Asymmetric Syntheses Promoted by Organoselenium Reagents

Using chiral nonracemic electrophilic-organoselenium-reagents-asymmetric alkoxy-, hydroxy-, azido- and amido-selenenylation of alkenes were effected with high diastereoselectivity. These reagents have also been employed in catalytic amounts to promote one-pot selenenylation-deselenenylation processes. The asymmetric cyclization of properly substituted alkenes diastereoselectively afforded lactons, tetrahydrofurans oxazolines, thiazolines, pyrrolidines, isoxazolidines, 1,2-oxazines, and cyclic nitrones. Enantiopure dioxane, morpholine, tetrahydrofuran, oxazolidin-2-one and aziridine derivatives were prepared from alkenes, PhSeX, and optically active nucleophiles or substrates.     

Nickel-Catalyzed Arylative Cyclizations of Alkyne- and Allene-Tethered Electrophiles using Arylboron Reagents

The use of arylboron reagents in metal-catalyzed domino addition–cyclization reactions is a well-established strategy for the preparation of diverse, highly functionalized carbo- and heterocyclic products. Although rhodium- and palladium-based catalysts have been commonly used for these reactions, more recent work has demonstrated nickel catalysis is also highly effective, in many cases offering unique reactivity and access to products that might otherwise not be readily available. This review gives an overview of nickel-catalyzed arylative cyclizations of alkyne- and allene-tethered electrophiles using arylboron reagents. The scope of the reactions is discussed in detail, and general mechanistic concepts underpinning the processes are described.     

Synthetic Aspects of Metal-Catalyzed Oxidations of Amines and Related Reactions

The metabolism of amines is governed by a variety of enzymes such as amine oxidase, flavoenzyme, and cytochrome P-450. A wide variety of compounds are produced such as ammonia and alkaloids in selective and clean oxidation reactions that proceed under mild reaction conditions. Simulation of the functions of these enzymes with simple transition metal complex catalysts may lead to the discovery of biomimetic, catalytic oxidations of amines and related compounds. Indeed, metal complex catalyzed oxidations have been found to proceed with high efficiency. The first section of this review discusses the dehydrogenative oxidations of amines with transition metal catalysts by transition metal catalysts that simulate amine oxidase. The second section highlights the catalytic oxidation of secondary amines to nitrones by simulation of flavoenzymes. The third section describes the simulation of the function of cytochrome P-450 with lowvalent ruthenium complexes and peroxides. Biomimetic ruthenium-catalyzed oxidations of tertiary amines, secondary amines, and other substrates such as amides, β-lactams, nitriles, alcohols, alkenes, ketones, and even nonactivated hydrocarbons can be performed selectively under mild conditions. These three general approaches provide highly useful strategies for synthesis of fine chemicals and biologically active compounds such as alkaloids, amino acids, and β-lactams.     

Reagents with a Crystalline Coat

Tetrakis(dimethoxyphenyl)adamantane (TDA) readily forms crystalline inclusion complexes with reactive, toxic, or malodorous reagents, such as benzoyl chloride, acetyl chloride, cyclohexyl isocyanide, phosphorus trichloride, and trimethylsilyl chloride. The crystals are stable and largely free of the problematic properties of the free reagents. When exposed to solvents such as DMSO or MeOH, the reagents react, and a large portion of the TDA precipitates. The TDA‐coated reagents may lead to a safer way of storing, handling, and delivering reagents, and ultimately to synthetic protocols that do not require fume hoods.     

Cu‐Catalyzed Asymmetric Allylic Alkylation of Phosphonates and Phosphine Oxides with Grignard Reagents

An efficient and highly enantioselective copper‐catalyzed allylic alkylation of phosphonates and phosphine oxides with Grignard reagents and Taniaphos or phosphoramidites as chiral ligands is reported. Transformation of these products leads to a variety of new phosphorus‐containing chiral intermediates.     

Enantioselective Formation of Cyano‐Bearing All‐Carbon Quaternary Stereocenters: Desymmetrization by Copper‐Catalyzed N‐Arylation

The enantioselective construction of all‐carbon quaternary stereocenters is one of the most challenging fields in asymmetric synthesis. An asymmetric desymmetrization strategy offers an indirect and efficient method for the formation of all‐carbon stereocenters. An enantioselective formation of cyano‐bearing all‐carbon quaternary stereocenters in 1,2,3,4,‐tetrahydroquinolines and 2,3,4,5‐tetrahydro‐1H‐benzo[b]azepines by copper‐catalyzed desymmetric N‐arylation is demonstrated. The cyano group at the prochiral center plays a key role for the high enantioselectivity and works as an important functional group for further transformations. DFT studies provide a model which successfully accounts for the origin of enantioselectivity.     

