Synthesis Of Allenes Research Articles

Enantiocontrolled Connective Synthesis of Allenes by Carbenoid Eliminative Cross-Coupling between α-(Methylthio)vinylcuprate Species and α-(Carbamoyloxy)alkylboronates

AbstractA convenient enantiocontrolled synthesis of allenes (R1R2C=C=CHR3, R1 = aryl/alkyl, R2, R3 = alkyl) is described based on carbenoid eliminative cross-coupling (CEXC) between geometrically pure higher-order α-(methylthio)vinylcuprates, generated in situ by carbocupration of thioalkynes (then activation by addition of n-BuLi), and enantioenriched α-(carbamoyloxy)alkylboronates (15 examples, 30–78% yield, 15–95% ee). The stereochemical fidelity of this CEXC process is substrate dependent, a phenomenon tentatively attributed to a putative organocopper-mediated allene racemization pathway.

Palladium-Catalyzed Asymmetric Cycloaddition/Cope Rearrangement Relay: Synthesis of Chiral Endocyclic Allenes

AbstractThe synthesis of chiral endocyclic allenes, especially the medium-sized ones, remains a challenge in allene chemistry due to unfavorable tension and difficult stereocontrol. Herein, an efficient protocol for the construction of chiral nine-membered endocyclic allenes via palladium-catalyzed asymmetric cycloaddition/Cope rearrangement relay of vinyl carbonates with activated enynes is highlighted. This process provides rapid access to a variety of chiral nine-membered endocyclic allenes in good yields with excellent enantioselectivities. In particular, a chiral P,S-ligand shows good performance on stereoinduction, generating central and axial chirality in a single transformation, which is rationalized by DFT calculations and by a proposed transition state.1 Introduction2 Pd-Catalyzed Asymmetric Cycloaddition/Cope Rearrangement Relay3 Plausible Mechanism and Stereochemical Outcome4 Conclusion and Outlook

Modular and Selective Access to Functionalized Alkynes and Allenes via the Intermediacy of Propargylic Acetates

We report an efficient one-pot, two-step procedure for the modular synthesis of α-difunctionalized alkynes and trisubstituted allenes by sequential cross-coupling of benzal gem-diacetates with organozinc or -copper reagents in the absence of external transition metals. The intermediacy of propargylic acetates enables the divergent and selective synthesis of these valuable products. This method features its readily accessible substrates, relatively mild conditions, wide scope, and scalability in practical synthesis.

Stereodivergent Synthesis of Allenes with α,β‐Adjacent Central Chiralities Empowered by Synergistic Pd/Cu Catalysis

AbstractThe stereodivergent synthesis of allene compounds bearing α,β‐adjacent central chiralities has been realized via the Pd/Cu‐catalyzed dynamic kinetic asymmetric alkylation of racemic allenylic esters. The matched reactivity of bimetallic catalytic system enables the challenging reaction of racemic aryl‐substituted allenylic acetates with sterically crowded aldimine esters smoothly under mild reaction conditions. Various chiral non‐natural amino acids bearing a terminal allenyl group are easily synthesized in high yields and with excellent diastereo‐ and enantioselectivities (up to >20 : 1 dr, >99 % ee). Importantly, all four stereoisomers of the product can be readily accessed by switching the configurations of the two chiral metal catalysts. Furthermore, the easy interconversion between the uncommonη3‐butadienyl palladium intermediate featuring a weak C=C/Pd coordination bond and a stable Csp2−Pd bond is beneficial for the dynamic kinetic asymmetric transformation process (DyKAT).

Stereodivergent Synthesis of Allenes with α,β-Adjacent Central Chiralities Empowered by Synergistic Pd/Cu Catalysis.

The stereodivergent synthesis of allene compounds bearing α,β-adjacent central chiralities has been realized via the Pd/Cu-catalyzed dynamic kinetic asymmetric alkylation of racemic allenylic esters. The matched reactivity of bimetallic catalytic system enables the challenging reaction of racemic aryl-substituted allenylic acetates with sterically crowded aldimine esters smoothly under mild reaction conditions. Various chiral non-natural amino acids bearing a terminal allenyl group are easily synthesized in high yields and with excellent diastereo- and enantioselectivities (up to >20 : 1 dr, >99 % ee). Importantly, all four stereoisomers of the product can be readily accessed by switching the configurations of the two chiral metal catalysts. Furthermore, the easy interconversion between the uncommon η3 -butadienyl palladium intermediate featuring a weak C=C/Pd coordination bond and a stable Csp2 -Pd bond is beneficial for the dynamic kinetic asymmetric transformation process (DyKAT).

