Applications carbonyl ylide

The application of 1,3-dipolar cycloaddition processes to the synthesis of substituted tetrahydrofurans has been investigated, starting from epoxides and alkenes under microwave irradiation. The epoxide 85 was rapidly converted into carbonyl ylide 86 that behaved as a 1,3-dipole toward various alkenes, leading to quantitative yields of tetrahydrofuran derivatives 87 (Scheme 30). The reactions were performed in toluene within 40 min instead of 40 h under classical conditions, without significantly altering the selectivi-ties [64]. 

As with any modern review of the chemical Hterature, the subject discussed in this chapter touches upon topics that are the focus of related books and articles. For example, there is a well recognized tome on the 1,3-dipolar cycloaddition reaction that is an excellent introduction to the many varieties of this transformation [1]. More specific reviews involving the use of rhodium(II) in carbonyl ylide cycloadditions [2] and intramolecular 1,3-dipolar cycloaddition reactions have also appeared [3, 4]. The use of rhodium for the creation and reaction of carbenes as electrophilic species [5, 6], their use in intramolecular carbenoid reactions [7], and the formation of ylides via the reaction with heteroatoms have also been described [8]. Reviews of rhodium(II) ligand-based chemoselectivity [9], rhodium(11)-mediated macrocyclizations [10], and asymmetric rho-dium(II)-carbene transformations [11, 12] detail the multiple aspects of control and applications that make this such a powerful chemical transformation. In addition to these reviews, several books have appeared since around 1998 describing the catalytic reactions of diazo compounds [13], cycloaddition reactions in organic synthesis [14], and synthetic applications of the 1,3-dipolar cycloaddition [15]. 

In more recent work, Chiu and co-workers [167, 168] have reported an intramolecular 1,3-dipolar cycloaddition approach toward the pseudolaric acids 85, in which the di-polarophile is an unactivated 1,1-disubstituted alkene. Hence, treatment of the diazo ketone 86 with catalytic Rh2(OAc)4 furnished a mixture of tricyclic products 87 and 88 in nearly equal proportions (Scheme 19.13). The synthesis of 2-pyridones [169] and their application to the ipalbidine core [170] has been described. The pentacyclic skeleton of the aspidosperma alkaloids was prepared via the cycloaddition of a push-pull carbonyl ylide [171]. The dehydrovindorosine alkaloids 89 have also been investigated, in which the a-diazo-/ -ketoester 90 undergoes a facile cycloaddition to furnish 91 in... 

Carbonyl ylides (1) are highly reactive dipoles that have been proposed as key intermediates in a variety of reactions since the 1960s (Fig. 4.1). Since these early reports, there has been a virtual explosion in the study of these unstable intermediates both at the theoretical level and more recently in their application to organic synthesis. This chapter will focus on the structure, generation, and chemical reactions of carbonyl ylides and will review the literature since 1984. 

The exact structure of carbonyl ylides has been the subject of a variety of theoretical investigations over the past few decades since their intermediacy was suggested in 1965 during the cycloaddition reaction of substituted epoxides (1). Houk et al. (2) has undertaken a detailed smdy of the carbonyl ylide structure and reactivity by the application of computational methods (Fig. 4.3). 

Carbonyl ylides can be viewed as an adduct between a carbonyl group and a carbene and, in fact, some ylides have been prepared this way (see above). The application of carbonyl ylides to the synthesis of complex natural products has been greatly advanced by the finding that stabilized carbenoids can be generated by the decomposition of ot-diazocarbonyl compounds with copper and rhodium complexes. The metallocarbenoids formed by this method are highly electrophilic on carbon and readily add nucleophiles such as the oxygen of many carbonyl derivatives to form carbonyl ylides. This type of reaction is in fact quite old with the first report being the addition of diazomalonate and benzaldehyde (33,34). 

Over the last 15 years, Padwa et al. (73,74) have been heavily involved with the study and application of carbonyl ylides as cycloaddition precursors in synthesis. Their work has helped make the tandem ylide formation-dipolar cycloaddition process a synthetically accessible transformation. Much of Padwa s early work focused on determining the extent and limitations of this methodology. Many of the early systems were carbocyclic in nature and helped define basic parameters such as... 

