Carbonyl ylides structural studies

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 study of the carbonyl ylide structure and reactivity by the application of computational methods (Fig. 4.3). 

NMR spectroscopic studies f111,13C, and 31P) are consistent with the dipolar ylide structure and suggest only a minor contribution from the ylene structure.234 Theoretical calculations support this view.235 The phosphonium ylides react with carbonyl compounds to give olefins and the phosphine oxide. 

Synthesis, Structural Studies, and Reactivity of Carbonyl Ylides. . . ... 

SYNTHESIS, STRUCTURAL STUDIES, AND REACTIVITY OE CARBONYL YLIDES... 

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. 

Alkaloids are another family of compounds that are easily accessible from synthetic routes utilizing carbonyl ylides. The complex structure of naturally occurring alkaloids has been the driving force for the generation of new carbonyl ylide methodology. These studies have resulted in the discovery of several new reaction manifolds as well as the total synthesis of several natural products. 

Thus far, in the alkaloid series discussed, the nitrogen atom has always been part of the core of the alkaloid structure, rather than acting in a dipolarophilic manner in the cycloaddition of the carbonyl ylide. Recently, Padwa et al. (117) addressed this deficiency by conducting model studies to synthesize the core of ribasine, an alkaloid containing the indanobenzazepine skeleton with a bridging ether moiety (Scheme 4.57). Padwa found that indeed it was possible to use a C = N it-bond as the dipolarophile. In the first generation, a substituted benzylidene imine (219) was added after formation of the putative carbonyl ylide from diazoketone 218. The result was formation of both the endo and exo adduct with the endo adduct favored in an 8 1 ratio. This indicates that the endo transition state was slightly favored as dictated by symmetry controlled HOMO—LUMO interactions. 

While most of the initial studies have involved the transition metal-catalyzed decomposition of a-carbonyl diazo compounds and have been reviewed [3-51], it appears appropriate to highlight again some milestones of these transformations, since polycyclic structures could be nicely assembled from acyclic precursors in a single step. Two main reactivities of metalo carbenoids derived from a-carbonyl diazo precursors, namely addition to a C - C insaturation (olefin or alkyne) and formation of a ylid (carbonyl or onium), have been the source of fruitful cascades. Both of these are illustrated in Scheme 27 [52]. The two diazo ketone functions present in the same substrate 57 and under the action of the same catalyst react in two distinct ways. The initially formed carbenoid adds to a pending olefin to form a bi-cyclop. 1.0] intermediate 58 that subsequently cyclizes to produce a carbonyl ylide 59, that is further trapped intramolecularly in a [3 + 2] cycloaddition. The overall process gives birth to a highly complex pentacyclic structure 60. 

Studies on thiamine (vitamin Bi) catalyzed formation of acyloins from aliphatic aldehydes and on thiamine or thiamine diphosphate catalyzed decarboxylation of pyruvate have established the mechanism for the catalytic activity of 1,3-thiazolium salts in carbonyl condensation reactions. In the presence of bases, quaternary thiazolium salts are transformed into the ylide structure (2), the ylide being able to exert a cat ytic effect resembling that of the cyanide ion in the benzoin condensation (Scheme 2). Like cyanide, the zwitterion (2), formed by the reaction of thiazolium salts with base, is nucleophilic and reacts at the carbonyl group of aldehy s. The resultant intermediate can undergo base-catalyzed proton... 

Tetrakis(l,T-binaphthyl-2,2 -diyl phosphate) complexes (119) are reported to be much more effective catalysts than the more commonly used carboxylate complexes for enantioselective intramolecular, tandem, carbonyl ylide forma-tion/cycloaddition of a-diazo- -keto esters. The ring-opening reactions of epoxides with diphenyl phosphorazidate (120) have been investigated. A wide range of epoxide substrates have been studied and the products, (121) or (122), depend on the substrate structure. The microbial hydroxylation of novel phos-... 

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. 

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]. 

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