1,4-Diazaspiro[2.2]pentanes as a flexible platform for the synthesis of diamine-bearing stereotriads.
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.
Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, Wisconsin 53706, USA.
Jared W
JW
Rigoli
Luke A
LA
Boralsky
John C
JC
Hershberger
Dagmara
D
Marston
Alan R
AR
Meis
Ilia A
IA
Guzei
Jennifer M
JM
Schomaker
D003959:Diamines / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013141:Spiro Compounds / Q000737:chemistry*; D013237:Stereoisomerism
C572730:1,4-diazaspiro(2.2)pentane; D003959:Diamines; D013141:Spiro Compounds