying the combinations of catalyst enantiomers, all four stereoisomers of the products with two vicinal stereocenters are accessible with high enantio-and diastereoselectivity. The products of the Michael addition, 1,5-aldehyde esters, can be readily transformed into a variety of other valuable enantioenriched structures, including those bearing three contiguous stereocenters in an acyclic system, thus providing an efficient route to an array of structural and stereochemical diversity.

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“…Since the pioneer work by Cozzy and co-workers, on the organocatalyzed asymmetric α-alkylation of aldehydes using such alcohols through an enamine activation mode, 2 several examples have recently appeared, the majority following a similar strategy. 3 Despite the versatility of activated methylene compounds, such as dicarbonyl compounds, β-keto esters, α-cyanoacetates, α-nitroacetates, β-keto sulfones, etc., as building blocks which are easily transformed into other functionalities and the multiple strategies reported for their activation employing chiral catalysts, 4 reported methodologies for their use as prochiral nucleophiles in asymmetric alkylations with benzylic alcohols remain rare. To the best of our knowledge, there are only two reports in this regard recently reported by Nishibayashi and our group, disclosing the asymmetric alkylation of β-keto phosphonates 5 and β-keto esters 6 respectively, catalyzed by BOX-Cu(OTf) 2 -type complexes (Scheme 1).…”

mentioning

confidence: 99%

Bis(2-aminobenzoimidazole)-Organocatalyzed Asymmetric Alkylation of Activated Methylene Compounds with Benzylic and Allylic Alcohols

2014

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The first organocatalyzed asymmetric alkylation of activated methylene compounds using benzylic and allylic alcohols as alkylating agents through dual hydrogen bond activation in an S N 1-type reaction is reported. This green protocol employs a bis(2-aminobenzoimidazole) in combination with an achiral Brønsted acid as a bifunctional catalytic system and gives the alkylation products with moderate to good enantioselectivities. Although the scope of the reaction is limited, this methodology can be considered as complementary to existing metal-catalyzed processes. In addition, modest results were obtained in a first attempt to perform a metal-free asymmetric Tsuji-Trost reaction using allylic alcohols. Finally, the recovery and reusability of the organocatalyst is also achieved.The asymmetric alkylation of prochiral carbon nucleophiles using benzylic alcohols as alkylating agents, through an S N 1-type reaction, has emerged over the last few years an environmentally friendly alternative route to the previously reported and well-established methodologies for enantioselective C-C bond formation, since this process has perfect atom-economy and only generates water as a byproduct. 1 However, the prochiral carbon nucleophiles that have been used to date seem to be limited to the use of aldehydes. Since the pioneer work by Cozzy and co-workers, on the organocatalyzed asymmetric α-alkylation of aldehydes using such alcohols through an enamine activation mode, 2 several examples have recently appeared, the majority following a similar strategy. 3 Despite the versatility of activated methylene compounds, such as dicarbonyl compounds, β-keto esters, α-cyanoacetates, α-nitroacetates, β-keto sulfones, etc., as building blocks which are easily transformed into other functionalities and the multiple strategies reported for their activation employing chiral catalysts, 4 reported methodologies for their use as prochiral nucleophiles in asymmetric alkylations with benzylic alcohols remain rare. To the best of our knowledge, there are only two reports in this regard recently reported by Nishibayashi and our group, disclosing the asymmetric alkylation of β-keto phosphonates 5 and β-keto esters 6 respectively, catalyzed by BOXCu(OTf) 2 -type complexes (Scheme 1). Scheme 1 Previous asymmetric alkylations of active methylene compounds with benzylic alcoholsContinuing with this research 7 and based on the experience of our group in organocatalyzed asymmetric reactions involving activated methylene compounds in Michael-type additions, 8 we envisaged a possible metalfree strategy through dual hydrogen bond activation (Figure 1) that would represent the first organocatalyzed version of this transformation. The results of this study are presented herein. Figure 1 Hypothetic dual hydrogen bond activation working modelFirstly, in the search for optimal reaction conditions we selected the reaction between bis[4-(dimethylamino)phenyl]methanol (1a), which would produce a rather stable carbocationic intermediate (E = -7.02) 9 and ethyl 2-oxocyclope...

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Iminium Activation in Catalytic Enantioselective Conjugate Additions

Cited by 15 publications

References 235 publications

Control of the Dual Reactivity (Iminium-Dienamine) of β-Arylmethyl α,β-Unsaturated Aldehydes in Organocatalytic 1,3-Dipolar Cycloadditions with N-Benzoyl C,N-Cyclic Azomethine Imines

Control of the Dual Reactivity (Iminium-Dienamine) of β-Arylmethyl α,β-Unsaturated Aldehydes in Organocatalytic 1,3-Dipolar Cycloadditions with N-Benzoyl C,N-Cyclic Azomethine Imines

Stereodivergent Carbon–Carbon Bond Formation between Iminium and Enolate Intermediates by Synergistic Organocatalysis

Bis(2-aminobenzoimidazole)-Organocatalyzed Asymmetric Alkylation of Activated Methylene Compounds with Benzylic and Allylic Alcohols

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