Isothiocyanates: happy-go-lucky reagents in organic synthesis.

Owing to their unique structural features, isothiocyanates (ITCs) are a class of highly useful and inimitable reagents as the -NCS group serves both as electrophile and nucleophile in organic synthesis. ITCs share a rich legacy in organic, medicinal, and combinatorial chemistry. Compared to their oxygen equivalents, isocyanates, ITCs are easily available, less unpleasant, and somewhat less harmful to work with (mild conditions) which makes them happy-go-lucky reagents. Functionalized ITCs can finely tune the reactivity of the -NCS group and thus can be exploited in the late-stage functionalization processes. This review's primary aim is to outline ITC chemistry in the construction and derivatization of heterocycles through the lens of sustainability. For ease and brevity, the sections are divided based on reactive centers present in functionalized ITCs and modes of cyclisation. Scrutinizing their probable unexplored directions for future research studies is also addressed.

Access to Chromenopyrrole via Tandem [3 + 2] Cycloaddition and Intramolecular C-O Coupling.

A mild and concise method for the synthesis of chromenopyrrole from 2'-hydroxychalcone is devised. The reaction proceeds via an initial [3 + 2] cycloaddition on the C═C bond of 2'-hydroxychalcone and 1,3-dipolarophile, generated in situ by the reaction of ethyl isocyanoacetate and AgOAc. This is then followed by an intramolecular C-O bond formation with the -OH group and C5-H of the in situ generated pyrrole, leading to chromenopyrroles.

Base-Promoted Synthesis of S-Arylisothiazolones via Intramolecular Dehydrative Cyclization of α-Keto-N-acylsulfoximines.

A base (Et3N)-promoted synthesis of 1,4-diarylisothiazolones from α-keto-N-acylsulfoximines has been achieved. The reaction proceeds via α-hydrogen abstraction from sulfoximine, followed by an intramolecular nucleophilic attack at the keto carbonyl to form a tert-hydroxy isothiazolone intermediate. The 1,4-substituted isothiazolone is obtained after dehydration via an E1cB path. This one-pot synthesis of isothiazolinones has a broad substrate scope, has a high atom economy, and provides products with good yields. The ΔELUMO-HOMO is calculated using Gaussian 16 at the B3LYP/6-31G(d,p) level of theory.

Pd(II)-Catalyzed Three-Component Synthesis of Furo[2,3-d]pyrimidines from ß-Ketodinitriles, Boronic Acids, and Aldehydes.

A Pd(II)-catalyzed three-component synthesis of 2,4,6-triarylfuro[2,3-d]pyrimidines from ß-ketodinitriles, boronic acids, and aldehydes has been developed. The participation of both nitrile (-CN) groups led to the concurrent construction of furo-pyrimidine via the formation of C-C, C═C, C-O, C-N, and C═N bonds. The compounds show excellent photoluminescence properties with absorption maxima ranging from 348 to 387 nm and emission from 468 to 533 nm. The synthetic utility of the protocol was further demonstrated through a few postsynthetic manipulations.

Synthesis of Chromenopyrroles (Azacoumestans) from Functionalized Enones and Alkyl Isocyanoacetates.

Elegant synthetic strategies for chromenopyrroles (azacoumestans) have been devised via cycloaddition of 2-hydroxychalcone/cyclic enones and alkyl isocyanoacetate, followed by lactonization. Herein, ethyl isocyanoacetate acts as a C-NH-C-C═O synthon contrary to its hitherto applications as a C-NH-C synthon. Subsequently, pentacyclic-fused pyrroles were also constructed from the o-iodo benzoyl chromenopyrroles using the Pd(II) catalyst.

NIS-initiated photo-induced oxidative decarboxylative sulfoximidation of cinnamic acids.

N-Iodosuccinimide catalyzed, visible-light-induced oxidative decarboxylative cross-coupling between cinnamic acids and NH-sulfoximines is presented. This strategy results in the formation of α-keto-N-acyl sulfoximines via the construction of two new CO bonds and one C-N bond. The in situ-generated N-iodosulfoximine serves as the light-absorbing species in the absence of any external photosensitizer. The keto carbonyl and amidic carbonyl oxygen in the resulting product originate from dioxygen and water respectively.

Transformable Transient Directing Group-Assisted C(sp2)-H Activation: Synthesis and Late-Stage Functionalizations of o-Alkenylanilines.

The isocyanate group in aryl isocyanates serves as a transformable transient directing group in a Ru(II)-catalyzed ortho olefination leading to o-alkenylanilines. In alcoholic solvents, aryl isocyanates are transformed into carbamates, which initiate the insertion of acrylates via o-C-H activation. In particular, tAmOH serves the dual role of solvent-cum transient directing mediator. The o-alkenylanilines are converted into azacoumarins and subsequently into C-4 aryl-substituted azacoumarins using aryl iodides as coupling partners via Pd(II)-catalyzed C-H functionalizations.

Updates on hypervalent-iodine reagents: metal-free functionalisation of alkenes, alkynes and heterocycles.

Hypervalent iodine (HVI) chemistry is a rapidly growing subdomain of contemporary organic chemistry because of its enormous synthetic applications. The high nucleofugality of the phenyliodonio group (-I+Ph) and its radical nature, serving as a single-electron oxidant makes HVI compounds highly valuable in organic synthesis. Due to the feasibility and benignity, reactions that rely solely on HVI reagents as promoters have received particular interest. Considering their great influence and synthetic potential, we contribute a brief synopsis on this field with a specific emphasis on metal-free functionalisations of alkenes, alkynes and heterocycles. The discussion is divided according to the type of substrate and reaction type and elaborated with mechanism and representative examples.

Correction: Updates on hypervalent-iodine reagents: metal-free functionalisation of alkenes, alkynes and heterocycles.

Correction for 'Updates on hypervalent-iodine reagents: metal-free functionalisation of alkenes, alkynes and heterocycles' by Anjali Dahiya et al., Org. Biomol. Chem., 2022, DOI: 10.1039/d1ob02233d.

Visible-Light-Mediated Difunctionalization of Alkynes: Synthesis of ß-Substituted Vinylsulfones Using O- and S-Centered Nucleophiles.

An inimitable illustration of a green-light-induced, regioselective difunctionalization of terminal alkynes has been disclosed using sodium arylsulfinates and carboxylic acids in the presence of eosin Y as the photocatalyst. The present methodology is further demonstrated by employing NH4SCN as an S-centered nucleophile instead of carboxylic acid. The mechanistic investigation reveals a radical-induced iodosulfonylation followed by a base-mediated nucleophilic substitution. The mechanism is supported by various studies, viz., radical-trapping experiment, fluorescence quenching, and CV studies. In this protocol, (Z)-ß-substituted vinylsulfones are obtained, exclusively covering a broad range of alkynes and nucleophiles, which are often unaddressed. The present strategy can tolerate structurally discrete substrates with steric bulk and different electronic properties, which provides a straightforward and practical pathway for the synthesis of highly functionalized (Z)-ß-substituted vinylsulfones. Herein, C-O and C-S bonds are assembled simultaneously with the concomitant introduction of important functional groups, viz., ester, thiocyanate, and sulfone.