Carbonyl ylides alkaloid systems

In an alternative approach to annulation across the indole 2,3-tt system, Padwa and coworkers have reported approaches to the pentacyclic and hexacyclic frameworks of the aspidosperma and kopsifoline alkaloids respectively that involve as the key step a Rh(II)-promoted cyclization-cycloaddition cascade <06OL3275, 06OL5141>. As illustrated in their approach to ( )-aspidophytine 150, Rh2(OAc)4-catalyzed cyclization of a diazo ketoester 148 affords a carbonyl ylide dipole that undergoes [3+2]-cycloaddition across the indole 2,3-tt bond to generate 149 <06OL3275>. 

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. 

Padwa has reported an approach to the ring system of the ribasine alkaloids 98 [174], using an intramolecular 1,3-dipolar cycloaddition of the a-diazo ketone 99 to produce the pentacyclic skeleton 100 (Scheme 19.17). Wood [175] used an intermolecular 1,3-dipolar cycloaddition of a carbonyl ylide for the total synthesis of ( )-epoxysorbicilli-nol 101 (Scheme 19.18). The key cycloaddition in this approach is the conversion of 102 to the natural product core 103, which sets the substitution pattern around the entire ring system in a single step. 

A series ofQ -diazo-/9-(o-carbomethoxy)-substituted aryl ketones were prepared and employed as model systems for a synthetic approach towards the alkaloid, ribasine (114) [116]. The six-membered ring carbonyl ylide dipoles were generated from the o-allyl-substituted diazo ketoester 112 and Rh2(OAc)4 to access the cycloadduct 113 (Scheme 35). This result constitutes a promising model study towards the synthesis of the alkaloid, ribasine (114). 

Keywords 13-Dipoles Alkaloids Asymmetric synthesis Azides Azomethine imines Azomethine ylides Carbonyl ylides Cycloaddition Mesoionic systems Nitrile oxides Nitrones... 

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