Alkyne-alkene-carbonyl cycloaddition

This formal [2h-2h-2] alkyne/alkene/carbonyl cycloaddition proceeds through the opening of the cyclopropyl carbene intermediate 1-4 by the carbonyl group to form oxonium cation 1-5, which undergoes nucleophilic attack by the vinylgold intermediates in a Prins-type cyclization to give tetrahydropyranyl cation 1-6. 

A second category of silene reactions involves interactions with tt-bonded reagents which may include homonuclear species such as 1,3-dienes, alkynes, alkenes, and azo compounds as well as heteronuclear reagents such as carbonyl compounds, imines, and nitriles. Four modes of reaction have been observed nominal [2 + 2] cycloaddition (thermally forbidden on the basis of orbital symmetry considerations), [2 + 4] cycloadditions accompanied in some cases by the products of apparent ene reactions (both thermally allowed), and some cases of (allowed) 1,3-dipolar cycloadditions. 

Interaction of a carbonyl group with an electrophilic metal carbene would be expected to lead to a carbonyl ylide. In fact, such compounds have been isolated in recent years 14) the strategy comprises intramolecular generation of a carbonyl ylide whose substituent pattern guarantees efficient stabilization of the dipolar electronic structure. The highly reactive 1,3-dipolar species are usually characterized by [3 + 2] cycloaddition to alkynes and activated alkenes. Furthermore, cycloaddition to ketones and aldehydes has been reported for l-methoxy-2-benzopyrylium-4-olate 286, which was generated by Cu(acac)2-catalyzed decomposition of o-methoxycarbonyl-m-diazoacetophenone 285 2681... 

Abstract The transition metal mediated conversion of alkynes, alkenes, and carbon monoxide in a formal [2 + 2+1] cycloaddition process, commonly known as the Pauson-Khand reaction (PKR), is an elegant method for the construction of cyclopentenone scaffolds. During the last decade, significant improvements have been achieved in this area. For instance, catalytic PKR variants are nowadays possible with different metal sources. In addition, new asymmetric approaches were established and the reaction has been applied as a key step in various total syntheses. Recent work has also focused on the development of CO-free conditions, incorporating transfer carbonylation reactions. This review attempts to cover the most important developments in this area. 

Isosydnones (146) react with alkynes to give pyrazoles (150). For example, 4,5-diphenylisosydnone (146, R = R = Ph) and ethyl phenyl propiolate gives 4-ethoxycarbonyl-l,3,5-triphenylpyrazole (150, R = R = R = Ph, R = CO Et) identical with the product from 4,5-diphenylsydnone (1, R = R = Ph). The rate of 1,3-cycloaddition for isosydnones (146) is relatively slow in comparison with sydnones (1).2o, 04 number of other cycloaddition reactions of isosydnones with alkenes, alkynes, and carbonyl compounds have been reported. ... 

Metal complexes enable one to employ molecules that are thermally unreactive toward cycloadditions by taking advantage of their ability to be activated through complexation. Most of the molecules activated by transition-metal complexes involve C-C unsaturated bonds such as alkynes, alkenes, 1,3-dienes, allenes, and cyclopropanes. In contrast, carbonyl functionalities such as aldehydes, ketones, esters, and imines seldom participate in transition-metal-catalyzed carbonylative cycloaddition reactions. Recently, such a transformation was reported via the use of ruthenium complexes. 

