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. 2012 Mar 2;77(5):2446-55.
doi: 10.1021/jo3000282. Epub 2012 Feb 14.

1,4-Diazaspiro[2.2]pentanes as a flexible platform for the synthesis of diamine-bearing stereotriads

Jared W Rigoli  1 , Luke A Boralsky, John C Hershberger, Dagmara Marston, Alan R Meis, Ilia A Guzei, Jennifer M Schomaker
Affiliations

1,4-Diazaspiro[2.2]pentanes as a flexible platform for the synthesis of diamine-bearing stereotriads

Jared W Rigoli et al. J Org Chem. .

Abstract

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.

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Figures

Figure 1
Figure 1
Examples of biologically active molecules containing a C–N/C–N/C–O stereotriad.
Scheme 1
Scheme 1
Scheme 2
Scheme 2
See this image and copyright information in PMC

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