Catalytic cycloadditions carbonyl ylides

Mejla-Oneto and Padwa have explored intramolecular [3+2] cycloaddition reactions of push-pull dipoles across heteroaromatic jr-systems induced by microwave irradiation [465]. The push-pull dipoles were generated from the rhodium(II)-cata-lyzed reaction of a diazo imide precursor containing a tethered heteroaromatic ring. In the example shown in Scheme 6.276, microwave heating of a solution of the diazo imide precursor in dry benzene in the presence of a catalytic amount of rhodium I) pivalate and 4 A molecular sieves for 2 h at 70 °C produced a transient cyclic carbonyl ylide dipole, which spontaneously underwent cydoaddition across the tethered benzofuran Jt-system to form a pentacyclic structure related to alkaloids of the vindoline type. 

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... 

Mechanistic and theoretical investigation has been carried out on the carbonyl ylide formation and the subsequent 1,3-dipole addition, Ghemo- and stereoselectivity have been found to be affected by the ligands of the Rh(ii) catalysts.These results imply that in the cycloaddition process, the Rh(ii) catalyst may be associated with the 1,3-dipole. Theoretical calculation indicates that the Rh(ii) catalyst-associated ylide has the lowest energy in the catalytic cycle.The suggestion that metal complex-associated ylide may be involved in the cycloaddition has great implication for the asymmetric catalysis in this type of reaction. 

Ibata was the first to show that the masked carbonyl ylide embedded within the isomiinchnone framework would readily undergo 1,3-dipolar cycloaddition with various dipolarophiles [34], The isolable isomiinchnone 4 was observed to react with dimethyl fumarate to produce cycloadduct 7 which possesses the 7-oxa-2-azabicyclo[2.2.1]heptane skeleton. When the reaction of 1 was carried out using catalytic amounts of Cu(acac)2 in the presence of various dipolarophiles, smooth dipolar cycloaddition was observed to occur giving mixtures of endo and exo isomers. In most cases, the exo isomers were favored. All of Ibata s isomiinchnone cycloadditions contain aromatic substituent groups, presumably selected to facilitate dipole formation. The synthetic utility of the cycloaddition reaction is diminished, however, because of the low reactivity of the aromatic substituents toward further manipulation. 

The game is certainly not over, very recently catalytic enantioselective intermolecular cycloadditions of 2-diazo-3,6-diketoester of type 68 derived carbonyl ylides with alkene dipolarophiles have been developed [57]. Relying on chiral rhodium(II) clusters I and II, Hodgson et al. obtained very high enantioselectivities (up to 92% ee on 69) with norbornene as a trap, as disclosed in Scheme 31. 

Catalytic [3 + 2]-cycloaddition of the carbonyl and azomethine ylides 129 with olefins gives the five-membered heterocycles 130 (Scheme 45). Longmire et al. reported that the catalytic asymmetric [3 + 2]-cycloaddition of the azomethine ylides 131 with dimethyl maleate in the presence of AgOAc and a bis-ferrocenyl amide ligand 133 gave the pyrrolidine triesters 132 in excellent yields with very high enantiomeric excesses (Scheme 46).122 As described in section 8, the [3 + 2]-cycloaddition reaction of diazo compounds with olefins proceeds similarly through the formation of carbonyl ylides. 

Despite the great synthetic utihty of diazocarbonyl compounds in the generation of carbonyl ylide intermediates, definitive mechanistic studies on the metal-catalyzed cycloaddition of carbonyl yhdes are scarce. Among the various metal catalysts, dirhodium(II) catalysts are the most effective and versatile for diazo decomposition. Because of the rapid catalytic tmnovers of these reactions, structural information about the intermediates is difficult to obtain. A reasonable mechanism can be rationahzed on the basis of product distribution, and especially on the basis of enantioselective outcome of various carbonyl yhde reactions [55-63]. 

The formation of 5-membered ring carbonyl ylides from a 5-keto fimc-tionality was shown to undergo the intramolecular [3+2]-cycloaddition with alkenes or alkynes. An illustrative example [79] is the reaction of acyclic diazo ketone 71 with a catalytic quantity of rhodiiun(ll) acetate at room temperature to afford the polycyclic adduct 72 in 50% yield with complete diastereoselectivity (Scheme 21). This example shows that the intramolecular cycloadditions of 5-membered ring carbonyl ylide can take place across the unactivated 1-hexenyl zr-bond. 

Another successful catalytic enantioselective 1,3-dipolar cycloaddition of Qf-diazocarbonyl compounds using phthaloyl-derived chiral rhodium(II) catalysts has been demonstrated [ill]. Six-membered ring carbonyl ylide formation from the a-diazo ketone 80 and subsequent 1,3-cycloaddition with DMAD under the influence of 1 mol % of dirhodium(II) tetrakis[M-benzene-fused-phthaloyl-(S)-phenylvaline], Rh2(S-BPTV)4 101 [112], has been explored to obtain the cycloadduct 102 in up to 92% ee (Scheme 31). 

Scheme 13.26 catalytic asymmetric 1,3-dipolar cycloaddition of carbonyl ylide promoted by Yb(OTf)3/PyBOX. 

Synthesis of Heterocycles. Novel synthesis of 1,3-dioxolanes was suggested, which starts with the formation of an intermediate carbonyl ylide from dimethyl diazomalonate and a carbonyl compound (aldehyde or quinone) in the presence of catalytic amounts of Rh. Once formed, the ylide undergoes dipolar [3 + 2] cycloaddition with another equivalent of carbonyl compound to furnish a five-membered heterocycle (eqs 25 and 26). Employment of aldimines in this reaction allowed for preparation of 1,3-imidazolidines (eq 27) and 1,3-oxazolidines (eq 28). ... 

C-H Insertion. Catalytic C-H functionalization is a powerful approach for C-C bond formation. As described in the previous update, [Cu(acac)2]-catalyzed cycloaddition of a,j8-enones with dimethyl diazomalonate would afford dihydrofurans through carbonyl ylide formation (eq 24). Yet, when enaminone was employed as substrate in the same reaction, naphthalen-l(4//)-one was obtained as major product (eq 55). The authors suggested that the product formation may arise from the unusual carbenoid C-H insertion followed by aromatic nucleophilic substitution. 

RECENT ADVANCES IN CATALYTIC ASYMMETRIC 1,3-DIPOLAR CYCLOADDITIONS OF AZOMETHINEIMINES, NITRILE OXIDES, DIAZOALKANES, AND CARBONYL YLIDES... 

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