Ligand and substrate effects during Pd-catalyzed cyclizations of alkyne-tethered cyclohexadienones

Tello‐Aburto, Rodolfo; Kalstabakken, Kyle A.; Harned, Andrew M.

doi:10.1039/c3ob27491h

Cited by 50 publications

(13 citation statements)

References 63 publications

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“…Based on previous studies for the anti -acetoxylation of alkynes, 20 we initially tested model substrate 1a under a different survey of metal catalysts using AcOH both as a solvent and reagent ( Table 1 ). To our delight, we observed that Pd(OAc) 2 delivered the corresponding acetoxylated product Z - 2a in 86% isolated yield, with complete β-regio- and anti -stereoselectivities after 1 h at 80 °C (entry 1).…”

Section: Results and Discussionmentioning

confidence: 99%

Interplay between the Directing Group and Multifunctional Acetate Ligand in Pd-Catalyzed anti-Acetoxylation of Unsymmetrical Dialkyl-Substituted Alkynes

et al. 2022

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The cooperative action of the acetate ligand, the 2-pyridyl sulfonyl (SO 2 Py) directing group on the alkyne substrate, and the palladium catalyst has been shown to be crucial for controlling reactivity, regioselectivity, and stereoselectivity in the acetoxylation of unsymmetrical internal alkynes under mild reaction conditions. The corresponding alkenyl acetates were obtained in good yields with complete levels of β-regioselectivity and anti -acetoxypalladation stereocontrol. Experimental and computational analyses provide insight into the reasons behind this delicate interplay between the ligand, directing group, and the metal in the reaction mechanism. In fact, these studies unveil the multiple important roles of the acetate ligand in the coordination sphere at the Pd center: (i) it brings the acetic acid reagent into close proximity to the metal to allow the simultaneous activation of the alkyne and the acetic acid, (ii) it serves as an inner-sphere base while enhancing the nucleophilicity of the acid, and (iii) it acts as an intramolecular acid to facilitate protodemetalation and regeneration of the catalyst. Further insight into the origin of the observed regiocontrol is provided by the mapping of potential energy profiles and distortion–interaction analysis.

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Section: Results and Discussionmentioning

confidence: 99%

Interplay between the Directing Group and Multifunctional Acetate Ligand in Pd-Catalyzed anti-Acetoxylation of Unsymmetrical Dialkyl-Substituted Alkynes

et al. 2022

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“…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

Chem. Pharm. Bull.

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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.

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“…Harned and co-workers reported a regioselective Pd-catalyzed cyclization in 2009, 22 and an enantioselective variant was published in 2013. 23 Alkynetethered cyclohexadienones 47 underwent an acetoxylationcyclization sequence, providing bicyclic enones 48 with moderate selectivity in the presence of pinene-derived bipyridine ligand 49 (Scheme 10). Selectivity was found to be largely insensitive to substitution at the quaternary carbon of the cyclohexadienone, but highly sensitive to substitution on the tethered alkyne.…”

Section: Transition Metal-catalyzed Desymmetrizationsmentioning

confidence: 99%

Asymmetric transformations of achiral 2,5-cyclohexadienones

2014

Self Cite

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Cyclohexadienones are versatile platforms for performing asymmetric synthesis as evidenced by the numerous natural product syntheses that exploit their diverse reactivity profile. However, there are few general methods available for the direct asymmetric synthesis of chiral cyclohexadienones. To circumvent this problem, several researchers have developed catalytic asymmetric methods that employ readily available achiral 2,5-cyclohexadienones as substrates. Many of these reactions are desymmetrizations in which one of the enantiotopic alkenes of an achiral dienone is transformed. Others involve selective reaction at one alkene of an unsymmetrically substituted, achiral dienone. This review will cover advances in this area over the last 20 years and the application of these strategies in complex molecule synthesis.

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Ligand and substrate effects during Pd-catalyzed cyclizations of alkyne-tethered cyclohexadienones

Cited by 50 publications

References 63 publications

Interplay between the Directing Group and Multifunctional Acetate Ligand in Pd-Catalyzed anti-Acetoxylation of Unsymmetrical Dialkyl-Substituted Alkynes

Interplay between the Directing Group and Multifunctional Acetate Ligand in Pd-Catalyzed anti-Acetoxylation of Unsymmetrical Dialkyl-Substituted Alkynes

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

Asymmetric transformations of achiral 2,5-cyclohexadienones

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