Organocatalyzed Dearomative Cycloaddition of 2-Nitrobenzofurans and Isatin-Derived Morita–Baylis–Hillman Carbonates: Highly Stereoselective Construction of Cyclopenta[b]benzofuran Scaffolds

Organic Letters, Journal Year: 2019, Volume and Issue: 21(3), P. 660 - 664

Published: Jan. 14, 2019

The first organocatalyzed asymmetric dearomative cycloaddition between 2-nitrobenzofurans and isatin-derived Morita-Baylis-Hillman carbonates has been developed. Using a modified cinchona alkaloid as the catalyst, series of structurally diverse cyclopenta[ b]benzofuran derivatives with three contiguous stereocenters, including spiro-quaternary chiral center, could be smoothly obtained in excellent results (all cases >20:1 dr, up to 99% yield 98% ee). utility this method was showcased by versatile transformations product.

Language: Английский

---

Stereodivergent synthesis of enantioenriched azepino[3,4,5-cd]-indoles via cooperative Cu/Ir-catalyzed asymmetric allylic alkylation and intramolecular Friedel–Crafts reaction

Chemical Science, Journal Year: 2022, Volume and Issue: 13(17), P. 4801 - 4812

Published: Jan. 1, 2022

A stereodivergent synthesis of azepino[3,4,5- cd ]-indoles bearing three stereogenic centers was established via synergistic dual-metal catalysis followed by acid-promoted epimerization, and up to all eight stereoisomers could be predictably achieved.

Language: Английский

---

Organocatalyzed Asymmetric Dearomative Aza-Michael/Michael Addition Cascade of 2-Nitrobenzofurans and 2-Nitrobenzothiophenes with 2-Aminochalcones

The Journal of Organic Chemistry, Journal Year: 2019, Volume and Issue: 84(7), P. 4381 - 4391

Published: March 13, 2019

An organocatalyzed dearomative aza-Michael/Michael addition cascade of 2-nitrobenzofurans and 2-nitrobenzothiophenes with 2-aminochalcones has been developed, opening a new channel to access series optically active tetrahydrobenzofuro[3,2-b]quinolines tetrahydrobenzo[4,5]thieno[3,2-b]quinolines bearing three contiguous stereocenters excellent diastereo- enantioselectivities (all cases >20:1 dr, up 99% ee). This study features the first asymmetric reaction beginning aza-Michael addition. The potential applications methodology were demonstrated by preparative-scale experiment versatile transformations products.

Language: Английский

---

β-Substituted Alkenyl Heteroarenes as Dipolarophiles in the Cu(I)-Catalyzed Asymmetric 1,3-Dipolar Cycloaddition of Azomethine Ylides Empowered by a Dual Activation Strategy: Stereoselectivity and Mechanistic Insight

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(9), P. 3519 - 3535

Published: March 1, 2021

The catalytic asymmetric 1,3-dipolar cycloaddition reactions of azomethine ylides with various electron-deficient alkenes provide the most straightforward protocol for preparation enantioenriched pyrrolidines in organic synthesis. However, employment conjugated alkenyl heteroarenes as dipolarophiles such protocols to afford a class particularly important molecules medicinal chemistry is still great challenge. Herein, we report that β-substituted heteroarenes, challenging internal alkene substrates without strong electron-withdrawing substituent, were successfully employed first time Cu(I)-catalyzed ylides. This reaction furnishes large array multistereogenic heterocycles incorporating both biologically pyrrolidine and heteroarene skeletons good yields exclusive diastereoselectivity excellent enantioselectivity. Our extensive density functional theory (DFT) calculations proposed working model explain origin stereochemical outcome elucidated uncommon dual activation/coordination dipole dipolarophile by metal, which sterically bulky, rigid, monodentate phosphoramidite ligand triple-homoaxial chirality plays pivotal role providing an effective chiral pocket around metal center, resulting high additional coordination heteroatom substrate Cu also critical enhanced reactivity. predicted reverse enantioinduction corresponding monocyclic well regiospecific less reactive C═C bond one related diene substrate. Such unique steric effect-directed enantioswitching coordination-directed regioselectivity verified experimentally.

Language: Английский

---

Ag-Catalyzed Asymmetric Interrupted Barton–Zard Reaction Enabling the Enantioselective Dearomatization of 2- and 3-Nitroindoles

Organic Letters, Journal Year: 2022, Volume and Issue: 24(3), P. 826 - 831

Published: Jan. 14, 2022

We disclose a Ag-catalyzed asymmetric interrupted Barton–Zard reaction of α-aryl-substituted isocyanoacetates with 2- and 3-nitroindoles, which enables the dearomatization nitroindoles hence offers rapid access to an array optically active tetrahydropyrrolo[3,4-b]indole derivatives bearing three contiguous stereogenic centers, including two tetrasubstituted chiral carbon atoms pretty outcomes (up 99% yield, 91:9 dr, 96% ee). The synthetic potential protocol was showcased by gram-scale versatile transformations product.

Language: Английский

---

Enantioselective dearomative [3+2] cycloaddition of 2-nitrobenzofurans with aldehyde-derived Morita–Baylis–Hillman carbonates

Chemical Communications, Journal Year: 2019, Volume and Issue: 55(62), P. 9144 - 9147

Published: Jan. 1, 2019

The phosphine-catalyzed asymmetric dearomative [3+2] cycloaddition of 2-nitrobenzofurans with aldehyde-derived Morita-Baylis-Hillman (MBH) carbonates or allenoate was developed. reaction MBH resulted in a series cyclopentabenzofurans containing three contiguous stereocenters good to high yields, diastereoselectivities and enantioselectivities. use also gave the target product moderate enantioselectivity.

