1,3-dipolar cycloaddition reactions of nitrones with alkenes and alkynes are well-studied reactions in solution-phase organic chemistry. However, the number of studies concerned with their application in solid-phase organic synthesis is rather low compared to other 1,3-dipoles, e.g. azides or nitrile oxides. This tutorial review aims to summarise the main approaches towards the application of nitrones in 1,3-dipolar cycloaddition reactions on solid supports in addition to subsequent transformations with polymer-bound isoxazolidines and reactions using polymer-bound catalysts.
A series of 2-phenylisothiazol-3(2H)-one 1,1-dioxides 14a - q were synthesized by oxidation of isothiazolium perchlorates 12. The inhibition of the serine proteases cathepsin G, chymotrypsin and human leukocyte elastase (HLE) by 14 was investigated. Some 4,5-diphenyl substituted derivatives ( 14i - k) were found to inhibit HLE in a time-dependent manner and exhibited kobs/[I] values > 500 M−1s−1. 14k (kobs/[I] = 2400 M−1s−1), was the most potent HLE inhibitor of this series. Kinetic investigations led to the conclusion that 2-phenylisothiazol-3(2H)-one 1,1-dioxides interact with HLE at the active site as well as at another binding site, resulting in a complex type of inhibition.
In order to study hydrogen bonding networks in cyclic sulfin- and sulfonamides, X-ray structures were determined for 3-oxosultams 3a, c - e, 3-alkoxysultams 5b, f and 3-oxosultim 2f, all of which show predominantly weak intermolecular hydrogen bonds. The 3-oxosultam 3a forms tetrameric units by combining two symmetry-independent molecules through weak aromatic C-H· · ·O-S-O hydrogen bonds without participation of the carbonyl groups. The 3-oxosultam 3c, with two chloro substituents in the N-aryl ring show a polymer arrangement of the molecules through intermolecular association of the SO2 and CO groups also with the aromatic H-atoms of the aryl rings. Sultam 3d shows the first polymer chain in the 3-oxosultam series by the strong O-H· · ·O=C hydrogen bonds without participation of the SO2 group. Two new ‘head-to-head’ dimers with a 10-membered ring are found for 3-alkoxysultams 5b, 5f through weak C-H· · ·O-S-O hydrogen bonds. In the 3-oxosultim 2f weak intermolecular hydrogen bonds are observed to form a two-dimensional network with the two methylene groups, the carbonyl function and the chloro atom but, surprisingly, without the strong S-oxide acceptor group.
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