Photocatalytic reverse polarity Povarov reaction

Leitch, Jamie A.; Arriba, Ángel L. Fuentes de; Tan, Joanne; Hoff, Oskar; Martínez, Carlos; Dixon, Darren J.

doi:10.1039/c8sc01704b

Cited by 55 publications

(43 citation statements)

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“…Specifically, the generation of ketyl radical species ( e.g. d 1 umpolung operators) through the reduction of carbonyl derivatives has been a major focus 6. Since carbonyls are typically characterized by strongly negative redox potentials ( E 1/2 red = –1.93 V vs. SCE for benzaldehydes),7 the development of cooperative catalytic systems to effect said reduction potential have been highly explored to afford annulations, reductive couplings and radical–radical couplings (Fig.…”

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confidence: 99%

Reductive annulations of arylidene malonates with unsaturated electrophiles using photoredox/Lewis acid cooperative catalysis

2019

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Reductive annulations of arylidene malonates with unsaturated electrophiles using photoredox/Lewis acid cooperative catalysis

2019

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“…Previously, our group has reported that the use of bespoke Hantzsch ester reductants can modulate reactivity and in turn increase product yield and/or improve diastereoselectivity in reductive functionalization of imines . A survey of Hantzsch ester reductants (Scheme B, entries 2–4) demonstrated that methyl carboxyphenyl derivative ( HE4 ) led to increased conversion to product (90 %) and to a higher diastereomeric ratio (1.9:1, for further optimization details, see Supporting Information).…”

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Dearomative Photocatalytic Construction of Bridged 1,3‐Diazepanes

et al. 2020

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The construction of diverse sp3‐rich skeletal ring systems is of importance to drug discovery programmes and natural product synthesis. Herein, we report the photocatalytic construction of 2,7‐diazabicyclo[3.2.1]octanes (bridged 1,3‐diazepanes) via a reductive diversion of the Minisci reaction. The fused tricyclic product is proposed to form via radical addition to the C4 position of 4‐substituted quinoline substrates, with subsequent Hantzsch ester‐promoted reduction to a dihydropyridine intermediate which undergoes in situ two‐electron ring closure to form the bridged diazepane architecture. A wide scope of N‐arylimine and quinoline derivatives was demonstrated and good efficiency was observed in the construction of sterically congested all‐carbon quaternary centers. Computational and experimental mechanistic studies provided insights into the reaction mechanism and observed regioselectivity/diastereoselectivity.

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“…NMR spectra and physical properties matched those reported in literature. 14 Hantzsch Ester HE4 was synthesized according to a modified general procedure A. A flask equipped with a reflux condenser was charged with ethyl 3oxobutanoate (11.5 ml, 60 mmol), benzaldehyde (5.0 mL, 30 mmol) and ethanol (anhydrous, 50 mL).…”

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Reverse Polarity Reductive Functionalization of Tertiary Amides via a Dual Iridium-Catalyzed Hydrosilylation and Single Electron Transfer Strategy

et al. 2020

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A new strategy for the mild generation of synthetically valuable α-amino radicals from robust tertiary amide building blocks has been developed. By combining Vaska's complex-catalyzed tertiary amide reductive activation and photochemical single electron reduction into a streamlined tandem process, metastable hemiaminal intermediates were successfully transformed into nucleophilic α-amino free radical species. This umpolung approach to such reactive intermediates was exemplified through coupling with an electrophilic dehydroalanine acceptor, resulting in the synthesis of an array of α-functionalized tertiary amine derivatives, previously inaccessible from the amide starting materials. The utility of the strategy was expanded to include secondary amide substrates, intramolecular variants and late stage functionalization of an active pharmaceutical ingredient. DFT analyses were used to establish the reaction mechanism and elements of the chemical system that were responsible for the reaction's efficiency. Scheme 1. α-Functionalization strategies for amine synthesis from tertiary amides Scheme 3. Optimization studies for (A) Vaska's catalyzed amide hydrosilylation. (B) The photocatalytic reductive coupling of the silyl hemiaminal intermediate with DHA derivative. stituted structures delivered tertiary amine products, although a steric increase vs. reaction efficiency trend was observed. 19 Intramolecular Cyclization. We recognized the opportunity that this tandem amide activation protocolthrough tethering an alkene acceptor to the alkyl chain of the amide starting material-could be suitably leveraged towards the synthesis of complex heterocyclic amine frameworks. Accordingly, model substrates bearing a pendant α,β-unsaturated ester (1s-1t) were prepared, but initial studies demonstrated that these motifs did not readily undergo hydrosilylation using Vaska's catalyst (only around 80% conversion was achieved after 8 hours of reaction time), and furthermore significant quantities of over reduction side-product were isolated following the photocatalytic step. 20 Nevertheless, these initial challenges were circumvented when a derivative of Vaska's complex bearing triphenylphosphite ligands-previously reported by Nagashima 21-was employed in the hydrosilylation step instead (Scheme 5). Pleasingly, clean conversion to a stable silyl hemiaminal species was achieved within one hour, and subsequent subjection to the optimized photoredox conditions delivered the desired cyclic pyrrolidine (4s) and piperidine (4t) products in good yields. Scheme 5. Extension of the Vaska-photoredox system for reductive cyclization of tertiary amides Secondary Amide Activation. Recent endeavors by Chida and Sato, and Huang have demonstrated the utility of [Ir(COE)2Cl]2 complex in conjunction with Et2SiH2 reductant for the nucleophilic reductive functionalization of secondary amide building blocks, affording the corresponding α-branched secondary amine products. 4e,f Scheme 6. Reverse polarity, photocatalytic reductive functionalization of seconda...

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Photocatalytic reverse polarity Povarov reaction

Abstract: A reverse polarity photocatalysed Povarov reaction of imines and electron deficient alkenes is described.

Cited by 55 publications

References 50 publications

Reductive annulations of arylidene malonates with unsaturated electrophiles using photoredox/Lewis acid cooperative catalysis

Reductive annulations of arylidene malonates with unsaturated electrophiles using photoredox/Lewis acid cooperative catalysis

Dearomative Photocatalytic Construction of Bridged 1,3‐Diazepanes

Reverse Polarity Reductive Functionalization of Tertiary Amides via a Dual Iridium-Catalyzed Hydrosilylation and Single Electron Transfer Strategy

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