Among the carbonylative cycloaddition reactions, the Pauson-Khand (P-K) reaction, in which an alkyne, an alkene, and carbon monoxide are condensed in a formal [2+2+1] cycloaddition to form cyclopentenones, has attracted considerable attention [3]. Significant progress in this reaction has been made in this decade. In the past, a stoichiometric amount of Co2(CO)8 was used as the source of CO. Various additive promoters, such as amines, amine N-oxides, phosphanes, ethers, and sulfides, have been developed thus far for a stoichiometric P-K reaction to proceed under milder reaction conditions. Other transition-metal carbonyl complexes, such as Fe(CO)4(acetone), W(CO)5(tetrahydrofuran), W(CO)5F, Cp2Mo2(CO)4, where Cp is cyclopentadienyl, and Mo(CO)6, are also used as the source of CO in place of Co2(CO)8. There has been significant interest in developing catalytic variants of the P-K reaction. Rautenstrauch et al. [4] reported the first catalytic P-K reaction in which alkenes are limited to reactive alkenes, such as ethylene and norbornene. Since 1994 when Jeong et al. [5] reported the first catalytic intramolecular P-K reaction, most attention has been focused on the modification of the cobalt catalytic system [3]. Recently, other transition-metal complexes, such as Ti [6], Rh [7], and Ir complexes [8], have been found to be active for intramolecular P-K reactions. 

The reaction was first reported by Khand and Pauson et al. in 1973d It is the dicobalt octacarbonyl [Co2(CO)8l mediated or promoted one-step synthesis of a,p-unsaturated cyclopentenone from the [2+2+1] cycloaddition of alkyne, alkene and carbon monoxide, through an intermediate of alkynedicobalt hexacarbonyl complex. Therefore, this reaction is generally known as the Pauson-Khand reaction, Pauson-Khand cyclization, or Pauson-Khand cycloaddition. Occasionally, this reaction is also referred to as the Pauson-Khand annulation, Pauson-Khand multicomponent cycloaddition, Pauson-Khand carbonylative cocyclization, Pauson-Khand bicyclization, Khand annulation, Khand cycloaddition, Khand cyclization (cyclisation ), or Khand reaction.Among these names, the Pauson-Khand reaction is the one used most often. 

Murakami et al. reported a nickel-catalyzed alkyne/alkene insertion reaction into a C(carbonyl)-C(sp ) bond of cyclobutanones [21] and applied it to the enantioselective synthesis of benzobicyclo[2.2.2]octenones (Scheme 8.4) [22]. [2-f2] Cycloaddition of 1,2-divinylbenzene 24 with dichloroketene followed by... 

An extensive review of the synthesis of a wide variety of five-membered heterocyclic compounds, via the formal 3-1-2-cycloaddition reactions of aziridines with alkenes, alkynes, nitriles, carbonyl groups, and heterocumulenes, has been presented." Supercritical CO2 has been used as the solvent in the formal 3-1-2-cycloaddition reactions of A-benzyl- and A-cyclohexyl-2-benzoyl-3-phenylaziridines with allenoates to yield pyrrole derivatives." The Lewis acid-catalysed intramolecular formal 3-1-2-cycloaddition reactions of 2-methyleneaziridines with tethered alkenes or alkynes (23) yielded cw-octahydrocyclopenta[c]pyrroles (24) after reductive workup. The reaction mechanism proceeds in a stepwise manner via a 2-aminoallyl cation (Scheme The Cu(I)/DTBM-Segphos-catalysed 1,3-dipolar cycloaddition reactions of a-silylimines and activated alkenes yielded highly enriched 5-unsubstituted a-quaternary proline cycloadducts with excellent diastereo- and enantio-selectivities (73-99% The... 

Hydroxy-THISs react with electron-deficient alkynes to give nonisol-able adducts that extrude carbonyl sulfide, affording pyrroles (23). Compound 16 (X = 0) seems particularly reactive (Scheme 16) (25). The cycloaddition to benzyne yields isoindoles in low- yield. Further cyclo-addition between isoindole and benzyne leads to an iminoanthracene as the main product (Scheme 17). The cycloadducts derived from electron-deficient alkenes are stable (23, 25) unless highly strained. Thus the two adducts, 18a (R = H, R = COOMe) and 18b (R = COOMe, R = H), formed from 7, both extrude furan and COS under the reaction conditions producing the pyrroles (19. R = H or COOMe) (Scheme 18). Similarly, the cycloadduct formed between 16 (X = 0) and dimethylfumarate... 

