1.3- Dipolar cycloaddition reactions carbonyl ylides

Padwa and Prein (105,106) applied chiral, but racemic, isomiinchnone dipoles in diastereoselective 1,3-dipolar cycloadditions. The carbonyl ylide related isomiinch-none derivative rac-70 was obtained from the rhodium-catalyzed cyclization of diazo-derivative rac-69 (Scheme 12.24) (105). The reactions of the in situ formed dipole with a series of alkenes was described and in particular the reaction with maleic acid derivatives 71a-c gave rise to reaction with high selectivities. The tetracyclic products 72a-c were all obtained in good yield with high endo/ exo and diastereofacial selectivities. In another paper by the same authors, the reactions of racemic isomilnchnones having an exo-cyclic chirality was described (106). 

Muthusamy S, Gunanathan C et al (2004) Regioselective synthesis of mono- and bis-decahy-drobenzocarbazoles via tandem reactions of a-diazo ketones. Tetrahedron 60 7885-7897 Nambu H, Hikime M et al (2009) Asymmetric approach to the pentacyclic skeleton of aspidosperma alkaloids via enantioselective intramolecular 1,3-dipolar cycloaddition of carbonyl ylides catalyzed by chiral dirhodium(II) carboxylates. Tetrahedron Lett 50 3675-3678... 

Metal-carbenoid intermediates derived from diazo compoimds undergo a variety of useful reactions, including yUde formation, cyclopropanation and insertion. In recent years, several excellent reviews [1-19] and books [20-29] have appeared on various aspects of this chemistry. Several reviews on car-benoid chemistry have major sections on 1,3-dipolar cycloadditions of carbonyl ylides. Because of the historical central prominence of carbenoids derived from diazocarbonyl compounds, most reviews have tended to focus on these species. These carbenoids are capable of generating carbonyl ylide dipoles via inter- or intramolecular reactions (Fig. 1). 

The results suggest that the Lewis acid controls the stereoselectivity in the 1,3-dipolar cycloaddition of carbonyl ylides by coordination to the dipo-larophiles, as reported [105,106] for the reactions of nitrones. 

Padwa et al. have applied the 1,3-dipolar cycloaddition of carbonyl ylide 120 to cylopent-2-en-l-one to generate oxanorbomanone 121 as a 4 1 mixture of exo- and enifo-isomers. The process starts with the reaction of diazoketone 119 with Rh2(OAc)4 [155, 156] (Scheme 17). 

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]. 

Suga et al. (197) reported the first stereocontrolled 1,3-dipolar cycloaddition reactions of carbonyl ylides with electron-deficient alkenes using a Lewis acid catalyst. Carbonyl ylides are highly reactive 1,3-dipoles and cannot be isolated. They are mainly generated through transition metal carbenoid intermediates derived in situ from diazo precursors by treatment with a transition metal catalyst. When methyl o-(diazoacetyl)benzoate is treated with A-methylmaleimide at reflux... 

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. 

Table 8 1,3-Dipolar cycloaddition reactions of carbonyl ylides...

Common reactions of the ylide include (i) [2,3]-sigmatropic rearrangement of allylic, propargylic, and allenic ylides (ii) [l,2]-shift (Stevens rearrangement) (iii) 1,3-dipolar cycloaddition of the ylide generated from carbonyl compounds or imines with dipolarophiles, usually G=G or C=C bonds and (iv) nucleophilic addition/elimination, leading to the formation of epoxides or cyclopropanes (Figure 2). 

Intramolecular Cycloadditions of Carbonyl Ylides W. Eberbach, J. Brokatzky and H. Fritz, Angew. Chem., Int. Ed. Engl., 1980, 19, 47-48. a,(3-Unsaturated Heteroatomic Compounds in 1,3-Dipolar Addition Reactions V. A. Galishev, V. N. Chistokletov and A. A. Petrov, Russ. Chem. Rev. (Engl. Transl.), 1980, 49, 880-892. 

The Rh2(OAc)4-catalysed reactions of ethyl diazoacetate with substituted benzalde-hydes yielded 1,3-dioxolanes via an initially formed carbonyl ylide. Catalyst-dependent diastereo-control was observed only when p-mtxobenzaI dchydc was used as catalyst.104 The intramolecular cycloaddition of carbonyl ylide dipoles with tethered alkenyl 71-bonds is greatly enhanced by placing an sp1 centre on the tethered side-chain.105 The thermal reaction of 3-phenyloxirane-2,2-carbonitrile and 2-phenyl-3-thia-l-azaspiro-[4,4]non-l-ene-4-thione yields cis- and trans-cycloadducts via a regioselective 1,3-dipolar cycloaddition of an intermediate carbonyl ylide.106... 

Prompted by our earlier work dealing with the internal dipolar cycloaddition reaction of mesoionic oxazolium ylides of type 74, we subsequently studied the rhodium(II) catalyzed reactions of the related a-diazo ketoamide system 154 <97JOC2001 04OL3241 05JOC2206>. Attack of the amido oxygen at the rhodium carbenoid produces a push-pull carbonyl ylide dipole (i.e., 155) that is isomeric with the isomiinchnone class of mesoionic betaines. 

Examples of 1,3-dipoles include diazoalkanes, nitrones, carbonyl ylides and fulminic acid. Organic chemists typically describe 1,3-dipolar cycloaddition reactions [15] in terms of four out-of-plane 71 electrons from the dipole and two from the dipolarophile. Consequently, most of the interest in the electronic structure of 1,3-dipoles has been concentrated on the distribution of the four Jt electrons over the three heavy atom centres. Of course, a characteristic feature of this class of molecules is that it presents awkward problems for classical valence theories a conventional fashion of representing such systems invokes resonance between a number of zwitterionic and diradical structures [16-19]. Much has been written on the amount of diradical character, with widely differing estimates of the relative weights of the different bonding schemes. 

The third typical reaction of carbenes is combination with a nucleophile. Carbenes are electron-deficient species, so they combine with nucleophiles that have reactive lone pairs. Addition of a carbonyl O to a carbene gives a carbonyl ylide, a reactive compound useful for making furan rings by a 1,3-dipolar cycloaddition reaction (see Chapter 4). 

Carbonyl ylides in 1,3-dipolar cycloaddition reactions 02HC(59)253. 

The l,3-thiazole-5-thione (36) undergoes a regioselective 1,3-dipolar cycloaddition reaction with a carbonyl ylide. The ylide is thermally generated by the electrocyclic ring opening of the epoxide (37) to give the spirocyclic adducts (38a and 38b) <97HCA1190>. 

It is well known that di- and tetrahydrofurans can be obtained by inter- and intramolecular 1,3-dipolar cycloaddition reactions of carbonyl ylides with alkynes and alkenes. This methodology has also been shown to be of value in the preparation of a furanophane <92TL57>. 

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