Photocatalytic Radical Alkylation of Electrophilic Olefins by Benzylic and Alkylic Zinc-Sulfinates

Gualandi, Andrea; Mazzarella, Daniele; Ortega-Martínez, Aitor; Mengozzi, Luca; Calcinelli, Fabio; Matteucci, Elia; Monti, Fiorella; Armaroli, Nicola; Sambri, Letizia; Cozzi, Pier Giorgio

doi:10.1021/acscatal.7b01669

Cited by 46 publications

(19 citation statements)

References 59 publications

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“…To validate our proposal, we studied the Giese-type radical conjugate addition 22 to dimethyl fumarate 3a (Fig. 2b) [23][24][25][26] . The experiments were conducted in acetonitrile (CH3CN) using commercially available γ-terpinene as a cheaper and more stable surrogate of 1,4-CHD.…”

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confidence: 85%

Photochemical generation of radicals from alkyl electrophiles using a nucleophilic organic catalyst

et al. 2018

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Chemists extensively use free radical reactivity for applications in organic synthesis, materials science, and life science. Traditionally, generating radicals requires strategies that exploit the bond dissociation energy or the redox properties of the precursors. Here, we disclose a photochemical catalytic approach that harnesses different physical properties of the substrate to form carbon radicals. We use a nucleophilic dithiocarbamate anion catalyst, adorned with a well-tailored chromophoric unit, to activate alkyl electrophiles via an SN2 pathway. The resulting photon-absorbing intermediate affords radicals upon homolytic cleavage induced by visible light. This catalytic SN2-based strategy, which exploits a fundamental mechanistic process of ionic chemistry, grants access to open-shell intermediates from a variety of substrates that would be incompatible with or inert to classical radical-generating strategies. We also describe how the method's mild reaction conditions and high functional group tolerance could be advantageous for developing C-C bond-forming reactions, for streamlining the preparation of a marketed drug, for the late-stage elaboration of biorelevant compounds, and for enantioselective radical catalysis.Free radical chemistry offers powerful ways of making molecules that are often complementary to classical methods proceeding via ionic pathways 1 . This explains why radical processes have found application in material science, drug discovery, agrochemistry, and other disciplines 2 . Advances within the field have been spurred by the identification of effective radical-generating strategies. One traditional method relies on initiators 3 . Initiators are high-energy compounds (e.g. diazo compounds or peroxides), which, upon homolysis induced by heat or high-energy light, generate a reactive radical that can abstract a hydrogen or halogen atom from a substrate S (Fig. 1a, left panel). This approach ultimately relies on the bond dissociation energy (BDE) of S to form the target openshell intermediate I. Another classical route to radicals exploits the tendency of a substrate S to engage in redox processes, which can be triggered by stoichiometric oxidants/reductants 3 or by electrochemical means 4 (Fig. 1a, right panel). Radical ions emerging from the single-electron transfer (SET) event can then fragment to yield the target radical I. These classical strategies are powerful. However, they require relatively harsh conditions, including hazardous and toxic reagents, high temperatures, and/or UV-light irradiation, overall limiting the selectivity and the functional group tolerance of the ensuing radical process.A crucial step towards milder reaction conditions and, consequently, more selective reactions has been the use of substrates bearing thio functions and acting as both radical precursors and reactants (Fig. 1b, left). Methods introduced by Barton 5-7 and further popularized by Zard with xanthate transfer chemistry 8,9 greatly expanded the synthetic potential of radicals, but still relied on pu...

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confidence: 85%

Photochemical generation of radicals from alkyl electrophiles using a nucleophilic organic catalyst

et al. 2018

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“…The ultimate fate of these S-centered radicals does vary ( Scheme 2B ). Whereas certain alkyl sulfinates can undergo C–S bond dissociation to give alkyl radicals and SO 2 evolution at this point, 13 aryl sulfonyl radicals are much less prone to C–S scission. 14 Thus, these types of radicals could be intercepted by Ni 0 species A to generate a Ni I –SO 2 R species B .…”

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confidence: 99%

Engaging sulfinate salts via Ni/photoredox dual catalysis enables facile C_sp2–SO₂R coupling

et al. 2018

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“…Design plan. We hypothesized that sodium sulfinates would be the ideal reusable radical precursors, due to the unique properties of which: (i) sufinates have been recently employed as efficient sulfonyl coupling partners in photoredox catalysis [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] ; (ii) it is well known that the alkyl sulfones would be prone to undergo desulfonylation under basic conditions [63][64][65] . As depicted in Fig.…”

Section: Resultsmentioning

confidence: 99%

Photoredox-catalyzed branch-selective pyridylation of alkenes for the expedient synthesis of Triprolidine

et al. 2019

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Alkenylpyridines are important pharmaceutical cores as well as versatile building blocks in organic synthesis. Heck reaction represents one of the most powerful platform for the construction of aryl-substituted alkenes, nevertheless, examples for Heck type coupling of alkenes with pyridines, particularly with branched selectivity, remain elusive. Here we report a catalytic, branch-selective pyridylation of alkenes via a sulfinate assisted photoredox catalysis. This reaction proceeds through a sequential radical addition/coupling/elimination, by utilizing readily available sodium sulfinates as reusable radical precursors as well as traceless elimination groups. This versatile protocol allows for the installation of important vinylpyridines with complete branched selectivity under mild conditions. Furthermore, this catalytic manifold is successfully applied to the expedient synthesis of Triprolidine.

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Photocatalytic Radical Alkylation of Electrophilic Olefins by Benzylic and Alkylic Zinc-Sulfinates

Cited by 46 publications

References 59 publications

Photochemical generation of radicals from alkyl electrophiles using a nucleophilic organic catalyst

Photochemical generation of radicals from alkyl electrophiles using a nucleophilic organic catalyst

Engaging sulfinate salts via Ni/photoredox dual catalysis enables facile C_sp2–SO₂R coupling

Photoredox-catalyzed branch-selective pyridylation of alkenes for the expedient synthesis of Triprolidine

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Photocatalytic Radical Alkylation of Electrophilic Olefins by Benzylic and Alkylic Zinc-Sulfinates

Cited by 46 publications

References 59 publications

Photochemical generation of radicals from alkyl electrophiles using a nucleophilic organic catalyst

Photochemical generation of radicals from alkyl electrophiles using a nucleophilic organic catalyst

Engaging sulfinate salts via Ni/photoredox dual catalysis enables facile Csp2–SO2R coupling

Photoredox-catalyzed branch-selective pyridylation of alkenes for the expedient synthesis of Triprolidine

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Engaging sulfinate salts via Ni/photoredox dual catalysis enables facile C_sp2–SO₂R coupling