DFT study of the mechanism of Cu(I)-catalyzed and uncatalyzed intramolecular cyclopropanation of iodonium ylides

The mechanism of the Cu(I)-catalyzed and uncatalyzed intramolecular cyclopropanation of ketoesteric and diesteric iodonium ylides has been thoroughly explored by means of electronic structure calculation methods (DFT). All crucial reaction steps encapsulated in the entire catalyzed and uncatalyzed reaction pathways were scrutinized, while the elementary steps, the intermediates and transition states were identified through monitoring the geometric and energetic reaction profiles. It was found that CuCl efficiently catalyze the cyclopropanation of iodonium ylides only for their diesteric derivatives and their diazo analogues via stabilization of the respective carbene upon complexation with the metal center. For the ketoesteric iodonium ylides the CuCl catalyst does not affect the kinetics of the intramolecular cyclopropanation reactions which could proceed easily without the catalyst, in line with available experimental observations.     

Design, preparation, X-ray crystal structure, and reactivity of o-alkoxyphenyliodonium bis(methoxycarbonyl)methanide, a highly soluble carbene precursor

The preparation, X-ray structure, and reactivity of new, highly soluble, and reactive iodonium ylides derived from malonate methyl ester and bearing an ortho substituent on the phenyl ring are reported. These new reagents show higher reactivity than common phenyliodonium ylides in the Rh-catalyzed cyclopropanation, C-H insertion, and transylidation reactions under homogeneous conditions.     

Synthesis of Substituted Pyrido[1,2-a]benzimidazoles by Ruthenium-Catalyzed C−H Bond Activation and Tandem Cyclization of 2-Arylimidazo[1,2-a]pyridines with Iodonium Ylides

Ruthenium-catalyzed C−H bond activation and tandem cyclization of 2-arylimidazo[1,2-a]pyridines with iodonium ylides proceed efficiently. For the first time, the easily available iodonium ylides and inexpensive ruthenium complex were employed to synthesize pyrido[1,2-a]benzimidazole derivatives in good yields under simple and easy-to-operate conditions. Several primary mechanism investigations and synthetic applications involving gram-scale preparation, derivatization reactions and the transformation of iodonium ylide generated in situ have also been conducted.     

Organohypervalent iodine: development, applications, and future directions

The synthetic utility of organohypervalent iodine reagents will be illustrated by their use in the alpha-hydroxydimethylacetal formation reaction from enolizable ketones, alpha-hydroxylation, alpha-tosyloxylation, alpha-alkoxylation and arylation of ketones, carbon-carbon bond formation, and intramolecular cyclopropanation using iodonium ylides. The uses of these reagents in the Hunsdiecker reaction of carboxylic acids and Hofmann rearrangement of carboxamides is presented. Specific transformation in the cubane series are discussed. The syntheses of a wide range of heterocycle structures are also presented. A unifying pathway for virtually all these diverse reactions is offered; the central features being initial attack at the iodonium center, ligand coupling, with reductive elimination of iodobenzene to yield the product.     

1,2]- or [2,3]-rearrangement of onium ylides of allyl and benzyl ethers and sulfides via in situ-generated iodonium ylides

Iodonium ylides, generated in situ with bisacetoxyiodobenzene, are converted to allyl- or benzyl-substituted oxonium or sulfonium ylides via rhodium- or copper-catalyzed carbene transfer. Except for the S-benzyl example, the resulting ylides undergo rearrangement to the corresponding 2-substituted heterocycles. This demonstrates the first use of iodonium ylides as diazoketone surrogates for the generation and rearrangement of onium ylide intermediates. This abbreviated one-step method proceeds in comparable yields relative to the corresponding two-step route employing diazoketone intermediates.     

Asymmetric synthesis of cyclopropyl phosphonates using chiral terpenyl sulfonium and selenonium ylides

The asymmetric cyclopropanation of a vinylphosphonate using optically active sulfonium and selenonium ylides derived from (−)-menthol and (+)-limonene was developed. The ylides were generated in situ by the reaction of the corresponding sulfonium or selenonium salt in the presence of potassium carbonate or DBU as a base. The transfer of the CHPh and CHCO₂Et groups into the cyclopropane ring showed moderate diastereoselectivity and excellent enantioselectivity (up to 99:1) for the trans- and cis-products. The absolute configuration of phenyl cyclopropyl was assigned based on comparison to their tolyl analogues.     

