Protecting-Group-Free Site-Selective Reactions in a Metal–Organic Framework Reaction Vessel

Site-selective
organic transformations are commonly required in
the synthesis of complex molecules. By employing a bespoke metal–organic
framework (MOF, 1·[Mn­(CO)3N3]), in which coordinated azide anions are precisely positioned within
1D channels, we present a strategy for the site-selective transformation
of dialkynes into alkyne-functionalized triazoles. As an illustration
of this approach, 1,7-octadiyne-3,6-dione stoichiometrically furnishes
the mono-“click” product N-methyl-4-hex-5′-ynl-1′,4′-dione-1,2,3-triazole
with only trace bis-triazole side-product. Stepwise insights into
conversions of the MOF reaction vessel were obtained by X-ray crystallography,
demonstrating that the reactive sites are “isolated”
from one another. Single-crystal to single-crystal transformations
of the Mn­(I)-metalated material 1·[Mn­(CO)3(H2O)]Br to the corresponding azide species 1·[Mn­(CO)3N3] with sodium azide, followed
by a series of [3+2] azide–alkyne cycloaddition reactions,
are reported. The final liberation of the “click” products
from the porous material is achieved by N-alkylation
with MeBr, which regenerates starting MOF 1·[Mn­(CO)3(H2O)]Br and releases the organic products, as characterized
by NMR spectroscopy and mass spectrometry. Once the dialkyne length
exceeds the azide separation, site selectivity is lost, confirming
the critical importance of isolated azide moieties for this strategy.
We postulate that carefully designed MOFs can act as physical protecting
groups to facilitate other site-selective and chemoselective transformations.