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.

含氮立体三单元广泛存在于多种生物活性化合物中，但目前通用且灵活的合成此类化合物的方法主要局限于手性烯烃的转化。另一种合成策略则采用高化学选择性、区域选择性与立体选择性的丙二烯（allene）氧化反应，可在丙二烯的三个原始碳原子上分别引入全新的碳-杂原子键。本文报道了一种分子内/分子间丙二烯双氮丙环化（aziridination）反应，该反应有望作为关键步骤，用于构建含有邻位二胺基结构基元的立体三单元。所得的1,4-二氮杂螺[2.2]戊烷（1,4-diazaspiro[2.2]pentane, DASP）骨架含有两个电子特性不同的氮丙环，可与多种杂原子亲核试剂在C1位发生高度区域选择性的开环反应，生成手性N,N-缩醛胺。此外，该DASP中间体还可在C1与C3位同时发生双开环反应，得到对应于C3位形式开环的邻位二胺化产物。炔丙醇的手性可高效且高保真地转移至DASP骨架中，为构建对映富集的含氮立体三单元提供了全新的范式。