Visible-Light-Induced Homolysis of Earth-Abundant Metal-Substrate Complexes: A Complementary Activation Strategy in Photoredox Catalysis.

The mainstream applications of visible-light photoredox catalysis predominately involve outer-sphere single-electron transfer (SET) or energy transfer (EnT) processes of precious metal RuII or IrIII complexes or of organic dyes with low photostability. Earth-abundant metal-based Mn Ln -type (M=metal, Ln =polydentate ligands) complexes are rapidly evolving as alternative photocatalysts as they offer not only economic and ecological advantages but also access to the complementary inner-sphere mechanistic modes, thereby transcending their inherent limitations of ultrashort excited-state lifetimes for use as effective photocatalysts. The generic process, termed visible-light-induced homolysis (VLIH), entails the formation of suitable light-absorbing ligated metal-substrate complexes (Mn Ln -Z; Z=substrate) that can undergo homolytic cleavage to generate Mn-1 Ln and Z. for further transformations.

Stereospecific Syntheses of Enaminonitriles and ß-Enaminoesters via Domino Ring-Opening Cyclization (DROC) of Activated Cyclopropanes with Pronucleophilic Malononitriles.

Two novel synthetic protocols for the syntheses of highly functionalized five-membered carbocyclic enaminonitriles and ß-enaminoesters have been developed via domino ring-opening cyclization (DROC) and DROC/decarboxylative tautomerization of activated cyclopropanes with malononitrile pronucleophiles, respectively. Both of the efficient strategies (yield up to 93%) have been generalized with various donor-acceptor and acceptor cyclopropanes as well as with malononitrile derivatives. The stereospecific variants of the two SN2-type DROC strategies have also been developed by employing enantiopure donor-acceptor (DA) cyclopropanes to synthesize the corresponding nonracemic products with excellent stereoselectivities (dr up to >99:1, ee up to >99%).

Temperature-modulated diastereoselective transformations of 2-vinylindoles to tetrahydrocarbazoles and tetrahydrocycloheptadiindoles.

Direct and expedient access to densely substituted tetrahydrocarbazoles and tetrahydrocycloheptadiindoles bearing multiple contiguous stereocentres has been achieved via a two-fold divergent diastereoselective (dr up to >99 : 1) transformation of 2-vinylindoles. The high-yielding conversions (yield up to 87%) that are amenable for a wide range of substituted 2-vinylindoles proceed through Lewis acid-catalyzed [4 + 2] and [4 + 3] cyclization-aromatization cascade reactions, respectively, involving a heretofore-unprecedented reversal of the polarity (umpolung) of 2-vinylindoles. The two synthetic routes are effortlessly transposable into each other by merely modulating the temperature to furnish the corresponding products in a selective and exclusive fashion. In addition, another novel synthetic route to tetrahydroindolocarbazoles has been developed that advances via a formal [4 + 2] cyclization of 4-vinylindoles involving sequential C3 Michael addition-dearomatization-aromatization cascade reactions.

A Stereoselective Route to Tetrahydrobenzoxazepines and Tetrahydrobenzodiazepines via Ring-Opening and Aza-Michael Addition of Activated Aziridines with 2-Hydroxyphenyl and 2-Aminophenyl Acrylates.

A simple and efficient synthetic route to 2,3,4,5-tetrahydrobenzoxazepines and -benzodiazepines bearing easily functionalizable appendages has been developed by ring-opening of activated aziridines with 2-hydroxyphenyl acrylates and 2-aminophenyl acrylate, respectively, and subsequent intramolecular C-N bond formation through palladium-catalyzed aza-Michael reaction. The straightforward synthetic approach delivers the desired molecular scaffolds in high yields (up to 82%) with excellent stereoselectivity (ee up to 94%).

Enantioselective Aldol Reactions in Water by a Proline-Derived Cryptand and Fixation of CO2 by Its Exocyclic Co(II) Complex.

The secondary amine donors present in the bridges of a laterally nonsymmetric oxa-aza cryptand have been derivatized with l-proline to obtain the chiral cryptand L. The cryptand L efficiently catalyzed aldol reactions in water with up to 75% ee. On reacting with Co(II) perchlorate in the presence of KSCN, L readily formed the trinuclear complex {[Co3(L)2(NCS)6]·(15CH3CN)(5acetone)(6H2O)} (1). The complex 1 in combination with the cocatalyst tetrabutylammonium bromide (TBAB) formed an efficient catalytic system in the synthesis of cyclic carbonates from CO2 and epoxides at room temperature and atmospheric pressure.

Stereospecific Synthesis of 2-Iminothiazolidines via Domino Ring-Opening Cyclization of Activated Aziridines with Aryl- and Alkyl Isothiocyanates.

