Diastereoselective cyclopropanation of α,ß-unsaturated carbonyl compounds with vinyl sulfoxonium ylides.

Herein, we report a three-component stereoselective cyclopropanation of vinyl sulfoxonium ylides with indane 1,3-dione and aldehydes under mild reaction conditions. In contrast to previous reports, the present work shows that electrophilic addition selectively takes place at the α-position of the vinyl sulfoxonium ylide. The interesting feature of this approach is that the multicomponent reaction selectively proceeds because of the difference in nucleophilic reactivity of vinyl sulfoxonium ylides and indane 1,3-dione with electrophilic partners, such as aldehydes and in situ generated arylidenes. Additionally, density functional theory (DFT) studies were conducted to investigate the difference in the reactivity of these reactants, as well as to unveil the mechanism of this three-component reaction. Furthermore, non-covalent interactions of selectivity-determining transition states explain the origin of the diastereoselectivity of cyclopropanation.

Visible Light-Promoted Regioselective Benzannulation of Vinyl Sulfoxonium Ylides with Ynoates.

Herein, we report a highly regioselective [4 + 2]-annulation of vinyl sulfoxonium ylides with ynoates under light-mediated conditions. The reaction proceeds through the new dienyl sulfoxonium ylide, which undergoes photolysis under blue light irradiation to give highly substituted naphthalene scaffolds. The method presented here operates at room temperature and does not require the addition of an external photosensitizer. The in situ-generated dienyl sulfoxonium ylide absorbs light and acts as a photosensitizer for the formation of arenes. The synthetic potential of these benzannulations was further illustrated by various synthetic transformations and a scale-up reaction. Moreover, control experiments and quantum chemical calculations reveal the mechanistic details of the developed reaction.

Carbene-mediated stereoselective olefination of vinyl sulfoxonium ylides with diazo compounds and acetals.

The development of stereoselective olefination using sulfur ylide-derived vinyl carbenes with diazo esters and acetals is reported. Both reactions proceed through nucleophilic addition to electrophiles at the γ-position of an in situ-generated 2-alkoxy furan intermediate. The synthetic utility of the developed method is demonstrated by the total synthesis of rubrolide E. Detailed mechanistic investigations and quantum chemical calculations provide insight into the reaction mechanism.

Catalyst-Controlled Divergent Synthesis of 2H-Chromenes via [3 + 3] Annulation of Vinyl Sulfoxonium Ylides with Quinones.

Herein, we report the synthesis of 2H-chromenes via catalyst-controlled highly regioselective [3 + 3] annulation of vinyl sulfoxonium ylides with quinones. Under boron-catalyzed conditions, the reaction between the ylide and quinone resulted in the formation of 2H-chromene-4-carboxylates. In contrast, a different mechanistic pathway was observed when utilizing a Ru(II) catalytic system, which led to the formation of 2H-chromene-2-carboxylates through a furan intermediate.

Divergent Approach to Highly Substituted Arenes via [3 + 3] Annulation of Vinyl Sulfoxonium Ylides with Ynones.

Herein, we report the divergent benzannulation for highly substituted arenes using vinyl sulfoxonium ylides and ynones. The addition of ynone at the γ-position of vinyl sulfoxonium ylides leads to dienyl sulfoxonium ylide that can undergo selective annulation under different conditions to give m-terphenyls and parabens. Moreover, control experiments and quantum chemical calculations reveal two distinct reaction mechanisms for both annulations.

Synthesis and Applications of π-Conjugation-Extended Vinyl Sulfoxonium Ylides.

Herein, we report the synthesis of π-conjugation-extended vinyl sulfoxonium ylides from vinyl sulfoxonium ylide and electron-deficient alkynes. The new dienoate ylides are used in various transformations, such as X-H (X = S, O) insertion, halogenation, carbene-mediated transformation, and radical-mediated reductions to obtain a variety of conjugated dienoates.

Insights into the multifaceted applications of vinyl sulfoxonium ylides.

Sulfoxonium ylides are important synthetic precursors in various organic transformations. Their synthetic potential was well explored in the synthesis of various bioactive natural products and pharmaceuticals. Vinyl sulfoxonium ylide is a stabilized sulfoxonium ylide containing an electron-deficient alkene at the ylidic carbon. Similar to α-keto sulfoxonium ylides, these reagents can generate vinyl carbenes in the presence of metals under suitable conditions. These vinyl carbenes can be used for various organic transformations such as X-H (X = C, N, O, S) insertions, annulations, and rearrangement reactions. Due to the dipole structure of the vinyl sulfoxonium ylide, it can undergo electrophilic addition with electrophiles at the α-position. These reagents are used as synthons for various aromatic and heteroaromatic compound syntheses. Moreover, their stability and convenient handling make them potential replacements for thermally less stable vinyl diazo compounds. Herein, we provide an overview of early efforts in this area, with particular emphasis on our own recent development of vinyl sulfoxonium ylide-mediated transformations in the presence and absence of metal catalysis, and also give personal perspectives on the challenges and future scope for improving the application of vinyl sulfoxonium ylides.

Ir(I)-Catalyzed Synthesis of Furanones from Vinyl Sulfoxonium Ylides.

A method for the synthesis of allyl substituted γ-butenolides via carbonyl ylide rearrangement of vinyl sulfoxonium ylide-derived carbenes has been developed. At rt, the mechanism involves a carbonyl ylide generation/allyloxy furan formation/[3,3]-sigmatropic rearrangement/isomerization sequence for the generation of 3-allyl butenolides. At 70 °C, instead of the final isomerization step, the resulting [3,3]-sigmatropic rearrangement product undergoes further [3,3]-sigmatropic rearrangement to produce 5-allyl butenolide. In the absence of the catalyst, the reaction affords a diene via [2,3]-sigmatropic rearrangement.

