Most of the reactions I run can be split into two broad categories.  Some involve very sensitive compounds, full of fragile protecting groups or strained rings.  These compounds need to be treated with kid gloves, and consequently every step in the synthesis has to be carefully planned, slowly developed from test reactions, with every condition steadily tweaked to optimize yield and refine the purity of the final compound.  It’s not unusual for it to take a month or more to finally get a perfect setup, and the end result is a work of craft, something to be proud of and to show off at conferences.

And then there’s the other kind of reaction.  When your compound is about as sensitive as a brick the conditions really don’t matter.  Is the solvent still empty?  No problem, just grab some wet stuff from the bottle.  Acidic workup?  No worries, nothing’s going to happen as long the pH stays positive.  Heat?  Try to keep it below 150°C, or else the oil bath might start smoking.  On these days the only real question left is “how can I get this transformation done before lunch?”

There’s a couple of books I use to solve this pressing concern.  The first is “Modern Organic Synthesis in the Laboratory,” by Li, Limberakis and Pflum (all three work at Pfizer, of course).  Just what it says on the tin, the book makes a good first stop when you’re unfamiliar with an otherwise common procedure, and acts to distil the several thousand references from a simple Scifinder search to a few good leads.  Nowhere near as complete as something like Smith’s “Organic Synthesis,” it’s a starting point and a quick reference guide, and doesn’t try to be anything else.

The second book is specifically directed towards installing and removing protecting groups, “Protective Groups in Organic Synthesis,” by Wuts and Greene.  Essentially an encyclopaedia, it contains standard procedures for virtually every known protecting group, as well as more obscure conditions for some of the sensitive compounds I was talking about earlier.  The back of the book deserves special mention, because it is filled with reactivity tables, carefully documenting the susceptibility of every moderately common protecting group to the 70 or so most common environmental conditions (a small portion of these tables is reproduced on organic-chemistry.org).  While I’ve never had the time, I think careful study of those reactivity tables would be more instructive than an entire second year organic chemistry course, so grounded are they in basic electronic/steric interactions.

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