Iodine as Polarity-Reversal Catalyst: Synthesis of a Fused Heterocycle with Contiguous Stereocenters.

We report an unconventional I-catalyzed cascade reaction for the synthesis of angular triquinane derivatives with a fused heterocycle skeleton, leveraging enaminones and anilines as simple acyclic precursors. The key to success lies in I functioning as a polar-reversal catalyst, which alters the reactivity at the α-position of the enaminone and facilitates the first hexa-functionalization of an enaminone along with the formation of highly congested continuous stereocenters.

Recent advances in the synthesis of N-heterocycles from α-amino acids mediated by iodine.

The synthesis of N-heterocycles has received extensive attention from scientists considering their important role in organic synthesis, pharmaceuticals, and materials chemistry. α-Amino acids (α-AAs), both natural and non-natural, are structurally diverse, containing basic amino groups, acidic carboxyl groups, and various side-chain R groups in a single molecule. Given their structural properties and wide range of sources, they have undoubtedly become suitable synthetic building blocks for organic synthesis.

Intramolecular/Intermolecular Sequential Cyclization Accompanied by Double C-F Bond Cleavage: Access to Tricyclic Fluorine-Containing Pyrano[3,2-]chromenes.

Defluorinative cyclization of CF-alkenes has emerged as a reliable strategy for crafting intricate polycyclic frameworks. In this study, a facile defluorinative bicyclization approach was developed for the construction of 4,5-pyrano[3,2-]chromenes under mild conditions involving a sequence of intramolecular cyclization and intermolecular defluoroheterocyclization. A variety of polysubstituted 4,5-pyrano[3,2-]chromenes featuring C2-fluorine could be synthesized in good yields with excellent tolerance toward various functional groups.

Synthesis of 6--Spiro[4.5]decane Derivatives by Merging Ring-Opening of Benzo[]oxepines and Formal 1,2-Oxygen Migration.

A facile one-pot synthetic method has been developed for constructing 6--spiro[4.5]decane skeletons by merging the ring-opening of benzo[]oxepines and formal 1,2-oxygen migration reactions. More than 30 examples of the 6--spiro[4.

Advances in the self-organized total synthesis of natural products.

Natural product total synthesis has trailblazed in the era of multistep synthesis. The strategic application of existing synthetic methodologies and the stepwise construction that revolves around newly developed, tailored key steps, are two basic tactics in the principle of classic retrosynthetic analysis. However, a new synthetic model, termed self-organized total synthesis, has emerged in recent years, enabling the rapid creation of specific natural products by a one-pot reaction.

I-Induced Umpolung: Synthesis of a 1,6-Dihydrofuro[3,2-]pyrazolo[3,4-][1,4]thiazine Skeleton via an Unconventional 1,4-Dithiane-2,5-diol Reaction Mode.

In this paper, novel sulfur-containing 1,6-dihydrofuro[3,2-]pyrazolo[3,4-][1,4]thiazine skeletons were constructed from the simple and readily available materials enaminone, 5-aminopyrazole, and 1,4-dithiane-2,5-diol. Furthermore, a novel 1,4-dithiane-2,5-diol reaction mode has been developed through a double-dipole-reversal process induced by iodine that results in the formation of six new bonds and two new rings in a one-pot reaction. This method shows good substrate compatibility, and the products can be further modified with a variety of pharmaceuticals.

Rongalite/iodine-mediated C(sp)-H bond oximation and thiomethylation reaction of methyl ketones using copper nitrate as the [NO] reagent: synthesis of thiohydroximic acids.

In this work, a highly efficient rongalite/iodine-mediated oxime formation reaction for the preparation of thiohydroximic acids from methyl ketones by employing copper nitrate as the [NO] reagent has been developed. Notably, copper nitrate participated as both a catalyst and the mild oximation reagent in the transformation. This reaction is highly efficient and facile, with a broad substrate scope, especially for fused ring skeleton substrates, heterocyclic skeleton substrates, and acetyl-substituted natural products.

Divergent synthesis of pyrrolidone fused pyrimido[1,2-]indazole through selective trapping of an enone intermediate by 1-indazol-3-amine.

