Ylide compounds intramolecular cycloadditions

Highly stereoselective intramolecular cycloadditions of unsaturated N-substituted azomethine ylides have been conducted under microwave irradiation. Oritani reported that a mixture of the aldehyde 137 and N-methyl- or N-benzylglycine ethyl ester (138) on the surface of silica gel, irradiated under microwaves for 15 min, generated azomethine ylides 139 that subsequently underwent in situ intramolecular cycloadditions to afford the corresponding tricyclic compounds 140 in 79 and 81% yield, respectively (Scheme 9.42) [93],... 

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 contrast to considerations of 50 years ago, today carbene and nitrene chemistries are integral to synthetic design and applications. Always a unique methodology for the synthesis of cyclopropane and cyclopropene compounds, applications of carbene chemistry have been extended with notable success to insertion reactions, aromatic cycloaddition and substitution, and ylide generation and reactions. And metathesis is in the lexicon of everyone planning the synthesis of an organic compound. Intramolecular reactions now extend to ring sizes well beyond 20, and insertion reactions can be effectively and selectively implemented even for intermolecular processes. 

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. 

Dihydrofurans are valuable synthetic compounds. Nevertheless, little is known about intramolecular cycloaddition of carbonyl ylides to alkynes. In one example, alkynyl pyran-4-one (233) was cyclized to dihydrofuran (234 Scheme 69).128 Possibly this reaction proceeds via an oxidopyrylium ylide intermediate as shown. 

An example of an intramolecular cycloaddition reaction was offered by the mesoionic compound (129) which contains in the same molecule both a non-activated alkenic function and a cyclic thiocarbonyl ylide system. In an intramolecular [3 + 2] cycloaddition, (129) yields at 120 °C the tetracyclic primary adduct (130 90%) (81LA347). 

The simplest ylide generation method among the deprotonation route (Section II,D) consists of the condensation of N-substituted a-amino esters with carbonyl compounds. This procedure must be especially useful for utilization in intramolecular cycloadditions because the substrates for the cycloadditions are simply prepared in situ by reacting the carbonyl compounds (or secondary amines) bearing a trapping chain with secondary amines (or carbonyl compounds). 

Herein rhodium-catalyzed inter- and intramolecular cycloadditions of carbonyl ylides derived from a range of diazocarbonyl compounds leading to oxygen- and nitrogen-containing heterocyclic systems and natural products are discussed. We have focussed on the last five years for the most significant developments of the reactions of carbonyl ylides derived from diazocarbonyl compounds. 

Compounds in which a carbonyl or other nucleophilic functional group is close to a carbenoid carbon can react to give ylide intermediate.221 One example is the formation of carbonyl ylides that go on to react by 1,3-dipolar addition. Both intramolecular and intermolecular cycloadditions have been observed. 

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... 

The chemical behavior of heteroatom-substituted vinylcarbene complexes is similar to that of a,(3-unsaturated carbonyl compounds (Figure 2.17) [206]. It is possible to perform Michael additions [217,230], 1,4-addition of cuprates [151], additions of nucleophilic radicals [231], 1,3-dipolar cycloadditions [232,233], inter-[234-241] or intramolecular [220,242] Diels-Alder reactions, as well as Simmons-Smith- [243], sulfur ylide- [244] or diazomethane-mediated [151] cyclopropanati-ons of the vinylcarbene C-C double bond. The treatment of arylcarbene complexes with organolithium reagents ean lead via conjugate addition to substituted 1,4-cyclohexadien-6-ylidene complexes [245]. 

Fig. 4.14. Preparation of polycyclic compounds by intramolecular 1,3-dipolar cycloaddition of carbonyl ylides to alkenes 11301].

Friedrichsen and co-workers (135), along with Padwa, has utilized the carbonyl ylide cycloaddition to generate reactive furan moieties that can be further used in inter- or intramolecular Diels-Alder reactions to prepare aza- and carbocyclic compounds. Friedrichsen conducted a number of synthetic and theoretical studies on the reactivity, regioselectivity, and stereoselectivity of substituted furan formation and subsequent Diels-Alder reaction (Scheme 4.69). 

An attractive approach toward the preparation of polycyclic systems containing a thiophene ring involves the intramolecular [3 - - 2] cycloaddition of thiocarbonyl ylides. A number of representative examples were reported using mesoionic compounds. Gotthardt et al. (151) used l,3-dithiolium-4-olates such as 89 bearing an olefinic side chain. Upon heating to 120 °C in xylene, the polycyclic tetrahy-drothiophene 90 was formed (Scheme 5.33). 

Intramolecular [3- -2]-cycloadditions of thiocarbonyl ylides with nonactivated acetylenes have also been described. Most representative examples involved the use of mesoionic substrates. The initially formed polycyclic adducts of type 110 undergo spontaneous elimination of phenyl isocyanate (24,62,151). A typical example leading to compound 111 is shown in Scheme 5.40. 

Carbonyl ylides possess versatile reactivities, among which the 1,3-dipolar cycloaddition is the most common and important reaction. The reaction sequence of ylide formation and then 1,3-dipolar cycloaddition can occur in either inter- or intramolecular manner. When the reaction occurs intermolecularly, the overall reaction is a one-pot three-eomponent process leading to oxygen-containing five-membered cyclic compounds, as demonstrated by the example shown in Scheme 8. A mixture of diazo ester 64, benzaldehyde, and dimethyl maleate, upon heating to reflux in CH2CI2 in the presence of 1 mol% rhodium(ii) perfluorobutyrate [Rh2(pfb)4], yields tetrahedrofuran derivative 65 in 49% yield as single diastereomer. " ... 

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