B.R.S.M. Tet. Lett. Is other people

1Apr/1211

Unnatural Products 4: Tetrahedrane

“Why does the tetrahedrane molecule fascinate the organic chemist? Is it the aesthetic appeal of the topology of the tetrahedron or the hope that the unusual bonding properties of this molecule could lead to otherwise inaccessible knowledge of general importance, or is it indeed the synthetic challenge of the highly reactive - if at all capable of existence - tetrahedrane, together with the sporting ambition to reach the goal first?” – Maier, 1988

This bonus Unnatural Products post was written by guest blogger Ckellz from New Reactions, who has worked on far more strained systems than most of us ever will. If anyone else fancies writing a post, get in touch. Enjoy! --BRSM.

When I first found out that BRSM was doing a series on unusual and platonic hydrocarbons, I immediately became really excited and nostalgic. I spent a good part of my undergraduate research career working on strained systems (which culminated in the synthesis of a highly strained bicyclobutane bearing a CF3 group). During my time in Dr. Tilley's lab tetrahedrane 4 often came up as a topic of discussion (Dr. Tilley's goal is ultimately the synthesis of this elusive molecule) and how we thought it was a very interesting molecule that might actually be quite stable. So when I was reading the posts about cubane, I commented that I had a good deal of knowledge about its smaller C4 cousin. The next morning I received a very nice e-mail from BRSM asking me to do a guest post about tetrahedrane and I jumped at the opportunity!

While most chemists view these sort of strained platonic systems as having no real use, they do provide the organic chemist with unique synthetic challenges and, if a chemist can successfully synthesize one of these molecules, that chemist earns a good deal of prestige within the community. But are they really useless? I'd like to think that they are not and let me use tetrahedrane as an example. 4 has been well studied theoretically and several derivatives of it have in fact been prepared. Theoretical values for ΔHfo298 of tetrahedrane range from approximately 125-130 kcal mol-1. For a molecule of its size, that's quite large, but let me give you some perspective. If we take it to be somewhere in between there, let's say 128 kcal mol-1, we can use the following formula to deduce its ΔHcombo298

C4H4(g) + 5O2(g) →   4CO2(g) + 2H2O(g)

ΔH =  4(-393.5) +2(-241.8) - 563  =  -2.6 MJ mol-1

With this in hand, we can calculate the MJ L-1 of 4 to be -50 MJ L-1 (using a conservative estimate that tetrahedrane in a liquid state has a density of 1.0). Since strained hydrocarbons tend to have densities that exceed 1.0 g mL-1, this number is likely to be much higher. But I did say I want to give you some perspective, right? -50 MJ L-1 is 25% higher than the current leading jet/missile fuel JP-10.

But if a molecule is so strained, can it actually exist? What would it look like? What could keep it from simply falling apart?  To address these questions, I firmly believe that just like cubane, 2, (which also was thought to be impossible to synthesize) 4 will be quite stable. Many studies indicate that, once formed, it will be trapped in an energetic well which would prevent isomerization despite the bent bonds (large degree of s-character) it's likely to have. Supporting this conclusion is the fact that at least nineteen stable derivatives of 4 have been synthesized to date:

The first of these compounds, tetrakis(tert-butyl)tetrahedrane 5, was prepared by Maier in 1978. The original route relied heavily on photolysis but alternatively 5 could be obtained by the reversible isomerization of a cyclobutadiene precursor.

It's interesting to note that 5 was highly stable and was obtained as a crystalline solid. Maier's synthesis set the precedent for work involving tetrahedrane to date: wrap the core with bulky groups with the belief that this would prevent it from falling apart. Later, this concept was called the "corset effect" for obvious reasons. In that same vein, sometime later Maier replaced one of the t-butyl groups with other sterically large groups such as adamantyl, dimethylphenylsilyl, iso-propoxydimethylsilyl, trimethylsilyl, trimethylgermyl and iso-propyl.

It wasn't until 2001-2002 that a somewhat more useful species of tetrahedrane was prepared by Maier: tetrakis(trimethylsilyl)tetrahedrane, 12. One of Maier associates, Akira Sekiguchi, collaborated with him on the synthesis of this compound and has continued to explore its properties.

Most notably, treatment of this compound with methyllithium lead to the preparation of the tris(trimethylsilyl)tetrahedranyllithium, 13. Due to the nature of tetrahedrane's structure, the carbon atoms mimic being acetylenic (sp hybridized) rather than actually sp3. This enhances electron demand and makes the TMS groups of this derivative quite labile to nucleophilic attack. Methyllithium therefore attacks one of the TMS groups to yield tetramethylsilane (ironically also TMS) and the lithiated tetrehedranyl compound. This lithiated compound reacts with a variety of electrophiles (such as the hydrogen on cyclopentadiene or a methyl group in dimethyl sulfate) to give novel tetrahedranes (14 and 15). These compounds can be exposed to air and do not react even up to temperatures of 100 oC, giving credence to my earlier claim that tetrahedrane itself may be very stable.