Metal-free intramolecular cyclopropanation of alkenes through iodonium ylide methodology

Intramolecular cyclopropanation of alkenes occurs thermally with iodonium ylides in the absence of conventional metal catalysts such as Rh(II) and Cu(II). In rigid molecular systems conversions are near quantitative. A mechanism is proposed involving formal 2+2 cycloaddition followed by reductive elimination of PhI to yield the cyclopropane.     

An improved synthesis of cyclopropanes from stabilized phosphonates and 1,2-dioxines

Addition of stabilized Horner-Wadsworth-Emmons (HWE) phosphonates to substituted 1,2-dioxines leads to diastereomerically pure di- and trisubstituted cyclopropanes in high yields and represents a viable alternative to ylides in the cyclopropanation reaction involving 1,2-dioxines. While yields are comparable, reaction times with these stabilized phosphonates were accelerated and the diastereoselectivity for this cyclopropanation reaction was significantly greater than for the previously reported examples employing ylides.     

Formal Asymmetric (4+1) Annulation Reaction between Sulfur Ylides and 1,3‐Dienes

A highly enantioselective synthesis of functionalized cyclopentanoids by a formal asymmetric (4+1) annulation strategy was developed. The methodology consists of a stereoselective cyclopropanation reaction between chiral sulfur ylides and 1,3‐dienes followed by a, in situ, stereospecific MgI₂‐catalyzed rearrangement of vinylcyclopropanes. This method is distinguished by a remarkable compatibility with functional groups and a high stereocontrol.     

Scope and limitations of cyclopropanations with sulfur ylides

The rates of the reactions of the stabilized and semistabilized sulfur ylides 1a-g with benzhydrylium ions (2a-e) and Michael acceptors (2f-v) have been determined by UV-vis spectroscopy in DMSO at 20 °C. The second-order rate constants (log k(2)) of these reactions correlate linearly with the electrophilicity parameters E of the electrophiles 2 as required by the correlation log k(2) = s(N + E), which allowed us to calculate the nucleophile-specific parameters N and s for the sulfur ylides 1a-g. The rate constants for the cyclopropanation reactions of sulfur ylides with Michael acceptors lie on the same correlation line as the rate constants for the reactions of sulfur ylides with carbocations. This observation is in line with a stepwise mechanism for the cyclopropanation reactions in which the first step, nucleophilic attack of the sulfur ylides at the Michael acceptors, is rate determining. As the few known pK(aH) values for sulfur ylides correlate poorly with their nucleophilic reactivities, the data reported in this work provide the first quantitative approach to sulfur ylide reactivity.     

Enantioselective organocatalytic cyclopropanations. The identification of a new class of iminium catalyst based upon directed electrostatic activation

A new method for enantioselective organocatalytic cyclopropanation is described. This study outlines the identification of a new class of iminium catalyst based on the concept of directed electrostatic activation (DEA). This novel organocatalytic mechanism exploits dual activation of ylide and enal substrates through a proposed electrostatic activation and stereodirected protocol. Formation of trisubstituted cyclopropanes with high levels of enantio- and diastereoinduction is accomplished for a variety of alpha,beta-unsaturated aldehydes and sulfonium ylides. In addition, mechanistic studies have found that this cyclopropanation reaction exhibits enantioselectivity and reactivity profiles that are in accord with the proposed DEA step.     

Direct Cyclization of Tertiary Aryl Amines with Iodonium Ylides

Described herein is a direct cyclization of simple tertiary aryl amines with iodonium ylides leading to a broad range of N‐heterocycles. Completely different from the known reactivity of iodonium ylides, the finding reported herein is that an iodonium ylide is capable of cleaving a C(sp³)−H bond and accepting two hydrogen atoms of a tertiary aryl amine, thus inducing a novel cyclization process. This transformation can proceed without the assistance of a transition‐metal catalyst and eliminates the need for the premodification of the amine or the use of an additional initiator/oxidant.     

