Amines containing bridged bicyclic carbon skeletons are desirable building blocks for medicinal chemistry. Herein, we report the conversion of bicyclo[1.1.1]pentan-1-amines to a wide range of polysubstituted bicyclo[3.1.1]heptan-1-amines through a photochemical, formal (4 + 2)-cycloaddition of an intermediate imine diradical. To our knowledge, this is the first reported method to convert the bicyclo[1.1.1]pentane skeleton to the bicyclo[3.1.1]heptane skeleton. Hydrolysis of the imine products gives complex, sp 3 -rich primary amine building blocks.
Literature reports describe tetraethynylethylene (TEE)
as unstable
but tetravinylethylene (TVE) as stable. The stabilities of these two
known compounds are reinvestigated, along with those of five unprecedented
TEE-TVE hybrid compounds. The five new C10 hydrocarbons
possess a core, tetrasubstituted CC bond carrying all possible
combinations of vinyl and ethynyl groups. A unified strategy is described
for their synthesis, whereupon cross-conjugated ketones are dibromo-olefinated
then cross-coupled. Due to an incorrect but nonetheless widely held
belief that acyclic π-bond rich hydrocarbons are inherently
unstable, a standardized set of robustness tests is introduced. Whereas
only TVE survives storage in neat form, all seven hydrocarbons are
remarkably robust in dilute solution, generally surviving exposure
to moderate heat, light, air, and acid. The first X-ray crystal structure
of TEE is reported. Subgroups of hybrids based upon conformational
preferences are identified through electronic absorption spectra and
associated computational studies. These new acyclic π-bond rich
systems have extensive, untapped potential for the production of stable,
conjugated carbon-rich materials.
An extremely concise total synthesis of a potent phosphodiesterase-4 inhibitory natural product, selaginpulvilin D, is reported. The synthesis features a one-pot, 3-fold electrophilic aromatic substitution sequence to assemble a 9,9-diarylfluorene core. The approach allows access to useful quantities of a selaginpulvilin natural product for the first time.
<div>Detailed herein is the development of a photochemical intermolecular formal [3+2] cycloaddition between cyclopropylimines and substituted alkenes to generate cyclopentylimines. The Schiff base auxiliary of the cyclopropylimine was designed to enable a masked N-centered radical approach in which the requisite open-shell character was achieved upon excitation with violet light. The cycloaddition products were directly converted to N-functionalized aminocyclopentanes via N-acylation and solvolysis, thus offering a three-step, one-pot procedure for the production of diversely-substituted aminocyclopentanes. The photochemical component of this reaction sequence was demonstrated to operate in continuous flow and was amenable to gram-scale production.</div>
Detailed
herein is the development of a photochemical intermolecular
formal [3+2] cycloaddition between cyclopropylimines and substituted
alkenes to generate aminocyclopentane derivatives. The Schiff base
of the cyclopropylimine was designed to enable a masked N-centered
radical approach in which the requisite open-shell character was achieved
upon excitation with visible light. The cycloaddition products were
directly converted to N-functionalized aminocyclopentanes via solvolysis
and N-acylation. The photochemical component of this reaction sequence
was demonstrated to operate in continuous flow.
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