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1,4-Diazaspiro[2.2]pentanes as a Flexible Platform for the Synthesis of Diamine-Bearing Stereotriads

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posted on 2012-03-02, 00:00 authored by Jared W. Rigoli, Luke A. Boralsky, John C. Hershberger, Dagmara Marston, Alan R. Meis, Ilia A. Guzei, Jennifer M. Schomaker
Nitrogen-containing stereotriads occur in a number of biologically active compounds, but general and flexible methods to access these compounds are limited mainly to the manipulation of chiral olefins. An alternative approach is to employ a highly chemo-, regio-, and stereocontrolled allene oxidation that can install a new carbon–heteroatom bond at each of the three original allene carbons. In this paper, an intramolecular/intermolecular allene bis-aziridination is described that offers the potential to serve as a key step for the construction of stereotriads containing vicinal diaminated motifs. The resultant 1,4-diazaspiro[2.2]­pentane (DASP) scaffolds contain two electronically differentiated aziridines that undergo highly regioselective ring openings at C1 with a variety of heteroatom nucleophiles to give chiral N,N-aminals. Alternatively, the same DASP intermediate can be induced to undergo a double ring-opening reaction at both C1 and C3 to yield vicinal diaminated products corresponding to formal ring opening at C3. The chirality of a propargyl alcohol is easily transferred to the DASP with good fidelity, providing a new paradigm for the construction of enantioenriched nitrogen-containing stereotriads.