Intramolecular cycloadditions carbonyl ylide generation

A review about the rearrangement and cycloaddition of carbonyl ylides generated from a-diazo compounds is available <2001CSR50>. Enantioselective intramolecular cyclopropanations of allyl 2-diazo-3-silanyloxybut-3-enoates to yield cyclopropyl 7-butyrolactones have been investigated with a variety of chiral rhodium catalysts. The best results were obtained with Rh2(PTTL)4, where enantioselectivity culminated at 89% ee (Equation 99) <2005TA2007>. 

Bicyclization. Carbonyl ylides generated via decomposition of diazoketones and internal trapping can be put to good use. Accessibility of oxabridged tricyclic by an intramolecular [3 +2] cycloaddition has profound significance to the elaboration of the core structure of platensimycin, and the possibility has been studied. Initial experimentation showed the preponderant formation of an isomeric skeleton but by halogen substitution (change of HOMO coefficient) on the dipolarophilic alkene the desired intermediate can be prepared as the major product. 

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... 

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. 

Lycorine is an alkaloid that has attracted attention from both the synthetic community and pharmacologists. Prior synthetic approaches have included inter-and intramolecular Diels-Alder cycloaddition. Based on a similar retrosynthetic disconnection, Padwa and co-workers (106,109) chose to use a push-pull carbonyl ylide cycloaddition with a disubstituted pyrrolidinone core to generate a tricyclic substrate. The major difference for this synthetic smdy was the availability of a labile proton a to the carbonyl moiety (Scheme 4.53). 

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). 

Benzo[ ]thiophene participates in intramolecular dipolar cycloaddition with an in situ generated carbonyl ylide the reaction fails with the corresponding thiophene <2006JA10589>. 

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). 

A review of the methods for the generation of cyclic carbonyl ylides from intramolecular carbene additions has recently appeared [64]. This intermediate was first exploited as the An component for cycloaddition reactions by Ibata [65]. ort/io-Disubstituted carboalkoxy aryl diazoketones such as 54 were decomposed by copper complexes, generating six-membered ring carbonyl ylides. These transient intermediates underwent subsequent intermolecular cycloadditions in the presence of ethylenic and acetylenic reagents to give predominantly exo products containing the oxabicyclo[3.2.1] nucleus, Eq. 38. 

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). 

One recent example of applying this process was reported by Johnson et al. for the preparation of furan derivatives (Scheme 16.12) [19]. This reaction involved the rhodium(II)-catalyzed intermolecular generation of carbonyl ylides A or B from diazosulfone (18) and aldehydes 19 or 21, respectively. The 1,3-dipolar cycloaddition of the resulting carbonyl ylides with an intramolecular tethered alkyne moiety or dimethyl acetylenedicarboxylate (DMAD, an intermolecular process), followed by elimination of phenylsulfinic acid, could access furan derivatives. 

The reaction mechanism proposed for the LiBr/NEta induced azomethine ylide cycloadditions to a,p-unsaturated carbonyl acceptors is illustrated in Scheme 11.10. The ( , )-ylides, reversibly generated from the imine esters, interact with acceptors under frontier orbital control, and the lithium atom of ylides coordinates with the carbonyl oxygen of the acceptors. Either through a direct cycloaddition (path a) or a sequence of Michael addition-intramolecular cyclization (path b), the cycloadducts are produced with endo- and regioselectivity. Path b is more likely, since in some cases Michael adducts are isolated. 

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