Intramolecular Rauhut Currier Reaction Research Articles

Phosphine-promoted intramolecular Rauhut-Currier/Wittig reaction cascade to access (hetero)arene-fused diquinanes.

We describe the first phosphine-promoted intramolecular Rauhut-Currier reaction that triggers an intramolecular Wittig process assembling new classes of diquinanes. The one-pot strategy provides ready access to simple diquinanes and various (hetero)arene-fused diquinanes incorporated with up to two contiguous all-carbon quaternary centers under metal-free and neutral conditions. We showcased the generality of the method on a broad range of substrates and demonstrated its synthetic utility in accessing various advanced intermediates relevant to natural product synthesis and material science.

An Asymmetric Intramolecular Rauhut-Currier Reaction Initiated by Chiral Selenolate-BINOL Complexes

This work reports the new method of Rauhut-Currier reaction (RC) with the use of lithium selenolates, which provided up to 80% yield in a non-asymmetric IRC reaction. Therefore, our paper involves the search for an efficient chiral additive in the asymmetric version. The influence of various reaction parameters, such as solvent, additives, temperature, and time, was examined. The results for the non-asymmetric version were significantly higher with the presence of water, but surprisingly different observations were obtained in the asymmetric version. Here, the chiral scandium complex with tertiary amine played an important role. The reaction carried out in the presence of chiral complexes gave the expected product with up to 60% yield and up to 70% ee.

Asymmetric Intramolecular Rauhut-Currier Reaction and Its Desymmetric Version via Double Thiol/Phase-Transfer Catalysis.

An asymmetric intramolecular Rauhut-Currier reaction of linear bis(enones) has been achieved via double activation catalysis of thiols and phase transfer substances, furnishing both enantioenriched cyclohexene and cyclopentene derivatives (up to 95% ee). Furthermore, the desymmetric version of prochiral substrates was developed under similar catalysis, producing the frameworks bearing an additional tertiary or even quaternary stereogenic center with moderate to excellent diastereo- and enantioselectivity (up to 95% ee, >19:1 dr).

Ferrocene-based bifunctional organocatalyst for highly enantioselective intramolecular Rauhut–Currier reaction

Three series of novel ferrocene-based bifunctional chiral phosphines have been designed and synthesized. Thethiourea-phosphine A7 showed good performance in enantioselective intramolecular Rauhut–Currier reaction of bis(enones), giving the corresponding products in good yield with up to 98% ee. Moreover, with amino acid derived amide-phosphine B3, optically active α-methylene-δ-valerolactone was obtained in 88% yield and > 99.9% ee utilizing the enantioselective intramolecular Rauhut-Currier reaction of chalcone derivative.

Acrylamide in Rauhut-Currier reaction; intramolecular isomerization of activated alkenes for quinolone synthesis

Acrylamides are fundamental Michael acceptors which have been used profoundly in synthetic, medicinal and polymer chemistry. However, due to their lower reactivity they have been least used in Morita-Baylis-Hillman (MBH) reaction and have been out of its vinylogus version Rauhut Currier (RC) reaction. Herein, use of acrylamide in RC reaction is being presented. Intramolecular RC reaction followed by [1,3]-H shift led to the synthesis of quinolone moiety. DABCO catalyzed IRC reaction of acrylamide at 80 °C in presence of water, was found to work on a number of precursors. En route chemo selective, gram scale method for ambiphilic, versatile precursor 2-amino chalcone is also reported. Chemoselective and economical conversion of 2-nitro chalcone to 2-aryl quinoline has also been developed.

Phosphine-catalyzed intramolecular Rauhut-Currier reaction: enantioselective synthesis of hydro-2H-indole derivatives.

A highly enantioselective intramolecular Rauhut-Currier reaction catalyzed by a multifunctional chiral aminophosphine catalyst was reported. A series of hydro-2H-indole derivatives that bear an all-carbon quaternary center were obtained in high yields (up to 94%), and excellent diastereo- and enantioselectivities (up to >20 : 1 dr and >99% ee). And this reaction could be performed on a gram scale using 2 mol% catalyst loading.