Lewis acid catalyzed domino ring-opening cyclization of activated aziridines with aryl and alkyl isothiocyanates has been accomplished leading to the formation of a wide variety of highly substituted and functionalized 2-iminothiazolidines with excellent diastereo- and enantiospecificity (de, ee up to >99%). The reaction proceeds via a Lewis acid catalyzed SN2-type ring-opening of the activated aziridine followed by a concomitant 5-exo-dig cyclization in a domino fashion to furnish the 2-iminothiazolidine derivative in excellent yields (up to 99%).

Syntheses of imidazo-, oxa-, and thiazepine ring systems via ring-opening of aziridines/Cu-catalyzed C-N/C-C bond formation.

A simple and unpredicted synthetic pathway toward racemic and scalemic tetrahydrodibenzoimidazoazepines has been invented serendipitously proceeding through an S(N)2-type ring-opening of N-activated aziridines with 2-bromobenzylamine followed by a hitherto unprecedented cascade cyclization reaction sequence comprising a Cu-catalyzed cross dehydrogenation C-N coupling and an Ullmann C-C bond formation reaction. The tetrahydrobenzoxazepine and the tetrahydrobenzothiazepine derivatives have also been synthesized via the ring-opening of aziridines with 2-bromobenzyl alcohols and -mercaptan, respectively, followed by Cu-catalyzed N-arylation reaction.

Organic Photoredox-Catalyzed S-Trifluoromethylation of Aromatic and Heteroaromatic Thiols.

A visible-light-mediated trifluoromethylation protocol was developed for the conversion of (hetero)aromatic thiols to their respective S-trifluoromethylated derivatives employing trifluoromethanesulfonyl chloride (CF3SO2Cl) as a cost-effective source of trifluoromethyl radical (CF3·) and a highly reducing organophotocatalyst, 3DPA2FBN. The developed methodology is operationally simple, providing access to a diverse range of products in up to 92% yield. A plausible mechanism has been postulated based on preliminary mechanistic studies, including irradiation on/off, UV-vis studies, and radical trapping experiments.

Water-Dispersible, Magnetically Recyclable Heterogeneous Cobalt Catalyst for C-C and C-N Cross-Coupling Reactions in Aqueous Media.

A cobalt catalyst supported on an iron oxide core, denoted as γ-Fe2O3@PEG@THMAM-Co, has been prepared and characterized by Fourier transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray mapping, thermogravimetry differential thermogravimetry, vibrating sample magnetometry, and inductively coupled plasma. Polyhydroxy end groups in the shell make the catalyst particles dispersible in water, allowing Hiyama, Suzuki, and C-N cross-coupling reactions of aryl iodides and bromides. The catalyst could be recovered by magnetic decantation and reused for at least five successive runs with a negligent decrease in its activity or changes in its morphology. Water as a solvent without requiring additives, surfactants, or organic co-solvents, as well as an abundant and low-cost cobalt catalyst combined with facile recovery, low leaching, and scalability, provides an environmentally and economically attractive alternative to established palladium-catalyzed C-C and C-N coupling reactions.

Syntheses of chiral ß- and γ-amino ethers, morpholines, and their homologues via nucleophilic ring-opening of chiral activated aziridines and azetidines.

Lewis acid catalyzed quaternary ammonium salt mediated highly regioselective ring-opening of chiral activated aziridines and azetidines with alcohols to nonracemic ß- and γ-amino ethers has been developed. The reaction mainly proceeds via an S(N)2 pathway, and the partial racemization of the starting substrate was effectively controlled by using quaternary ammonium salts. ß- and γ-amino ethers are obtained with high enantio- and diastereospecificity (ee up to >99%, de up to 99%). The methodology was further extended to synthesize morpholines and their homologues with high enantiospecificity (ee up to 90%) when halo alcohols were employed as the nucleophiles.

Accessing HIV-1 Protease Inhibitors through Visible-Light-Mediated Sequential Photocatalytic Decarboxylative Radical Conjugate Addition-Elimination-Oxa-Michael Reactions.

A photocatalytic decarboxylative radical conjugate addition-elimination-oxa-Michael reaction of hydroxyalkylated carboxylic acids with cyclopentenones is developed to construct diverse cyclopentanonyl-fused functionalized 5-7 membered cyclic ethers. The stereoselective synthetic strategy is amenable to substructural variation, establishing a direct total synthetic route to two diastereomers of C3-amino cyclopentyltetrahydrofuranyl-derived potent HIV-1 protease inhibitors with low nanomolar IC50 values.

Stereoselective Synthesis of Hexahydroimidazo[1,2-a]quinolines via SN2-Type Ring-Opening Hydroarylation-Hydroamination Cascade Cyclization of Activated Aziridines with N-Propargylanilines.

