Ladderanes Get a Step-up

A solid-state intermolecular synthesis of ladderanes that provides gram amounts of these unusual compounds in quantitative yields has been developed by assistant chemistry professor Leonard R. MacGillivray and graduate students Tomislav Frii and the late Xiuchun Gao of the University of Iowa [Angew. Chem. Int. Ed., 43, 232 (2004)].

Ladderanes feature a series of fused cyclobutane rings that chemists believe could impart unique electronic properties or serve as spacers to separate metals or functional groups for a potential new class of optoelectronic materials. Several groups have made short ladderanes with limited success, building them up from halogenated cyclobutenes, from alkenes and alkynes, or by fusing together polyenes [Angew. Chem. Int. Ed., 42, 2822 (2003)]. One problem, MacGillivray notes, is that in solution the ladder precursors are probably too disorganized to align and react properly.

The discovery of natural ladderanes in 2002 also has spurred interest in the molecules. The natural compounds have three or five fused cyclobutane rings and serve as membrane lipids in ammonium-oxidizing bacteria that participate in nitrogen cycling in the oceans. The process by which the bacterial ladderanes are made is still unknown, but it's suspected that enzymes are involved in a process that positions the precursors via noncovalent bonds, allowing them to react.

Following this cue, MacGillivray's group recently developed a template-directed solid-state strategy to preorganize molecules that can then be photodimerized to form targeted compounds [Chem. Comm., 2003, 1306]. For ladderanes, the template is formed by cocrystallizing trans-bis(4-pyridyl)polyenes with 5-methoxyresorcinol. The resorcinol holds the ends of two polyene molecules together through hydrogen-bonding interactions.

The ladderanes are produced by irradiating powdered samples of the templated polyenes with UV light for several days. Using NMR spectroscopy to monitor the reaction, the researchers conclude that the polyenes probably undergo stepwise [2 + 2] cycloaddition reactions that "zip" the molecules together. Using a diene and a triene, the Iowa chemists prepared ladderanes containing three and five cyclobutane rings, respectively.

"It was a pleasant surprise to realize that the approach worked perfectly," MacGillivray says. "We are now focused on pushing the method to construct longer ladders and more complex targets."

"The synthesis of the 3- and 5-ladderanes is a crowning achievement," says chemistry professor Bruce M. Foxman of Brandeis University. "The work provides both a new subclass of solid-state photocycloaddition products and an elegant example of how the careful planning and execution of a solid-state methodology may open the door to a simple, high-yield synthesis of an elusive class of molecules."