Spirocyclic compounds are attractive targets in organic synthesis because of their broad distribution in biologically active natural products and pharmaceuticals, [1] as well as their increasing use in a range of important chemical and technological processes, such as asymmetric synthesis and organic optoelectronics. [2] On this basis the development of novel methods for the construction of spirocyclic frameworks is of considerable importance, particularly when these methods give rise to the enantioselective formation of an all-carbon quaternary stereocenter, which itself is considered to be a challenging transformation. [3,4] Over the past decade, extensive work on organocatalyzed asymmetric conjugated additions of trisubstituted carbon nucleophiles to electron-deficient alkenes demonstrated that these reactions represent an attractive solution to the problem of selectively generating quaternary stereocenters. [4] Recently several organocatalytic cascade processes involving Michael additions have been successfully applied to the synthesis of spirocyclic compounds. [5] These methods, are based on Michael or Michael/ aldol-type sequences and provide access to spiro-oxindoles, spirobenzofuranones, or spiro-3,4-dihydropyrans with high stereocontrol. The use of novel substrate combinations and the development of new cascade or one-pot reactions are significant advances in this field, thus making the asymmetric assembly of structurally diverse spirocyclic compounds possible from simple and readily available precursors. In this field and in continuation of our efforts to expand the scope of privileged organocatalysts in the field of selenium chemistry, [6,7] we herein report the first highly enantioselective synthesis of spirolactones starting from racemic cyclic bketoesters and the vinyl selenone catalyzed by bifunctional cinchona-alkaloid-derived catalysts. The operationally simple, one-pot Michael addition/cyclization sequence is based on the peculiar properties of the phenylselenonyl substituent, which plays a dual role as an electron-withdrawing group, during the addition step, and as a leaving group, during the cyclization by intramolecular nucleophilic substitution.
Initial studies were performed with an excess of the tertbutyl b-ketoester 1 a and the easily available vinyl selenone 2 in toluene in the presence of a catalytic amount of anhydrous Na 2 CO 3 (Scheme 1).