Synthesis of cyclopentenyl and cyclohexenyl ketones via [3 + 2] and [4 + 2] annulations of 1,2-allenic ketones简

In this paper, an efficient synthesis of cyclopentenyl ketones and cyclohexenyl ketones through tertiary phosphine catalyzed [3 ＋ 2] and [4 ＋ 2] annulations of 1,2-allenic ketones with activated alkenes has been developed. Compared with published synthetic methods on cyclopentenyl ketones and cyclohexenyl ketones, the protocols developed in this paper have the advantages such as readily available starting materials, mild reaction conditions and high efficiency.     

Gas-Phase Synthesis of Reactive Molecules Using Adsorbed Reagents

Base-induced elimination reactions have found wide application in the synthesis of strained alkenes. The method is often complicated by a competing process in which the incipient alkene is trapped by nucleophilic addition of the base. Recent studies have shown that the bi-molecular side reactions can be avoided when bases such as potassium tert-but-oxide are supported on an inert surface like silica gel and the reaction is carried out in vacuo. This vacuum gas-solid reaction (VGSR) procedure has the additional advantage that very unstable species may be isolated under conditions that allow detailed studies of their physical and chemical properties. The scope of this procedure has been extended to include the use of fluoride salts supported on glass helices to effect the elimination of β-halosilanes. The fluoride route to strained alkenes is particularly attractive since the reaction may be carried out at very moderate temperatures and the starting materials are readily available. This review describes the development of this vacuum gas-phase procedure and its application in the synthesis and characterization of small-ring alkenes and bicycloalkenes, including methylene-cyclopropene, spiropentadiene, bicyclo-propenyls, 1,2- and 1,3-bridged cyclo-propenes, and other simple cyclo-propenes.     

双功能TiSn-Beta分子筛限域的串联Lewis酸催化烯烃生成1,2-二醇

1,2-二醇主要由环氧化合物水合产生、广泛用于防冻剂,聚酯树脂和医药等化学品中间体的生产.研究表明,具有Lewis酸性的含锡沸石分子筛在环氧化物的水合反应中表现出优异的催化性能.环氧化合物是众所周知的碳亲电体之一,主要由烯烃环氧化生成.含Ti(Ⅳ)沸石,如Ti-Beta和TS-1,是烯烃环氧化反应的高效催化剂.串联催化可以将多步反应整合为一次反应,无需分离中间体,有效缩短合成路线,提高生产效率.因此,双功能Ti和Sn分子筛有望应用于烯烃制二醇的串联催化反应中,即烯烃在Ti活性位点上发生环氧化反应,随后在Sn位点上发生水合反应,进而串联一步生成1,2-二醇.在沸石分子筛中产生孤立的多功能活性位点是将多步反应整合成串联催化反应的一种有吸引力的设计策略.本文通过简单且可规模制备的后合成路线构建了双功能TiSn-Beta分子筛,并用于烯烃串联催化制1,2-二醇反应.一方面,该反应中的过氧化氢溶液既能提供氧化剂(如H2O2)用于烯烃环氧化反应,又能提供环氧化合物水合反应的亲核试剂(如H2O);同时TiSn-Beta作为一种高效双功能催化剂,孤立的Ti和Sn活性中心可以有效地将烯烃环氧化反应和环氧化物水合反应串联在沸石微反应器中,实现烯烃一步转化为1,2-二醇.另一方面,沸石的限域效应较好地保证了烯烃环氧化和环氧化物水合的高串联速率和目标产物的高选择性,在最优的反应条件下,1,2-二醇选择性高达90%以上,收率接近70%.本文结果表明沸石分子筛是构筑多功能孤立活性位点的理想载体,为其他串联反应催化剂的设计提供了良好的借鉴.     

Highly stereoselective method to prepare bis-phenylchalcogen alkenes via addition of chalcogenolate to phenylseleno alkynes

The preparation of bis-phenylchalcogen alkenes starting from phenylseleno alkynes is described. The nucleophilic species of selenium, tellurium and sulfur were generated in situ from the reaction of the respective diphenyl dichalcogenide with NaBH₄ in PEG-400 as solvent. The chalcogenolate anions were efficiently and selectively added to a variety of phenylselenoalkynes at mild conditions, furnishing the respective (Z)-1,2-bis-phenylchalcogen alkenes in good yields.     

