Enantio- and Diastereoselective Betti/aza-Michael Sequence: Single Operated Preparation of Chiral 1,3-Disubstituted Isoindolines

Takizawa, Shinobu; Sako, M.; Abozeid, Mohamed A.; Kishi, Kenta; Wathsala, H. D. P.; Hirata, Shuichi; Murai, Kenichi; Fujioka, Hiromichi; Sasai, Hiroaki

doi:10.1021/acs.orglett.7b02693

Cited by 22 publications

(6 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A Mannich product with an appropriately tethered cinnamate ester was treated with Cs 2 CO 3 to afford isoindoline 8g via an intramolecular aza-Michael addition reaction (Scheme ). Given their biological importance and recent interest in the synthesis of isoindoline derivatives, this transformation is particularly notable. Additionally, our products can be further elaborated using cross-coupling chemistry, as demonstrated by the Sonogashira reaction performed on 3ae .…”

mentioning

confidence: 99%

Zn-ProPhenol Catalyzed Enantio- and Diastereoselective Direct Vinylogous Mannich Reactions between α,β- and β,γ-Butenolides and Aldimines

et al. 2017

View full text Add to dashboard Cite

We report a Zn-ProPhenol catalyzed reaction between butenolides and imines to obtain tetrasubstituted vinylogous Mannich products in good yield and diastereoselectivity with excellent enantioselectivity (97 to >99.5% ee). Notably, both α,β- and β,γ-butenolides can be utilized as nucleophiles in this transformation. The imine partner bears the synthetically versatile N-Cbz group, avoiding the use of the specialized aryl directing groups previously required in related work. Additionally, the reaction can be performed on gram scale with reduced catalyst loading as low as 2 mol %. The functional group-rich products can be further elaborated using a variety of methods.

show abstract

mentioning

confidence: 99%

Zn-ProPhenol Catalyzed Enantio- and Diastereoselective Direct Vinylogous Mannich Reactions between α,β- and β,γ-Butenolides and Aldimines

et al. 2017

View full text Add to dashboard Cite

show abstract

“…However, brief descriptions of the examples reported to date, including the main author, year of publication and type of catalyst employed are specified in Table 1. Strategies involving Mannich/IMAMR, [47][48][49][50][51][52][53][54][55][56][57][58][59] α-aminoxylation/ IMAMR, [60][61][62][63][64] aza-Friedel-Crafts/IMAMR, [65] cross metathesis/ IMAMR, , [18,28] aza-Morita-Baylis-Hillman/IMAMR, [66] Robinson annulation/IMAMR, [67][68][69][70][71] oxa-Mannich/IMAMR, [72] aza-Henry/IMAMR, [73] peptide coupling/IMAMR, [38] aza-Rahuhut-Currier/IMAMR, [74] Betti/IMAMR, [75] enamine formation/IMAMR [76] and carbene insertion/IMAMR [77] are collected in this table.…”

Section: Tandem Reactions Non-initiated By An Imamrmentioning

confidence: 99%

Two Decades of Progress in the Asymmetric Intramolecular aza‐Michael Reaction

Sánchez‐Roselló

Escolano

Gaviña

et al. 2021

The Chemical Record

View full text Add to dashboard Cite

The asymmetric intramolecular aza-Michael reaction (IMAMR) is a very convenient strategy for the generation of heterocycles bearing nitrogen-substituted stereocenters. Due to the ubiquitous presence of these skeletons in natural products, the IMAMR has found widespread applications in the total synthesis of alkaloids and biologically relevant compounds. The development of asymmetric versions of the IMAMR are quite recent, most of them reported in this century. The fundamental advances in this field involve the use of organocatalysts. Chiral imidazolidinones, diaryl prolinol derivatives, Cinchone-derived primary amines and quaternary ammonium salts, and BINOL-derived phosphoric acids account for the success of those methodologies. Moreover, the use of N-sulfinyl imines with a dual role, as nitrogen nucleophiles and as chiral auxiliaries, appeared as a versatile mode of performing the asymmetric IMAMR.

show abstract

“…α-Substituted α,β-unsaturated carbonyl compounds can be readily accessed by the Rauhut-Currier (RC) reaction, also called the vinylogous MBH reaction, through the coupling of two different α,β-unsaturated enones wherein one acts as a latent enolate. 85) As part of our research into the development of enantioselective domino reactions, [41][42][43][44][45][46][47][48][49][50][51][52][86][87][88][89][90] we became interested in designing sequences to address optically active α-methylidene-γ-lactams. We envisioned that the amidation of 28 with 27, followed by the BA-LB-catalyzed carbon-carbon bond-forming reaction of intermediary 29, would result in the generation of α-methylidene-γ-lactams 30 in high yield with high enantiocontrols (Chart 13).…”

Section: Stereoselective Synthesis Of α-Methylidene-γ-lactams By Amidmentioning

confidence: 99%

Organocatalytic Synthesis of Highly Functionalized Heterocycles by Enantioselective aza-Morita–Baylis–Hillman-Type Domino Reactions

Takizawa

2020

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

Organocatalytic enantioselective domino reactions are an extremely attractive methodology, as their use enables the construction of complex chiral skeletons from readily available starting materials in two or more steps by a single operation under mild reaction conditions. Thus, these reactions can save both the quantity of chemicals and length of time typically required for the isolation and/or purification of synthetic intermediates. Additionally, no metal contamination of the products occurs, given that organocatalysts include no expensive or toxic metals. The aza-Morita-Baylis-Hillman (aza-MBH) reaction is an atom-economical carbon-carbon bond-forming reaction between α,β-unsaturated carbonyl compounds and imines mediated by Lewis base (LB) catalysts, such as nucleophilic phosphines and amines. aza-MBH products are functionalized chiral β-amino acid derivatives that are highly valuable as pharmaceutical raw materials. Although various enantioselective aza-MBH processes have been investigated, very few studies of aza-MBH-type domino reactions have been reported due to the complexity of the aza-MBH process, which involves a Michael/ Mannich/H-transfer/β-elimination sequence. Accordingly, in this review article, our recent efforts in the development of enantioselective domino reactions initiated by MBH processes are described. In the domino reactions, chiral organocatalysts bearing Brønsted acid (BA) and/or LB units impart synergistic activation to substrates, leading to the easy synthesis of highly functionalized heterocycles (some of which have tetrasubstituted and/or quaternary carbon stereocenters) in high yield and enantioselectivity.

show abstract

Enantio- and Diastereoselective Betti/aza-Michael Sequence: Single Operated Preparation of Chiral 1,3-Disubstituted Isoindolines

Cited by 22 publications

References 72 publications

Zn-ProPhenol Catalyzed Enantio- and Diastereoselective Direct Vinylogous Mannich Reactions between α,β- and β,γ-Butenolides and Aldimines

Zn-ProPhenol Catalyzed Enantio- and Diastereoselective Direct Vinylogous Mannich Reactions between α,β- and β,γ-Butenolides and Aldimines

Two Decades of Progress in the Asymmetric Intramolecular aza‐Michael Reaction

Organocatalytic Synthesis of Highly Functionalized Heterocycles by Enantioselective aza-Morita–Baylis–Hillman-Type Domino Reactions

Contact Info

Product

Resources

About