Enantioselective synthesis of tetrasubstituted allenes via addition/arylation tandem reaction of 2-activated 1,3-enynes

Enantioselective synthesis of tetrasubstituted allenes via addition/arylation tandem reaction of 2-activated 1,3-enynes

Adventures in 1,1-Diphenylacetone Dianion Chemistry

AbstractThe present personalized account highlights reactions of the dianion of 1,1-diphenylacetone and its applications. From a study directed towards the regioselectivity of such reactions a new allene synthesis via allene dianions was found by serendipity. In addition, reactions of allene dianions with various electrophiles have been studied.1 Introduction2 Cyclizations of the Dianion of 1,1-Diphenylacetone2.1 Reaction with Bis(cyclopentadienyl)zirconium Dichloride2.1 Reactions with Dichlorosilanes2.1 Reactions with Difluorosilanes2.1 Reactions with Ketones and Dielectrophiles3 Regioselectivity of Dianion Reactions4 Allene Dianions from Silyl Enol Ethers5 Scope of the Reactions of Allene Dianions6 Reactions of Allene Dianions with Ketones7 Reactions of Allene Dianions with Nitriles8 Conclusions

Organocatalytic synthesis of axially chiral tetrasubstituted allenes.

Asymmetric organocatalysis is a growing method for the synthesis of axially chiral tetrasubstituted allenes, the most challenging one among allene syntheses. In this method, chiral organocatalysts such as phase-transfer catalysts, peptides, disulfonimides, and binaphthyl/bispiro phosphoric acids have displayed remote control of regio- and stereoselectivity. Highly functionalized enantiopure allenes including those with an adjacent tertiary or quaternary stereocenter have been efficiently prepared with high levels of regio-, diastereo-, and enantioselectivity using this method. Several mechanistic pathways, including electrophilic addition to cumulenolate or zwitterionic enolate intermediates, alkynylogous Mukaiyama aldol reaction, nucleophilic addition to quinone methides, and dearomative addition to imino esters, were proposed. The method is necessary for providing access to axially chiral tetrasubstituted allenes, which can be utilized for the preparation of novel ligands, natural products, and organic materials, particularly those having complex structures. This review covers the enantioselective organocatalytic synthesis of these tetrasubstituted allenes and the mechanistic insights into the formation of the chiral axis up to July 2022.

Stereodivergent Synthesis of Allenes with α,β-Adjacent Central Chiralities Empowered by Synergistic Pd/Cu Catalysis

Stereodivergent Synthesis of Allenes with <i>α</i>,<i>β</i>-Adjacent Central Chiralities Empowered by Synergistic Pd/Cu Catalysis

Allenyl Radicals in Organic Synthesis: Challenges and Recent Advances

AbstractAllenyl radicals are rarely employed as intermediates for the synthesis of allenes probably owe to the lack of convenient methods for their generation and the high reactivity of short‐lived allenyl radicals. However, strategies take advantage of allenyl radicals are considered as a significant complement to reactions which couldn't proceed via an allenyl ionic pathway. As a result, several important methods have been developed in the past decades. Herein, this review is aimed to summarize the recent advance in reactions involving allenyl radicals by highlighting some outstanding challenges and confirming potential areas of improvement, which would offer an inspiration for future studies

Dimorpholinoacetylene and Its Use for the Synthesis of Tetraaminocyclobutadiene Species.