An oxidant-controlled divergent synthesis of a pyrrolidone fused pyrimido[1,2-]indazole skeleton was developed through selective cyclization of an generated enone intermediate and 1-indazol-3-amine. The one-pot, metal-free process formed three C-N bonds, one C-C bond, and a tetrasubstituted carbon stereocenter containing a hydroxyl group. This method not only allowed for the synthesis of over 60 new pyrrolidone fused pyrimido[1,2-]indazole derivatives, but was also compatible with the transformation of complex active molecules and the derivation of target products.

One-Pot Total Synthesis of Natural Products Nitramarine, Nitraridine, and Analogues via a Cascade Oxidation/Pictet-Spengler Condensation/Annulation Process.

A cascade oxidation/Pictet-Spengler condensation/annulation process has been developed for the one-pot total synthesis of nitramarine, nitraridine, and their analogues. The procedure proceeded with easily available quinolines and tryptophan derivatives. A simple and metal-free approach, wide substrate scope, and functional group tolerance make it applicable for the synthesis of diverse bioactive nitramarine, nitraridine, and their derivatives.

-Benzylhydroxylamine as a novel synthetic block in "C1N1" embedding reaction α-C(sp)-H activation strategy.

A novel process using -benzylhydroxylamine hydrochloride as a "C1N1 synthon" in [2+2+1] cyclization for the construction of 1,2,5-trisubstituted imidazoles has been described for the first time. The key to realizing this process lies in capturing arylamines by generated novel acyl ketonitrone intermediates. Subsequent tautomerization activates the α-C(sp)-H of -benzylhydroxylamines, and thus breaks through its inherent reaction mode and achieves , α-C site-selective cyclization.

Synthesis of β,β-Dithioketones by Merging C-C and C-S Bond Cleavage in [1 + 1 + 1 + 1 + 1 + 1] Annulation.

An unconventional [1 + 1 + 1 + 1 + 1 + 1] annulation process was developed for the construction of β,β-dithioketones by merging C-C and C-S bond cleavage. In this reaction, rongalite concurrently served as triple C1 units, dual sulfur(II) synthons, and a reductant for the first time. Mechanism investigation indicated that the reaction involved the self-mediated valence state change of rongalite.

I-DMSO-Mediated Construction of 2,3- and 2,4-Disubstituted Pyrimido[1,2-]indazole Skeletons.

An efficient synthetic method for constructing 2,3- and 2,4-disubstituted pyrimidio[1,2-]indazole skeletons through I-DMSO-mediated and substrate-controlled regioselective [4 + 2] cyclization is reported. The reaction conditions are mild, its operation is simple, and the substrate scope is wide. More than 60 pyrimidio[1,2-]indazole derivatives have been synthesized, providing a new methodology for constructing related molecules and potentially enriching bioactive-molecule libraries.

Iodine-Promoted Thioylation and Dicarbonylation of Enaminone α-C Sites: Synthesis of Fully Substituted Thiazoles via C═C Bond Cleavage.

A novel iodine-promoted difunctionalization of α-C sites in enaminones was demonstrated as a means of synthesizing a variety of fully substituted thiazoles by constructing C-C(CO), C-S, and C-N bonds. This transformation allows the realization of enaminones as unusual aryl C2 synthons and simultaneously allows the thioylation and dicarbonylation of α-C sites. A preliminary mechanistic study was performed and indicated that the cleavage of C═C bonds in enaminones involves a bicyclization/ring-opening and oxidative coupling sequence.

Azide-free cyclization reaction access to 4-aryl--1,2,3-triazoles: -toluenesulfonyl hydrazide and sulfamic acid as nitrogen sources.

An iodine-mediated cyclization has been developed to 4-aryl--1,2,3-triazoles, with -toluenesulfonyl hydrazide and sulfamic acid used as nitrogen sources. Sulfamic acid plays a crucial role in this reaction by both acting as a substrate and providing an acidic environment. This reaction offers a metal- and azide-free strategy to access -1,2,3-triazoles.

Reductive Formylation of Nitroarenes Mediated by Rongalite.

