Herbert Brown (1998) - A General Asymmetric Synthesis Based on Chiral Organoboranes

Herbert Brown (1998)

A General Asymmetric Synthesis Based on Chiral Organoboranes

Herbert Brown (1998)

A General Asymmetric Synthesis Based on Chiral Organoboranes

Comment

This is the last talk of H. C. Brown in Lindau, for which a recording is currently available. Brown lectured at Lindau Meetings during twenty years and while his topic, organoboron chemistry, remained a constant during all this time, its dimension expanded significantly. So did the technical possibilities: while the pictures and schemes supporting Browns first Lindau lecture were analogously projected by an aide, the present lecture relies on a computer based slideshow. Unfortunately, Brown’s slides are not available anymore and so, Brown’s 1980 and 1998 lectures have to serve as a case example of the detrimental effect of information technology on the structure of language. While the 1980 lecture is easy to follow, even without seeing the actual projections, the 1998 lecture is almost impossible to grasp in its entire detail.In any case, unless educated in organic chemistry, you will probably ask yourself what that mysterious “ee” is, that Brown repeatedly mentions. One thing that seems to be certain is that the higher the ee the better... and indeed: the ee refers to a special kind of selectivity of an organic reaction, the enantiomeric excess. A reaction with a high ee selectively yields one of two possible enantiomers and may hence be used for so-called asymmetric syntheses. A nice way to understand what enantiomers are is to think of a pair of gloves: they are made from the same materials, they weigh the same and they feel the same but yet they are different, as one fits the right hand and one the left. In other words: they are mirror images. Still, the differences are crucial: fighting cold hands with left hand gloves only would not solve the problem, no matter how many of them are available.What appears to be an idle thought in the field of gloves is of prime importance in pharmaceutical research. Much like gloves, certain drug molecules can only fulfil their purpose if their chirality “fits”, i.e. if they occur as the correct enantiomer. In other instances, they may do a lot of damage. Contergan, a drug given to pregnant women as treatment of morning sickness around 1960 is now well-known for causing severe birth defects. The active substance, thalidomide, occurs as two enantiomers, only one of which can sustain contergan’s disruptive effect on child development.Due to the significant influence of chirality on the efficiency of many bioactive substances, pharmaceutical companies nowadays are required to strictly control impurities by undesired enantiomers. This is why reactions with high ee’s are so desirable. And Brown and his team have developed quite a few of them, as he points out in his talk. An efficient synthetic route to the well-known antidepressant Prozac is only one of many significant results mentioned.The reactions discussed thereby all have one thing in common: the chemical element boron. Brown, who had worked with boron all his scientific life, systematically built up its application in synthetic organic chemistry - from a landmark synthesis of one of the simplest boron compounds, diborane (B2H6), published in 1944, to the asymmetric syntheses of complex pharmaceuticals discussed in this talk.Although it might appear that the end of the flagpole has been reached in this particular area, Brown liked to repeatedly point out in his talks that even supposedly well-researched fields offer a lot of room for surprises. In 1959, when he tried to publish the hydroboration reaction, which can be considered the basis for his share of the 1979 Nobel Prize in Chemistry, reviewers were not in favour, stating that boron compounds had been around for a hundred years already and that no significant effect on organic chemistry could be expected from them. Some 40 years later, Brown’s lecture is a late triumph over this scepticism.Another 12 years later, a former PostDoc in Brown’s lab, Akira Suzuki, should share the 2010 Nobel Prize in Chemistry for his work on organoboron-based, palladium-catalysed cross-couplings. A further success of boron, which Brown was not able to witness anymore: in 2004, at the age of 92, he passed away after a heart attack.David Siegel

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