Enantioselective desymmetrization of cyclohexadienones via an intramolecular Rauhut–Currier reaction of allenoates

The Rauhut–Currier (RC) reaction represents an efficient method for the construction of carbon–carbon bond in organic synthesis. However, the RC reactions involving allenoate substrates are very rare, and in particular, asymmetric intramolecular RC reaction of allenoates is yet to be discovered. Here, we show that the intramolecular RC reaction proceeds smoothly in the presence of 1 mol% β-ICD, and bicyclic lactones are obtained in high yields and with excellent enantiomeric excesses. With the employment of γ-substituted allenoates as racemic precursors, a novel dynamic kinetic resolution of allenes via RC reaction is observed, which allows for facile synthesis of highly enantiomerically enriched allenes.

ChemInform Abstract: Nucleophilic Catalysis in the Enantioselective Synthesis of α‐Methylidene‐δ‐lactones.

AbstractAn L‐valine‐derived phosphine is successfully applied as catalyst for the intramolecular Rauhut—Currier reaction of acrylates (I) and (III) leading to chiral α‐methylidene‐δ‐lactones (II) and (IV), respectively.

Nucleophilic Catalysis in the Enantioselective Synthesis of α-Methylidene-δ-lactones

A new method for the preparation of optically active ­α-methyl­idene-δ-lactones is presented. The developed strategy utilizes an intramolecular Rauhut–Currier reaction for a facile construction of the α-methylidene-δ-lactone framework. The reaction is catalyzed by a chiral phosphine and employs the principles of nucleophilic catalysis. It benefits from operational simplicity and uses readily available starting materials.

The first report of Lewis acid reagents in the intramolecular Rauhut–Currier reaction

The first report of Lewis acid use in intramolecular Rauhut–Currier reactions is described. Titanium Lewis acids lead to rapid Rauhut–Currier reactions in the case of two classic substrates. More importantly, titanium and tin Lewis acids were the only successful reagent for a more complex substrate, thereby illustrating the potential for Lewis acid reagents to facilitate challenging intramolecular Rauhut–Currier reactions that fail with traditional reagents.

ChemInform Abstract: Design, Synthesis, and Application of a Chiral Sulfinamide Phosphine Catalyst for the Enantioselective Intramolecular Rauhut—Currier Reaction.

AbstractA novel class of chiral phosphine catalysts is introduced and successfully employed in the enantioselective intramolecular Rauhut‐Currier reaction.

ChemInform Abstract: Enantioselective Synthesis of Chromanones via a Peptidic Phosphane Catalyzed Rauhut—Currier Reaction.

AbstractBiologically active α‐methylene‐δ‐valerolactones are enantioselectively obtained by intramolecular Rauhut—Currier reaction using a new bifunctional dipeptidic phosphane catalyst which is accessible in only four steps from cheap commercially available amino acids.

ChemInform Abstract: Highly Enantioselective Intramolecular Rauhut—Currier Reaction Catalyzed by Chiral Thiourea—Phosphine.

Abstract A highly enantioselective intramolecular Rauhut–Currier reaction of bis(enones) has been developed by employing bifunctional thiourea–phosphine organocatalysts based on a chiral cyclohexane scaffold. In the presence of 10 mol % of thiourea–phosphine 1h, the desired products were obtained in good yields with up to 99% ee.

Enantioselective Synthesis of Chromanones via a Peptidic Phosphane Catalyzed Rauhut-Currier Reaction.

The enantioselective intramolecular Rauhut-Currier reaction has been developed using a bifunctional dipeptidic phosphane catalyst, providing a direct access to biologically active α-methylene-δ-valerolactones in high yields and enantiomeric excesses. The novel catalyst is accessible in only four steps from commercial sources and exhibits unusual binding selectivities for a small molecule, suggesting the possibility for long-range interactions between the catalyst and the substrate.