Towards the Design of New Materials: Regio- and Stereoselective (Cyclo-) Polymerization of 1-Alkynes and 1,6-Heptadiynes

Summary. The metathesis polymerization, respectively cyclopolymerization, of 1-alkynes and 1,6-heptadiynes using well-defined group VIA transition metal initiators is summarized. For purposes of comparison, selected quaternary catalytic systems used as alternatives as well as the properties of the resulting materials will be presented. Special consideration is given to the mechanistic advancements that have been made during the last decade, which allow the tailor-made synthesis of conjugated materials with interesting optical and electronic properties. E-mail: michael.r.buchmeiser@uibk.ac.at Received November 20, 2002; accepted November 21, 2002     

Stereoselective Synthesis of Functionalized 1,3-Enynes through Recyclable Copper(I)-Catalyzed Three-Component Reaction of Terminal Alkynes,Diazoesters and Aldehydes

A highly efficient heterogeneous copper(I)-catalyzed three-component coupling of terminal alkynes, diazoesters and aldehydes has been achieved by using 10 mol% of copper(I) iodide complex [N,N-CuI-MCM-41] anchored on 2-aminoethylamino-modified mesoporous material MCM-41 as the catalyst under mild conditions, delivering a wide variety of 2-alkoxycarbonyl-substituted (E)-1,3-enynes in mostly good to high yields with excellent stereoselectivity. The heterogenized copper(I) complex can be facilely prepared from inexpensive reagents by using a simple procedure and exhibits a remarkably higher catalytic activity than CuI, and can be recycled more than ten times without a significant drop in its catalytic efficiency. This protocol represents the first example of heterogeneous copper-catalyzed stereoselective construction of functionalized 1,3-enynes from simple and commercially available starting materials.     

Copper‐Catalyzed Alkynylboration of Alkenes with Diboron Reagents and Bromoalkynes

An efficient method for the synthesis of homopropargylboronates by copper‐catalyzed alkynylboration of alkenes with diboron reagents and bromoalkynes has been developed. The alkynylboration reaction features high selectivity and efficiency, mild reaction conditions, wide substrate scope, and functional‐group compatibility, and is a highly attractive complement to existing methods for the synthesis of homopropargylboronates. Both the boryl and alkynyl groups are good potential functional groups for the subsequent manipulations that provide access to a variety of important molecule structures.     

Hetero-aggregate compounds of aryl and alkyl lithium reagents: a structurally intriguing aspect of organolithium chemistry

Organolithium compounds are often depicted as mononuclear species. However, such compounds are in fact aggregated species and can form hetero-aggregates containing different organic groups, including heteroatom groups. In reactions involving organolithium reagents, the "pure" homo-aggregate organolithium compound can change into a hetero-aggregate, which has a different structure and reactivity to the homo-aggregate. This fact is often overlooked. When there are chiral centers in the organolithium reagent or the substrate, diastereoselective self-assembly (the preferential formation of a particular diastereoisomeric aggregate) plays a role. The importance of these contributions in understanding the structure and reactivity patterns of organolithium reagents is the focus of this Minireview.     

The Regio‐ and Stereoselective Synthesis of trans‐2,3‐Dihydropyridine N‐oxides and Piperidines

Reactivity N? Own : Pyridine N‐oxides can be used for the complete regio‐ and stereoselective synthesis of trans‐substituted piperidines. The sequential addition of Grignard reagents and aldehydes or ketones to pyridine N‐oxides yields a complete regio‐ and stereoselective trans 2,3‐addition reaction in high yields, and the substituted 2,3‐dihydropyridine N‐oxide can be reduced to form 2,3‐trans‐substituted piperidines (see scheme).