Sekiguchi has continued to work on preparing new tetrahedranes in the ensuing years since the preparation of tetrahedranyllithium.  Exploiting this lithiated tetrahedrane as a synthon for other tetrahedranes, the dimeric hexakis(trimethylsilyl)tetrahedranyltetrahedrane, 16, was realized in 2005 by a somewhat nifty trick. By combining tetrakis(trimethylsilyl)tetrahdrane with methyllithium in THF, one forms the THF ligated tetrahedranyllithium. To remove any remaining methyllithium, [15]crown-5 was used to extract out  tetrahedranyllithium. Treatment of this ligated species with half an equivalent of copper(I) cyanide at -78 oC formed the cuprate in situ which could then be oxidized with molecular oxygen to give the dimer. Now that's the easy part. To purify it, Sekiguchi and co-workers needed to use 'gel-permeation chromatography in toluene followed by HPLC (MeOH/t-BuOMe 1:1) equipped with a recycling system' to obtain a 3% yield!

Other ventures using tetrahedranyllithium fared much better for Sekiguchi. Preparation of perfluoroaryltetrahedranes proved to be far less difficult. Reacting tetrahedranyllithium with hexafluorobenzene afforded a mixture of 2,3,4,5,6-pentafluoro-1-[tris(trimethylsilyl)tetrahedranyl]benzene and 2,3,5,6-tetrafluoro-1,4-bis[tris(trimethylsilyl)tetrahedranyl]benzene (say those five times fast :P) which could be separated using HPLC to give 36% isolated yield of the former and 25% isolated yield of the latter. Unfortunately, despite their best efforts, Sekiguchi and co-workers could not avoid double addition into hexafluorobenzene due to the fact that the second substitution is much faster than the first. However, by blocking the 4-position on the ring with a phenylacetylene group, selective mono-addition into the aromatic system was realized to give the tetrahedrane substituted extended π-conjugated system in 31% yield.

Most recently, sulfur-substituted tetrahedranes have been prepared by Sekiguchi and co-workers. By reacting tetrahedranyllithium with aryl disulfides, one can obtain very good yields (at least in my opinion) of tetrahedranyl sulfides. Three new tetrahedranes were prepared in this manner: phenyl tris(trimethylsilyl)tetrahedranyl sulfide, 4-nitrophenyl tris(trimethylsilyl)tetrahedranyl sulfide, 2,4-dinitrophenyl tris(trimethylsilyl)tetrahedranyl sulfide in 55%, 52% and 30% yields respectively. Moreover, the simple phenyl system could be oxidized to phenyl tris(trimethylsilyl)tetrahedranyl sulfone using m-CPBA in 90% yield, giving a fourth tetrahedrane!



But where will we go from here? Will Sekiguchi move to putting yet another group on tetrahedrane? What about removing more of the TMS groups? Can one make the tetranitro derivative? Is the corset-effect really necessary at all and, if not, how can we prepare tetrahedrane itself? There are still so many questions to be answered about this tiny molecule. I hope you've enjoyed our tour through tetrahedrane and it history. Ckellz...Signing off...

 

  1. See 5, 6, 7, 8 and 9 for the experimental details of the various Maier preps.

 

Comments (11) Trackbacks (0)
  1. TMS-acetylenes solvolyse to free acetylenes with K2CO3 in methanol, I wonder if they tried a milder method for desylilation than MeLi for the tetrahedrane…

    • As far as I know…No? I thought that as well, I also wondered if there would be a way to take off more than just one silyl group…My guess is that the MeLi worked so well that they are just running with it for now…

  2. Note that you could theoretically replace the carbon atoms in any compound with tetrahedranes (i.e., tetrahedrane itself is “tetrahedranylized” methane). Has anyone looked at tetrahedranylized tetrahedrane (C16H4)? If you tetrahedranylized an infinite number of times you’d get a new form of carbon (vaguely reminiscent of a quasicrystal). Another thought – anyone consider the analog of tetrahedrane with CC inserted into each edge? There are all sorts of interesting possibilities here…

  3. I wonder if it would be possible to make aza-tetrahdrane. The mono-opened form, azabicyclobutane is obtained easily by treating 2,3-dibromo-1-propylamine with BuLi and distillation at atmospheric pressure, it happily co-distills with water and THF at 60C and does not polymerize as long as you keep it away from an acid.

  4. I’m not sure about a diaza or a boron-nitrogen based tetrahedrane, but a all silyl one has been made: http://pubs.acs.org/doi/abs/10.1021/ja0305050 Its even more caged than tetrahedrane!

    • the strain energy of all-Si-tetrahedron should be considerably less than that off tetrahedrane. I heard of explanation why elements with available low-lying d orbitals have less problem with low angles. White phosphorus is perfectly happy forming tetrahedral P4 molecules and R-S-R angle is around 90 degrees.

  5. Whether it is possible in derivate (15) to replace next trimethylsilyl group on lithium and to synthesize di(methyl)-di(trimethylsilyl)tetrahedrane?


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