Metal-mediated reactions azomethine ylides

Metal-mediated processes represent an important advance in azomethine ylide chemistry, allowing reactions to proceed at ambient temperatures. They also allow for the possibility of chiral catalysis, which is a little explored area as yet, but represents an exciting development allowing for the induction of enantiocontrol without the need for stoichiometric stereocontrolling units. 

However, replacement of LiBr with AgOAc inverted the ratio of exo to endo products. For Ar = 334, the major adduct was isolated in 42% yield with an endo/ exo ratio of 1 1.7, while Ar = 335 gave 333 in 36% yield with an endo/exo ratio of 1 2.3. Note that attempts at the thermal reaction met with low yields of complex reaction mixmres containing all possible regio- and stereoisomers. This smdy exemplifies the value of metal mediation in the stereo- and regiocontrol of azomethine ylide cycloadditions. 

Although Grigg et al. (97) have been prolific authors in azomethine ylide chemistry, probably their greatest contribution has been in the development of metal-mediated technologies, leading to elegant solutions to the problems of regio-, stereo-, and enantiocontrol over reactions. Typically, EtaN or DBU deprotonation of amino esters, with subsequent metalation of the anion, led to the formation of stabilized, metallo-1,3-dipolar systems (340), often to the extent where isolation is possible (Scheme 3.115). 

The greater part of this chapter is concerned with the Diels-Alder and hetero-Diels-Alder reaction. The asymmetric version of both of these reactions can be catalysed with metal-based Lewis acids and also organocatalysts. The catalytic asymmetric 1,3-dipolar cycloaddition of nitrones and azomethine ylides is also discussed. Again, most success in this area has been achieved using metal-based Lewis acids and the use of organocatalysts is begiiming to be explored. This chapter concludes with a brief account of recent research into the asymmetric [2+2]-cycloaddition, catalysed by enantiomerically pure Lewis acids and amine bases, and also the Pauson-Khand [2- -2- -l] cycloaddition mediated by titanium, rhodium and iridium complexes. 

Dipolar cycloaddition reactions constitute a powerful and convergent tool for the preparation of various heterocyclic compounds, which have been widely applied in the synthesis of numerous natural products, pharmaceuticals, and functional materials. The chemistry of 1,3-dipolar cycloaddtion reactions has been well documented in a number of reviews [3]. In this section the focus is on transition-metal-mediated 1,3-dipolar cycloaddition reactions with some important 1,3-dipoles, including azides, diazoalkanes, carbonyl ylides, and azomethine ylides, rather than a full review of the reactions of all types of 1,3-dipoles. 

Similar to carbonyl ylides, azomethine ylides are normally generated as transient species in situ, and a number of protocols have been established so far [22]. Among them, the transition-metal-mediated procedures have enj oyed great privileges in terms of milder reaction conditions, better selectivities, and broad functional group tolerance. This part focuses on the recent development of transition-metal-mediated in situ generation of (metal-containing) azomethine ylides as well as their applications for the synthesis of aromatic compounds. 

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