I’ll interrupt the series of posts on the brilliant article [ Science vol. 377 eabn5582 pp. 1 –> 20 ’22 ] to talk about working with the very frightening diazo methane 61 years ago.
I was able to convince Woodward to let me work on an idea of mine to show that carbenes were generated by photolysis of a diazo compound (this was suspected but not known at the time).
Here’s the idea
l. Condense acrylic acid with cyclopentadiene by a Diels Alder reaction. Because of steric effects the acid points below the ring
2. Form the acyl chloride
3. React with diazoMethane to form the diazocarbonyl (no change in the orientation of the carbonyl relative to the ring.
4. Photolyze — if a carbene is formed, it’s in perfect position to form a cyclopropane on the other side of the ring which if formed would pretty much prove the point.
Diazomethane was known to be quite explosive, and I spent a lot of time tiptoing around the lab when working with it. Combine this with the worst lab technique in the world and I couldn’t get things to work. Subsequently the idea was shown to be correct, and an enormous amount of work has been done on carbenes.
So why interrupt the flow of posts about the brilliant [ Science vol. 377 eabn5582 pp. 1 –> 20 ’22 ] ?
Because Science vol. 377 pp. 649 – 654 ’22 reports a simple (and nonexplosive) way to form carbenes from aldehydes. Here’s what they say
“Common aldehydes are readily converted (via stable a-acyloxy halide intermediates) to electronically diverse (donor or neutral) carbenes to facilitate >10 reaction classes. This strategy enables safe reactivity of nonstabilized carbenes from alkyl, aryl, and formyl aldehydes via zinc carbenoids. Earth-abundant metal salts [iron(II) chloride (FeCl2), cobalt(II) chloride (CoCl2), copper(I) chloride (CuCl)] are effective catalysts for these chemoselective carbene additions to s and p bonds.”
How I wished I had this back then.
Chemiotics II 