The new diaminoacetylene (DAA) dimorpholinoacetylene (3) was prepared from 1,1-dimorpholinoethene (1) by bromination to form the dibromoketene aminal 2, which upon lithiation afforded 3 through a Fritsch-Buttenberg-Wiechell rearrangement. Heating 3 at elevated temperatures resulted in a complete conversion into the dimer 1,1,2,4-tetramorpholino-1-buten-3-yne (4), which was used for the synthesis of four-membered cyclic bent allene (CBA) transition-metal complexes of the type [(CBA)MLn ] (5-7; MLn =AuCl, RhCl(COD), RhCl(CO)2 ; CBA=1,3,4,4-tetramorpholino-1,2-cyclobutadiene; COD=1,5-cyclooctadiene). The reaction of 3 with tetraethylammonium bromide gave 1,2,3,4-tetramorpholinocyclobutenylium bromide (8), which reacted with bromine to form 1,2,3,4-tetra(morpholino)cyclobutenediylium bis(tribromide) (9). Compound 9 represents the first fully characterized compound containing a tetraaminocyclobutadiene dication and displays a nearly planar C4 N4 core as shown by X-ray diffraction analysis. Detailed quantum chemical calculations were performed to assess the aromaticity of tetraaminocyclubutadiene dications by employing the Nucleus Independent Chemical Shift (NICS) method and current density analysis.

Divergent Synthesis of Fluorinated Alkenes, Allenes, and Enynes via Reaction of 2-Trifluoromethyl-1,3-enynes with Carbon Nucleophiles.

Herein, inorganic base K3PO4 promoted divergent synthesis of CF3-substituted allenes, cyclopentenes, alkynes, and fluorinated enynes via regioselective nucleophilic addition of carbon nucleophiles to 2-trifluoromethyl-1,3-enynes was developed. With the choice of different carbon nucleophiles, various fluorinated compounds could be obtained under K3PO4/DMF reaction system. When malononitriles were used as nucleophiles, CF3-substituted allenes, cyclopentenes, and alkynes could be obtained, respectively. By using 1,3-dicarbonyl compounds as nucleophiles, ring-monofluorinated 4H-pyrans could be prepared, and 1,1-difluoro-1,3-enynes could be furnished with the participation of diethyl malonate. Moreover, these five kinds of fluorinated allenes, alkenes, and enynes are valuable building blocks.

Copper-catalyzed reaction of alkyl trifluoromethyl diazoalkane for the synthesis of trifluoromethyl allenes

Generation of an unprecedented alkyl trifluoromethyl diazoalkane from sulfinyl imine via three steps has been achieved, which has been applied in a Cu-catalyzed coupling reaction with alkynes. This reaction is conducted under mild conditions and a series of variously substituted alkynes are well tolerated affording trifluoromethyl allenes in up to 91% yield, which provides an efficient way for the synthesis of trifluoromethyl allenes.

Organocatalytic synthesis of chiral allene catalyzed by chiral phosphoric acid via asymmetric 1,8-addition of indole imine methide: Mechanism and origin of enantioselectivity

Organocatalytic synthesis of chiral allene can be successfully achieved through the reaction between propargylic alcohol and 3-phenylindole catalyzed by chiral phosphoric acid with high yield and high enantioselectivity. The detailed reaction mechanism and origin of enantioselectivity were uncovered by quantum mechanical calculations. The results indicate that the reactions undergo the dehydration process, the C–C bonding reaction, the hydrogen abstraction and the regeneration of catalyst. Eight possible pathways were found and the most favorable reaction paths leading to the major and minor products were evaluated which were consistent with the experimental results. The distortion/interaction analyses of the transition states in enantioselectivity-determining steps confirm the most favorable pathway in leading the major product. QTAIM and IGM analyses are used to illustrate the role of intermolecular interactions. EDA analysis is also employed to understand the origin of selectivity. This work would provide insightful viewpoints on the asymmetric organocatalytic reaction by chiral phosphoric acid.

One-Pot Assembly and Synthetic Applications of Geminal Acyl/Alkoxy Tetrasubstituted Allenes.

Polysubstituted allenes are useful synthetic intermediates in many applications, offering structural complexity, modularity, and their axial chirality in further transformations. While acyl and alkoxy-substituted allenes are known, there are currently few examples of allenes containing both functionalities and no reports of geminally substituted acyl/alkoxy allenes being isolated and characterized. Herein, we report the synthesis of tetrasubstituted allenes featuring a novel geminal acyl/alkoxy substitution. These unique "push-pull" allenes are bench-stable and exhibit interesting reactivity in several applications.