Integrating aryl chlorides into nickel-catalyzed 1,1-difunctionalization of alkenes

Difunctionalization of alkenes have developed into an important type of reactions for rapidly and efficiently assemble complex molecules. While extensive advancements have been achieved by the assistance of transition metal catalysis, the employment of cheap, abundant aryl chlorides as coupling partner is still a challenging task in this field. Herein, we report our first achievement in 1,1-difunctionalization of alkenes with aryl chlorides as coupling partners. The success is predominantly ascribed to the judicious selection of 1,2-diamine ligand. This study provides an efficient protocol for the synthesis of secondary benzyl boronates from easily accessible feedstock chemicals. Furthermore, the distinguished features of this method include excellent 1,1-regio- and chemoselectivity, good functional group tolerance and easily-operational catalytic reaction conditions.     

Silver-catalyzed decarboxylative cross-coupling of α-keto acids with alkenes giving approach to chalcones

A silver-catalyzed decarboxylative cross-coupling of α-keto acids with alkenes is reported. The method, with a wide range of substrate tolerance and mild operational conditions, can produce various chalcone derivatives in moderate to high yields from easily available starting materials.     

Solvent- and transition metal-free synthesis of spiro[cyclopropane-1,3-oxindoles] from cyclic diazoamides

A highly efficient method to synthesize spiro[cyclopropane-1,3-oxindoles] from cyclic diazoamides and mono-substituted or 1,2-disubstituted alkenes under solvent- and transition metal-free conditions is reported. The reaction offers proficient access to synthetically useful and biologically important spiro[cyclopropane-1,3-oxindoles]. The advantageous features of this sustainable method are being metal-free, shorter reaction time, cost-effectiveness, eco-friendliness and excellent yields. The selectivity and yield are comparable with transition metal-catalyzed cyclopropanation reactions.     

Divergent and Selective Light Alkene Cross-Coupling

Light olefins are abundantly manufactured in the petroleum industry and thus represent ideal starting materials for modern chemical synthesis. Selective and divergent transformations of feedstock light olefins to value-added chemicals are highly sought-after but remain challenging. Herein we report an exceptionally regioselective carbonickelation of light alkenes followed by in situ trapping with three types of nucleophiles, namely a reductant, base, or Grignard reagent. This protocol enables efficient 1,2-hydrofunctionalization, dicarbofunctionalization, and branched-selective Heck-type cross-coupling of light alkenes with aryl and alkenyl reagents to streamline access to diverse alkyl arenes and complex alkenes. Harnessing bulky N-heterocyclic carbene ligands with acenaphthyl backbones for nickel catalysts is crucial to attain high reactivity and selectivity. This strategy provides a rare, modular, and divergent platform for upgrading feedstock alkenes and is expected to find broad applications in medicinal chemistry and industrial processes.     

Synthesis of Enantioenriched 1,2-cis Disubstituted Cycloalkanes by Convergent NiH Catalysis

Enantioenriched multi-substituted cycloalkanes constitute an essential class of compounds in pharmaceuticals, natural products and agrochemicals. Here we report an NiH-catalyzed asymmetric migratory hydroalkylation process for the efficient and selective construction of such compounds. Through a dynamic kinetic asymmetric transformation (DYKAT), easily accessible racemic and isomeric mixtures of cycloalkenes could be directly utilized as starting materials, convergently producing thermo-dynamically disfavored chiral 1,2-cis disubstituted cycloalkanes bearing vicinal stereocenters with high levels of regio-, diastereo- and enantioselectivity. In addition, prochiral cyclic alkenes can be also employed, and deliver chiral 1,2-cis disubstituted cycloalkanes through desymmetrization process.     

