A group at GSK has published a paper in Angewandte Chemie on the kinds of reactions that medicinal chemists use, and why they use them. The conclusions will come as no surprise to anyone practicing in the field. The workhorse reactions were condensations (amides, etc.), palladium-catalyzed couplings, and alkylations. And if you look at the reactions used to generate arrays (small libraries) of compounds simultaneously, those reactions almost take over the list.
Why is that? Well, for one thing, because those reactions tend to work. You'll almost always get product out of them - no small thing. You really, really don't want to spend time tweaking a reaction just to make it produce something, not when the odds of any individual product working are still small. And you can also get a good amount of structural diversity off-the-shelf, by using the huge numbers of commercial amines, acids, aryl boronic acids, and so on. They're also fast reactions, for the most part: set 'em up one day, work 'em up the next, and on to the next analogs.
The authors list some criteria that new reactions would need to order to make the list: not fussy about conditions (temperature, time, order of addition, atmosphere, etc.), compatible with polar solvents, tolerant of a wide range of functional groups, easy to dispense, easy to clean up, and so on. They mention that there's been funding in the UK over the last few years (as there has been here) for discovery of new chemistries that would meet this standards, but (reading between the lines) it doesn't seem as if anything major has made it up the charts yet.
Their other take-home is that people who specialize in running arrays can usually do them more efficiently than those who set them up just once in a while. They suggest that it takes a slightly different sort of person to be good at this:
. . . Owing to their focus on and expertise with arrays, we have found that the array chemists can make, purify, analyze, and register array compounds more efficiently than the program medicinal chemists. They are frequently also more effective in delivering a higher percentage of products from the array in greater yield and purity.
The team has a unique skill set and mindset. We have found that an array chemist should be highly organized, show attention to detail, be manually dexterous, be comfortable with repeatedly delivering to deadlines, and have an ability to work with often introverted and occasionally obstreperous program chemists ! This combination of characteristics is uncommon amongst chemists.
As an obstreperous program chemist myself, I should resent that remark. But you know, they're probably right. . .