Hydrogen-Bond Mediated Catalysis by Chiral Bis-Amidinium Salts

• Applicant: Professor Dr. Michael Göbel
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2007 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 40137539

Bisamidines derived from malodinitrile and chiral 1,2-diamines are complementary in structure to monocarbonyl compounds such as aldehydes and ketones. They can be used either as chiral bases or, in the mon opro ton ated form, as mild electrophilic catalysts to promote Diels-Alder and ene reactions as well as Friedel-Crafts reactions. In the next funding period, we wish to incorporate sterically more demanding 1,2-diamines to achieve high levels of enantioselectivity. Reactions that require activation by strong Lewis acids will be catalyzed by new types of dicationic amidinium salts. Dicationic amidinium salts derived from 1,3-dicyanobenzene have already demonstrated their catalytic potential with 1,2-dicarbonyl substrates. We expect largely improved selectivities in this class of catalysts as well when the phenyl groups at the chiral centers will be replaced by bigger residues such as tbutyl. Several new examples of axially-chiral amidines have been synthesized. We could now identify a catalyst for the Diels-Alder step of the Quinkert-Dane estrone synthesis which is superior to classical titanium based Lewis acids in terms of yield and stereoselectivity. Simple recrystallization afforded enantiopure key intermediates, available in both absolute configurations. A second axially-chiral amidinium salt could catalyze the cycloaddition of l-methyl-2- vinylindole and nitrostyrene in 67% ee. Based on this result, we plan to investigate analogous reactions with 2-vinyI-3-aIkylindoles. Cycloadducts accessible in this process may be interesting intermediates to synthesize parts of the aspidosperma or strychnos alkaloid skeleton.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1179: Organocatalysis