Molecular LEGO. 1. Substrate-Directed Synthesis via Stereoregular Diels-Alder Oligomerizations

Peter R. Ashton, George R. Brown, Neil S. Isaacs, Daniele Giuffrida, Franz H. Kohnke*, John P. Mathias, Alexandra M Z Slawin, Diane R. Smith, J. Fraser Stoddart, David J. Williams

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

175 Scopus citations


The diastereoselective synthesis and structural characterization of a wide range of wholly-synthetic cyclic and acyclic polyacene derivatives has been achieved. These novel compounds are notable for (i) their rigidity, (ii) their highly-ordered structures, and (iii) the high stereochemical precision which governs their formation. A key feature in the success of the synthetic methodology described is the development of a repetitive Diels-Alder reaction sequence in which three distinct levels of diastereoselectivity are expressed during each cycloaddition involving bisdiene and bisdienophilic building blocks, i.e., each cycloaddition occurs with treble diastereoselectivity. Both the bisdienes and bisdienophiles are based upon the (7-oxa)bicyclo[2.2.1]heptane ring system in which the stereoelectronic characteristics, that are inherent within this rigid bicyclic framework, are used to dictate their subsequent modes of reaction. Importantly, the bisdienes 7 and 18 exhibit different rates of monoand bisaddition of dienophiles to their two exocyclic s-cis-butadiene units. Therefore, a rational, stepwise oligomerization procedure for the synthesis of [12]cyclacene derivatives has been employed in which sequential use is made of thermally-promoted and high pressure-promoted cycloadditions to assemble the desired molecular structures. The exceptionally high solubilities exhibited by many of these adducts in organic solvents have (i) assisted in their isolation and purification by chromatography, (ii) aided their structural characterization by spectroscopic techniques, and (iii) enhanced their potential for further synthetic elaboration. Extending the size of the bisdiene building block from 7 to 26 has allowed the synthesis of a family of undecacene derivatives which are capable of forming [14]cyclacene derivatives. The treble diastereoselectivity that is observed in each cycloaddition between the bisdiene and bisdienophilic building blocks is identified as a kinetically-controlled transition state phenomenon. Bond formation proceeds with the maximum staggering of the bonds under construction with respect to the vicinal bonds located at the bridgehead positions on the bisdienophiles and, subsequently, with the minimization of torsional strain within the rigid bicyclic framework of the dienophile in the transition state. The potential importance of these molecular beltlike compounds as precursors to a wide range of novel hydrocarbon molecules—such as the cyclacenes, the collarenes, and the beltenes—is illustrated by the synthetic progression from the [12]cyclacene derivative we have dubbed kohnkene 13 to [12]collarene 55. Finally, it is suggested that, by extending the role played in the design processes of molecular structures to include information—such as stereoelectronic factors and pyramidalization—that is inherently present within certain structural types, both the controlled creation of chirality and the rapid assembly of highly-ordered three-dimensional molecular structures may be preprogramed.

Original languageEnglish (US)
Pages (from-to)6330-6353
Number of pages24
JournalJournal of the American Chemical Society
Issue number16
StatePublished - Jul 1 1992

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry


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