The last comprehensive survey of this area dates back to 1984, when the two-volume set edited by Padwa, 1,3-Dipolar Cycloaddition Chemistry, appeared. Since then, substantial gains in the synthetic aspects of this chemistry have dominated the area, including both methodology development and a body of creative and conceptually new applications of these [3+ 2]-cycloadditions in organic synthesis. The focus of this volume centers on the utility of this cycloaddition reaction in synthesis, and deals primarily with information that has appeared in the literature since 1984. Consequently, only a selected number of dipoles are reviewed, with a major emphasis on synthetic applications. Both carbonyl ylides and nitronates, important members of the 1,3-dipole family that were not reviewed previously, are now included. Discussion of the theoretical, mechanistic, and kinetic aspects of the dipolar-cycloaddition reaction have been kept to a minimum, but references to important new work in these areas are given throughout the 12 chapters. 

Mejia-Oneto JM, Padwa A (2006) Application of the Rh(II) cyclization/cycloadditi(Hi cascade for the total synthesis of (H—)-aspidophytine. Org Lett 8 3275-3278 Mejia-Oneto JM, Padwa A (2008) Total synthesis of the alkaloid (+—)-aspidophytine based on carbonyl ylide cycloaddition chemistry. Helv Chim Acta 91 285-302 Hong X, France S et al (2006) Cycloaddition protocol for the assembly of the hexacyclic framework associated with the kopsifoline alkaloids. Org Lett 8 5141-5144 Hong X, France S et al (2007) A dipolar cycloaddition approach toward the kopsifoline alkaloid framework. Tetrahedron 63 5962-5976... 

Abstract Carbon d ylide dipoles are important intermediates with great application in heterocyclic chemistry. Here, we show how the rhodium-catalyzed a-diazocarbonyl compounds are employed in the generation of carbonyl ylides and their effective use for the synthesis, as well as functionalization, of heterocycles. Herein we discuss recent advancements in this field mainly describing the synthesis and importance of various oxygen-and nitrogen-containing heterocyclic systems and natural products from a-diazocarbonyl compounds. 

The metal-catalyzed decomposition of diazo compounds in the presence of carbonyl compounds is a well-established reaction to generate a carbonyl ylide intermediate. Several new developments have revolutionized this area of chemistry and are included in this review. Most notably, major advances have occurred in catalyst design, such that highly chemoselective, diastereoselect-ive and enantioselective carbenoid transformations can now be achieved. Furthermore, it has been recognized that a wide array of carbenoid structures can be utilized in this chemistry, leading to a broad range of synthetic applications. 

Herein, a comparison is presented of the chemical differences that exist among the 1,3-dipolar cycloaddition reactions of acychc or cyclic carbonyl ylides with the major classes of dipolarophiles. It is hoped that this work will provide a useful reference and stimulate further efforts in this sphere, which has further potential for varied synthetic applications towards heterocycles and natural products. 

In another important application of this methodology, ( )-illudin M (79), a toxic sesquiterpene [91,92] isolated from the jack-o -lantern mushroom, has been synthesized [93] by Kinder and co-workers via the spirocyclic carbonyl ylide 48. Rh2 (OAc)4-mediated decomposition of or-diazo ketone 47 in the presence of cyclopentenone 77 afforded the key cycloadduct 78 as a single diastereomer, bearing the complete skeleton of the natural product. Functional group manipulations of the adduct 78 led to a total synthesis of ( )-illudin M (79) (Scheme 23). Padwa and co-workers also executed the syntheses of illudin, ptaquilosin and the closely related isodehydroilludin [78,94] using carbonyl yUdes. This carbonyl ylide cyclization-cycloaddition cascade approach (Scheme 23) has been further extended towards a short synthesis of the acylfulvenes [95], pterosin [79] and pterosin family of sesquiterpenes [96-99]. 

Similar to carbonyl ylides, azomethine ylides are normally generated as transient species in situ, and a number of protocols have been established so far [22]. Among them, the transition-metal-mediated procedures have enj oyed great privileges in terms of milder reaction conditions, better selectivities, and broad functional group tolerance. This part focuses on the recent development of transition-metal-mediated in situ generation of (metal-containing) azomethine ylides as well as their applications for the synthesis of aromatic compounds. 

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