Language: Английский

---

Enantioselective Synthesis of Fused Polycyclic Tropanes via Dearomative [3 + 2] Cycloaddition Reactions of 2-Nitrobenzofurans

Organic Letters, Journal Year: 2019, Volume and Issue: 22(1), P. 164 - 167

Published: Dec. 23, 2019

A straight synthetic approach to fused polycyclic tropane scaffold formation through an asymmetric dearomatization cycloaddition process of 2-nitrobenzofurans with cyclic azomethine ylides was successfully developed. In the presence a chiral copper complex, derived from Cu(OAc)2 and diphosphine ligand, series derivatives were obtained in high yields (75–91%) excellent enantioselectivities (90–98%). The utility this method showcased by facile transformation product.

Language: Английский

---

Organocatalytic Asymmetric Dearomatization of 3-Nitroindoles and 3-Nitrobenzothiophenes via Thiol-Triggered Diastereo- and Enantioselective Double Michael Addition Reaction

Organic Letters, Journal Year: 2019, Volume and Issue: 21(14), P. 5452 - 5456

Published: June 28, 2019

Organocatalytic asymmetric dearomatization of 3-nitroindoles and 3-nitrobenzothiophenes by reaction with ethyl 4-mercapto-2-butenoate has been developed. A range chiral tetrahydrothiopheneindolines tetrahydrothiophenebenzothiophenes bearing three contiguous stereocenters are obtained in high yields good diastereoselectivities excellent enantioselectivities. This is the first example thiol-triggered catalytic 3-nitrobenzothiophenes.

Language: Английский

---

Catalytic Asymmetric Dearomative 1,3-Dipolar Cycloaddition of 2-Nitrobenzothiophenes and Isatin-Derived Azomethine Ylides

Organic Letters, Journal Year: 2021, Volume and Issue: 23(21), P. 8600 - 8605

Published: Oct. 21, 2021

An enantioselective dearomative 1,3-dipolar cycloaddition of 2-nitrobenzothiophenes and isatin-derived azomethine ylides with a bifunctional hydrogen-bonding thiourea catalyst was established, giving polyheterocyclic compounds in excellent results (up to 99% yield, >20:1 dr for all cases up ee). The enantioselectivity could be reversed by the squaramide containing same chiral source as catalyst. DFT calculations revealed origin observed stereochemistry reversal enantioselectivity.

Language: Английский

---

Chiral 1,2-Diaminocyclohexane-α-Amino Acid-Derived Amidphos/Ag(I)-Catalyzed Divergent Enantioselective 1,3-Dipolar Cycloaddition of Azomethine Ylides

Heterocycles, Journal Year: 2021, Volume and Issue: 104(1), P. 123 - 123

Published: Dec. 9, 2021

A series of chiral 1,2-diaminocyclohexane--amino acid-derived amidophosphanes in combination with silver(I) salts, have been developed to cooperatively catalyze the azomethine ylides-involved 1,3-dipolar cycloaddition different electron-deficient alkenes.Among these, (1S,2S)-1,2-cyclohexanediamine-L-tert-leucine-derived amidphos/Ag(I) has demonstrated as being a highly efficient catalytic system cis-1,2-disubstituted olefins-involved ylides, including aromatic, heteroaromatic, aliphatic, and 2-substituted affording various fully substituted pyrrolidines high excellent yields (up 97% yield) enantioselectivities ee).Interestingly, (1R,2R)-1,2-cyclohexanediamine-L-tert-leucine-derived can efficiently terminal olefin-involved cycloaddition, giving 2,4,5-tri-substituted up 92% yield ee.123 HETEROCYCLES, Vol.104, No. 1, 2022mainly focus on bidentate P,P-ligands, 3 P,N-ligands, 4 P,S-ligands, 5 N,N-ligands, 6 N,O-ligands, 7 et al.Recently, by our group multifunctional ligands ions successfully applied diastereo-and enantioselectivities. 8 amidophosphane precatalysts scaffolds cinchona alkaloids, 1,2-diphenylethylenediamines α-amino acids devised.Owning performance amidophosphanes, it was commendable exploit other skeleton types amidophosphanes.Chiral 1,2-diaminocyclohexanes, rich easily available sources, which are widely derived organic small molecule catalysts field asymmetric synthesis, 9 not reported related applications amidphos/Ag(I)-catalyzed cycloaddition.Therefore, is necessary develop 1,2-diaminocyclohexanes-derived expand its application.Here, we report class 1,2-diaminocyclohexane-α-amino Ag(I) divergently enantiocatalyzed ylides olefins construct endo-pyrrolidine derivatives four contiguous stereocenters endo-pyrrolidines moderate enantioselectivities, respectively (Scheme 1).Scheme 1. Divergent enantioseletive RESULTS AND DISCUSSIONAccording procedures, 1a-e were obtained from (1R,2R)-or (1S,2S)-1,2-cyclohexanediamine natural 2).8a Amidophosphanes 1a-d synthesized corresponding (1S,2S)-1,2-cyclohexanediamines acids, N-Boc-(S)-phenylglycine, 124

Language: Английский

---