Palladium/Copper‐Catalyzed Oxidative Arylation of Terminal Alkenes with Aroyl Hydrazides

An unprecedented oxidative arylation reaction of terminal alkenes with simple aroyl hydrazides has been developed under aerobic conditions for the stereoselective synthesis of 1,2‐disubstituted alkenes. A range of aroyl hydrazides underwent palladium/copper‐catalyzed oxidative Mizoroki–Heck reaction with terminal alkenes open to air in a 1:1 mixture of dimethyl sulfoxide and acetonitrile to give structurally diverse 1,2‐disubstituted alkenes in moderate to excellent yields with excellent regio‐ and E‐selectivity. The reaction tolerated a wide variety of functional groups, such as alkoxy, hydroxy, amino, fluoro, chloro, bromo, cyano, nitro, ester, amide, imide, phosphine oxide, and sulfone groups, and, moreover, molecular oxygen and dimethyl sulfoxide were demonstrated to serve as terminal oxidants. This study provides a useful method for the stereoselective synthesis of 1,2‐disubstituted alkenes through direct transformation of the vinylic C?H bonds in terminal alkenes.     

One-pot reductive coupling of N-acylcarbamates with activated alkenes: application to the asymmetric synthesis of pyrrolo[1,2-a]azepin-5-one ring system and (-)-xenovenine

The one-pot reductive coupling of N-acylcarbamates with activated alkenes is described. The method is based on partial reduction of N-acylcarbamates with DIBAL-H, followed by N-acyliminium ion formation and SmI(2)-mediated radical coupling with activated alkenes. Both acyclic and cyclic N-acylcarbamates can be used as stable substrates, and a range of activated alkenes serve as effective radical receptors. The reductive coupling of l-N-acylcarbamates 12/13 gave 2,5-disubstituted pyrrolidine derivatives in high trans-diastereoselectivities. The reductive coupling with penta-2,4-dienoate proceeded exclusively in a 1,6-addition fashion, producing a single non-conjugated E-isomer. On the basis of this method, a three-step construction of pyrrolo[1,2-a]azepin-5-one 16, the skeleton of many stemona alkaloids and lehmizidine alkaloids, and a seven-step synthesis of (-)-xenovenine (pyrrolizidine cis-223H, ent-6), the unnatural enantiomer of the frog/ant venom alkaloid possessing potent inhibitory activity towards nAChR channel, were achieved starting from L-12.     

Asymmetric dihydroxylation reactions leading to novel chiral ferrocene derivatives

Several ferrocenyl alkenes were used as starting materials for asymmetric dihydroxylation reactions. Although they turned out to be unreactive employing Sharpless' standard conditions, by systematic variation of the reaction conditions the desired novel ferrocenyl diols could be obtained in good yields and in enantiomeric excesses up to >99%.     

Photoredox-Catalyzed Addition of Carbamoyl Radicals to Olefins: A 1,4-Dihydropyridine Approach

Functionalization with C1-building blocks are key synthetic methods in organic synthesis. The low reactivity of the most abundant C₁-molecule, carbon dioxide, makes alternative carboxylation reactions with CO₂-surrogates especially important. We report a photoredox-catalyzed protocol for alkene carbamoylations. Readily accessible 4-carboxamido-Hantzsch esters serve as convenient starting materials that generate carbamoyl radicals upon visible light-mediated single-electron transfer. Addition to various alkenes proceeded with high levels of regio- and chemoselectivity.     

Palladium-catalyzed convenient one-pot synthesis of multi-substituted 2-pyrones via transesterification and alkenylation of enynoates

An efficient one-pot protocol for the synthesis of multi-substituted 2-pyrone derivatives from internal alkynes and unactivated alkenes is reported. The methodology involves difunctionalization of internal alkynes by using Pd(II) as a catalyst alongwith X-Phos as ligand via 6-endo transesterification and subsequent alkenylation pathway. Notable features include simple and easily available starting materials, including a range of unactivated alkenes, reduced synthetic steps and mild reaction conditions with high efficiency.     

Transition-metal-free catalysts for the sustainable epoxidation of alkenes: from discovery to optimisation by means of high throughput experimentation

Transition-metal-free oxides were studied as heterogeneous catalysts for the sustainable epoxidation of alkenes with aqueous H?O? by means of high throughput experimentation (HTE) techniques. A full-factorial HTE approach was applied in the various stages of the development of the catalysts: the synthesis of the materials, their screening as heterogeneous catalysts in liquid-phase epoxidation and the optimisation of the reaction conditions. Initially, the chemical composition of transition-metal-free oxides was screened, leading to the discovery of gallium oxide as a novel, active and selective epoxidation catalyst. On the basis of these results, the research line was continued with the study of structured porous aluminosilicates, gallosilicates and silica-gallia composites. In general, the gallium-based materials showed the best catalytic performances. This family of materials represents a promising class of heterogeneous catalysts for the sustainable epoxidation of alkenes and offers a valid alternative to the transition-metal heterogeneous catalysts commonly used in epoxidation. High throughput experimentation played an important role in promoting the development of these catalytic systems.     

