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. 2023 Feb 22;14(11):2821-2825.
doi: 10.1039/d3sc00001j. eCollection 2023 Mar 15.

1-Azahomocubane

Tyler Fahrenhorst-Jones  1 , David L Marshall  2 , Jed M Burns  1 , Gregory K Pierens  3 , Robert E Hormann  4 , Allison M Fisher  4 , Paul V Bernhardt  1 , Stephen J Blanksby  2 , G Paul Savage  5 , Philip E Eaton  4 , Craig M Williams  1
Affiliations

1-Azahomocubane

Tyler Fahrenhorst-Jones et al. Chem Sci. .

Abstract

Highly strained cage hydrocarbons have long stood as fundamental molecules to explore the limits of chemical stability and reactivity, probe physical properties, and more recently as bioactive molecules and in materials discovery. Interestingly, the nitrogenous congeners have attracted much less attention. Previously absent from the literature, azahomocubanes, offer an opportunity to investigate the effects of a nitrogen atom when incorporated into a highly constrained polycyclic environment. Herein disclosed is the synthesis of 1-azahomocubane, accompanied by comprehensive structural characterization, physical property analysis and chemical reactivity. These data support the conclusion that nitrogen is remarkably well tolerated in a highly strained environment.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. (a) Parent homocubane and cubane skeletons, along with an example of the aza evolution (3). (b) The three possible azahomocubanes containing a tertiary nitrogen atom – positions 1/8, 2/7 (enantiomer 3/6) and 4/5 are interchangeable pairs. (c) Reported azahomocubanes – hypothesised 7 and synthesised 8. (d) 1-Azahomocubane comparative bond distances given in Ångstroms [M062X-D3/Def2TZVPP] – nitrogen atom highlighted in blue, carbon in pale yellow, and hydrogen in white.
Scheme 1
Scheme 1. (a) Retrosynthesis of 4 from 9. (b) Synthesis of spirocyclopropyl methyl azahomocubane (11 and 12; diastereomers tentatively assigned) via nitrene 14.
Scheme 2
Scheme 2. Synthesis of 1-azahomocubane (4), and the corresponding salts (21 and 22), via the seco-azacubane ester (15) arising from an acid promoted azide rearrangement.
Scheme 3
Scheme 3. Ring opened product 24 and azanorsnoutane 25.
Fig. 2
Fig. 2. (a) Calculated geometries of 4 in Ångstroms. (b) X-ray crystal structure analysis of 4 as a 2 : 1 complex with silver perchlorate – ellipsoids shown at 50% probability.
See this image and copyright information in PMC

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