Modular Synthesis of Multifunctionalized CF3-Allenes through Selective Activation of Saturated Hydrocarbons

Catalytic 1,4-dicarbofunctionalization of 1,3-enynes is a powerful strategy for the synthesis of polysubstituted allenes. Despite impressive progress, such a strategy is still restricted to the use of alkyl-metallic reagents or pre-activated radical precursors, thus limiting its functional group compatibility and atom economy. Herein, we report that through the combination of decatungstate photo-hydrogen atom transfer and nickel catalysis, a three-component 1,4-dicarbofunctionalization of 2-trifluoromethyl-1,3-enynes is achieved. This strategy allows the modular synthesis of tetrasubstituted CF3-allenes under exceptionally mild conditions. A variety of electrophiles such as aryl bromides, alkenyl bromides, acyl chlorides, and alkynyl bromides were successfully employed as traps to lead to the desired products. Another significant advantage is that the most abundant hydrocarbons are used as feedstocks, and a wide range of synthetically versatile functional groups and complex drug-like structures can be easily incorporated. Based on experimental and density functional theories, a possible catalytic cycle involving 1,3-nickel rearrangement is proposed.

Synthesis of Tetrasubstituted Allenes via Visible-Light-Promoted Radical 1,3-Difunctionalization of Alkynyl Diazo Compounds.

Herein, we described an unprecedented process for generating allenyl radicals through radical addition to alkynyl diazo compounds followed by a 1,2-radical shift with the loss of nitrogen. Using this protocol, radical 1,3-difunctionalization of alkynyl diazo compounds for the synthesis of tetrasubstituted allenes with RSO2X (X = SeR', SR', and I) as the radical sources was developed. The reactions were promoted by visible light without photocatalyst and any additives.

Back Cover: Catalytic Regio‐ and Enantioselective Protonation for the Synthesis of Chiral Allenes: Synergistic Effect of the Counterion and Water (Angew. Chem. Int. Ed. 27/2022)

A chiral Lewis acid accelerated asymmetric Pudovik addition/[1,2]-phospha-Brook rearrangement is described by Shunxi Dong, Qian Peng, Xiaoming Feng, and co-workers in their Research Article (e202203650). Control experiments and theoretical calculations revealed that a synergistic effect of the counterion and water was critical for the regio- and enantioselective protonation after the [1,2]-phospha-Brook rearrangement.

Rücktitelbild: Catalytic Regio‐ and Enantioselective Protonation for the Synthesis of Chiral Allenes: Synergistic Effect of the Counterion and Water (Angew. Chem. 27/2022)

Eine chirale Lewis-Säure beschleunigt die asymmetrische Pudovik-Addition/[1,2]-Phospha-Brook-Umlagerung, wie Shunxi Dong, Qian Peng, Xiaoming Feng und Mitarbeiter in ihrem Forschungsartikel berichten (e202203650). Kontrollexperimente und theoretische Berechnungen zeigen, dass ein synergistischer Effekt des Gegenions und von Wasser für die regio- und enantioselektive Protonierung nach der [1,2]-Phospha-Brook-Umlagerung entscheidend ist.

Catalytic Regio‐ and Enantioselective Protonation for the Synthesis of Chiral Allenes: Synergistic Effect of the Counterion and Water

AbstractA highly enantioselective tandem Pudovik addition/[1,2]‐phospha‐Brook rearrangement of α‐alkynylketoamides with diarylphosphine oxides was achieved with a N,N′‐dioxide/ScIII complex as the catalyst. This protocol features broad substrate scope, high regio‐ and enantioselectivity, and good functional‐group compatibility, providing a straightforward route to various trisubstituted allenes with a diarylphosphinate functionality in good yields with high enantioselectivities (up to 97 % yield, 96 % ee). Control experiments and theoretical calculations revealed that a synergistic effect of the counterion and water was critical for the regio‐ and enantioselective protonation after [1,2]‐phospha‐Brook rearrangement. The synthetic utility of this methodology was demonstrated by the conversion of products into complex bridged polycyclic architectures through intramolecular dearomatizing arene/allene cycloaddition.