Recent trends in the synthesis and applications of ß-iodovinyl sulfones: a decade of progress.

Direct vicinal difunctionalization of π-systems has emerged as a powerful platform for constructing multiple bonds in a single synthetic operation using simple chemical feedstocks. Over the past decade, there has been exponential growth in the direct construction of successive C-S and C-I bonds using a wide variety of sulfonyl and iodide reactants through 1,2-iodosulfonylation of alkynes in a regio- and stereo-selective manner. In this review, we mainly focus on the recent developments in the preparation of ß-iodovinyl sulfones and their practical applications in organic synthesis. The most promising photoredox and electrochemical transformations for synthesizing ß-iodovinyl sulfones are also reviewed. The multifunctional ß-iodovinyl sulfones have recently been burgeoning as versatile synthetic precursors due to the combination of vinyl iodide and vinyl sulfone moieties, essential building blocks for diverse synthetic manipulations. We hereby present the chemistry of ß-iodovinyl sulfones, which can be classified into numerous sections based on the sulfonyl surrogates, and potential synthetic approaches are systematically outlined.

Pd(II)-Catalyzed Tandem Cycloannulative-Alkenylation of o-Alkynyl-Phenols/Anilines with (E)-ß-Iodovinyl Sulfones: A Direct Strategy To Construct 3-(Vinyl sulfonyl)benzoheterole Derivatives.

Benzoheteroles and vinyl sulfones are the most promising pharmaceutical relevance motifs, yet the hybrid analogues of these scaffolds still need to be explored. We report herein a general and highly efficient Pd(OAc)2-catalyzed intramolecular cyclization and vinylation of o-alkynylphenols/o-alkynylanilines with (E)-ß-iodovinyl sulfones under mild reaction conditions. A direct C(sp2)-C(sp2) cross-coupling is enabled for the diversity-oriented synthesis of vinyl sulfone-tethered benzofurans and indoles in good to high yields with excellent stereoselectivity. Notably, this tandem process was consistent at the gram scale, and in situ, generation of 2-(phenylethynyl)phenol has also been utilized in a scalable synthesis. Late-stage synthetic transformations were also further explored, including isomerization and desulfonylative-sulfenylation. Moreover, several control experiments were accomplished, and we proposed a plausible mechanism based on existing experimental results.

Unified Radical Sulfonylative-Annulation of 1,6-Enynols with Sodium Sulfinates: A Modular Synthesis of 2,3-Disubstituted Benzoheteroles.

Benzoheteroles are valuable scaffolds in medicinal chemistry, but the direct synthesis of 3-vinyl benzoheterole analogues remains unexplored. A rationally designed new class of 1,6-enyne-containing propargylic alcohols has been prepared for the modular synthesis of 3-alkenyl benzoheteroles. Ag-catalyzed cascade radical sulfonylative-cycloannulation of 1,6-enynols with sodium sulfinates is realized to access a wide variety of 2,3-disubstituted benzoheteroles in good to high yields. Moreover, a three-component coupling of 1,6-enynols, aryldiazonium salts, and Na2S2O5 (as an SO2 surrogate) has been achieved to deliver benzoheterole derivatives in moderate to good yields. Of note, a scalable reaction and late-stage synthetic transformations were successfully demonstrated. A plausible mechanism is also presented based on the existing experimental results and control experiments.

Solvent-Driven Mono- and Bis-sulfenylation of (E)-ß-Iodovinyl Sulfones with Thiols for Flexible Synthesis of 1,2-Thiosulfonylalkenes and 1,2-Dithioalkenes.

The nature of solvent is a key factor for stereoselective mono- and bis-thiolation of (E)-ß-iodovinyl sulfones with thiols under basic conditions. A novel and unprecedented vicinal bisthiolation of (E)-ß-iodovinyl sulfones with thiols under the influence of K2CO3/DMSO at room temperature for quick assembly of (E)-1,2-dithio-1-alkenes is presented. Solvent-induced stereoselective monosulfenylation of (E)-ß-iodovinyl sulfones with thiols has also been established for the synthesis of both (E)- and (Z)-1,2-thiosulfonylethenes in MeCN and MeOH, respectively. Moreover, K2CO3-mediated desulfonylative-sulfenylation of (Z)-1,2-thiosulfonylethenes with thiols in DMSO furnished unsymmetrical (Z)-1,2-dithio-1-alkenes for the first time. The solvent-dependent versatile reactivity of (E)-ß-iodovinyl sulfones has been successfully explored to provide a set of (E)-/(Z)-1,2-dithio-1-alkenes and (E)-/(Z)-1,2-thiosulfonyl-1-alkenes in good to high yields with excellent stereoselectivities. Notably, this operationally simple process utilizes a broad substrate scope with good functional group tolerance and compatibility. The efficacy of the process has been proven for gram-scale reactions, and plausible mechanistic models are outlined on the basis of experimental results and control experiments.

Synthesis and applications of sodium sulfinates (RSO2Na): a powerful building block for the synthesis of organosulfur compounds.