The meso-ionic l,3-dithiol-4-ones (134) participate - in 1,3-dipolar cycloaddition reactions giving adducts of the general type 136. They show a remarkable degree of reactivity toward simple alkenes including tetramethylethylene, cyclopentene, norbomene, and norbor-nadiene as well as toward the more reactive 1,3-dipolarophilic olefins dimethyl maleate, dimethyl fumarate, methyl cinnamate, diben-zoylethylene, A -phenylmaleimide, and acenaphthylene. Alkynes such as dimethyl acetylenedicarboxylate also add to meso-ionic 1,3-dithiol-4-ones (134), but the intermediate cycloadducts are not isolable they eliminate carbonyl sulfide and yield thiophenes (137) directly. - ... 

Ester derivatives are also capable of forming carbonyl ylides and can undergo traditional cycloaddition with activated alkenes and alkynes and can even undergo reactions with heterodipolarophiles. Padwa was able to generate ester derived... 

Use orbital interaction theory to develop the orbitals of the 2-oxaallyl system, R2C— —CR2, also known as a carbonyl ylide. Show why 2-oxaallyl readily reacts with alkenes and alkyne in a 4 + 2 cycloaddition reaction (an example may be found in El-Saidi, M. Kassam, K. Pole, D. L. Tadey, T. Warkentin, J., J. Am. Chem. Soc., 1992, 114, 8751-8752). 

By analogy with the formation of dihydropyrans from unsaturated carbonyl compounds and alkenes (see Section 2.24.2.7.l(i)), the synthesis of 4//-pyrans from the [4 + 23-cycloaddition of unsaturated carbonyl compounds and alkynes would seem to offer some potential. Such a reaction has indeed proved of value, but examples are largely restricted to the use of ynamines as the dienophile (76BSF987). 

Dihydroisoxazoles with a substituent at nitrogen are most conveniently prepared by 1,3-dipolar cycloaddition of nitrones to alkenes or alkynes. Nitrones are usually prepared in situ from carbonyl compounds and /V-(alkyl)hydroxylamines (Figure 15.10). 

In recent years there has been a growing interest in the use of carbonyl ylides as 1,3-dipoles for total synthesis.127-130 Their dipolar cycloaddition to alkenic, alkynic and hetero multiple bonded dipolaro-philes has been well documented.6 Methods for the generation of carbonyl ylides include the thermal and photochemical opening of oxiranes,131 the thermal fragmentation of certain heterocyclic structures such as A3-l,3,4-oxadiazolines (141) or l,3-dioxolan-4-ones132-134 (142) and the reaction of carbenes or car-benoids with carbonyl derivatives.133-138 Formation of a carbonyl ylide by attack of a rhodium carbenoid... 

Linn and Benson discovered in 1963 the ability of tetracyanoethylene oxide (145) to react with alkenes and alkynes at elevated temperatures in [3 + 2] cycloadditions.139 The kinetics of the reaction of (145) with styrene revealed that the formation of (147) is preceded by a first-order step consisting of the electrocyclic ring opening to the carbonyl ylide (146 Scheme 33). 

Transition-metal mediated carbene transfer from 205 to benzaldehyde generates carbonyl ylides 211 which are transformed into oxiranes 216 by 1,3-cyclization, into tetrahydrofurans 212, 213 or dihydrofurans 214 by [3 + 2] cycloaddition with electron-deficient alkenes or alkynes, and 1,3-dioxolanes 215 by [3 + 2] cycloaddition with excess carbonyl compound120 (equation 67). Related carbonyl ylide reactions have been performed with crotonaldehyde, acetone and cyclohexanone (equation 68). However, the ylide generated from cyclohexanone could not be trapped with dimethyl fumarate. Rather, the enol ether 217, probably formed by 1,4-proton shift in the ylide intermediate, was isolated in low yield120. In this respect, the carbene transfer reaction with 205 is not different from that with ethyl diazoacetate121, whereas a close analogy to diazomalonates is observed for the other carbonyl ylide reactions. 

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