Modular and Practical 1,2-Aryl(Alkenyl) Heteroatom Functionalization of Alkenes through Iron/Photoredox Dual Catalysis**

Efficient methods for synthesizing 1,2-aryl(alkenyl) heteroatomic cores, encompassing heteroatoms such as nitrogen, oxygen, sulfur, and halogens, are of significant importance in medicinal chemistry and pharmaceutical research. In this study, we present a mild, versatile and practical photoredox/iron dual catalytic system that enables access to highly privileged 1,2-aryl(alkenyl) heteroatomic pharmacophores with exceptional efficiency and site selectivity. Our approach exhibits an extensive scope, allowing for the direct utilization of a wide range of commodity or commercially available (hetero)arenes as well as activated and unactivated alkenes with diverse functional groups, drug scaffolds, and natural product motifs as substrates. By merging iron catalysis with the photoredox cycle, a vast array of alkene 1,2-aryl(alkenyl) functionalization products that incorporate a neighboring azido, amino, halo, thiocyano and nitrooxy group were secured. The scalability and ability to rapid synthesize numerous bioactive small molecules from readily available starting materials highlight the utility of this protocol.     

Visible Light Induced Three-Component 1,2-Dicarbofunctionalization of Alkenes and Alkynes

Harnessing visible-light in organic synthesis is one of the most effective methods that aligns with green and sustainable chemistry principles and hence skyrocketed in the last two decades. Similarly, three-component 1,2-dicarbofunctionalization of alkenes and alkynes has recently been a great choice to construct complex molecular systems in an easy and rapid manner. Therefore, light-induced reactions can be an excellent alternative to carry out 1,2-dicarbofunctionalization reactions, and very recently, organic chemists across the globe have fascinated us with their interesting articles. In this present review, we have summarized the recent advancements in the area of visible light induced three-component 1,2-dicarbofunctionalization of alkenes and alkynes till March 2023. We have categorized the discussion based on the catalysts used to carry out the transformations for better understanding and different important aspects of these transformations have also been covered.     

Synthesis of trisubstituted isoxazoles via in situ trapping strategy from α-nitro carbonyl compounds and methyl ketones or terminal aryl alkenes

A highly efficient domino method for the synthesis of trisubstituted isoxazoles has been established from α-nitro carbonyl compounds and methyl ketones or terminal aryl alkenes. Simple and readily available starting materials, mild reaction conditions and very simple operation are significant advantages of the reaction.     

TBAF-mediated reactions of 1,1-dibromo-1-alkenes with thiols and amines and regioselective synthesis of 1,2-heterodisubstituted alkenes

An efficient synthesis of trisubstituted alkenes including 1,2-heterodisubstituted alkenes has been described. Reactions of thiols and amines with 1,1-dibromo-1-alkenes in the presence of TBAF·3H(2)O afford (Z)-2-bromovinyl sulfides and (Z)-2-bromovinyl amines regio- and stereoselectively. The reaction proceeds under catalyst-free conditions with high efficiency. The coupling reactions of the obtained products bearing bromine atoms with phenylacetylene and phenylboronic acid gave trisubstituted alkenes in good to excellent yields. Cross-coupling with various N, O, S, and P nucleophiles selectively generated 1,2-N,O, 1,2-N,S, 1,2-S,P, 1,2-S,S, and 1,2-S,O heterodisubstituted alkenes.     

Radical Monofluoroalkylative Alkynylation of Olefins by a Docking–Migration Strategy

A radical‐mediated monofluoroalkylative alkynylation of alkenes is disclosed for the first time. The reaction demonstrates a remarkably broad substrate scope in which both activated and unactivated alkenes are suitable starting materials. The concurrent addition of an alkynyl and a monofluoroalkyl group onto an alkene proceeds through a docking–migration sequence, affording a vast array of valuable fluoroalkyl‐substituted alkynes. Many complex natural products and drug derivatives are readily functionalized, demonstrating that this method can be used for late‐stage alkynylation.