Bidirectional Iterative Approach to Sequence-Defined Unsaturated Oligoesters.

Herein, we describe the development of a new strategy for the synthesis of unsaturated oligoesters via sequential metal- and reagent-free insertion of vinyl sulfoxonium ylides into the O-H bond of carboxylic acid. Like two directional coupling of amino acids (N- to C-terminal and C- to N-terminal) in peptide synthesis, the present approach offers a strategy in both directions to synthesize oligoesters. The sequential addition of the vinyl sulfoxonium ylide to the carboxylic acids (acid iteration sequence) in one direction and the sequential addition of the carboxylic acids to the vinyl sulfoxonium ylide (ylide iteration sequence) in another direction yield (Z)-configured unsaturated oligoesters. To perform this iteration, we have developed a highly regioselective insertion of vinyl sulfoxonium ylide into the X-H (X = O, N, C, S, halogen) bond of acids, thiols, phenols, amines, indoles, and halogen acids under metal-free reaction conditions. The insertion reaction is applied to a broad range of substrates (>50 examples, up to 99% yield) and eight iterative sequences. Mechanistic studies suggest that the rate-limiting step depends on the type of X-H insertion.

Catalyst Controlled Site- and Stereoselective Rhodium(II) Carbene C(sp3)-H Functionalization of Allyl Boronates.

Rhodium(II) catalyst-controlled site- and stereoselective carbene insertion into the distal allylic C(sp3)-H bond of allyl boronates is reported. The optimum chiral catalyst for this reaction is Rh2(S-TPPTTL)4. The fidelity and asymmetric induction of this catalytic transformation allows for a highly diastereoselective and enantioselective C-C bond formation without interference from the allyl boronate functionality. The resulting functionalized allyl boronates are susceptible to stereoselective allylations, generating products with control of stereochemistry at four contiguous stereogenic centers.

Ru-Catalyzed Benzannulation of Vinyl Sulfoxonium Ylide with Electron-Deficient Alkynes and Alkenes.

Herein, we report carbene-mediated benzannulation of vinyl sulfoxonium ylides with electron-deficient alkynes and alkenes to synthesize oxygenated arenes. This protocol features excellent regioselectivity, a broad substrate scope, and mild reaction conditions. Mechanistic studies revealed that the reaction proceeds through furan generation, cycloaddition, ring cleavage, and aromatization cascades. The synthesized arenes have been utilized in diverse product transformations and arene ring homologation.

Distal Allylic/Benzylic C-H Functionalization of Silyl Ethers Using Donor/Acceptor Rhodium(II) Carbenes.

Regio- and stereoselective distal allylic/benzylic C-H functionalization of allyl and benzyl silyl ethers was achieved using rhodium(II) carbenes derived from N-sulfonyltriazoles and aryldiazoacetates as carbene precursors. The bulky rhodium carbenes led to highly site-selective functionalization of less activated allylic and benzylic C-H bonds even in the presence of electronically preferred C-H bonds located α to oxygen. The dirhodium catalyst Rh2 (S-NTTL)4 is the most effective chiral catalyst for triazole-derived carbene transformations, whereas Rh2 (S-TPPTTL)4 works best for carbenes derived from aryldiazoacetates. The reactions afford a variety of δ-functionalized allyl silyl ethers with high diastereo- and enantioselectivity. The utility of the present method was demonstrated by its application to the synthesis of a 3,4-disubstituted l-proline scaffold.

Iron-Catalyzed Carbenoid-Transfer Reactions of Vinyl Sulfoxonium Ylides: An Experimental and Computational Study.

A method for the generation of unprecedented vinyl carbenoids from sulfoxonium ylides has been developed and applied in the synthesis of a diverse array of heterocycles such as indolizines, pyrroles, 3-pyrrolin-2-ones, and furans. The reactions proceed by FeBr2 catalysis under mild reaction conditions with a broad substrate scope. A reaction pathway involving iron carbenoids is proposed based on a series of control experiments and DFT calculations.

Rhodium-Catalyzed Synthesis of Sulfur Ylides via in Situ Generated Iodonium Ylides.

A convenient strategy for the synthesis of sulfur ylides via rhodium-catalyzed coupling of in situ generated iodonium ylides with sulfides or sulfoxides has been developed. A wide range of sulfur ylides were obtained in moderate to good yields from inexpensive sulfur compounds and active methylene compounds with a short reaction time (MW, 5-10 min) or 12-16 h at rt. Furthermore, these sulfoxonium ylides were used as novel acceptor/acceptor carbenes for N-H insertion reactions.

Synthesis of Indoles and Pyrroles Utilizing Iridium Carbenes Generated from Sulfoxonium Ylides.

Metal carbenes can undergo a myriad of synthetic transformations. Sulfur ylides are potential safe precursors of metal carbenes. Herein, we report cascade reactions that involve carbenoids derived from sulfoxonium ylides for the efficient and regioselective synthesis of indoles and pyrroles. The tandem action of iridium and Brønsted acid catalysts enables rapid assembly of the heterocycles from unmodified anilines or readily accessible enamines under microwave irradiation. The key mechanistic steps are the catalytic transformation of the sulfoxonium ylide into an iridium-carbene complex, followed by N-H or C-H functionalization of an aniline or enamine, respectively, and a final acid-catalyzed cyclization. The present method was successfully applied to the synthesis of the densely functionalized pyrrole subunit of atorvastatin.

Desulfonylative Methenylation of ß-Keto Sulfones.

A one-step strategy for the synthesis of α-methenyl ketones from ß-keto sufones is reported. Success of the methodology is elaborated for the synthesis of chromanones and isoflavanones in one-step.