This review highlights the preparation of sodium sulfinates (RSO2Na) and their multifaceted synthetic applications. Substantial progress has been made over the last decade in the utilization of sodium sulfinates emerging as sulfonylating, sulfenylating or sulfinylating reagents, depending on reaction conditions. Sodium sulfinates act as versatile building blocks for preparing many valuable organosulfur compounds through S-S, N-S, and C-S bond-forming reactions. Remarkable advancement has been made in synthesizing thiosulfonates, sulfonamides, sulfides, and sulfones, including vinyl sulfones, allyl sulfones, and ß-keto sulfones. The significant achievement of developing sulfonyl radical-triggered ring-closing sulfonylation and multicomponent reactions is also thoroughly discussed. Of note, the most promising site-selective C-H sulfonylation, photoredox catalytic transformations and electrochemical synthesis of sodium sulfinates are also demonstrated. Holistically, this review provides a unique and comprehensive overview of sodium sulfinates, which summarizes 355 core references up to March 2020. The chemistry of sodium sulfinate salts is divided into several sections based on the classes of sulfur-containing compounds with some critical mechanistic insights that are also disclosed.

A straightforward and convenient synthesis of functionalized allyl thiosulfonates and allyl disulfanes.

A practical, highly flexible and eco-friendly method has been developed for the synthesis of allyl thiosulfonates using Morita-Baylis-Hillman (MBH) allyl bromides and sodium arylthiosulfonates, which were readily assembled without any reagent/catalyst. Moreover, the allyl thiosulfonates were successfully transformed into a set of two synthetically viable diallyl disulfanes and unsymmetrical allyl disulfanes in the presence of Cs2CO3. The present protocols are operationally simple and convenient to generate a wide range of functionalized allyl thiosulfonates and allyl disulfanes in good to excellent yields.

Alkynyl Thioethers in Gold-Catalyzed Annulations To Form Oxazoles.

Non-oxidative, regioselective, and convergent access to densely functionalized oxazoles is realized in a functional-group tolerant manner using alkynyl thioethers. Sulfur-terminated alkynes provide access to reactivity previously requiring strong donor-substituted alkynes such as ynamides. Sulfur does not act in an analogous donor fashion in this gold-catalyzed reaction, thus leading to complementary regioselective outcomes and addressing the limitations of using ynamides.

Synthesis of the 1-phenethyltetrahydroisoquinoline alkaloids (+)-dysoxyline, (+)-colchiethanamine, and (+)-colchiethine.

Asymmetric total syntheses of the 1-phenethyl-1,2,3,4-tetrahydroisoquinoline alkaloids (+)-dysoxyline (1), (+)-colchiethanamine (2), and (+)-colchiethine (3) are described. In the synthetic routes, coupling of a key, enatiomerically pure 1-(sulfonylmethyl)tetrahydroisoquinoline with aromatic aldehydes, performed by using the Julia-Kocienski reaction, afforded the corresponding 1-(ß-styryl)-substituted tetrahydroisoquinolines with complete retention of the absolute configuration at the C1 carbon atom. Functionalization of the products generated in these processes by using four- or five-step sequences gave the target alkaloids 1-3.

Highly efficient organocatalytic kinetic resolution of activated nitroallylic acetates with aldehydes via conjugate addition-elimination.

A novel, efficient, and unprecedented organocatalytic kinetic resolution has been developed. For the first time, a variety of nitroallylic acetates 1a-i have been resolved with aldehydes in the presence of 2 (2.5 mol %) via conjugate addition-elimination. The densely functionalized products 3a-o were obtained with excellent enantioselectivities (up to >99% ee), and unreacted substrates 1a-i were recovered with good to excellent optical purity (up to 98% ee).

Pyrrolidinyl-camphor derivatives as a new class of organocatalyst for direct asymmetric Michael addition of aldehydes and ketones to beta-nitroalkenes.

Practical and convenient synthetic routes have been developed for the synthesis of a new class of pyrrolidinyl-camphor derivatives (7 a-h). These novel compounds were screened as catalysts for the direct Michael addition of symmetrical alpha,alpha-disubstituted aldehydes to beta-nitroalkenes. When this asymmetric transformation was catalyzed by organocatalyst 7 f, the desired Michael adducts were obtained in high chemical yields, with high to excellent stereoselectivities (up to 98:2 diastereomeric ratio (d.r.) and 99 % enantiomeric excess (ee)). The scope of the catalytic system was expanded to encompass various aldehydes and ketones as the donor sources. The synthetic application was demonstrated by the synthesis of a tetrasubstituted-cyclohexane derivative from (S)-citronellal, with high stereoselectivity.

Simple and facile synthesis of tetralone-spiro-glutarimides and spiro-bisglutarimides from Baylis-Hillman acetates.

A simple and convenient synthesis of di(E)-arylidene-tetralone-spiro-glutarimides from Baylis-Hillman acetates via an interesting biscyclization strategy involving facile C-C and C-N bond formation is described. Also, one-pot multistep transformation of the Baylis-Hillman acetates into di(E)-arylidene-spiro-bisglutarimides is presented.

TiCl4 catalyzed tandem construction of C-C and C-O bonds: a simple and one-pot atom-economical stereoselective synthesis of spiro-oxindoles.

An atom-economical stereoselective synthesis of [{1-acetyl-5-methyl-6,8-dioxabicyclo(3.2.1)octane}-7-spiro-3'-(indolin-2'-one)] derivatives, containing both the oxindole and 6,8-dioxabicyclo(3.2.1)octane moieties via TiCl(4) catalyzed coupling of 2-acetyl-6-methyl-2,3-dihydro-4H-pyran with isatin derivatives is described.

Simple, facile, and one-pot conversion of the Baylis-Hillman adducts into functionalized 1,2,3,4-tetrahydroacridines and cyclopenta[b]quinolines.

A simple, facile, and one-pot synthesis of functionalized 1,2,3,4-tetrahydroacridines and cyclopenta[b]quinolines from the Baylis-Hillman alcohols, i.e., 2-[hydroxy(2-nitroaryl)methyl]cycloalk-2-enones, is described.