Azomethines 5,6-dihydro-2-amino

Non-stabilized a, p y, 5-unsaturated azomethine ylides (158), generated by the decarboxylation method from 3,3-diarylpropenals (156) and secondary amino acids (157), have been found to undergo [1,7]-electrocyclization followed by a [1,5]-hydrogen shift, to yield 2,3-dihydro-17/-2-benzazepines (159). 

Dodd and co-workers (5) reported the first known synthesis of 11//-indolizino[8,7-h]indoles by the cycloaddition reaction of a nonstabilized ylide 21 and diethylacetylene dicarboxylate (DEAD). The azomethine ylide, formed by the alkylation of the 3,4-dihydro-p-carboline (22) with trimethylsilyl methyl triflate to the triflate salt, followed by in situ desilyation with cesium fluoride, underwent cycloaddition with DEAD at low temperature. The expected major cycloadduct 23 was isolated, along with quantities of a minor product 24, presumed to have been formed by initial reaction of the ylide with 1 equiv of DEAD and the intermediate undergoing reaction with a further equivalent of DEAD before cyclization. Dodd offers no explanation for the unexpected position of the double bond in the newly generated five-membered ring, although it is most likely due to post-reaction isomerization to the thermodynamically more stable p-amino acrylate system (Scheme 3.5). 

This chapter deals mainly with the 1,3-dipolar cycloaddition reactions of three 1,3-dipoles azomethine ylides, nitrile oxides, and nitrones. These three have been relatively well investigated, and examples of external reagent-mediated stereocontrolled cycloadditions of other 1,3-dipoles are quite limited. Both nitrile oxides and nitrones are 1,3-dipoles whose cycloaddition reactions with alkene dipolarophiles produce 2-isoxazolines and isoxazolidines, their dihydro derivatives. These two heterocycles have long been used as intermediates in a variety of synthetic applications because their rich functionality. When subjected to reductive cleavage of the N—O bonds of these heterocycles, for example, important building blocks such as p-hydroxy ketones (aldols), a,p-unsaturated ketones, y-amino alcohols, and so on are produced (7-12). Stereocontrolled and/or enantiocontrolled cycloadditions of nitrones are the most widely developed (6,13). Examples of enantioselective Lewis acid catalyzed 1,3-dipolar cycloadditions are summarized by J0rgensen in Chapter 12 of this book, and will not be discussed further here. 

Enantioselective total synthesis of ((47J,5iS)-5-Amino-4-(2,4,5-tri-fluorophenyl) cyclohex- l-enyl)-(3-(trifluoromethyl)-5,6-dihydro-[l, 2,4]tri-azolo[4,3-a]pyrazin-7(877)-yl)methanone ABT-341 (708), a DPP4 (dipeptidyl peptidase IV) inhibitor, has been completed in diphenylprolinol silyl ether (707), in the one-pot, multicomponent, reaction of nitroalkene (704), acetaldehyde (703), vinyl phosphonate (706) and amine (705) (Scheme 178) A novel, catalytic, asymmetric Michael addition of azomethine ylide (710) with p-substituted tetraethyl alkyhdene bisphosphates (709) has been realised in the presence of a chiral copper(I)/TF-Bipham-Phos (712) complex. This system provided enantioenriched unnatural i -amino acid derivatives (711) containing gem-bisphosphonates in high yields with... 

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