Design, Synthesis, and Application of a Chiral Sulfinamide Phosphine Catalyst for the Enantioselective Intramolecular Rauhut–Currier Reaction

AbstractA novel class of chiral sulfinamide phosphine catalysts (Xiao‐Phos) are reported, which can be easily prepared from inexpensive commercially available starting materials. The Xiao‐Phos catalysts showed good performance in enantioselective intramolecular Rauhut–Currier reactions, generating α‐methylene‐γ‐butyrolactones in high yields with up to 99 % ee under mild conditions. Moreover, kinetic resolution and parallel kinetic resolution were also observed with the use of two different substituted racemic precursors.

Design, synthesis, and application of a chiral sulfinamide phosphine catalyst for the enantioselective intramolecular Rauhut-Currier reaction.

A novel class of chiral sulfinamide phosphine catalysts (Xiao-Phos) are reported, which can be easily prepared from inexpensive commercially available starting materials. The Xiao-Phos catalysts showed good performance in enantioselective intramolecular Rauhut-Currier reactions, generating α-methylene-γ-butyrolactones in high yields with up to 99% ee under mild conditions. Moreover, kinetic resolution and parallel kinetic resolution were also observed with the use of two different substituted racemic precursors.

Highly enantioselective intramolecular Rauhut–Currier reaction catalyzed by chiral thiourea–phosphine

A highly enantioselective intramolecular Rauhut–Currier reaction of bis(enones) has been developed by employing bifunctional thiourea–phosphine organocatalysts based on a chiral cyclohexane scaffold. In the presence of 10mol% of thiourea–phosphine 1h, the desired products were obtained in good yields with up to 99% ee.

ChemInform Abstract: Facile Synthesis of α‐Methylidene‐γ‐butyrolactones: Intramolecular Rauhut—Currier Reaction Promoted by Chiral Acid—Base Organocatalysts.

AbstractHighly functionalized α‐methylidene‐γ‐butyrolactones are formed enantioselectively from prochiral dienone enolates in the presence of chiral organocatalysts (CHOC).

Rhodium‐Catalyzed Asymmetric Arylative Cyclization of meso‐1,6‐Dienynes Leading to Enantioenriched cis‐Hydrobenzofurans

Chiral cis-hydrobenzofurans represent a uniquemotif existing in numerous natural products, for instance, isoambrox, haterumaimide I, rosenonolactone, incarviditone, and millingtonine A (Scheme 1a). Owing to their diverse biological activities, a great deal of attention has been paid to the development of efficient methods toward their enantioselective syntheses. One of the most straightforward and powerful ways to construct such a framework is the catalytic asymmetric desymmetrization of cyclohexadienones (Scheme 1b). In recent elegant reports, Rovis and co-workers demonstrated the feasibility of using chiral-NHC-catalyzed intramolecular Stetter reactions for the asymmetric desymmetrization of cyclohexadienones to prepare chiral cis-hydrobenzofuranones. Very recently, Sasai and co-workers described the use of bifunctional chiral phosphinothiourea catalysts in a intramolecular Rauhut–Currier reaction for the enantioselective discrimination of cyclohexadienones. Although these protocols proved to be highly effective, their efforts were mainly focused on the application of chiral organocatalysts in intramolecular reactions with a limited substrate scope. Moreover, transition metal catalyzed asymmetric desymmetrization of cyclohexadienones is quite scarce. During our continuous efforts in exploring rhodium/chiral diene-catalyzed asymmetric arylation, we envisioned that a rhodium-catalyzed tandem arylrhodation/conjugate addition reaction of cyclohexadienone-containing 1,6-dienynes, which are accessible from dearomatization of corresponding phenols, would provide a novel approach to these enantioenriched cis-hydrobenzofurans (Scheme 1c). However, two major concerns need to be addressed in this rhodium-catalyzed asymmetric desymmetrization process.

Facile synthesis of α-methylidene-γ-butyrolactones: intramolecular Rauhut–Currier reaction promoted by chiral acid–base organocatalysts

The acid–base organocatalyzed intramolecular Rauhut–Currier (RC) reaction of the dienone enolates has been developed. The enantioselective RC process produces the highly functionalized α-methylidene-γ-butyrolactones as a single diastereomer with up to 98% ee.