Robin

The unprecedented use of gem-difluoro sulfinates in visible-light photocatalysis for the construction of new C−C bonds in a chiral fashion is presented. This was tackled by rerouting the chemical pathway of alkyl sulfonyl radicals from traditional sulfonylation to alkylation performance. The efficacy of these sulfinates for assisting SO₂ extrusion is shown by allowing the installation of CF₂-bearing scaffolds, a modern task in the pharmaceutical arena.

Abstract

The generation of sulfonyl radicals has long been known as a flexible strategy in a wide range of different sulfonylative transformations. Meanwhile their use in alkylation processes has been somehow limited due to their inherent difficulty in evolving to less-stable radicals after sulfur dioxide extrusion. Herein we report a convenient strategy that involves gem-difluorinated sulfinates as an “upgrading-mask”, allowing these precursors to decompose into their corresponding alkyl radicals. The electron–donor character of sulfinates in the formation of an electron donor–acceptor (EDA) complex with transient iminium ions is displayed, achieving the first example of a stereocontrolled light-driven insertion of gem-difluoro derivatives into unsaturated aldehydes. This methodology is compatible with flow conditions, maintaining identical levels of enantiocontrol.

A new catalytic approach to selective functionalization of the strong C−F bonds in polyfluorinated aliphatic esters and amides is reported, affording a diverse array of important partially fluorinated motifs through hydrodefluorination, defluoroalkylation, and defluoroalkenylation. Straightforward downstream chemistry towards fluorinated alcohols, amines and drug derivatives highlights the potential of the protocol.

Abstract

Selective C−F bond functionalization of perfluoalkyl units has huge potential towards accessing functionalized organofluorinated compounds, but remains challenging due to the high C−F bond strength and inherent selectivity challenges. We report a new catalytic approach to the selective functionalization of strong C−F bonds in polyfluorinated aliphatic esters and amides. This simple reaction proceeds in mild and operational fashion with divergent conversions, including hydrodefluorination, defluoroalkylation, and defluoroalkenylation, affording a diverse array of important partially fluorinated motifs. Straightforward downstream chemistry towards fluorinated alcohols, amines and drug derivatives highlights the potential of the protocol.

Single and selective C−F bond activation of trifluoromethyl ketones via visible-light photoredox catalysis is achieved in the presence of HFIP solvent. Trapping of photo-catalytically generated difluoromethyl radical to acrylamide derivatives furnishes an essential class of difluoromethyl-containing oxindole scaffolds. A high level of DFT calculations strongly supports our proposed mechanistic pathway for this novel transformation.

Abstract

A visible light photoredox catalytic method for the selective cleavage of single strong C−F bond in trifluoromethyl ketones is reported. Single electron reduction of trifluoromethyl ketones generates difluoromethyl radicals which can be engaged in intermolecular C−C bond formation with N-methyl-N-arylmethacrylamides to furnish fluorine-containing oxindole derivatives in good yields. The reaction shows excellent chemoselectivity with good functional group tolerance under mild conditions. 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) as a solvent plays a critical role for the selective single C−F bond cleavage. High-level DFT calculations are depicted to shed light on the mechanism.

A two-dimensional oxonium-embedded COF with vinylene linkages was synthesized by condensation of a trimethyl-substituted pyrylium with a tritopic aromatic aldehyde derivative, which was readily converted to a neutral pyridine-cored COF by in situ replacing oxonium with nitrogen atoms under the treatment of ammonia.

Abstract

Embedding heteroatoms into the main backbones of polymeric materials has become an efficient tool for tailoring their structures and improving their properties. However, owing to comparatively harsh heteroatom-doping conditions, this has rarely been explored in covalent organic frameworks (COFs). Herein, upon aldol condensation of a trimethyl-substituted pyrylium salt with a tritopic aromatic aldehyde, a two-dimensional oxonium-embedded COF with vinylene linkages was achieved, which was further converted to a neutral pyridine-cored COF by in situ replacement of oxonium ions with nitrogen atoms under ammonia treatment. The two heteroatom-embedded COFs are conceptually isoelectronic with each other, featuring similar geometric structures but different electronic structures, rendering them capable of catalyzing the visible-light-promoted multi-component synthesis of tri-substituted pyridine derivatives with good recyclability.

Abstract

The direct carboxylation of inert aryl C−H bond catalyzed by abundant and cheap nickel is still facing challenge. Herein, we report the Ni-catalyzed direct carboxylation of aryl C−H bonds in benzamides under 1 atm of CO₂ to afford various methyl carboxylates or phthalimides, dealing with different post-processing. The reaction displays excellent functional group tolerance and affords moderate to high carboxylation yields under mild conditions. Detail mechanistic studies suggest that a Ni(0)−Ni(II)−Ni(I) catalytic cycle may be involved in this reaction.

