Enantioselective Synthesis of Di- and Tri-Arylated All-Carbon Quaternary Stereocenters via Copper-Catalyzed Allylic Arylations with Organolithium Compounds

Guduguntla, Sureshbabu; Gualtierotti, Jean‐Baptiste; Goh, Shermin S.; Feringa, Ben L.

doi:10.1021/acscatal.6b01681

Cited by 29 publications

(14 citation statements)

References 86 publications

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“…37, 38 Feringa later showed that aryllithium reagents can be deployed directly in copper-catalyzed allylic substitutions of allyl bromides using triazolium-derived NHC ligand XIII , although incomplete regioselectivity was observed. 39 More recently, Hoveyda 40 and Hayashi 41, 42 applied more tractable organoboronates to the asymmetric vinylation and arylation of γ,γ-disubstituted allylic phosphates under non-cryogenic conditions. Finally, Sawamura and Ohmiya showed that azoles bearing acidic C-H bonds are subject to direct deprotonation-allylic substitution under the conditions of copper catalysis.…”

Section: Acyclic Quaternary Carbon Stereocentersmentioning

confidence: 99%

Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

2017

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Whereas numerous asymmetric methods for formation of quaternary carbon stereocenters in cyclic systems have been documented, the construction of acyclic quaternary carbon stereocenters with control of absolute stereochemistry remains a formidable challenge. This review summarizes enantioselective methods for the construction of acyclic quaternary carbon stereocenters from achiral or chiral racemic reactants via transition metal catalysis.

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Section: Acyclic Quaternary Carbon Stereocentersmentioning

confidence: 99%

Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

2017

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“…Mostly known as convenient, air-stable precursors to N -heterocyclic carbenes (NHCs) used in organocatalytic transformations, − 1,2,4-triazolium salts also form upon deprotonation of NHC ligands for transition metal catalysts. − Beyond the field of catalysis, these 1,2,4-triazole-based ligands form phosphorescent cyclometalated complexes with the substituents on the carbene ligand being key to their tunable emission wavelengths, − while other late transition metal complexes containing 1,2,4-triazole ligands have shown promising in vitro anticancer activity in studies involving breast, colon, lung, skin, liver, and cervical cancer as well as leukemia. − N -Aryl-substituted 1,2,4-triazoles are also frequent building blocks in organic compounds with biological activity. − Although less common than imidazolium or 1,2,3-triazolium salts, 1,2,4-triazolium salts have been successfully used as ionic liquids for dissolving cellulose …”

Section: Introductionmentioning

confidence: 99%

Catalytic Preparation of 1-Aryl-Substituted 1,2,4-Triazolium Salts

et al. 2019

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1,4-Diaryl- and 1-aryl-4-alkyl-substituted 1,2,4-triazolium salts are convenient air-stable precursors to carbenes used both as organocatalysts or as ligands for transition metal complexes. Traditionally, they are prepared via a multistep synthetic pathway with the low-yielding formation of the triazolium ring occurring in the last step. We have developed an alternative two-step synthesis involving the conversion of a primary amine or aniline derivative to the corresponding 4-substituted triazole followed by a copper-catalyzed arylation with diaryliodonium salts. This transition metal-catalyzed arylation can be carried out under mild conditions in acetonitrile and is tolerant toward both water and oxygen. Additionally, the high functional group tolerance of the protocol described here gives easy access to triazolium salts containing heterocyclic substituents or sulfides.

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“…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). 9f,g The successful conversion of these latter types of congested substrates in transformations leading to compounds having vicinal tetrasubstituted carbon centers would greatly expand the application potential of VCCs and advance the synthesis of otherwise elusive carbon stereocenters.…”

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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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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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Enantioselective Synthesis of Di- and Tri-Arylated All-Carbon Quaternary Stereocenters via Copper-Catalyzed Allylic Arylations with Organolithium Compounds

Cited by 29 publications

References 86 publications

Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

Catalytic Preparation of 1-Aryl-Substituted 1,2,4-Triazolium Salts

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

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