A novel synthetic approach for the construction of 1,2,3,3a,4,5-hexahydroimidazo[1,2-a]quinolines in good yields (up to 75%) with excellent stereoselectivity (dr up to 94:6, ee up to >99%) under one-pot domino ring-opening cyclization (DROC) conditions has been developed. The DROC protocol proceeds through a Lewis acid catalyzed SN2-type ring-opening of activated aziridines with N-propargylanilines followed by intramolecular cyclization comprising concomitant hydroarylation and hydroamination steps in a domino fashion.

Diels-Alder reactions and electrophilic substitutions with atypical regioselectivity enable functionalization of terminal rings of anthracene.

Reversing the regioselectivity of the renowned Diels-Alder reaction by overriding the usual thermodynamic and kinetic governing factors has always been a formidable challenge to synthetic organic chemists. Anthracenes are well-known to undergo [4 + 2]-cycloadditions with dienophiles at their 9,10-positions (central ring) over 1,4-positions (terminal ring) guided by the relative aromatic stabilization energy of the two possible products, and also by harboring the largest orbital coefficients of the highest occupied molecular orbital (HOMO) at the 9,10-positions. We, herein, report a 1,4-selective [4 + 2]-cycloaddition strategy of 9,10-unsubstituted anthracenes by installing electron-donating substituents on the terminal rings which is heretofore unprecedented to the best of our knowledge. The developed synthetic strategy does not require any premeditated engagement of the 9,10-positions either with any sterically bulky or electron-withdrawing substituents and allows delicate calibration of the regioselectivity by modulating the electron-donating strength of the substituents on the terminal rings. Likewise, the regioselective functionalization of the terminal anthracene ring in electrophilic substitution reactions is demonstrated. A mechanistic rationale is offered with the aid of detailed computational studies, and finally, synthetic applications are presented.

Copper's rapid ascent in visible-light photoredox catalysis.

Visible-light photoredox catalysis offers a distinct activation mode complementary to thermal transition metal catalyzed reactions. The vast majority of photoredox processes capitalizes on precious metal ruthenium(II) or iridium(III) complexes that serve as single-electron reductants or oxidants in their photoexcited states. As a low-cost alternative, organic dyes are also frequently used but in general suffer from lower photostability. Copper-based photocatalysts are rapidly emerging, offering not only economic and ecological advantages but also otherwise inaccessible inner-sphere mechanisms, which have been successfully applied to challenging transformations. Moreover, the combination of conventional photocatalysts with copper(I) or copper(II) salts has emerged as an efficient dual catalytic system for cross-coupling reactions.

Stereospecific Synthesis of 1,4,5,6-Tetrahydropyrimidines via Domino Ring-Opening Cyclization of Activated Aziridines with α-Acidic Isocyanides.

An expeditious synthetic route to access structurally diverse 1,4,5,6-tetrahydropyrimidines via domino ring-opening cyclization of activated aziridines with α-acidic isocyanides has been established. The transformation proceeds via Lewis acid mediated SN2-type ring opening of activated aziridines with α-carbanion of the isocyanides followed by a concomitant 6- endo- dig cyclization in a domino fashion to furnish the 1,4,5,6-tetrahydropyrimidine derivatives in excellent yields (up to 84%) and also in diastereo- and enantiomerically pure form (dr >99:1, ee >99%).

Stereoselective synthesis of 3-spiropiperidino indolenines via SN2-type ring opening of activated aziridines with 1H-indoles/Pd-catalyzed spirocyclization with propargyl carbonates.

3-Spiropiperidino indolenines have been synthesized via novel Lewis acid-catalyzed SN2-type ring opening of activated aziridines with 1H-indoles followed by Pd-catalyzed dearomative spirocyclization with propargyl carbonates in up to 88% yields. The step and pot-economic transformation comprises sequential C-C, C-N, and C-C bond forming steps generating two stereogenic centers including an all-carbon quaternary stereocenter to furnish the products in diastereomerically pure (dr >99 : 1) forms with excellent enantiomeric excess (ee up to >99%). The synthetic versatility of the strategy has been illustrated by converting the synthesized products into spirocyclic indolenine 2-piperidinones, dihydropiperidines, and 5-alkynylated piperidines.

Syntheses of Tetrahydrobenzoazepinoindoles and Dihydrobenzodiazepinoindoles via Ring-Opening Cyclization of Activated Aziridines with 2-(2-Bromophenyl)-1H-indoles.

Two efficient, modular, step- and pot-economic strategies to access various 5,6,7,12-tetrahydrobenzo[2,3]azepino[4,5-b]indoles and 6,7-dihydro-5H-benzo[5,6][1,4]diazepino[1,7-a]indoles are disclosed that advance via SN2-type regioselective ring opening of enantiopure aziridines with 2-(2-bromophenyl)-1H-indoles at their C3 and indolyl N centers, respectively, followed by Cu-mediated C-N cyclization which furnishes the products in excellent yields with outstanding enantiomeric excesses (up to >99%).