Visible-Light-Activated Catalytic Enantioselective β-Alkylation of α,β-Unsaturated 2-Acyl Imidazoles Using Hantzsch Esters as Radical Reservoirs

Assis, Francisco F. de; Huang, Xiaoqiang; Akiyama, Midori; Pilli, Ronaldo A.; Meggers, Eric

doi:10.1021/acs.joc.8b01588

Cited by 66 publications

(36 citation statements)

References 65 publications

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“…4-alkyl-1,4-dihydropyridines (2) were prepared according to literature procedure. [5][6][7][8] Compounds 2a -2c, 2d -2i are known, 2e and 2j are new compounds and were prepared following General procedure I. Compound 2h is a known compound and was prepared following General procedure II.…”

Section: S3: Typical Procedures For the Preparation Of Substituted Dhp Estersmentioning

confidence: 99%

“…Pd-catalyzed asymmetric allylic substitution reactions of vinyl epoxides 7 and vinyl cyclic carbonates (VCCs) 8 serving as prochiral electrophilic allylic surrogates have been recently reported as efficient approaches to forge compounds featuring a tetrasubstituted carbon stereocenter. While only a handful of studies report the efficient use of olefin-substituted VCCs in allylic alkylation (Scheme 1b, R 2 -R 4 ≠ H) 9 and more particularly towards branched allylic products, 9h,i as far as we are aware only two reports exist that briefly discuss the use of more elaborate carbonate ring substituted congeners (Scheme 1b, R 5 and R 6 ≠ H).…”

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confidence: 99%

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Asymmetric Synthesis of Homoallylic Alcohols Featuring Vicinal Tetrasubstituted Carbon Centers via Dual Pd/Photoredox Catalysis

et al. 2021

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a 1a (0.10 mmol), 2a (0.15 mmol), Ir(ppy)2(dtbbpy)PF6 (1.0 mol%), Pd2(dba)3 (2.5 mol%), L* (6.0 mol%), Cs2CO3 (0.10 mmol) were combined in CH3CN (2.0 mL) at 25 °C under blue LED radiation (445 nm, 0.7 A, corresponding to a photon flux of 1.2 µeinstein/s) for 2 h. Yields and b/l ratios were determined by 1 H NMR analysis using CH2Br2 as an internal standard. Enantiomeric ratios (er) were determined by UPC2. b In the absence of Cs2CO3. c In the absence of Ir(ppy)2(dtbbpy)PF6. d In the dark. e In the absence of Cs2CO3, under blue LED radiation (445 nm, 1.0 A, corresponding to a photon flux of 1.6 µeinstein/s).The use of other diphosphine ligands (L9-L15) did not improve the process outcome (entries 9-15). Further variations of the protocol (entries 16-19) were first carried out with (R)-DTBM-SegPhos being cheaper than (R)-3,5-tBu-MeOBIPHEP, but providing nearly the same regio-and enantiocontrol (cf., entries 4 versus 5). In the absence of Cs2CO3, 3aa was obtained in a slightly higher yield and er (entry 16 versus 4), and therefore was omitted for the optimized conditions (vide infra). Omitting the iridium PC (entry 17) gave 3aa in 25% yield suggesting that Hantzsch ester 2a could itself also serve as a photoreductant to form a radical cation that subsequently generates, through homolytic cleavage, the requisite alkyl radical for the CC coupling. 12 As expected, no product was detected without blue LED irradiation, but by further increasing the light intensity, the yield of 3aa increased to 71% (entry 19). With these alternative conditions in hand, we then re-used (R)-3,5-tBu-MeOBIPHEP L5 as ligand, which afforded the product in 75% yield and with an er of 89:11 (entry 20).Scheme 2. Product scope using various VCCs to generate quaternary carbon stereocenters. Reaction conditions: 1 (0.10 mmol), 2a (0.15 mmol), Ir(ppy)2(dtbbpy)PF6 (1.0 mol%), Pd2(dba)3 (2.5 mol%), (R)-3,5-tBu-MeOBIPHEP L5 (6.0 mol%), CH3CN (2 mL), 2 h, blue LED (445 nm, 1 A, corresponding to a photon flux of 1.6 µeinstein/s). Yields of the isolated, column-purified products are reported. The enantiomeric ratios (er values) were determined by UPC2. The b/l ratios were determined by 1 H NMR analysis.With these optimized conditions we then examined the generality of similar substrate combinations providing homoallylic alcohols with quaternary carbon stereocenters (Scheme 2, 3aa-3ja). Variation of the aryl substituents on the VCC in the presence of Hantzsch ester 2a generally provided the homoallylic alcohols with remarkable branch-selectivity (b:l >95:5) and in appreciable isolated yields of up to 78% (3ga). Good enantio-induction levels of up to 89:11 er for the majority of the products were achieved except for 3fa, 3ha and 3ja. Whereas for 3ha the presence of the thiophen-2-yl group could interfere through coordination to Pd(allyl) intermediates, the use of a VCC with an additional substituent (R 1 = Ph, 1j) on the vinyl group hence increasing the steric demand substrate activation was detrimental to both the product yield (33%) and optical purity ...