Synlett
DOI: 10.1055/a-1684-0380

A visible-light photocatalytic generation of iminoxyl radicals has been accomplished under oxidant-free conditions. This approach offers a mild, atom-economical, and redox-neutral synthesis of 5-methylisoxazolines through radical hydroxygenation of β,γ-unsaturated oximes in the absence of an additional hydrogen source.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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A photocatalytic method for the synthesis of amides and peptides is reported. Synergistic cooperation between a cobaloxime and a photoredox catalyst removes the elements of H₂O through the use of PPh₃ as a gentle organic reductant. The deoxygenative method is compatible with gram-scale peptide synthesis and applicable to peptide fragment condensation and SPPS, which may find applications in both organic synthesis and pharmaceutical production.

Abstract

Phosphine-mediated deoxygenative nucleophilic substitutions, such as the Mitsunobu reaction, are of great importance in organic synthesis. However, the conventional protocols require stoichiometric oxidants to trigger the formation of the oxyphosphonium intermediates for the subsequent nucleophilic additions. Through dual catalysis of photoredox and cobaloxime, we realized a radical strategy for the catalytic formation of acyloxyphosphonium ions that enables direct amidation. The deoxygenative protocol exhibits a broad scope and has been used in the late-stage amidation of drug molecules. In addition to batch reactions, a continuous-flow reactor was developed, enabling rapid peptide synthesis on gram scale. The successful assembly of a tetrapeptide on the solid support further demonstrated the versatility of this photocatalytic system. Moreover, experimental and computational studies are consistent with the hypothesis of acyloxyphosphonium ions being formed as the key intermediates.

Synthesis
DOI: 10.1055/a-1647-7292

The modular synthesis of carbazole functionalized phthalimides (PIs) and their applicability as catalyst in selected photocatalytic transformations are reported. The developed synthetic approach provides high variability of phthalimide considering that the synthesis of the phthalimide core can be easily performed. Starting from fluorophthalic acid anhydrides, the corresponding fluorophthalimides were prepared with various amines, and the fluoro function ensured the introduction of carbazoles into the phthalimide framework through aromatic nucleophilic substitution. Besides the synthetic developments, some of the carbazolyl phthalimides were tested in four different photocatalytic transformations, which showed attractive and comparable activity to the known 4-CzIPN and noble metal complexes.
[...]

Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Nature Chemistry, Published online: 04 November 2021; doi:10.1038/s41557-021-00807-x

The direct synthesis of new (Z)-(1-alken-1-yl)pentafluoro-λ⁶-sulfanes was performed via the photoinitiated anti-hydropentafluorosulfanylation of terminal alkynes. The reaction of SF₅Cl with 24 substrates in the presence of (TMS)₃SiH as a H-atom donor gave access to the undocumented Z-isomer. The origins of this unusual selectivity were investigated by DFT calculations, which provide a better understanding of the geometry and reactivity of SF₅-substituted vinylic radicals.

Abstract

A photoinitiated anti-hydropentafluorosulfanylation of terminal alkynes using SF₅Cl and (TMS)₃SiH as the hydrogen atom donor is reported. This transformation generates selectively (Z)-(1-alken-1-yl)pentafluoro-λ⁶-sulfanes (Z:E : >85:15), thus allowing the preparation of this previously unknown geometrical isomer. DFT calculations highlight that the selectivity is due to the intrinsic preference of SF₅-substituted vinylic radicals to adopt a cis geometry, and to increased steric contacts during the transition structures leading to the minor (E)-products.

The first catalytic enantioselective conjugate addition of allyl groups to α,β-unsaturated aldehydes is disclosed. The chemistry exploits the visible-light-excitation of chiral iminium ions to activate allyl silanes towards the formation of allylic radicals, which are then stereoselectively intercepted with high α-regioselectivity, complete chemoselectivity, and moderate to good enantioselectivity.

Abstract

We report the first catalytic enantioselective conjugate addition of allyl groups to α,β-unsaturated aldehydes. The chemistry exploits the visible-light-excitation of chiral iminium ions to activate allyl silanes towards the formation of allylic radicals, which are then intercepted stereoselectively. The underlying radical mechanism of this process overcomes the poor regio- and chemoselectivity that traditionally affects the conjugate allylation of enals proceeding via polar pathways. We also demonstrate how this organocatalytic strategy could selectively install a valuable prenyl fragment at the β-carbon of enals.

A mild visible light-induced palladium-catalyzed alkyl Heck reaction of diazo compounds and N-tosylhydrazones is reported. This method features Brønsted acid assisted generation of hybrid palladium C(sp³)-centered radical intermediate and broad reaction scope, highlighting the diverse applicability and the potential utility of this protocol in late-stage functionalization.

Abstract

A mild visible light-induced palladium-catalyzed alkyl Heck reaction of diazo compounds and N-tosylhydrazones is reported. A broad range of vinyl arenes and heteroarenes with high functional group tolerance, as well as a range of different diazo compounds, can efficiently undergo this transformation. This method features Brønsted acid-assisted generation of hybrid palladium C(sp³)-centered radical intermediate, which allowed for new selective C−H functionalization protocol.

Nature Communications, Published online: 07 September 2021; doi:10.1038/s41467-021-25628-x