     

Regiocontrolled and Stereoselective Syntheses of Tetrahydrophthalazine Derivatives using Radical Cyclizations

Tetrahydrophthalazine derivatives have found important applications in pharmaceutical research, but existing synthetic methods are unable to access them regio- and stereoselectively. Here, a new approach is presented that addresses these challenges by utilizing a 6-endo-trig radical cyclization in the key step. The desired tetrahydrophthalazines can be accessed in high yields (55–98 %) and high diastereoselectivities for the trans-product (>95:5) starting either from readily accessible hydrazones, or from the corresponding aldehydes and substituted Boc-hydrazides in a one-pot process. The synthetic versatility of the tetrahydrophthalazine core was demonstrated by its straightforward conversion to dihydro-phthalazines, phthalazines, or pyrazolo dione derivatives. Furthermore, the N−N bond was reduced to afford a new route to 1,4-diamines.     

Copper-Catalyzed Addition of Grignard Reagents to in situ Generated Indole-Derived Vinylogous Imines

Chiral indole derivatives are ubiquitous motifs in pharmaceuticals and alkaloids. Herein, the first protocol for catalytic asymmetric conjugate addition of Grignard reagents to various sulfonyl indoles, offering a straightforward approach for the synthesis of chiral 3-sec-alkyl-substituted indoles in high yields and enantiomeric ratios is presented. This methodology makes use of a chiral catalyst based on copper phosphoramidite complexes and in situ formation of vinylogous imine intermediates.     

Selective Synthesis by Use of Lewis Acids in the Presence of Organocopper and Related Reagents. New Synthetic Methods (61)

Organometallic compounds with pronounced nucleophilicity such as organocopper and organolithium compounds, and powerful electrophiles, such as BF₃ and AlCl₃, are generally thought to be incompatible under normal, homogeneous reaction conditions. As a matter of course, it is anticipated that the two species cannot coexist and undergo transmetalation reactions. To our surprise, however, RCu and BF₃ are compatible at low temperature. RCu·BF₃ and related organocopper-Lewis acid reagents exhibit new and unique reactivities and selectivities: in conjugate additions, e.g., not only activation but also high regio-, stereo-, and chemo-selectivity as well as very high asymmetric induction is observed; allylic derivatives are alkylated regioselectively, and reaction towards carbonyl groups, imines, epoxides, aziridines, ethers, acetals, orthoformates, and pyridinium salts is in each case found to be selective. RLi·BF₃ and related organolithium-Lewis acid reagents also exhibit noteworthy selectivities and reactivities. These complex reagents are utilized in the key steps of the total synthesis of many important natural products, such as certain terpenes, steroids, and alkaloids.     

Synthesis of Trisubstituted Ureas by a Multistep Sequence Utilizing Recyclable Magnetic Reagents and Scavengers

Unprecedented magnetic borohydride exchange (mBER), magnetic Wang aldehyde (mWang) and magnetic amine resins were prepared from highly magnetic polymer‐coated cobalt or iron nanoparticles. Microwave irradiation was used to obtain excellent degrees of functionalization (>95 %) and loadings (up to 3.0 mmol g^?1) in short reaction times of 15 min or less. A small library of ureas and thioureas was synthesized by the exclusive application of these magnetic resins. As a first step, a reductive amination of aromatic and aliphatic aldehydes was carried out with mBER. The excess of primary amine needed to complete the reaction was subsequently scavenged selectively by mWang. Simple magnetic decantation from the resins resulted in secondary amines in good to excellent yields and purities. The used magnetic resins were efficiently regenerated and reused for the next run. In a second step, the secondary amines were converted to trisubstituted (thio)ureas in excellent yields and purities by stirring with an excess of iso(thio)cyanate, which was scavenged by addition of the magnetic amine resin after completion of the reaction. The whole reaction sequence is carried out without any purification apart from magnetic decantation; moreover, conventional magnetic stirring can be used as opposed to the vortexing required for polystyrene resins.     

Highly Regio- and Stereoselective Synthesis of Mannose-Containing Oligosaccharides with Acetobromo Sugars as the Donors and Partially Protected Mannose Derivatives as the Acceptors via Sugar Orthoester Intermediates

An orthoester formation/rearrangement sequence , in which 1,2-O-ethylidenated mannose or partially protected mannosides function as the glycosyl acceptors and simple acetobromo sugars as the glycosyl donors (see reaction scheme), provides an efficient and highly regio- and stereoselective route to mannose-containing 1→6, 1→3, and 3,6-branched oligosaccharides with exclusive 1,2-trans linkage.