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Section: S3: Typical Procedures For the Preparation Of Substituted Dhp Estersmentioning

confidence: 99%

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confidence: 99%

Asymmetric Synthesis of Homoallylic Alcohols Featuring Vicinal Tetrasubstituted Carbon Centers via Dual Pd/Photoredox Catalysis

et al. 2021

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“…); the omission of the catalyst only provided 7 a in a much lower yield even after prolonging time (Table , entry 2: 20 % yield). To improve the enantioselectivity, a comparison of steric environments between ΛCo1 and Meggers’ catalyst ΛRh1 (Figure , M=Rh, X=S) was performed. As shown in Figure , the coordination of a chiral diamine unit with a Co center, though being favored to induce the chirality of the metal center, makes the steric tert ‐butyl groups distant from the plane comprising of Co, Cl, and O atoms (S ΛCo1 =5.05 Å vs. S ΛRh1 =4.57 Å).…”

Section: Figurementioning

confidence: 99%

“…Control experiments showed that both visible light and photocatalyst are necessary (Table , entries 9 and 10), and replacement of the central metal Co with other 3d metals (that is, Mn, Fe, Ni, Cu, and Zn), 4d metals (that is, Ru and Rh) or the 5d metal Ir, only results in lower or even no enantioselectivity (see the Supporting Information for details). Consistent with the control experiments, UV/Vis absorption and cyclic voltammetry studies of ΔCo1 complex and ΔCo1 – 5 a complex indicated that both of these two complexes cannot be a bifunctional catalyst in this transformation (see the Supporting Information for details) …”

Section: Figurementioning

confidence: 99%

Exploration of a Chiral Cobalt Catalyst for Visible‐Light‐Induced Enantioselective Radical Conjugate Addition

et al. 2019

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Chiral catalysts tolerating photochemical reactions are in great demand for the vast development of visible-lightinduced asymmetric synthesis.N ow,c hiral octahedral complexes based on earth-abundant metal and chiral N 4 ligands are reported. One well-defined chiral Co II -complex is shown to be an efficient catalyst in the visible-light-induced conjugated addition of enones by alkyl and acyl radicals,p roviding synthetically valued chiral ketones and 1,4-dicarbonyls in 47-> 99 %yields with up to 97:3 e.r.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

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“…Very recently, the concept could be extended to the use of Hantzsch esters 56 as alkyl radical reservoirs (Scheme ) . The authors assumed that both mechanisms A and B could operate simultaneously.…”

Section: Metal‐centered Chirality Catalysismentioning

confidence: 99%

Acyl‐Imidazoles: A Privileged Ester Surrogate for Enantioselective Synthesis

et al. 2019

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Since the first report by Evans in asymmetric Friedel-Crafts reactions, the use of acyl-imidazoles has blossomed as powerful ester/amide surrogates. The imidazole scaffold indeed displays stability and special activation features allowing both better reactivity and selectivity in traditional ester/amide functionalizations: α-(enolate chemistry), β-(conjugate additions), α,β-(cyclo-additions) or γ/δ-(vinylogous). An overview of the contemporary and growing interest in acyl-imidazoles in metal-and organo-catalyzed transformations (bio-hybrid catalytic systems will be fully described in a back-to-back Minireview) will be highlighted. Moreover, post-functionalization expediencies are also going to be discussed in this Minireview. Scheme 1. Synthesis of acyl-imidazoles by Okamoto and co-workers.Scheme 2. Synthesis of α,β-unsaturated acyl-imidazoles. . α-Alkylation of 2-naphthylmethyloxy acyl-imidazoles through PTC catalysis. NPM = 2-naphthylmethyl.Scheme 47. Chemo-and enantioselective oxidative cycloetherification of 2acyl-imidazoles with chiral quaternary ammonium salts. (please, change the chemdraw scheme 47; a new one is given) Scheme 48. Organocatalyzed enantioselective conjugate addition of aryl trifluoroborate to α,β-unsaturated 2-acyl 1-methylimidazole. 2 3 4 5 6 7 8

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Visible-Light-Activated Catalytic Enantioselective β-Alkylation of α,β-Unsaturated 2-Acyl Imidazoles Using Hantzsch Esters as Radical Reservoirs

Cited by 66 publications

References 65 publications

Asymmetric Synthesis of Homoallylic Alcohols Featuring Vicinal Tetrasubstituted Carbon Centers via Dual Pd/Photoredox Catalysis

Asymmetric Synthesis of Homoallylic Alcohols Featuring Vicinal Tetrasubstituted Carbon Centers via Dual Pd/Photoredox Catalysis

Exploration of a Chiral Cobalt Catalyst for Visible‐Light‐Induced Enantioselective Radical Conjugate Addition

Acyl‐Imidazoles: A Privileged Ester Surrogate for Enantioselective Synthesis

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