Dr Lee Higham
Lee Higham's web page
Air-Stable Chiral Primary Phosphines
(Angewandte Chem., 2006, 45, 7248-7251)
Primary phosphines are often overlooked as useful precursors because they have a fearsome reputation as volatile, toxic and spontaneously flammable (occasionally explosive) compounds. Phosphines such as 1,2-bis(phosphino)ethane and phenyl phosphine can be difficult and dangerous to handle — some suppliers no longer sell primary phosphines in the UK. We have however, recently discovered a new class of air-stable chiral primary phosphines which appear to owe their stability to the relatively large degree of conjugation present in the binaphthyl backbone see photograph.
Even more intriguing is the solution stability of these compounds in bench
chloroform see the chart below.
It is known that the sterically bulky supermesityl phosphine is resistant to
air oxidation, but we seem to have unearthed two trends for non-bulky
aromatic phosphines.
In the neat state the phosphines which are oils are, perhaps unsurprisingly,
more sensitive to oxidation than the solids but when dissolved in bench
chloroform the resistance to oxidation appears to correlate with the degree
of conjugation in the aryl backbone; thus binaphthyl is more stabilising
than naphthyl, which is more stable than phenyl and tetrahydronaphthyl.
We have also studied the coordination chemistry, electrochemistry and acidity of these compounds. Our next paper will describe the use of these phosphines as precursors in preparing new families of chiral ligands for three catalytic asymmetric transformations.
Phosphorus in Medicine
In a collaborative project with Professor Jon Dilworth at Oxford we are
investigating the use of certain phosphorus compounds with multiple
functionality as imaging agents for disease.
Hydrophilic Phosphines
(see, e.g. Dalton, 2004, 45, 7248–7251)
We have a long-standing interest in polar organic and aqueous phase
organometallic chemistry, and we have recently prepared an interesting
chiral derivative. Watch this space!
Phosphorus Ylide Chemistry
(Journal of Organic Chemistry, 2007, 72, 8780–8785)
The Ramirez ylide 1 reacts with substituted acetylenes to give adducts 2
that go on to react further and produce azulenes with a novel
1,3,5,6-substitution pattern.
Azulenes are compounds with numerous applications in cosmetics,
optoelectonics and pharmaceuticals.
We had been investigating whether geminal substituted alkenes could also be used in the reaction but we found that azulenes could not be isolated. From a mechanistic point of view this seemed surprising; we had already shown that a carbonyl group on the β carbon is a prerequisite. We reinvestigated what on the face of it is quite simple chemistry; it had been reported in the literature that the Ramirez ylide reacts with a number of electrophiles at the 2 position of the 5-membered ring; in actual fact we have discovered that, contrary to a number of reports, the position of substitution depends on the identity of the electrophile. Substitution occurs at the 2 position for acetylenes and the nitrosyl group as reported, but for geminal alkenes we get substitution at the 3 position. Contrary to the literature findings, formyl and tricyanovinyl substitution also occurs at the 3 position as established by X-ray crystallography and 2D NMR. Mechanistically, 3 substitution renders azulene formation difficult. |
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