Pioneering Work on Catenanes, Rotaxanes, and a Knotane in the University of Freiburg 1958–1988

Abstract

Research at the University of Freiburg is summarized which aimed at realizing catenanes, rotaxanes, and a molecular knot from 61–62 until 41 years ago. Taking a fresh view at ansa‐compounds – distinct from those in which he had been interested for other reasons before – Arthur Lüttringhaus began to tackle syntheses of catenanes in 1957. The first isolation of a pure catenane (37) succeeded in 1964 jointly with Gottfried Schill. Most of the progress made in the sequel was due to Schill alone or achieved under his direction; in addition, a few follow‐up studies were published without Schill or Lüttringhaus being their authors. The major feats of these endeavors were the syntheses of the following molecules: (1) the first catenanes (38 – de‐acetyl‐41, 74) without a ring in any constituent (this feature makes them unique till today; the catenane 74 holds the additional record of being the only all‐hydrocarbon catenane till now); the first [3]catenanes at all (obtained as a mixture of constitutional isomers C2v‐97 and C2h‐97); the first [3]catenanes exhibiting topological isomerism (89, iso‐89, and neo‐iso‐89); the rotaxanes 70 [which had the design peculiarity of being convertible into a catenane (74)], 113 (Schill's #1‐rotaxane), and 115; the pre‐knotane rac‐dia‐iso‐123 [provided it was obtained and not (only) its topological isomer dia‐iso‐123]. – For due perspectives, pertinent studies of third parties are included, too: 1) Wasserman's reports on the isolation of the catenane 8 are analyzed in great detail; the conclusion is that the identity of 8 was never established. 2) Schill's oscillating rotaxane 70 from 1988, which is subject to a reversible and non‐degenerate ring migration (→ iso‐70), is supplemented by Stoddart's much faster oscillating rotaxane 71 from 1991, which undergoes a reversible and degenerate ring migration (→ 71 instead of → iso‐71) and was dubbed “molecular shuttle”. 3) The first [3]catenanes from the groups of Schill (97; 1969), Sauvage (98 and 99; 1985), and Stoddart (100–102; 1991) are juxtaposed. 4) The Harrisons' synthesis of the rotaxane 106 by a most noteworthy solid‐phase approach (1967) is recalled in the context of Schill's synthesis of the rotaxane 113 (1967 or 1969). 5) Attempts at threading α‐cyclodextrin by long‐chain 1,ω‐dithiols (→ 130) and ring‐closing the latter oxidatively for obtaining catenated disulfides failed in Lüttringhaus' 1957/1958 studies; in contrast, Stoddart's threading permethyl‐β‐cyclodextrin (133) by the long‐chain 1,ω‐diamine 132 and ring‐closing the latter by a double condensation with terephthaloyl dichloride was successful by providing 3 % of the catenated bislactame 134 in 1993. The concluding section characterizes the synthetic strategies towards catenanes and rotaxanes developed in Freiburg as “template‐based”. This differs from the Nobel Prize Committee's assessment.

Knotting matters: orderly molecular entanglements

“…Covalent templates and scaffolds were used in many early attempts at the synthesis of interlocked and entwined molecules. 88 Schill, one of the pioneers of this approach, was unsuccessful in efforts to synthesize a molecular trefoil knot using a covalent template based on quinone. 89 The failure was partly due to the lengthy and rather convoluted synthesis necessary because of the synthetic methods available at the time, but removing the template attached to the putative knotted strand through several chemically robust covalent bonds was also problematic.…”

[2]Catenane Synthesis via Covalent Templating

“…For this work however, we were specially inspired by Schill and colleagues, who, by the synthesis of a catenane, prepared a MiM for the first time and pioneered the field of covalently templated MiM synthesis [25–27] . In one study (Scheme 1, route A ), they took advantage of a directing ketal group to join a macrocycle (in red) to a properly functionalized linear thread (in blue) in a perpendicular fashion [28] .…”

“…[23,24] For this work however,w ew eres pecially inspiredb yS chill and colleagues, who,b yt he synthesis of ac atenane,p repared aM iM for the first time and pioneered the field of covalently templated MiM synthesis. [25][26][27] In one study (Scheme 1, route A), they took advantage of ad irectingk etal group to join am acrocycle (in red) to ap roperly functionalized linear thread( in blue) in ap erpendicular fashion. [28] The resulting intermediate can adopt two conformations, ap rerotaxane-like one 1,w ith the threadp ositioned within the ring, and at rivial one 1',w hich are in an equilibrium lying far to the left.…”

Dynamic Covalent Chemistry for Synthesis and Co‐conformational Control of Mechanically Interlocked Molecules

“…Inspired by the landmark works by Schill, [21] van Maarseveen recently reported an elegant strategy to synthesize [2]catenanes via dynamic covalent templating. The authors had previously reported a way to control conformation of linear molecular chains to access so called quasi [1]catenanes and quasi [1]rotaxanes -molecules with shapes resembling rotaxanes and catenanes but where the different components are permanently connected with covalent bonds.…”

“…[14] Using these reversible covalent bonds, unique dynamic applications in for example sensors, [15][16] functional materials [17] and biomaterials, [18] catalysis, [19] as well as drug discovery [20] have been reported. Although the usefulness of conditionally reversible covalent bonds for assembling mechanically interlocked molecules was recognized early on, [21] it is only recently that dynamic covalent chemistry has been used extensively for the synthesis of rotaxanes, catenanes and knots. [22][23] Dynamic exchange in MIMs can be used for either synthetic or functional purposes (Figure 1).…”