Herein, we disclose a straightforward approach to access transition-metal-free reductive -formylation of nitroarenes. This reaction integrates the dual role of rongalite, which acts as a reductant and a C1 building block concurrently. This provides an alternative method for the synthesis of -aryl formamides from nitroarenes, including the construction of a C-N bond.

I-DMSO-Mediated Transannulation of Benzo[]isoxazol-3-amine: Direct Access to 2,4,5-Substituted Pyrimidine Derivatives.

An I-DMSO-mediated multicomponent [3+1+2] cascade annulation reaction using aryl methyl ketones, enaminones, and benzo[]isoxazol-3-amine as substrates has been developed. This metal-free reaction involved the transannulation of benzo[]isoxazol-3-amines with the formation of two C-N bonds and a C-C bond in one pot. Notably, a pyrimidine ring with a 1,4-dicarbonyl scaffold could efficiently transform into a pyrimido[4,5-]pyridazine skeleton.

An I-DMSO catalytic manifold enabled aromatization for C-ring editing of podophyllotoxone.

The precise aromatization of the C-ring of podophyllotoxone to access value-added dehydropodophyllotoxin derivatives conventionally requires the use of equivalent amounts of unsustainable oxidants and suffers from inefficiencies. Taking advantage of the hydridic character of the C8 and C8' of podophyllotoxone, we have developed an I-DMSO catalytic manifold that enables a green and selective dehydrogenative aromatization to overcome these synthetic challenges. An unprecedented dehydrogenative amination of podophyllotoxone derivatives was also realized using aniline as the reaction partner.

One Stone, Three Birds: One-Pot Synthesis of Pyrido[3,2-]phenoxazin-5-one Derivatives from -Aminophenols with Triple Roles, Paraformaldehyde, and Enaminones via the Povarov Reaction.

A novel multicomponent cascade cyclization reaction in one pot for the preparation of pyrido[3,2-]phenoxazin-5-ones from simple -aminophenols, paraformaldehyde, and enaminones has been established. It is noteworthy that -aminophenol plays multiple roles serving as both a bis-nucleophile and an iminoquinone precursor, which can in situ generate aminophenoxazinones to undergo the Povarov reaction for the first time to yield pyrido[3,2-]phenoxazin-5-ones with a high efficiency. Moreover, the photoluminescence of pyrido[3,2-]phenoxazin-5-ones has polarity sensitivity and features aggregation-induced emission (AIE) characteristics, which is promising for bioimaging and theranostic applications.

Synthesis of primary propargylic alcohols from terminal alkynes using rongalite as the C1 unit.

Here, an efficient leaving group-activated methylene alcohol strategy for the preparation of primary propargyl alcohols from terminal alkynes by employing the bulk industrial product rongalite as the C1 unit has been described. The reaction avoids the low-temperature reaction conditions and inconvenient lithium reagents required for the classical method of preparing primary propargylic alcohols. Preliminary mechanistic studies showed that the reaction may not proceed formaldehyde intermediates, but through the direct nucleophilic attack of the terminal alkyne on the carbon atom of rongalite by activation through SO as a leaving group.

I-Promoted -Diarylethene Involved Aza-Diels-Alder Reaction and Wagner-Meerwein Rearrangement: Construction of 2,3,4-Trisubstituted Pyrimido[1,2-]indazole Skeletons.

A [3 + 1 + 2] cyclization-rearrangement reaction scheme was developed to synthesize pyrimido[1,2-]indazoles from aryl methyl ketones, 3-aminoindazoles, and -diarylethenes. This metal-free process proceeds via a sequential aza-Diels-Alder reaction and Wagner-Meerwein rearrangement, and a possible reaction mechanism was demonstrated based on control experiments. This method exhibits good substrate compatibility and allows simple reaction conditions.

Direct Hydrodefluorination of CF-Alkenes via a Mild S2' Process Using Rongalite as a Masked Proton Reagent.

A concise and efficient hydrodefluorination process was developed for the synthesis of -difluoroalkenes. This reaction employs rongalite as a masked proton source and does not require any additional catalysts or reductants. Notably, trifluoromethyl alkenes having both terminal and internal double bonds are compatible with this process, allowing for a wider range of substrates.