Reaction of unstabilized iodonium ylides with organoboranes

[reaction: see text] Exposure of monocarbonyl iodonium ylides, generated by the ester exchange of (Z)-(2-acetoxyvinyl)-lambda(3)-iodanes with EtOLi, to organoboranes results in a 1,2-shift of a carbon ligand from boron to the ylide carbons, which probably generates hitherto uncharacterized alpha-boryl ketones.     

A Facile Synthesis of Bicyclo[4,1, O]Heptan-2-ones by Telluronium Ylides

The cyclopropanation reaction of cyclohexenones with telluronium ylides was studied. The products were proved to be the derivatives of bicyclo[4, 1, 0]heptan-2-one.     

Divergent and Chemoselective Transformations of Thioamides with Designed Carbene Equivalents

The reactions of thioamides with ortho-nitro-substituted iodonium ylides proceeded under mild conditions to give enaminones or thiazoles, depending on the iodonium ylide used. This protocol allowed the use of protic solvents, including aqueous solutions, and therefore coupling reactions with complex molecules such as peptides or steroids were possible. A mild and efficient method for the synthesis of various iodonium ylides was established. DFT calculations suggested that the halogen bonding between a thioamide and iodonium ylide was important in this chemoselective coupling reaction. The potential use of enaminones conjugated with pharmaceuticals as prodrugs was also demonstrated.     

A quantum chemical study of the interaction of carbenes with 2-alkenylfurans and thiophenes

The study of the interaction mechanism of monoalkenyl-substituted furans and thiophenes with carbenes was performed by AM 1 and MNDO methods. The energy profiles of two pathways were calculated, one leading to ylide formation and the second to cyclopropanation species. The insertion of methyl groups into the vinyl fragment does not change the energetic parameters of path 1. The reactivity of the exocyclic double bond was shown to depend on the degree of substitution. The calculations prove the presence of the intermediate ylide formation, based on experimental data. The stability of the ylides is determined by the heights of the cycloaddition barrier and the one of the reversed reaction 1 as shown by calculations.     

Single‐Electron‐Transfer (SET)‐Induced Oxidative Biaryl Coupling by Polyalkoxybenzene‐Derived Diaryliodonium(III) Salts

Metal‐free oxidative C? C coupling by using polyalkoxybenzene‐derived diaryliodonium(III) salts as both the oxidant and aryl source has been developed. These salts can induce single‐electron‐transfer (SET) oxidation to yield electron‐rich arenes and subsequently transfer the polyalkoxyphenyl group into in situ generated aromatic radical cations to produce biaryl products. The reaction is promoted by a Lewis acid that activates the iodonium salts. It has been revealed that the reactivity of the salts under acidic conditions is quite different to their known behavior under basic conditions. The reactivity preference of a series of iodonium salts in the SET oxidation and their ligand transfer abilities have been systematically investigated and the results are summarized in this report.     

Fused dihydrofurans from the one-pot,three-component reaction of 1,3-cyclohexanedione,iodobenzene diacetate and alkenes

The one-pot, three-component reactions of substituted 1,3-cyclohexanediones, iodobenzene diacetate and alkenes, under photochemical activation, yields fused dihydrofuran derivatives in good yield via the in situ formation of iodonium ylides.     

原位生成的烯丙基磷叶立德与醛的化学反应性研究

介绍了我们小组最近有关原位生成的烯丙基磷叶立德与醛的化学反应性研究结果.在化学计量叔膦作用下,烯丙基碳酸酯或联烯酸酯经原位生成的烯丙基磷叶立德活性中间体,与醛发生高度立体选择性的三组分Wittig烯化反应和vinylogous Wittig烯化反应,该类反应为合成多取代1,3-二烯衍生物提供了简单、高效的新方法;在催化量叔膦作用下,γ-甲基联烯酸酯经烯丙基磷叶立德关键中间体与醛发生多个膦催化的环化反应,为五元、六元含氧杂环化合物的合成提供了原子经济性的方法.通过氘代实验和核磁跟踪等方法,对上述反应机理进行了初步探索.     

Alkenyl C-H insertion of iodonium ylides into pyrroles: studies toward the total syntheses of tolmetin and amtolmetin guacil

The thermal-catalyzed or photochemical reaction of iodonium ylides with pyrroles yields exclusively alpha-substituted pyrroles in moderate to good yields. [reaction: see text]