Azomethine imines, alkynyl

C,A-Cyclic azomethine imines undergo an inverse-electron-demand 1,3-cycloaddition with electron-rich alkenes using a BINOL-derived diacid catalyst, excellent chemo- and enantio-selectivities have been reported. " Asynometric alkynylation of cyclic azomethine imines has been carried out using copper(I) and a chiral Brpnsted acid as catalysts. ... 

A. A -Bicychc pyrazolidin-3-ones 31, potentially bioactive heterocycles, are also constructed by the [3+2] cycloaddition of Fischer alkynyl carbene complexes 28 with azomethine imines 29 via isolable metal-carbene intermediates 30 (Scheme 5.8) [17]. 

SCHEME 5.8 [3+2] Cycloaddition of Fischer alkynyl carbene complexes 28 with azomethine imines 29. 

Alkynyl azomethine ylides containing an aryl bridge have been shown to undergo cyclization. Thus, tautomerization of imine (137) afforded an azomethine ylide which cyclized to give two diastereomeric dihydropyrroles and traces of aromatized product (Scheme 42).56 The activated cyclic ylide (138), generated via the desilylation route, underwent cyclization to afford dihydropyrrole (139) in 42% yield.67b The structure of (139) is closely related to erythramine. The structurally related non-stabilized azomethine ylide (140) did not cyclize, tautomerizing to the corresponding enamine instead. 

A similar concept was applied to the two-component synthesis of indoles 164 via cydoisomerization of alkynyl imines 162 (Scheme 9.61) [220]. N-(Alkoxymethyl) indoles 164 were readily prepared through the Cu(I)-catalyzed cyclization-hydroxyla-tion reaction of the imine precursors 162 in the presence of a variety of external O-nucleophiles 163, such as alcohols and phenols, with good functional group compatibility. The authors believe that this domino reaction begins with the Cu( I)-activation of alkyne 162 toward 5-ewdo-digcyclization to form a cydic metal-containing azomethine... 

Recently, Iwasawa established a set of transition metal-catalyzed protocols for an efficient construction of N l-C2-fused polycydic indole skeletons via a cycloisomerization-cycloaddition domino reaction of alkynyl imines 172 [222-224]. It was shown that the latter substrates, upon activation with transition metal catalysts, such as W(0), Pt(II), and Au(III), generate reactive azomethine ylide intermediates 174 similar to 166 (Scheme 9.64). Interception of such yUdes with a variety of suitably substituted alkenes 17S via a [3 - - 2]-cydoaddition affords fused indole products 177 through a transient formation of the corresponding metallocarbenoids 176. Transformation of terminal alkynyl imines proceeds with a 1,2-H shift in the 176, whereas... 

Ag-catalyzed in situ generation of azomethine ylides from alkynyl A-benzylidene glycinates 35 and their reaction with electron-deficient alkynes 36 were demonstrated by Su and Porco (Scheme 16.17) [26]. This reaction is supposed to be initiated by cycloisomerization of alkynyl imines 35 to isoquinolinium species A with the assistance of AgOTf. Subsequent proton transfer would afford azomethine ylides B with regeneration of Ag(I). 1,3-Dipolar cycloaddition with alkynes 36 followed by aerobic oxidation may furnish pyrroloisoquinoline products 37. It is worth noting that various types of electron-deficient alkynes, irrespective of internal and terminal alkynes, are applicable to this reaction. 

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